Article

Pain catastrophizing is strongly associated with subjective outcomes, but not with inflammatory assessments in rheumatoid arthritis patients

Arthritis Care & Research

August 2017
70(5)

DOI:10.1002/acr.23339

Authors:

Hilde Berner Hammer

Diakonhjemmet Hospital (Norway)

Objectives: Pain catastrophizing is conceptualized as a negative cognitive-affective response to anticipated or actual pain and has been associated with important pain-related outcomes. The objective of this prospective study of established rheumatoid arthritis (RA) patients was to explore how pain catastrophizing was related to patient-reported outcomes (PROs), composite scores and assessments of inflammatory activity. Methods: RA patients starting bDMARD were examined at baseline and after 1, 2, 3, 6 and 12 months with PROs (joint pain/patient's global VAS, MHAQ, RAID score), clinical and laboratory assessments (tender/swollen joint count, assessor's global VAS, ESR/CRP), ultrasound (US) (grey scale/power Doppler of 36 joints and 4 tendons) and pain catastrophizing. The composite scores DAS28, CDAI and SDAI were calculated. Statistical calculations included independent samples T-test, paired samples T-test, one-way ANOVA, Pearson's correlations, linear and logistic regression. Results: Of 209 patients included, 152 (72.7%) completed 12 months follow-up. Pain catastrophizing, PROs, clinical and inflammatory assessments decreased significantly (p<0.001). Pain catastrophizing was strongly correlated with the PROs and composite scores (p<0.001) but not with the inflammatory parameters (swollen joint count, CRP, GS/PD US). Patients with higher levels of pain catastrophizing had higher PROs and composite scores during the study (p<0.001) but not inflammatory assessments. Baseline pain catastrophizing was negatively associated with achievement of remission at 6 and 12 months (p<0.05). Conclusions: Pain catastrophizing was strongly associated with PROs and composite measures, but not markers of inflammation. High levels of pain catastrophizing reduced the likelihood of achieving composite score remission and should be a factor to consider in a treat to target strategy. This article is protected by copyright. All rights reserved.

The Adherence and Outcomes Benefits of Using a Connected, Reusable Auto-Injector for Self-Injecting Biologics: A Narrative Review

Article

Full-text available

Sep 2023

Many biologics are now self-administered by patients at home. A variety of self-injection devices are available, including vials and syringes, prefilled syringes, and spring-driven prefilled pens or auto-injectors. Each has advantages and drawbacks, and different devices suit different patients. For example, some patients have difficulty achieving consistent and successful self-injection due to poor manual dexterity, or experience anxiety at the prospect of self-injection or injection-site pain. These factors can reduce patients’ medication adherence and overall experience. Furthermore, while self-injection brings patients many benefits, the proliferation of single-use injection devices has implications for environmental sustainability, including the reliance on single-use plastics, repeated freighting requirements, and need for incineration as hazardous waste. Recently developed, innovative electromechanical auto-injector devices offer technological enhancements over existing devices to overcome some of these issues. Features include customisable injection speeds or durations, consistent rate of injection, electronic injection logs and reminders, and step-by-step, real-time instructions. Indeed, a growing body of evidence points to higher adherence rates among patients using electromechanical devices compared with other devices. Further, with time, the reusability of electromechanical devices may prove to lighten the environmental impact compared with disposable devices, especially as research continues to optimise their sustainability, driven by increased consumer demands for environmental responsibility. This narrative review discusses the differences between prefilled syringes, spring-driven prefilled pens, and electromechanical devices. It also explores how these features may help reduce injection-associated pain and anxiety, improve patient experience, connectivity and adherence, and drive sustainability of biologic drugs in future.

Non-Inflammatory Pain in Inflammatory Arthritis

Article

Full-text available

Dec 2022

Dhivya Das

"Non-inflammatory" pain, pain that is not associated with measures of inflammation, is common in patients with inflammatory arthritis including rheumatoid arthritis (RA). One important cause of non-inflammatory pain is concomitant fibromyalgia. Systematic review has shown that fibromyalgia is common in inflammatory arthritis including RA affecting 1 in 5 patients and is associated with higher disease activity scores due to inflated tender joint count and patient global assessment. Consequently, many patients with RA and concomitant fibromyalgia may fail to reach treatment target and switch to alternate disease modifying drugs frequently. European Alliance of Association for Rheumatology has highlighted that concomitant fibromyalgia is an important consideration in assessing difficult-to-treat RA. The incidence and prevalence of fibromyalgia are higher in RA than the general population raising the possibility that fibromyalgia may be "secondary "to RA rather than a concomitant disease. The precise mechanisms whereby patients with RA develop fibromyalgia are unknown. In this review, we discussed fibromyalgia in RA, its clinical impact and epidemiology as well as data suggesting fibromyalgia might be "secondary". Lastly, we reviewed potential pathogenic mechanisms which included inflammatory cytokines sensitizing nociceptive neurones, temporal summation, also known as windup, from chronic pain and impaired coping from poor quality sleep and mental well-being. Deciphering the exact mechanisms may lead to treatment strategies that prevent development of secondary fibromyalgia and will address a common factor associated with difficult to treat RA.

Early response to JAK inhibitors on central sensitization and pain catastrophizing in patients with active rheumatoid arthritis

Article

Full-text available

May 2022
InflammoPharmacology

Objectives To evaluate the effect of 4 weeks of treatment with Janus kinase inhibitors (JAKis) on central sensitization (CS) and pain catastrophizing, and to determine the pain-related variables predictive of disease activity improvement, in patients with active rheumatoid arthritis (RA). Methods Consecutive RA patients with active disease starting a JAKi have been enrolled in this prospective observational study. Patients have been assessed at baseline and after 4 weeks of treatment. The evaluation was comprehensive of disease activity [Simplified Disease Activity Index (SDAI) and ultrasonographic (US) score] and of questionnaires aimed at investigating primarily CS [Central Sensitization Inventory (CSI)] and pain catastrophizing [Pain Catastrophizing Scale (PCS)]. Differences ( Δ values) between the final and baseline were studied with the t test, Δ values of the variables were correlated with each other using Pearson’s test, and predictor variables for improvement in SDAI were also investigated using multivariate regression analysis. Results A total of 115 patients were evaluated. Overall, all variables demonstrated significant improvement between baseline and final except the US score. In particular, CSI decreased from 36.73 to 32.57 ( p < 0.0001), PCS decreased from 32.46 to 28.72 ( p = 0.0001). Δ SDAI showed a significant correlation with both Δ PCS and Δ CSI ( r = 0.466 and 0.386, respectively, p < 0.0001). Δ PCS was the only variable predictive of an improvement in SDAI (coefficient = 0.500, p = 0.0224). Conclusion JAKis would appear to have a positive effect on pain-related variables, particularly CS and pain catastrophizing, for the genesis of which extra-synovial mechanisms are responsible.

Swollen, but not tender joints, are independently associated with ultrasound synovitis: Results from a longitudinal observational study of patients with established rheumatoid arthritis

Article

Sep 2019
ANN RHEUM DIS

Objectives: Joint swelling and tenderness are considered a proxy for inflammation in patients with rheumatoid arthritis (RA). With ultrasound-detected inflammation as reference, our objectives were to explore on patient and joint level the associations between ultrasound synovitis and joint swelling, tenderness and patient-reported joint pain (PRJP). Methods: 209 patients with established RA were examined six times during 12 months with assessment of 32 joints in upper/lower extremities for joint swelling/tenderness and Grey scale (GS)/power Doppler (PD) synovitis. PRJP was assessed on a manikin. Correlations between different sum scores were at each examination calculated using Spearman's rho (r), agreement at joint level was examined by Cohen's kappa and logistic regression models were used to explore the associations between joint assessment and GS/PD scores. Results: At patient level, swollen joints were strongly correlated with GS/PD sum scores (r=0.64-0.88), while tender joints were primarily associated with PRJP (r=0.54-0.68). At joint level, GS/PD pathology had higher agreement with swelling (kappa 0.54-0.57) than tenderness (kappa 0.20-0.21) or PRJP (0.23-0.25). Higher percentages of joints were swollen according to increasing GS/PD scores, independently of joint tenderness. However, joints being tender, but not swollen, were not associated with GS/PD scores. Receiver operating curves showed swollen but not tender joints to be associated with GS/PD scores. Conclusions: Swollen joints were strongly associated with ultrasound detected synovitis at both patient and joint level, while this association was not found for tender joints. These results may question if tender joints reflect ongoing inflammation in established RA.

Serum etanercept concentrations in relation to disease activity and treatment response assessed by ultrasound, biomarkers and clinical disease activity scores: Results from a prospective observational study of patients with rheumatoid arthritis

Article

Full-text available

Dec 2021

Objectives To identify the therapeutic range for etanercept and to assess the incidence of anti-etanercept antibody formation. Methods Associations between etanercept serum concentration and disease activity as well as treatment response were examined in a longitudinal observational study of rheumatoid arthritis patients starting etanercept. Disease activity was assessed by ultrasound (grey scale and power Doppler), 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index, plasma calprotectin and C reactive protein. Etanercept concentration and anti-etanercept antibodies were analysed using automated in-house fluorescence assays. Results A total of 89 patients were included, whereof 66% were biological disease-modifying antirheumatic drug (DMARD) naïve and 91% used concomitant synthetic DMARD. At 3 months, the median etanercept concentration was 1.8 (IQR 1.1–2.5) mg/L. Longitudinal associations were found between etanercept concentration and disease activity assessed by plasma calprotectin, C reactive protein and DAS28, but not between etanercept concentration and improvement in disease activity by any of the parameters at 3, 6 or 12 months of treatment. Etanercept concentrations were not significantly different among patients who achieved response or remission, compared with non-response or non-remission. Hence, no therapeutic range could be identified. None of the patients developed anti-etanercept antibodies. Conclusion Despite the use of sensitive and objective markers of inflammation, a therapeutic range could not be identified for etanercept. Hence, this study suggests that proactive therapeutic drug monitoring is unlikely to benefit rheumatoid arthritis patients treated with etanercept, but a potential benefit in certain clinical situations cannot be excluded.

Central sensitization, illness perception and obesity should be considered when interpreting disease activity in axial spondyloarthritis

Article

Full-text available

Jan 2021

Objectives Many patients with axial spondyloarthritis (axSpA) report persistent pain even when treated with anti-inflammatory agents. Our aim was to explore the presence of central sensitization (CS) and different types of illness perceptions in patients with axSpA, and to assess their associations with disease activity assessments. Methods Consecutive outpatients from the GLAS cohort were included. Besides standardized assessments, patients filled out the Central Sensitization Inventory (CSI), Illness Perception Questionnaire (IPQ-R) and Pain Catastrophizing Scale (PCS). Univariable and multivariable linear regression analyses were used to investigate the association between questionnaire scores, patient characteristics and disease activity assessments ASDASCRP, BASDAI and CRP. Results We included 182 patients with a mean symptom duration of 21.6 years. Mean ASDASCRP was 2.1, mean BASDAI 3.9, and median CRP 2.9. Mean CSI score was 37.8 (scale 0–100) and 45% of patients scored ≥40, indicating a high probability of CS. CSI score, IPQ-R domain identity (number of symptoms the patient attributes to their illness), and IPQ-R domain treatment control (perceived treatment efficacy), and obesity were significantly and independently associated with both ASDASCRP and BASDAI, explaining a substantial proportion of variation in these disease activity scores (R2=0.35 and R2=0.47, respectively). Only obesity was also independently associated with CRP. Conclusion CS may be common in patients with long-term axSpA. CS, as well as specific illness perceptions and obesity were all independently associated with the widely used (partially) patient-reported disease activity assessments ASDASCRP and BASDAI. Treating physicians should take this into account in the follow-up and treatment of their patients.

Understanding and Minimising Injection-Site Pain Following Subcutaneous Administration of Biologics: A Narrative Review

Article

Full-text available

Dec 2020

Injection-site pain (ISP) is a subjective side effect that is commonly reported with the subcutaneous administration of biological agents, yet it may only be a concern to some. Multiple factors related to the product formulation, such as pH, volume and excipients, and/or to the injection process have the potential to contribute to ISP, while patient-related factors, such as low body weight, gender and age, can make an individual more susceptible to experiencing ISP. While total elimination of ISP remains unlikely with any subcutaneously administered agent, it can be minimised by helping the patient to develop a confident and competent injection technique via robust and effective training. Careful management of patient expectations along with open discussion regarding the potential risk of ISP may serve to minimise treatment-related anxieties and, importantly, allow the patient to remain in control of his/her treatment. Other interventions to help minimise ISP include psychological interventions, allowing biologics to reach room temperature prior to injection, using the most suitable injection device for the individual patient and selecting an alternative drug formulation, when available. Productive patient–physician communication remains important in order to support and optimise treatment experience and adherence, while also providing the opportunity for patients to discuss any ISP-related issues.

Fatigue is cross-sectionally not associated with objective assessments of inflammation, but changes in fatigue are associated with changes of disease activity assessments during biologic treatment of patients with established rheumatoid arthritis

Article

Full-text available

Oct 2020

Objective The associations between fatigue and disease activity in patients with rheumatoid arthritis (RA) have not been defined. The present objectives were to explore in RA patients the cross-sectional and longitudinal relation of fatigue with subjective as well as objective assessments of disease activity. Methods RA patients were consecutively included when initiating biologic disease-modifying anti-rheumatic drugs (DMARDs) and assessed at baseline, 1, 2, 3, 6, and 12 months with investigation of fatigue, patient-reported outcome measures (PROMs; joint pain and patient’s global disease activity, MHAQ, pain catastrophizing, Mental Health score), clinical examinations (examiner’s global disease activity, 28 tender and swollen joint counts), and laboratory variables (ESR, CRP, calprotectin). Ultrasound examinations (semi-quantitative scoring (0–3)) with grey scale and power Doppler were performed of 36 joints and 4 tendons. Statistics included one-way analysis of variance, Pearson’s correlations, and multiple linear and logistic regression analysis. Results A total of 208 RA patients (mean (SD) age 53.2 (13.2) years, disease duration 9.8 (8.5) years) were included. Fatigue levels diminished during follow-up (mean (SD) baseline/12 months; 4.8 (2.8)/3.0 (2.5) ( p < 0.001)). Substantial correlations were cross-sectionally found between fatigue and PROMs (median (IQR) r=0.61 (0.52-0.71)) but not with the objective inflammatory assessments. During follow-up, baseline fatigue was associated with PROMs ( p < 0.001) but not with objective inflammatory assessments. However, change of fatigue was associated with change in all variables. Higher baseline fatigue levels were associated with lower clinical composite score remission rates. Conclusion Fatigue was cross-sectionally associated to subjective but not to objective disease assessments. However, change of fatigue during treatment was associated to all assessments of disease activity. Trial registration number Anzctr.org.au identifier ACTRN12610000284066, Norwegian Regional Committee for Medical and Health Research Ethics South East reference number 2009/1254 Key Points • In this longitudinal study of patients with established RA, fatigue was associated with patient reported outcome measures at each visit, but not with objective assessments of inflammation including calprotectin and comprehensive ultrasound examinations .• Changes in fatigue during biological treatment were associated with changes in patient reported outcome measures, clinical, laboratory and ultrasound assessments .• Baseline fatigue was associated with all patient reported outcome measures, but not objective assessments of inflammation at all the prospective visits .• Higher baseline fatigue levels were associated with lower remission rates as assessed by clinical composite scores .

Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis

Article

Full-text available

Oct 2020

Background Musculoskeletal ultrasound (MSUS) and the multi-biomarker disease activity (MBDA) score are outcome measures that may aid in the management of rheumatoid arthritis (RA) patients. This study evaluated tofacitinib response by MSUS/MBDA scores and assessed whether baseline MSUS/MBDA scores or their early changes predict later clinical response. Methods Twenty-five RA patients treated with tofacitinib were assessed at baseline, 2, 6 and 12-weeks. Power doppler (PDUS) and gray scale (GSUS) ultrasound scores, MBDA score, clinical disease activity index (CDAI), and disease activity score (DAS28) were obtained. Pearson correlations and multiple linear regression models were used to evaluate associations and identify predictors of response to therapy. Results MSUS, MBDA scores, CDAI, and DAS28 improved significantly over 12 weeks ( p < 0.0001). Baseline MSUS and MBDA score correlated with each other, and with 12-week changes in CDAI/DAS28 (r = 0.45–0.62, p < 0.05), except for GSUS with DAS28. Two-week change in MSUS correlated significantly with 12-week changes in CDAI/DAS28 (r = 0.42–0.57, p < 0.05), except for early change in PDUS with 12-week change in CDAI. Regression analysis demonstrated significant independent associations between baseline PDUS/MBDA score and 6-week change in CDAI/DAS28, with adjustment for baseline CDAI/DAS28 (all p < 0.05); and between baseline MBDA scores and 12-week change in DAS28 ( p = 0.03). Conclusions RA patients treated with tofacitinib for 12 weeks demonstrated improvement by clinical, imaging, and biomarker end-points. Baseline PDUS and MBDA score were predictive of CDAI and DAS28 responses. This is the first study to evaluate early measurements of MSUS and MBDA score as predictors of clinical response in RA patients treated with tofacitinib. Trial registration ClinicalTrials.gov NCT02321930 (registered 12/22/2014).

Musculoskeletal ultrasonography versus conventional radiography: Correlation with DAS28 and MDHAQ scores in early rheumatoid arthritis

Article

Full-text available

Dec 2024
J INT MED RES

Objectives To compare the value of musculoskeletal ultrasound (MSUS) with conventional radiography in the detection of patients with early rheumatoid arthritis (RA) and to correlate the sonographic findings with disease activity, and functional disability scores. Methods Patients >18 years of age with RA ≤2 years who satisfied the 2010 EULAR/ACR classification criteria for rheumatoid arthritis and disease activity score 28 (DAS28) >2.6, were enrolled. Plain radiographs and MSUS examinations were performed on 18 joints bilaterally. DAS28 and multi-dimensional health assessment questionnaire (MDHAQ/RAPID) scores were assessed. Results Forty patients (35 women, 5 men), mean age 41 ± 12 years, and mean disease duration 11 ± 5 months, were included. In total, 720 joints were examined. The number of hand joints affected by erosions via MSUS was 3.28-fold the number detected by X-ray. Sonographic evidence of synovitis and active erosion significantly correlated with MDHAQ, DAS28 and inflammatory biomarkers. Conclusion Joint sonography was superior to conventional radiography in early detection of structural joint damage and active disease in patients with early RA which correlated with disease activity and functional ability scores.

Raspodjela reumatologa u Hrvatskoj -izazovi centralizacije i heterogenosti reumatološke struke Distribution of rheumatologists in Croatia -challenges of centralization and heterogeneity of the rheumatology workforce

Article

Full-text available

Jul 2024
Lijec Vjesn

Comparative analysis of centrally mediated and inflammatory pain experiences amongst patients diagnosed with rheumatoid arthritis: A multimethods study

Article

Full-text available

Jun 2024
HEALTH EXPECT

Background The identification of pain originating from distinct biological processes may lead to individualised pain treatment. In this study, we aimed to explore the pain experiences of patients with rheumatoid arthritis (RA), differentiating between those predominantly exhibiting features of peripheral inflammatory versus centrally mediated pain. Methods Through a multimethods approach we (i) quantitatively analysed the differences in pain descriptors between patients diagnosed with RA experiencing peripheral inflammatory and centrally mediated pain, utilising the Short Form‐McGill Pain Questionnaire which includes the pain visual analogue scale (VAS) and (ii) qualitatively explored their subjective pain experiences grounded in the biopsychosocial model, commonly applied in chronic pain. Results Participants with centrally mediated pain reported higher pain scores on the VAS, used a wider range of pain descriptors, and a higher proportion selected each descriptor compared to those with inflammatory pain (p < .001). The qualitative analysis revealed the centrally mediated pain group's experiences were overwhelming and relentless, struggling to precisely articulate the nature of their pain. In contrast, individuals with inflammatory pain expressed their pain in more tangible terms and shared their adaptive and coping strategies. Importantly, both groups revealed the substantial psychological, functional and social impacts of their pain, highlighting the often ‘invisible’ and misunderstood nature of their symptoms. Conclusion This study has gained a deeper insight into the pain experiences of patients living with RA, particularly in differentiating between centrally mediated and inflammatory types of pain, potentially facilitating a more individualised approach to pain treatment. Patient Contribution Patients actively participated in the study conception and design. This engagement includes collaboration with key stakeholders, such as members of the National Rheumatoid Arthritis Society and Patient Research Partners (PRPs), who provided continuous feedback and guidance throughout the research process. Specifically, the qualitative element was coproduced with two PRPs, who were involved in co‐leading the focus groups and data analysis.

Effect of Central Sensitization in Patients with Familial Mediterranean Fever, Axial Spondyloarthritis, and Both Diseases

Article

Full-text available

Sep 2023

Objective: Our aim in this study was to evaluate the level of central sensitization (CS) in patients having familial Mediterranean fever (FMF), axial spondyloarthritis (axSpA), and both diseases (axSpA/FMF). Methods: This study included 30 FMF, 30 axSpA, 30 axSpA/FMF patients, and 30 healthy controls (HCs). The presence of CS was investigated by the Central Sensitization Inventory (CSI) questionnaire. In order to evaluate the effect of CS on patient groups, clinical features, disease activity, quality of life, sleep quality, depression, and anxiety frequency were examined. The patients were divided into groups according to the presence and severity of CS and their results were compared. Results: The mean age of all participants was 28.4±5.7 years and 67 (55.8%) of them were male. The erythrocyte sedimentation rate (ESR) value was significantly higher in axSpA and axSpA/FMF groups than in FMF and HCs groups (p<0.001). ESR value was significantly higher in the FMF group than in the HCs group (p<0.001). C-reactive protein (CRP) value was significantly higher in the axSpA/FMF group than in the axSpA and HCs groups (p=0.001). CSI-Part A value was significantly higher in the axSpA, FMF, and axSpA/FMF group than in the HCs group (p<0.001). CSI-Part A value did not differ significantly between axSpA/FMF, axSpA, and FMF groups (p>0.05). The presence of chronic fatigue syndrome was found to be significantly higher in the FMF group than in the axSpA and HCs groups (p<0.05). Fibromyalgia syndrome was significantly higher in the axSpA/FMF group than in the axSpA, FMF, and HCs groups (p<0.05). Conclusions: In this study, the CS score was found to be significantly higher in axSpA and FMF patients compared to the HCs group. There was no difference between the disease groups in terms of CS score.

Remission, response, retention and persistence to treatment with disease-modifying agents in patients with rheumatoid arthritis: a study of harmonised Swedish, Danish and Norwegian cohorts

Article

Full-text available

Sep 2023

Objective Precision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study cohorts can be achieved and investigate how the observed proportions reaching remission vary across remission criteria, study types, disease-modifying antirheumatic drugs (DMARDs) and countries, and how they relate to other treatment outcomes. Methods We used data from eight existing large-scale, clinical RA registers and a pragmatic trial from Sweden, Denmark and Norway. In these, we defined three types of treatment cohorts; methotrexate monotherapy (as first DMARD), tumour necrosis factor inhibitors (TNFi) (as first biological DMARD) and rituximab. We developed a harmonised study protocol defining time points during 36 months of follow-up, collected clinical visit data on treatment response, retention, persistence and six alternative definitions of remission, and investigated how these outcomes differed within and between cohorts, by treatment. Results Cohort sizes ranged from ~50 to 22 000 patients with RA. The proportions reaching each outcome varied across outcome metric, but with small to modest variations within and between cohorts, countries and treatment. Retention and persistence rates were high (>50% at 1 year), yet <33% of patients starting methotrexate or TNFi, and only 10% starting rituximab, remained on drug without other DMARDs added and achieved American Congress of Rheumatology/European Alliance of Associations for Rheumatology or Simplified Disease Activity Index remission at 1 year. Conclusion Harmonisation of data from different RA data sources can be achieved without compromising internal validity or generalisability. The low proportions reaching remission, point to an unmet need for treatment optimisation in RA.

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF-inhibitor: results from 13 European registries

Article

Full-text available

Jun 2023

Objectives: In bio-naïve patients with Psoriatic arthritis (PsA) initiating a Tumour Necrosis Factor inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. Methods: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes, were defined as common predictors. Results: In the pooled cohort (n = 13 369), six-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6,954, n = 5,275 and n = 13 369, respectively). Baseline predictors of remission, moderate response and 12-month drug retention were identified, five common across all three outcomes. Odds ratios (95% confidence interval) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (< 2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP >10 vs ≤ 10 mg/l: 1.52 (1.22-1.89) and one mm increase in patient fatigue score: 0.99 (0.98-0.99). Conclusion: Baseline predictors of remission, response and adherence to TNFi were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalisable from the country- to disease-level.

Design Development of the SMARTCLIC®/CLICWISE® Injection Device for Self-Administered Subcutaneous Therapies: Findings from Usability and Human Factor Studies

Article

Full-text available

May 2023
ADV THER

Introduction: An easy-to-use, multiuse, single-patient, electromechanical autoinjector, the SMARTCLIC®/CLICWISE® injection device, was recently developed to improve the self-administration options available to patients with chronic inflammatory disease treated with biologic agents. An extensive series of studies were conducted to guide the design and development of this device and to ensure its safety and effectiveness. Methods: Participants in two user preference studies and three formative human factor (HF) studies evaluated evolving iterations of the autoinjector device, dose dispenser cartridge, graphical user interface, and informational materials; participants in a summative HF test subsequently assessed the final proposed commercially representative product. In the user preference studies, rheumatologists and patients with chronic inflammatory disease, interviewed online and in-person, provided feedback on the design and functionality of four prototypes. In the HF studies, the safety, effectiveness, and usability of adapted prototypes were assessed under simulated-use conditions by patients with chronic inflammatory disease, caregivers, and healthcare professionals (HCPs). The safety and effectiveness of the final refined device and system were confirmed in a summative HF test by patients and HCPs in simulated-use scenarios. Results: Rheumatologists (n = 204) and patients (n = 39) interviewed in the two user preference studies provided feedback on the device size, feature ergonomics, and usability that guided prototype development in the subsequent formative HF studies. Observations from patients, caregivers, and HCPs (n = 55) participating in the latter studies yielded additional critical design revisions that culminated in development of the final device and system. Of 106 injection simulations conducted in the summative HF test, all resulted in successful medication delivery, and no potential harms were associated with injection-related use events. Conclusion: Findings from this research facilitated development of the SmartClic/ClicWise autoinjector device and demonstrated that it could be used safely and effectively by participants representative of the intended-use population of patients, lay caregivers, and HCPs.

The relationship between meaning of life, perceived social support, spiritual well-being and pain catastrophizing with quality of life in migraine patients: the mediating role of pain self-efficacy

Article

Full-text available

Jan 2023

Background Migraine is a neurological disease that has several physical and psychological complications, which is characterized by disability and impaired quality of life. Aims The aim of this study was to explore the mediating role of pain self-efficacy in the relationship between meaning of life, perceived social support, spiritual well-being and pain catastrophizing with quality of life in migraine sufferers. The relationship between these factors with quality of life (QOL) was not fully explored in migraine patients. Method This study was a correlational study of structural equations. Therefore, 300 patients with migraine who referred to one of the specialized neurological treatment centers in Zanjan in 2021 were recruited based on the inclusion criteria. Patients also completed the World Health Organization Quality of Life Scale (WHOQOL-BREF), Meaning in Life Questionnaire, Multidimensional Scale of Perceived Social Support, Spiritual Well-Being Scale, Pain Catastrophizing Scale, Pain Self-Efficacy Questionnaire. Finally, the hypotheses were then analyzed with correlation coefficient and path analysis method by using SPSS-26 and LISREL-10.2 programs. Results The results of the present study showed that pain self-efficacy has a mediating role in the relationship between meaning of life and quality of life (B = 0.015), perceived social support with quality of life (B = 0.022), spiritual well-being with quality of life (B = 0.021), as well as pain catastrophizing with quality of life (B = − 0.015). Conclusion According to the results of this study, by considering the role of self-efficacy of pain, it is possible to develop the programs to strengthen and improve the meaning of life, perceived social support, spiritual well-being and also reduce pain catastrophizing, in order to improve the quality of life of patients with migraine.

Exploring pain catastrophizing and its associations with low disease activity in rheumatic inflammatory disorders

Article

Full-text available

Jan 2023
RHEUMATOL INT

Pain catastrophizing is a maladaptive mechanism associated with the exaggerated experience of pain, increased rumination and feelings of helplessness. The main objective of this study was to explore whether increased pain catastrophizing is independently associated with a lower proportion of low disease activity (LDA) in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA). Demographics, comorbidities, treatment, disease activity measures and patient-reported outcome data were recorded in RA, PsA and axSpA patients. Pain catastrophizing score (PCS) was assessed using a standardised questionnaire. For each diagnosis, composite disease activity scores with distinct cut-off values for LDA, i.e. DAS28-CRP (RA), DAPSA (PsA) and ASDAS-CRP (axSpA) were calculated and used as the dependent variable in logistic regression reflecting LDA achieved. A total of one thousand two hundred and twenty nine patients were included: 580 with RA, 394 with PsA and 255 with axSpA. In the multivariable analysis, pain catastrophizing was independently associated with LDA rates in axSpA (OR 0.33, 95% CI [0.12, 0.88]) amongst tested groups. In RA (OR 0.90, 95% CI [0.64, 1.28]) and PsA (OR 0.77, 95% CI [0.55, 1.07]), a statistically significant association was not observed. Higher PCS was independently associated with not achieving LDA in axSpA. Our data, however, indicate that pain catastrophizing, which also reflects a patient’s personality traits and coping abilities, plays a less important role for the patient than general pain perception.

Mitochondrial function, grip strength, and activity are related to recovery of mobility after a total knee arthroplasty

Article

Full-text available

Nov 2022
CTS-CLIN TRANSL SCI

Low muscle quality and a sedentary lifestyle are indicators for a slow recovery after a total knee arthroplasty (TKA). Mitochondrial function is an important part of muscle quality and a key driver of sarcopenia. However, it is not known whether it relates to recovery. In this pilot study, we monitored activity after TKA using a wrist mounted activity tracker and assessed the relation of mitochondrial function on the rate of recovery after TKA. Additionally, we compared the increase in activity as a way to measure recovery to traditional outcome measures. Patients were studied 2 weeks before TKA and up to 6 months after. Activity was monitored continuously. Baseline mitochondrial function (citrate synthase and complex [CP] 1–5 abundance of the electron transport chain) was determined on muscle tissue taken during TKA. Traditional outcome measures (Knee Injury and Osteoarthritis Outcome Score [KOOS], timed up‐and‐go [TUG] completion time, grip, and quadriceps strength) were performed 2 weeks before, 6 weeks after, and 6 months after TKA. Using a multivariate regression model with various clinical baseline parameters, the following were significantly related to recovery: CP5 abundance, grip strength, and activity (regression weights 0.13, 0.02, and 2.89, respectively). During recovery, activity correlated to the KOOS‐activities of daily living (ADL) score (r = 0.55, p = 0.009) and TUG completion time (r = −0.61, p = 0.001). Mitochondrial function seems to be related to recovery, but so are activity and grip strength, all indicators of sarcopenia. Using activity trackers before and after TKA might give the surgeon valuable information on the expected recovery and the opportunity to intervene if recovery is low.

The associations of psychological symptoms and cognitive patterns with pain and pain sensitization in people with hand osteoarthritis

Article

Full-text available

May 2022

Objective To examine whether psychological symptoms and cognitive patterns are associated with self-reported pain and pain sensitization in people with hand osteoarthritis (OA). Design In the Nor-Hand study (n = 300), people with hand OA self-reported psychological symptoms (Hospital Anxiety and Depression Scale), cognitive patterns (Pain catastrophizing Scale and Arthritis Self-Efficacy Scale) as well as their pain severity in hands, overall pain and multi-joint pain. Central pain sensitization was measured clinically by temporal summation and pressure pain threshold tests. We examined whether psychological symptoms and cognitive patterns were cross-sectionally associated with pain using linear regression. Beta coefficients (β) per one standard deviation of the independent variable were presented. Stratified analyses were performed in cases of significant interactions (p < 0.10). Results Higher levels of anxiety and depressive symptoms and pain catastrophizing and low levels of self-efficacy were statistically significantly associated with higher levels of hand pain by Numeric Rating Scale than (β = 0.43, 0.48 and −0.57, respectively). Similar associations were found for overall pain, but not for measures of central pain sensitization. In stratified analyses, anxiety and depressive symptoms were more strongly related with pain in subgroups with younger age and higher comorbidity burden. Pain catastrophizing was more strongly related with pain in subgroups with younger age, overweight/obesity, higher comorbidity burden and poor sleep. Conclusion Psychological symptoms and cognitive patterns were associated with self-reported OA pain, especially in people with younger age, overweight/obesity, higher comorbidity burden and poor sleep. No associations were found for psychological symptoms and cognitive patterns with pain sensitization.

Improvement in disease activity among patients with rheumatoid arthritis who switched from intravenous infliximab to intravenous golimumab in the ACR RISE registry

Article

Full-text available

Mar 2022

Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR’s Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6–9- and 9–12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6–9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p < 0.0001) and were durable through 9–12 months of treatment. Real-world patients with moderate-to-high disease activity who switched from IV-infliximab to IV-golimumab demonstrated significant and sustained improvements post-switch as measured by the CDAI. Key Points • This study used real-world data from the Rheumatology Informatics System for Effectiveness (RISE) registry to evaluate the efficacy of directly switching from intravenous (IV)-infliximab to IV-golimumab to control rheumatoid arthritis (RA) disease activity. • Most IV-infliximab patients had moderate-to-high disease activity at the time of the switch. • On average, IV-golimumab was effective in improving RA disease activity after switching from IV-infliximab as measured by the Clinical Disease Activity Index. • These data suggest that real-world RA patients with persistent symptoms despite treatment with IV-infliximab may realize improved disease control with a switch to IV-golimumab.

Pain catastrophizing in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: biopsychosocial perspective and impact on health-related quality of life

Article

Full-text available

Apr 2022
RHEUMATOL INT

Pain catastrophizing (PC), defined as tendency to describe pain in more exaggerated terms, to ruminate more or to feel helpless about it. Main objective was to illuminate PC in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), revealing its prevalence and associations from a biopsychosocial perspective, including its association with health-related quality of life (HRQoL). Measures reflecting the biological, social and psychological perspective were recorded in RA, PsA and axSpA outpatients. Biological variables including demographics, disease activity and patient reported outcomes (PROs) along with variables reflecting psychological and social domains were collected. RAND12 questionnaire was used to explore HRQoL and standardized questionnaire was used to reveal pain catastrophizing score (PCS). 1229 patients were recruited (RA 580, PsA 394, axSpA 255). Mean (SD) PCS were for RA 1.88 (1.39), PsA 2.06 (1.45) and axSpA 2.27 (1.37). Proportion of pain catastrophizers (score ≥ 4) was not statistically different between RA (10.5%), PsA (12.7%) and axSpA (15.3%). Across all diagnoses, variables reflecting biological subjective domain explained more PCS variability (adjusted R2 35.3–49.9%) than psychological (28.4–33.6%), social (22.4–28.4%) and biological objective (4.3–9.9%) domains. HRQoL was significantly lower in pain catastrophizers across all diagnoses. No substantial differences in proportion of pain catastrophizers between RA, PsA and axSpA patients were found. Higher PCS (score ≥ 4) was best explained by biological subjective measures and corresponded with inferior HRQoL in all diseases. Several biological objectives, psychological and social measures were also associated with higher PCS.

Psychosocial Burden Predicts Sustained Remission in Early Rheumatoid Arthritis: Unraveling the Complex Interplay of Well‐Being and Disease Activity

Article

Full-text available

Nov 2022

Objective This study investigated how psychosocial aspects of disease affect the probability of achieving sustained remission in early rheumatoid arthritis (RA) and explored the directionality of this relationship. Methods Data were analyzed from the randomized controlled Care in Early RA trial. Sustained remission was defined as a continued Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) of <2.6 from weeks 16 to 104. Patients completed the Short Form 36 (SF‐36) health survey, Revised Illness Perception Questionnaire (IPQ‐R), and the Utrecht Coping List. These psychosocial variables were studied at baseline and at week 16 as predictors of sustained remission with logistic regression. Next, subgroups of patients in remission at week 16 were identified by Latent Profile Analysis based on these psychosocial indicators. Time to first loss of remission was then compared between groups by Cox proportional hazards regression. Finally, directionality of associations between psychosocial indicators and DAS28‐CRP was explored with cross‐lagged panel models (CLPMs). Results Sustained DAS28‐CRP remission was associated with higher SF‐36 scores and less passive coping at baseline and with higher SF‐36 scores and more positive IPQ‐R outcomes at week 16. Among patients in DAS28‐CRP remission at week 16 (n = 287), 2 subgroups were identified: a low psychosocial burden group (n = 231 of 287) and a high psychosocial burden group (n = 56 of 287). The low psychosocial burden group retained remission longer (hazard ratio 0.51 [0.35–0.73]). In the CLPM, temporal relationships between psychosocial well‐being and DAS28‐CRP were complex, bidirectional, and disease‐phase dependent. Conclusion Suboptimal psychosocial well‐being and negative illness perceptions predicted lower probability of sustained remission in an early RA cohort. Illness perceptions appeared to become more clinically relevant with time. Finally, 1 in 5 patients showed worse psychosocial outcomes despite early remission, and these patients tended to lose remission earlier.

Chronic Pain in Patients with Rheumatoid Arthritis

Article

Full-text available

Sep 2021
Curr Pain Headache Rep

Purpose of Review Chronic pain is highly prevalent in patients with rheumatoid arthritis (RA) and can cause various physical and psychological impairments. Unfortunately, the appropriate diagnosis of chronic pain syndromes in this population can be challenging because pain may be primary to RA-specific inflammation and/or secondary to other conditions, typically osteoarthritis (OA) and fibromyalgia (FM). This disparity further poses a clinical challenge, given that chronic pain can often be discordant or undetected with standard RA-specific surveillance strategies, including serological markers and imaging studies. In this review, we provide a robust exploration of chronic pain in the RA population with emphasis on epidemiology, mechanisms, and management strategies. Recent Findings Chronic pain associated with RA typically occurs in patients with anxiety, female sex, and elevated inflammatory status. Up to 50% of these patients are thought to have chronic pain despite appropriate inflammatory suppression, typically due to peripheral and central sensitization as well as secondary OA and FM. In addition to the standard-of-care management for OA and FM, patients with RA and chronic pain benefit from behavioral and psychological treatment options. Moreover, early and multimodal therapies, including non-pharmacological, pharmacological, interventional, and surgical strategies, exist, albeit with varying efficacy, to help suppress inflammation, provide necessary analgesia, and optimize functional outcomes. Summary Overall, chronic pain in RA is a difficult entity for both patients and providers. Early diagnosis, improved understanding of its mechanisms, and initiation of early, targeted approaches to pain control may help to improve outcomes in this population

Rheumatoid Arthritis Relapse and Remission – Advancing Our Predictive Capability Using Modern Imaging

Article

Full-text available

Jun 2021

Clinical remission has become an achievable target for the majority of patients with rheumatoid arthritis, but subclinical inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) has been demonstrated to be frequent in patients in clinical remission. Subclinical synovitis has been shown to be linked to both subsequent structural damage progression and a risk of flare, demonstrating that subclinical synovitis represents incomplete suppression of inflammation and questions whether it is appropriate only to use clinical composite scores as treatment target in clinical practice. Maintaining a state of remission has proven important as sustained clinical remission impacts long-term outcome regarding joint damage progression, physical function and quality of life. Treating subclinical inflammation has been attempted and has led to more frequent strict clinical remission and better physical function, but also to more adverse events. Thus, an overall benefit of incorporating imaging goals in treat-to-target strategies has not been documented. However, in patients in clinical remission on biological disease-modifying anti-rheumatic drugs, both ultrasound and MRI may aid in the clinical decision regarding whether drug tapering or even discontinuation should be attempted.

Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical remission despite being in ultrasound remission

Article

Full-text available

May 2021

Objectives Since subjective variables may reduce remission by composite disease activity scores (CDAS), the main objectives were to explore whether rheumatoid arthritis (RA) patients with mainly tender versuss mainly swollen joints had differences in patient reported outcome measures (PROMs), clinical or ultrasound assessments as well as in achieving remission defined by CDAS or ultrasound. Methods In a Nordic multicentre study, RA patients initiating tocilizumab were assessed by PROMs, clinical, laboratory and ultrasound assessments (36 joints, 4 tendons) at baseline, 4, 12 and 24 weeks. Remission was defined according to CDAI/Boolean or no Doppler activity present. Tender-Swollen joint differences (TSJD) were calculated. Statistics exploring changes over time/differences between groups included Wilcoxon, Mann–Whitney, Kruskal-Wallis and Spearman. Results 110 patients were included (mean (SD) age 55.6 (12.1) years, RA duration 8.7 (9.5) years). All PROMs, clinical, laboratory and ultrasound scores decreased during follow-up (p < 0.001). During follow-up, tender joint counts were primarily correlated with PROMs (r = 0.24–0.56 (p < 0.05–0.001)), and swollen joint counts with ultrasound synovitis scores (r = 0.33–0.72 (p < 0.05–0.001)). At 24 weeks patients with TSJD > 0 had higher PROMs and CDAI (p < 0.05–0.001) but lower ultrasound synovitis scores (p < 0.05). Remission by CDAI/Boolean was seen in 26–34% and by Doppler 53%, but only 2–3% of patients with TSJD > 0 achieved CDAI/Boolean remission. Conclusion Patients with more tender than swollen joints scored higher on subjective assessments but had less ultrasound synovitis. They seldom achieved CDAS remission despite many being in Doppler remission. If patients with predominantly tender joints do not reach CDAS remission, objective assessments of inflammation should be performed. Clinical trial identifier ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02046616

Rheumatoid Arthritic Pain

Chapter

Jan 2019

RA is a multifaceted disease associated with complex patterns of pain, increased likelihood of mental health concerns, and reduced quality of life. Given the widespread impact of the disease and related pain, a biopsychosocial approach to assessment and treatment is likely to best meet the varied needs of patients with RA. Both CBT and ACT have been shown to be effective in treating chronic pain and associated emotional symptoms in this population. These therapeutic approaches offer flexible frameworks, facilitating patient-centered care and affording opportunity for the integration of a variety of evidence-based techniques to help patients improve management of their disease, pain, emotional distress, and quality of life. Traditionally, psychosocial interventions for patients with RA have occurred within specialty mental health or pain settings; however, many patients never enter these settings, leaving significant unmet need. Behavioral health interventions for patients with RA recently are becoming more prominent in primary care and rheumatology settings. Collaborative care approaches. provide the benefit of a unified treatment team to comprehensively address patient needs and improve disease and pain self-management. Integrated health care for patients with chronic pain is cost-effective and associated with improved short- and long-term clinical outcomes. Patients with recurrent depressive episodes, who express greater distress, who have shorter disease duration, and/or who are at higher risk for chronic impairment appear to receive the greatest benefit from these types of interventions.

Intermetatarsal bursitis is frequent in patients with established rheumatoid arthritis and is associated with anti-cyclic citrullinated peptide and rheumatoid factor

Article

Full-text available

Oct 2019

Major Challenges in Rheumatology: Will We Ever Treat Smarter, Instead of Just Harder?

Article

Full-text available

Jun 2019

Association of Pain Centralization and Patient‐Reported Pain in Active Rheumatoid Arthritis

Article

Full-text available

Jul 2020

Objective Pain is a significant burden for patients with rheumatoid arthritis (RA) despite advancements in treatment. We undertook this study to examine the independent contribution of pain centralization to the pain experience of patients with active RA. Methods A total of 263 RA patients with active disease underwent quantitative sensory testing (QST), including assessment of extraarticular pressure pain thresholds (PPTs), temporal summation (TS), and conditioned pain modulation (CPM). The pain experience was assessed by a pain intensity numeric rating scale and the Patient‐Reported Outcomes Measurement Information System pain interference computerized adaptive test. We examined associations between QST measures and pain intensity and pain interference. Multiple linear regression models were adjusted for demographic and clinical variables, including swollen joint count and C‐reactive protein level. Results Patients with the lowest PPTs (most central dysregulation) reported higher pain intensity than patients with the highest PPTs (adjusted mean difference 1.02 [95% confidence interval (95% CI) 0.37, 1.67]). Patients with the highest TS (most central dysregulation) had higher pain intensity than those with the lowest TS (adjusted mean difference 1.19 [95% CI 0.54, 1.84]). CPM was not associated with differences in pain intensity. PPT and TS were not associated with pain interference. Patients with the lowest CPM (most centrally dysregulated) had lower pain interference than patients with the highest CPM (adjusted mean difference −2.35 [95% CI −4.25, −0.44]). Conclusion Pain centralization, manifested by low PPTs and high TS, was associated with more intense pain. Clinicians should consider pain centralization as a contributor to pain intensity, independent of inflammation.

Interrelationships of disease activity, central sensitization, psychosocial and lifestyle factors in axial spondyloarthritis

Article

Full-text available

Feb 2025

Objectives In a substantial portion of patients with axial spondyloarthritis (axSpA), disease activity scores remain high despite anti-inflammatory treatment. This is possibly due to factors beyond active inflammation including different pain mechanisms and psychosocial factors. Therefore, our aim was to build a biopsychosocial model to explore the interrelationships of Axial Spondyloarthritis Disease Activity Score (ASDAS) with central sensitization (CS), psychological and lifestyle factors in patients with axSpA. Methods Consecutive patients from the prospective Groningen Leeuwarden axSpA (GLAS) cohort were included in this cross-sectional study. Assessments included in the model were educational level, body mass index (BMI), questionnaires on CS, illness perception, pain catastrophizing, coping, anxiety and depression, physical activity (mSQUASH) and ASDAS. Structural equation modelling (SEM), a multivariate analysis testing hypothesized interrelationships between variables, was applied to investigate the effects of CS, psychosocial and lifestyle factors on ASDAS. Results 332 consecutive axSpA patients were eligible for analyses of which 59% were male, median symptom duration was 21 years, and mean ASDAS was 2.2 ± 0.9. The final SEM model had a satisfactory fit (RMSEA = 0.057 (95% CI 0.45–0.70), CFI = 0.936). Illness perception, CS and BMI had direct, significant, effects on ASDAS. Psychological well-being and educational level were significantly indirectly associated with ASDAS through illness perception. Conclusion Our analyses exploring the interrelationships of biopsychosocial factors related to ASDAS showed that factors beyond inflammation, especially illness perception and CS, seem to contribute significantly to ASDAS in patients treated for axSpA in our standard-of-care cohort, confirming the need for a biopsychosocial approach.

Ultrasound evaluation contrasts clinical disease activity evaluation in rheumatoid arthritis patients with concomitant anxiety or depression

Article

Jun 2024
SEMIN ARTHRITIS RHEU

Intense symptoms of pain are associated with poor sleep, fibromyalgia, depression and sleep apnea in patients with rheumatoid arthritis and psoriatic arthritis. A register based study

Article

Full-text available

May 2024
JOINT BONE SPINE

Pain catastrophizing in rheumatic diseases: prevalence, origin, and implications

Article

Full-text available

Apr 2024
RHEUMATOL INT

Pain is a crucial factor in rheumatic disorders, and reducing it is a primary goal of successful treatment. Adaptive pain-coping strategies can enhance this improvement, but maladaptive approaches such as pain catastrophizing may worsen overall patient well-being. This narrative review aims to provide a concise overview of the existing knowledge on pain catastrophizing in the most prevalent specific rheumatic disorders. The objective of this study was to improve understanding of this phenomenon and its implications, as well as to pinpoint potential directions for future research. We conducted searches in the MEDLINE/PubMed, SCOPUS, and DOAJ bibliography databases to identify articles related to pain catastrophizing in rheumatoid arthritis, psoriatic arthritis, axial spondylarthritis, systemic sclerosis, systemic lupus erythematosus, Sjögren’s syndrome, juvenile idiopathic arthritis, and osteoarthritis (non-surgical treatment). Data extraction was performed on November 1, 2023. The investigators screened the identified articles to determine their relevance and whether they met the inclusion criteria. Following a bibliography search, which was further expanded by screening of citations and references, we included 156 records in the current review. The full-text analysis centred on pain catastrophizing, encompassing its prevalence, pathogenesis, and impact. The review established the role of catastrophizing in amplifying pain and diminishing various aspects of general well-being. Also, potential treatment approaches were discussed and summarised across the examined disorders. Pain catastrophizing is as a significant factor in rheumatic disorders. Its impact warrants further exploration through prospective controlled trials to enhance global patient outcomes.

Relevance of Adalimumab Product Attributes to Patient Experience in the Biosimilar Era: A Narrative Review

Article

Full-text available

Mar 2024
ADV THER

Adalimumab (ADL, Humira®, reference product), an anti-TNF-α biologic, has transformed the treatment of chronic, immune-mediated inflammatory diseases. However, the high cost of ADL therapy has driven the development of more affordable ADL biosimilars, agents with no clinically meaningful differences from the reference product. This review summarizes the product attributes of reference ADL and the nine ADL biosimilars approved and available in the USA in relation to patient experience of injection-site pain (ISP). Product formulation, delivery volume and device features (e.g., type and needle gauge size) influence patient experience of ISP with potential clinical consequences. Citrate-free formulations generally cause less ISP; injection volumes of > 1.5 ml may be associated with increased ISP. Reference ADL and all ADL biosimilars offer a citrate-free formulation, and reference ADL and four ADL biosimilars offer a high-concentration solution that allows a smaller injection volume. All available ADL products are injected subcutaneously using either a pre-filled pen (PFP) or pre-filled syringe (PFS). Patients prefer the PFP, but the PFS permits better control over the speed and duration of injection. Smaller (29-gauge) needle outer diameter is associated with less ISP; reference ADL and seven ADL biosimilars offer a device with a 29-gauge needle. In the USA, an approved biosimilar can be designated “interchangeable,” allowing pharmacy-level substitution, where state law permits. In the USA, two ADL biosimilars have received interchangeability designation; others are seeking interchangeability designation from the Food and Drug Administration (n = 2), are being evaluated in clinical studies to support interchangeability (n = 2), or do not have/are not seeking interchangeability designation (n = 3). Product-related attributes influence patient experience of ISP caused by subcutaneous ADL injection. Reference ADL and ADL biosimilar products differ in their attributes, so discussion with patients about treatment options is essential to optimize adherence and outcomes.

Viewpoint: Supporting mental health in the current management of rheumatoid arthritis: time to act!

Article

Oct 2023

Although clinical outcomes of RA have vastly improved in recent years, the disease’s mental health impact has seemingly not decreased to the same extent. Even today, learning to live with RA is an active process involving several psychological, cognitive, behavioural and emotional pathways. Consequently, mental health disorders are more common in the context of RA than in the general population, and can be particularly detrimental both to patients’ quality of life and to clinical outcomes. However, mental health is a spectrum and represents more than the absence of psychological comorbidity, and supporting patients’ psychological wellbeing should thus involve a more holistic perspective than the mere exclusion or specific treatment of mental health disorders. In this viewpoint article, we build on mechanistic and historical insights regarding the relationship between RA and mental health, before proposing a practical stepwise approach to supporting patients’ mental health in daily clinical practice.

Comparison of Angio PLanewave UltraSensitive and Power Doppler Ultrasound in Detecting Synovial Blood Flow in Wrist and Finger Joints of Rheumatoid Arthritis Patients

Article

Sep 2023
ACAD RADIOL

Calprotectin, a sensitive marker of inflammation, is robustly assessed in plasma from patients with early or established rheumatoid arthritis by use of different laboratory methods

Article

Jun 2023
SCAND J CLIN LAB INV

Calprotectin (S100A8/S100A9, MRP8/MRP14) is a major leukocyte protein found to be more sensitive than C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) as a marker of inflammation in patients with rheumatoid arthritis (RA). The present objective was to explore the robustness of calprotectin assessments by comparing two different laboratory methods assessing calprotectin in plasma samples from patients with early or established RA. A total of 212 patients with early RA (mean (SD) age 52(13.3) years, disease duration 0.6(0.5) years) and 177 patients with established RA (mean (SD) age 52.9(13.0) years, disease duration 10.0(8.8) years) were assessed by clinical, laboratory, and ultrasound examinations. Frozen plasma samples (-80 °C) were analysed for calprotectin levels at baseline, 1, 2, 3, 6 and 12 months by use of either enzyme-linked immunosorbent assay (ELISA) or fluoroenzyme immunoassay (FEIA). The ELISA technique used kits from Calpro AS and the FEIA technology was assessed on an automated Thermo Fisher Scientific instrument. The results showed high correlations between the two methods at baseline and during follow-up, with Spearman correlation at baseline 0.93 (p < 0.001) in the early and 0.96 (p < 0.001) in the established RA cohorts. The correlations between each of the two calprotectin assessments and clinical examinations had similar range. Calprotectin correlated well with clinical examinations, with at least as high correlations as CRP and ESR. The present study showed similar results for the two analytical methods, supporting the robustness of calprotectin analyses, and suggest calprotectin in plasma to be included in the assessments offered by clinical routine laboratories.

The role of pain catastrophizing in pain perception among patients with rheumatoid arthritis without clinical signs of inflammation

Article

Feb 2023
Muscoskel Care

Objective: Pain in rheumatoid arthritis (RA) is considered to be associated with non-inflammatory factors, including physical disabilities, psychiatric disorders, and pain catastrophizing (PC). PC is reportedly a key driver in the development of pain in patients with RA without clinical signs of inflammation; however, previous studies enroled patients with RA who were potentially in an inflammatory state. Hence, our aim was to investigate the role of PC as the possible link between pain, physical disabilities, and psychiatric disorders in patients with RA without clinical signs of inflammation. Materials and methods: In this cross-sectional study, 81 patients with RA without clinical signs of inflammation were included; all patients had serum C-reactive protein levels <0.5 mg/dL, without any inflammatory joints. We examined the demographic and clinical data and administered the pain visual analogue scale (VAS), pain catastrophizing scale (PCS), Health Assessment Questionnaire Disability Index (HAQ-DI), and patient version of the Brief Scale for Psychiatric Problems in Orthopaedic Patients (pBS-POP). A series of multivariate-adjusted multiple regression analyses were performed to examine the associations between PC and pain intensity, physical disabilities, and psychiatric disorders. Results: We found associations between all the above-mentioned variables in separate models with HAQ-DI, pBS-POP, and PCS scores. However, in the model associated with pain VAS, the PCS score (β = 0.34, p = 0.0073) emerged as the only variable showing a statistically significant association. Conclusions: PC is associated with pain in patients with RA without clinical signs of inflammation, and this association may be mediated through pathways involving physical disabilities and psychiatric disorders.

Effect of biological DMARDs and JAK inhibitors in pain of chronic inflammatory arthritis

Article

Sep 2022
EXPERT OPIN BIOL TH

Introduction: The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs) and, more recently, of Janus kinase inhibitors (JAKi) has had a major impact on the long-term outcomes of chronic inflammatory arthritis (IA). However, the persistence of pain, even in patients with a complete pharmacological control of peripheral inflammation, represents an important clinical challenge in the treatment of IA. Areas covered: In this review, we provide an overview of possible mechanisms underlying pain in IA and its assessment, as well as the effects of bDMARDs and JAKi on pain management. Expert opinion: The overall data showed a good effect of bDMARDs and JAKi on pain, more pronounced for JAKi. However, it is challenging to distinguish the effect on the different types of pain (nociceptive, neuropathic, and nociplastic).

Controversies in rheumatology: Ultrasound for monitoring of RA – do we need it?

Article

Apr 2022

Clinical joint examination is the cornerstone for evaluation of patients with rheumatoid arthritis (RA). However, since large discrepancies have been shown even between experienced rheumatologists in evaluation of joint inflammation, and tender joints may have limited value in reflecting inflammation, ultrasound has in the last decennials been introduced in the clinical assessments of RA patients. Ultrasound has high accordance with other imaging modalities and enables detection of clinically difficult pathologies and contributes to assessments of joints difficult to evaluate clinically. However, there is no general agreement on the optimal use of ultrasound in rheumatology and the prevalence of machines as well as the level of experience is highly different across the countries. In addition, standardized use of ultrasound in treat-to-target follow-up of RA patients was found not to have any added value. Thus, how to use ultrasound in monitoring of RA patients is open for debate. The present article will discuss the pros and cons for using ultrasound in the clinical setting.

Pain catastrophizing hinders Disease Activity Score 28 – erythrocyte sedimentation rate remission of rheumatoid arthritis in patients with normal C‐reactive protein levels

Article

Oct 2021

Aim This study aimed to assess the relationship between pain catastrophizing and achievement of 28-joint Disease Activity Score-defined remission of rheumatoid arthritis (RA), considering the presence or absence of systemic inflammation, and to evaluate associated factors for pain catastrophizing. Method This cross-sectional study included 421 RA outpatients. The relationship between pain catastrophizing and remission was analyzed by adjusting several confounding factors. Univariable and multivariable analyses were performed to determine the relationship between pain catastrophizing and RA-related factors, comorbidities, and lifestyle habits. Results The prevalence of pain catastrophizing was 26%. Pain catastrophizing was negatively associated with remission (odds ratio 0.62, 95% confidence interval 0.38-1.00, P = .048). A multinomial logistic analysis showed that the presence of pain catastrophizing was an independent factor that was negatively correlated with the achievement of remission in the absence of systemic inflammation (odds ratio 0.51, 95% confidence interval 0.28-0.93, P = .029). Factors associated with elevated ratings on the Pain Catastrophizing Scale were a history of falls within the past year, a Health Assessment Questionnaire score >0.5, and smoking habit. Further, patients' subjective symptoms, including patient global assessment minus evaluator global assessment values ≥20 and high tender joint count minus swollen joint counts, were associated with elevated pain catastrophizing. Conclusion Pain catastrophizing is a major obstacle to achieving remission in RA patients with normal C-reactive protein levels. Advanced physical disability, smoking habit, and history of falls were associated with pain catastrophizing, in addition to patients' subjective symptoms.

The association between disease duration and mood disorders in rheumatoid arthritis patients

Article

Oct 2021

AimsThe mood disorders have been recognized as common comorbidities of rheumatoid arthritis (RA), however unknown in patients with different RA courses. Therefore, we aimed to investigate the status of mood disorders in early RA and non-early RA patients and further identify the associated factors for mood disorders.Methods Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were assessed in all enrolled RA patients. Besides clinical assessments, power Doppler and greyscale (GS) ultrasound of 28 joints was performed. The frequency of mood disorders was compared between early RA and non-early RA patients. Multivariate regression was used to identify the associated factors for mood disorders.ResultsTow hundred one RA patients were enrolled, with 76 early RA (disease duration ≤ 2 years) and 125 non-early RA (disease duration > 2 years). Mood disorders (depression and/or anxiety) were found in 42 (20.9%) patients. Depression was more frequently observed in early RA than non-early RA patients (26.3% vs. 14.4%, P = 0.036). A similar trend for anxiety was also observed in early RA compared to non-early RA patients, although the difference was insignificant (13.2% vs. 5.6%, P = 0.062). Disease duration (OR = 0.991, 95% CI 0.985–0.998, P = 0.009), health assessment questionnaire disability index (HAQ-DI) (OR = 1.045, 95% CI 1.005–1.086, P = 0.029) and GS synovitis score (OR = 1.065, 95% CI 1.017–1.115, P = 0.007) were identified as factors associated with depression. Disease duration (OR = 0.981, 95% CI 0.967–0.995, P = 0.009), HAQ-DI (OR = 1.071, 95% CI 1.013–1.133, P = 0.017) and GS synovitis score (OR = 1.072, 95% CI 1.012–1.136, P = 0.019) were identified to be associated with anxiety.Conclusions Depression and anxiety were almost doubled in frequency in early RA than in long-standing RA patients. RA patients with short disease duration, high HAQ-DI and GS score were more likely to be in depression and anxiety. Key Points • Mood disorders were more frequent in early RA than non-early RA patients. • More attention to psychological status is needed in RA patients. • RA patients with short disease duration, poor physical function and severe synovitis were more likely to have depression and/or anxiety.

Rheumatische Erkrankungen und neuropathischer SchmerzRheumatic diseases and neuropathic pain: Diagnose und TherapieDiagnosis and treatment

Article

Dec 2020

Pain is a leading symptom in inflammatory rheumatic diseases. For a long time it has been assumed that this pain is of nociceptive origin; however, in about one fifth of all patients the pain remains despite successful anti-inflammatory treatment and is not typically described as nociceptive by those affected. Recent studies indicate that some patients with rheumatoid arthritis (RA) experience pain with a neuropathic pain component. The treatment of neuropathic pain with damage to the somatosensory system differs markedly from the treatment of nociceptive pain in which the pain processing system is intact. Thus, the recognition and, above all, the more precise differentiation of the pain symptoms of affected patients make a decisive contribution to a successful treatment. With the help of a few points in the history and a physical examination, the assumption of the diagnosis neuropathic pain can often be rejected or substantiated. Pain with a neuropathic component does not adequately respond to typical analgesics. Instead, the high efficacy of co-analgesics, such as anticonvulsants and antidepressants, has been repeatedly proven.

The Clinical Disease Activity Index (CDAI) and the Routine Assessment of Patient Index Data3 (RAPID3) for Achievement of Treatment Strategies

Article

Dec 2020

Objective To compare the CDAI with the RAPID3 from two large US Registries. Methods Using a cross section of clinic visits within two registries we determined if the outcome of each metric would place the patient in remission (R), low (LDA), moderate (MDA), or high disease activity (HDA) using a CDAI with the assumption that a patient in MDA or HDA would be a candidate for acceleration of treatment. Results We identified significant disparities between the two indices in final disease categorization using each index system. For patients identified in LDA by CDAI, RAPID3 identified 20.4% and 28.3% as LDA in Corrona and BRASS respectively. For patients identified as MDA by CDAI, RAPID3 identified 36.2% and 31.1% as MDA in Corrona and BRASS respectively with the greatest disparities within each system identified for LDA and MDA activity by the CDAI (20.4% and 36.2% agreement of RAPID3 with CDAI respectively in Corrona and 28.3% and 31.1% agreement in BRASS). Overall comparison between CDAI and RAPID3 in the 4 disease categories resulted in estimated Kappa=0.285 in both. The RAPID3 scores indicated the potential for treat to target acceleration in 34.4% of patients in remission or LDA based on CDAI in Corrona and 27.6% in BRASS respectively Conclusion The RAPID3, based on patient reported outcomes, shows differences with CDAI categories of disease activity. The components of CDAI are not highly correlated with RAPID3 except for patient global. These differences could significantly impact the decision to advance treatment when using a treat to target regimen.

Trajectories of fatigue in actively treated patients with established rheumatoid arthritis starting biologic DMARD therapy

Article

Full-text available

Nov 2020

Objectives To define fatigue trajectories in patients with rheumatoid arthritis (RA) who initiate biological DMARD (bDMARD) treatment, and explore baseline predictors for a trajectory of continued fatigue. Methods One-hundred and eighty-four patients with RA initiating bDMARDs were assessed at 0, 1, 2, 3, 6 and 12 months. Swollen and tender joint counts, patient reported outcomes (PROMs), blood samples and ultrasound examinations were collected at each time point. Fatigue was assessed by the fatigue Numeric Rating Scale (0–10) from the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire. Clinically significant fatigue was predefined as fatigue ≥4. Three trajectories of interest were defined according to level of RAID fatigue: no fatigue (≤3 at 5/6 visits), improved fatigue (≥4 at start, but ≤3 at follow-up) and continued fatigue (≥4 at 5/6 visits). Baseline variables were compared between groups by bivariate analyses, and logistic regression models were used to explore baseline predictors of continued vs improved fatigue. Results The majority of patients starting bDMARD therapy followed one of three fatigue trajectories, (no fatigue; n=61, improved; n=33 and continued fatigue; n=53). Patients with continued fatigue were more likely to be anti–citrullinated protein antibody and/or rheumatoid factor positive and had higher baseline PROMs compared to the other groups, while there were no differences between the groups for variables of inflammation including. Patient global, tender joint count and anxiety were predictors for the continued fatigue trajectory. Discussion A trajectory of continued fatigue was determined by PROMs and not by inflammatory RA disease activity.

Pain Catastrophizing and Function In Individuals With Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis

Article

Mar 2019
CLIN J PAIN

Objectives: Pain catastrophizing (PC) is the most consistent psychosocial factor predicting of adjustment to chronic pain and may contribute to the development and long-term maintenance of chronic pain. The aim of this review was systematically review and critically appraise the concurrent and longitudinal associations between PC and both pain intensity and disability in individuals with chronic musculoskeletal pain (CMP). Materials and methods: An electronic search of PubMed, Scopus, AMED, CINAHL, PsycINFO, and PubPsych databases, as well as gray literature, was undertaken from inception until September 2018. Cross-sectional and longitudinal studies reporting on the associations between measures of PC, pain intensity, and disability were selected for review. Results: A total of 85 observational studies (92% cross-sectional) were included, with a total sample of 13,628 participants with CMP. Very low-quality evidence (based on the GRADE criteria) indicated that higher levels of PC were often, but not always, significantly associated with and prospectively predicted both chronic pain intensity and disability. Heterogeneity was large after conducting multiple meta-analyses. Discussion: Despite the very low quality of the available evidence, the general consistency of the findings highlights the potential role that PC may play in delaying recovery from CMP. Research that uses higher quality study designs and procedures would allow for more definitive conclusions regarding the impact of PC on pain and function.

Pain appraisal and quality of life in 108 outpatients with rheumatoid arthritis

Article

Nov 2019

Pain without inflammation

Article

Sep 2019
BEST PRACT RES CL RH

Jon Lampa

Chronic pain is a common symptom in rheumatic diseases, and the patient with pain and no signs of inflammation poses a challenge to the physician. Notably, all rheumatic diseases have components of non-inflammatory pain and a higher prevalence of fibromyalgia compared to the overall population. Hypothetically, a chronic pain stimulus may have stronger impact in a chronic inflammatory state, and the process towards a pain condition may be influenced by individual predisposition for development of chronic pain. In addition, the features of peripheral and central pain processing may be exacerbated by inflammation, and disturbed pain processing may be a feature contributing to widespread pain. We herein review and describe the prevalence of chronic pain and different pain modalities in the most common rheumatic diseases. In addition, the background mechanisms of non-inflammatory pain in rheumatic diseases are discussed. Finally, we here review the current strategies for pain management, with a special focus on non-inflammatory pain. The key message is that pain management should be individualized and based on a thorough pain analysis with investigation of the pain modality, localization and pain intensity. Other factors to consider are the underlying rheumatic disease and treatment, the patient's mental and physical health status and psychological factors.

Is a Fundamental Change in the Interpretation of Rheumatoid Arthritis Disease Activity Necessary?

Article

Dec 2018

William S. Wilke

Disease Activity Score (DAS) composite models are moderately precise and robust measures of disease severity when they are used in rheumatoid arthritis (RA) cohorts. They are less so when used for individual patients. This is because subjective components, patient global assessment of well-being and tender joint count, modified by factors other than RA biological disease activity, often obfuscate interpretation of disease activity. Comorbidities, especially distress, can disproportionately inflate these components. Fibromyalgia, essentially synonymous with distress, pain augmentation, and depression, is a common comorbidity. Its presence and severity can be determined by the Polysymptomatic Distress Scale (PSD). The differential effects of distress and fibromyalgia syndrome on the DAS can be demonstrated by manipulating information already there: the arithmetic differences or ratios of the tender joint count and swollen joint count and comparison of the modified disease activity score with 28 joints to the disease activity score with 28 joints-patient (DAS28-derived indices that measure the contribution of the relatively objective or relatively subjective components, respectively). The potentially more objective multibiomarker disease activity might also be used to test the severity of biological RA disease activity. These tools may be used to elucidate disproportionate values for subjective DAS model components, which then should facilitate identification of the underlying process factors, including depression, for potential treatment.

Changes in Beliefs, Catastrophizing, and Coping Are Associated With Improvement in Multidisciplinary Pain Treatment

Article

Full-text available

Aug 2001

To examine the associations between changes in cognitions and coping and multidisciplinary pain treatment outcomes, the authors had 141 patients with chronic pain complete measures of adjustment, beliefs, catastrophizing, and coping; in addition, their significant others rated patient physical functioning at pretreatment, posttreatment, and 6- and 12-month follow-ups. Decreases in guarding and resting and in the belief that pain signals damage were associated with decreases in patient disability. Increases in perceived control over pain and decreases in catastrophizing and in the belief that one is disabled were associated with decreases in self-reported patient disability, pain intensity, and depression. The results are consistent with the hypothesis, derived from cognitive−behavioral models of chronic pain, that the outcomes of multidisciplinary pain treatment are associated with changes in patient cognitions and coping responses.

Exploring a new ultrasound score as a clinical predictive tool in patients with rheumatoid arthritis starting abatacept: results from the APPRAISE study

Article

Full-text available

May 2016

Objectives To explore whether changes in a composite (power Doppler/greyscale ultrasound (PDUS)) synovitis score, developed by the OMERACT-EULAR-Ultrasound Task Force, predict disease activity outcomes in rheumatoid arthritis (RA). Methods Patients with RA who were methotrexate inadequate responders starting abatacept were evaluated. Individual joint PDUS scores were combined in the Global OMERACT-EULAR Synovitis Score (GLOESS) for metacarpophalangeal joints (MCPs) 2–5, all joints (22 paired) and a reduced (9 paired) joint set. The predictive value of changes in GLOESS at week 1–16 evaluations for clinical status and response (Disease Activity Score (DAS)28 (C reactive protein, CRP) <2.6; DAS28(CRP) ≤3.2; DAS28(CRP) ≥1.2 improvement) up to week 24, and correlations between DAS28 and GLOESS were assessed. Results Eighty-nine patients completed the 24-week treatment period. Changes in GLOESS (MCPs 2–5) from weeks 1 to 16 were unable to predict DAS28 outcomes up to week 24. However, significant improvements in GLOESS (MCPs 2–5) were observed at week 12 in patients with DAS28 ≥1.2 improvement at week 24 versus those who did not achieve that clinical response. In patients achieving DAS28 ≥1.2 improvement or DAS28 ≤3.2 at week 24, changes in GLOESS (22 and 9 paired joint sets) were greater in patients who already achieved DAS28 ≥1.2 at week 12 than in those who did not. No significant correlations were found between changes in DAS28 and GLOESS definitions at any time point. Conclusions PDUS was not correlated with clinical status or response as measured by DAS28-derived criteria, and PDUS changes were not predictive of clinical outcome. The discrepancies require further exploration. Trial registration number NCT00767325; Results.

Non-inflammatory Causes of Pain in Patients with Rheumatoid Arthritis

Article

Full-text available

Apr 2016
Curr Rheumatol Rep

Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered.

Association Between Widespread Pain Scores and Functional Impairment and Health-Related Quality of Life in Clinical Samples of Children

Article

Full-text available

Feb 2016

Unlabelled: Pain involving several body regions generally represents nervous system pathophysiology shifting from predominantly peripheral to more central. In adults, higher widespread pain scores are clinically meaningful and confer risk for poor response to treatment. It is unknown whether widespread pain is similarly important in children. To address this gap, we conducted an observational study examining 1) associations between widespread pain and functional impairment and health-related quality of life (HRQOL) in clinical pediatric samples, and 2) associations among sociodemographic factors and pain catastrophizing with widespread pain scores. Participants were 166 children aged 10 to 18 years from 3 samples (acute pain, presurgery, chronic pain). Children self-reported pain intensity, pain catastrophizing, functional impairment, and HRQOL. Children indicated pain locations on a body diagram, which was coded using the American College of Rheumatology definition of widespread pain. Results revealed higher widespread pain scores were associated with greater functional impairment with routine activities (F = 3.15, P = .02) and poorer HRQOL (F = 3.29, P = .02), adjusting for pain intensity, study group, and demographic characteristics. Older age (B = .11, P = .02), and Hispanic ethnicity (B = .67, P = .04) were associated with higher widespread pain scores. Findings support incorporating evaluation of widespread pain into pediatric pain assessment. Future research is needed to examine the longitudinal effect of widespread pain on children's treatment outcomes. Perspective: This article examines the association between widespread pain scores and functional impairment and HRQOL in community and clinical samples of children. Assessment of the spatial distribution of the pain experience provides unique information that may identify children at risk for poorer health.

Is Ultrasound a Better Target than Clinical Disease Activity Scores in Rheumatoid Arthritis with Fibromyalgia? A Case-Control Study

Article

Full-text available

Mar 2015
PLOS ONE

Our goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM). A matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM. Ultrasound (US) and clinical scoring were blinded for the presence of FM. Medians and proportions were compared by Mann-Whitney's test and McNemar's test, respectively. Spearman's rank correlation coefficients (rs) were calculated among clinical and US scores and differences were tested by r-to-z transformation test. Seventy-two women were included, out of 247 RA patients, mostly white, with median (IQR) age of 57.5 (49.3-66.8) years, with RA symptoms for 13.0 (6.0-19.0) years and FM symptoms for 6.0 (2.0-15.0) years. Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs and prednisone use was comparable between groups. Objective activity parameters were not different between groups. RA patients with FM had greater DAS28, SDAI and CDAI but similar GS-US7 and PD-US7. GS-US7 correlated with DAS28, SDAI and CDAI in patients with and without FM (rs = 0.36-0.57), while PD-US7 correlated with clinical scores only in patients without FM (rs = 0.35-0.38). To our knowledge, this is the first study to demonstrate that ultrasound synovitis scores are not affected by FM in RA patients. PD-US7 performed better than GS-US7 in long-standing RA patients with DAS28, SDAI or CDAI allegedly overestimated due to FM. Since sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients with FM.

Optimising ultrasonography in rheumatology

Article

Full-text available

Nov 2014

Ultrasonography is an imaging modality that has been utilised in clinical medicine since the 1950s. However, application to joints and rheumatic disease was delayed until appropriate advances in technology made it feasible. Since the 1990s, rheumatologists have embraced ultrasonography as a useful clinical tool and it has increasingly been applied in routine practice. Initial criticism correctly focused on a lack of validity data, recognition that this modality is highly user-dependent and that reliability was not established. In response, the rheumatological community identified relevant pathologies to study, starting with synovitis in rheumatoid arthritis, and set about defining the ultrasound abnormalities, followed by demonstrating the validity, reproducibility and responsiveness of these measures. Much work is now ongoing in the areas of enthesitis, gout and osteoarthritis. Additionally, the evidence base for ultrasonography in clinical practice is being investigated, in order to understand its appropriate place. Given the sensitivity of ultrasonography over clinical examination for detection of inflammation, this work will focus on its role in optimising diagnosis, directing therapy through accurate assessment of disease activity and understanding the optimal selection of joints for feasible disease monitoring. This review summarises the work undertaken to date, ongoing work and future challenges of optimising the role of ultrasonography in rheumatology.

The Pain Catastrophizing Scale: Development and Validation

Article

Full-text available

Jan 1996

In Study 1, the Pain Catastrophizing Scale (PCS) was administered to 425 undergraduates. Analyses yielded a three component solution comprising (a) rumination, (b) magnification, and (c) helplessness. In Study 2, 30 undergraduate participants were classified as catastrophizers (n = 15) or noncatastrophizers (n = 15) on the basis of their PCS scores and participated in an cold pressor procedure. Catastrophizers reported significantly more negative pain-related thoughts, greater emotional distress, and greater pain intensity than noncatastrophizers. Study 3 examined the relation between PCS scores, negative pain-related thoughts, and distress in 28 individuals undergoing an aversive electrodiagnostic medical procedure. Catastrophizers reported more negative pain-related thoughts, more emotional distress, and more pain than noncatastrophizers. Study 4 examined the relation between the PCS and measures of depression, trait anxiety, negative affectivity, and fear of pain. Analyses revealed moderate correlations among these measures, but only the PCS contributed significant unique variance to the prediction of pain intensity.

Pain Catastrophizing: An Updated Review

Article

Full-text available

Jul 2012

Lawrence Leung

Pain catastrophizing has been described for more than half a century which adversely affects the pain coping behavior and overall prognosis in susceptible individuals when challenged by painful conditions. It is a distinct phenomenon which is characterized by feelings of helplessness, active rumination and excessive magnification of cognitions and feelings toward the painful situation. Susceptible subjects may have certain demographic or psychological predisposition. Various models of pain catastrophizing have been proposed which include attention-bias, schema-activation, communal-coping and appraisal models. Nevertheless, consensus is still lacking as to the true nature and mechanisms for pain catastrophizing. Recent advances in population genomics and noninvasive neuroimaging have helped elucidate the known determinants and neurophysiological correlates behind this potentially disabling behavior.

Changes in pain catastrophizing predict later changes in fibromyalgia clinical and experimental pain report: Cross-lagged panel analyses of dispositional and situational catastrophizing

Article

Full-text available

Oct 2012
ARTHRITIS RES THER

Fibromyalgia (FM), characterized by wide-spread diffuse pain and sensory abnormalities, is associated with elevated indices of distress and pain-related catastrophizing compared to both pain-free samples and those with chronic pain conditions. Catastrophizing is a pervasive negative mental set, and is a strong predictor of negative pain-related outcomes such as clinical pain intensity, and physical disability. Situational catastrophizing, measured in the context of experimentally-induced pain, is strongly related to enhanced pain sensitivity, a core aspect of the pathophysiology of fibromyalgia. However, little is known regarding the temporal course of the association between catastrophizing and pain-related "outcomes". Most studies involve only static assessments of pain and catastrophizing at a single time point, which provides little insight into the direction of the observed associations. We sought to investigate the temporal relationships between catastrophizing and indices of both clinical pain (substudy 1) and experimentally-induced pain (substudy 2) in a larger randomized controlled longitudinal trial. Fifty-seven patients with FM completed catastrophizing, depression, and pain questionnaires as well as laboratory cold pressor pain testing at baseline, post-intervention and three month follow-up during a lifestyle physical activity study. Cross-lagged panel analyses were used to address these temporal relationships. In substudy 1, analyses revealed that pre-to-post changes in dispositional catastrophizing ratings prospectively accounted for unique variance in subsequent post-to-follow-up changes in clinical pain ratings (p = 0.005), while pre-to-post changes in pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. An identical pattern was observed experimentally in substudy 2, with pre-to-post changes in situational catastrophizing ratings prospectively accounting for unique variance in subsequent post-to-follow-up changes in experimental pain ratings (p = 0.014), while pre-to-post changes in pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. Specifically, initial alterations in catastrophizing were associated with subsequent alterations in clinical and experimentally induced pain. Controlling for levels of depression did not affect the results. These findings provide empirical evidence that catastrophizing processes might precede and contribute to subsequent alterations in the pain experience for FM patients. Trial Registration clinicaltrials.gov: NCT00383084.

The Pain Catastrophizing Scale: Development and Validation

Article

Full-text available

Dec 1995

In Study I, the Pain Catastrophizing Scale (PCS) was administered to 425 undergraduates. Analyses yielded a three component solution comprising (a) rumination, (b) magnification, and (c) helplessness. In Study 2, 30 undergraduate participants were classified as catastrophizers ( n = 15) or noncatastrophizers ( n = 15) on the basis of their PCS scores and participated in a cold pressor procedure. Catastrophizers reported significantly more negative pain-related thoughts, greater emotional distress, and greater pain intensity than noncatastrophizers. Study 3 examined the relation between PCS scores, negative pain-related thoughts, and distress in 28 individuals undergoing an aversive electrodiagnostic medical procedure. Catastrophizers reported more negative pain-related thoughts, more emotional distress, and more pain than noncatastrophizers. Study 4 examined the relation between the PCS and measures of depression, trait anxiety, negative affectivity, and fear of pain. Analyses revealed moderate correlations among these measures, but only the PCS contributed significant unique variance to the prediction of pain intensity. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

State and Trait Pain Catastrophizing and Emotional Health in Rheumatoid Arthritis

Article

Full-text available

Aug 2012
ANN BEHAV MED

Background Pain catastrophizing is a powerful predictor of pain adaptation, and both stable and time-varying aspects may influence overall emotional well-being. Purpose This study aims to test the independent influences of state and trait pain catastrophizing on the relationship between daily intensity and negative affect, positive affect, and depressive symptoms. Methods Daily diary data were collected for 30 days from a sample of 231 adults with a diagnosis of rheumatoid arthritis. Results State pain catastrophizing accounted for a significant proportion of the relationship between daily pain and each of the three examined daily outcomes. Greater trait pain catastrophizing significantly increased the effect of state pain catastrophizing on the relationship between pain intensity and the outcome variables in cross-sectional and time-lagged models. Conclusions The results of the current study indicate that state pain catastrophizing plays a prominent role in the adaptation to daily pain fluctuations, particularly for those with a propensity to catastrophize.

Overview of the Patient Perspective at OMERACT 10-Conceptualizing Methods for Developing Patient-Reported Outcomes

Article

Full-text available

Aug 2011

This overview draws out the main conclusions from the 4 workshops focused on incorporating the patient perspective into outcome assessment at the 10th Outcome Measures in Rheumatology (OMERACT 10) conference. They raised methodological issues about the choice of outcome domains to include in clinical trials, the development or choice of instruments to measure these domains, and the way these instruments might capture the impact of a disease and its treatment. The need to develop a more rigorous conceptual model of quantifying the way conditions affect health, and the need to ensure patients are directly involved in the decisions about domains and instruments, emerged clearly. The OMERACT participants voted to develop guidelines for domain and instrument selection, and conceptual and experimental work will be brought forward to revise and upgrade the OMERACT Filter.

Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study

Article

Full-text available

Jun 2011
ARTHRITIS RES THER

Disease remission has become a feasible goal for most rheumatoid arthritis (RA) patients; however, patient-reported symptoms, such as pain, may persist despite remission. We assessed the prevalence of pain in RA patients in remission according to the Disease Activity Score (DAS28-CRP4) and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria. Data were analyzed from RA patients in the Brigham Rheumatoid Arthritis Sequential Study with data at baseline and 1 year. DAS28 remission was defined as DAS28-CRP4 <2.6. The ACR/EULAR remission criteria included (a) one or more swollen joints, (b) one or more tender joints, (c) C-reactive protein ≤1 mg/dl, and (d) patient global assessment score ≤1. Pain severity was measured by using the pain score from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ). The associations between baseline clinical predictors and MDHAQ pain at baseline and 1 year were assessed by using multivariable linear regression. Among the 865 patients with data at baseline and 1 year, 157 (18.2%) met DAS28-CRP4 remission criteria at both time points. Thirty-seven (4.3%) met the ACR/EULAR remission criteria at baseline and 1 year. The prevalence of clinically significant pain (MDHAQ pain ≥4) at baseline ranged from 11.9% among patients meeting DAS28-CRP4 remission criteria to none among patients meeting ACR/EULAR remission criteria. Patient global assessment, MDHAQ function, MDHAQ fatigue, MDHAQ sleep, and arthritis self-efficacy were significantly associated with MDHAQ pain in cross-sectional (P ≤ 0.0005) and longitudinal analyses (P ≤ 0.03). Low swollen-joint counts were associated with high MDHAQ pain in longitudinal analyses (P = 0.02) but not cross-sectional analyses. Other measures of inflammatory disease activity and joint damage were not significantly associated with MDHAQ pain at baseline or at 1 year. Clinically significant pain continues among a substantial proportion of patients in DAS28 remission but not among those in ACR/EULAR remission. Among patients in DAS28 remission, patient global assessment, disability, fatigue, sleep problems, and self-efficacy are strongly associated with pain severity at baseline and 1 year, whereas inflammatory disease activity and joint damage are not significantly associated with elevated pain severity at either baseline or 1 year.

Subjective Sleep Quality and Ethnicity Are Interactively Related to Standard and Situation-Specific Measures of Pain Catastrophizing

Article

Full-text available

Jun 2011
PAIN MED

Sleep quality and ethnicity are related to a host of general health outcomes including the experience of pain, yet it remains unclear whether poor sleep quality and ethnicity might interactively affect pain catastrophizing and laboratory-evoked acute pain reports. The current study examined the cross-sectional associations of subjective sleep quality, ethnicity, and their interaction with pain catastrophizing and pain reports. Healthy (N = 149), ethnically diverse (58% Caucasian American, 23% Asian American, 19% African American) young adults were subjected to a cold pressor task (CPT). Prior to CPT, participants completed the Pittsburgh Sleep Quality Index and a standard version of the Pain Catastrophizing Scale (PCS). Following CPT, participants completed a situation-specific version of the PCS. Adjusted analyses revealed a significant sleep quality by ethnicity interaction for standard catastrophizing reports. Particularly, African Americans with poor overall sleep quality reported the greatest level of catastrophizing on the standard PCS relative to their Caucasian American and Asian American counterparts. Furthermore, African Americans with poorer sleep efficiency reported greater catastrophizing on the situation-specific PCS compared with Caucasian American and Asian Americans. Catastrophizing was significantly correlated with pain reports. These results suggest that African Americans with poorer sleep quality may be at greater risk for catastrophizing, a known contributor to more intense pain and increased pain-related emotional distress. Whether interventions that improve the sleep quality of ethnic minorities affect pain catastrophizing is in need of investigation.

Patient Perceptions Concerning Pain Management in the Treatment of Rheumatoid Arthritis

Article

Full-text available

Aug 2010
J INT MED RES

Previous qualitative studies have revealed discrepancies between patients' and physicians' perceptions of rheumatoid arthritis (RA) and its treatment. Questionnaires were administered to 2795 patients with RA (756 from Europe; 2039 from the USA) to measure patients' perceptions regarding pain management in RA. Although the majority of patients reported their RA as somewhat-to-completely controlled, 75% of European and 82% of US patients reported their pain as moderate-to-severe in the previous 2 months. The majority of European (60%) and US (65%) patients reported dissatisfaction with their arthritis pain. Patients' pain levels corresponded with their disease severity. A higher percentage of patients who reported severe pain were being treated for depression than those who had moderate or mild pain. Patients in the USA rated pain relief as the top required benefit from their RA medication. A comprehensive examination of patients' perspectives regarding pain could lead to better patient care and pain management strategies.

Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: A EULAR initiative

Article

Full-text available

Nov 2009
ANN RHEUM DIS

Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to "distribute 100 points" among the seven domains. The average ranks of importance of these domains were then computed. The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.

Comparison of two approaches to measuring change in health status in rheumatoid arthritis: The Health Assessment Questionnaire (HAQ) and modified HAQ

Article

Full-text available

Dec 1992

As an alternative to the calculation of change scores for health status questionnaires used in clinical trials or longitudinal studies, transitional questions have been developed for patients to assess changes directly themselves. Here the original Health Assessment Questionnaire (HAQ) is compared with a modified version of the HAQ (MHAQ) which contains transition questions used at follow up. These, together with a set of standard rheumatological tests, were all completed by 100 patients with rheumatoid arthritis on two occasions, three months apart. Change scores were calculated for the HAQ and for the clinical measures and compared with the MHAQ. The results were strikingly in favour of encouraging patients to assess their own degree of change through the use of transition questions in the MHAQ.

Recent Advances and Future Directions in the Biopsychosocial Assessment and Treatment of Arthritis

Article

Full-text available

Jun 2002

This article provides an overview of the emerging literature on biopsychosocial assessment and treatment for two of the most common forms of arthritis: osteoarthritis and rheumatoid arthritis. The article is divided into 3 parts. In the 1st part, the basic elements of the biopsychosocial approach to assessing and treating persons having arthritis is described. In the 2nd part, the authors evaluate studies of biopsychosocial approaches to the assessment of arthritis pain and disability. Six research areas are reviewed: learned helplessness, depression, stress, pain coping, self-efficacy, and the social context of arthritis. The 3rd part of the article reviews studies that testing the efficacy of biopsychosocial treatment approaches for persons having osteoarthritis and rheumatoid arthritis.

Assessment of inflammatory activity in rheumatoid arthritis: a comparative study of clinical evaluation with Grey Scale and Power Doppler ultrasonography

Article

Full-text available

Apr 2005

To compare the clinical assessment of overall inflammatory activity in patients with rheumatoid arthritis (RA) with grey scale and power Doppler (PD) ultrasonography (US). Ninety four consecutive patients with RA were included. Demographic and clinical data, C reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were recorded for each patient. The presence of tenderness, swelling, and a subjective swelling score from 1 to 3 were independently assessed by two rheumatologists, who reached a consensus in 60 joints examined in each patient. All patients underwent a US examination by a third blinded rheumatologist, using PD. US joint effusion, synovitis, and PD signal were graded from 1 to 3 in the 60 joints. Joint count and joint index for effusion, synovitis, and PD signal were recorded. A 28 joint count for clinical and US variables was calculated. Interobserver reliability of the US examination was evaluated by a fourth blinded rheumatologist. US showed significantly more joints with effusion (mean 15.2) and synovitis (mean 14.6) than clinical examination (mean 11.5, p<0.05). A significant correlation was found between joint count and joint index for swelling, US effusion, synovitis, and PD signal. The 28 joint count for effusion, synovitis, and PD signal correlated highly with the corresponding 60 joint counts. US findings correlated better with CRP and ESR than clinical measures. Interobserver reliability was better for US findings than for clinical assessment. US is a sensitive method for assessing joint inflammatory activity in RA, complementary to clinical evaluation.

Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: Validation of a clinical activity score

Article

Full-text available

Feb 2005
ARTHRITIS RES THER

Frequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs - termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) - would have comparable validity in clinical cohorts. Data sources comprised an observational cohort of 767 RA patients (average disease duration 8.1 +/- 10.6 years), and an independent inception cohort of 106 patients (disease duration 11.5 +/- 12.5 weeks) who were followed prospectively. Our clinically based hypothesis was statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with DAS28 (R = 0.89-0.90) and comparably to the correlation of SDAI with DAS28 (R = 0.90-0.91). In additional analyses, the CDAI when compared to the SDAI and the DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably to the agreement between DAS28 and DAS28-CRP. All three scores correlated similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45-0.47). The average changes in all scores were greater in patients with better American College of Rheumatology response (P < 0.0001, analysis of variance; discriminant validity). All scores exhibited similar correlations with radiological progression (construct validity) over 3 years (R = 0.54-0.58; P < 0.0001). APRs add little information on top (and independent) of the combination of clinical variables included in the SDAI. A purely clinical score is a valid measure of disease activity and will have its greatest merits in clinical practice rather than research, where APRs are usually always available. The CDAI may facilitate immediate and consistent treatment decisions and help to improve patient outcomes in the longer term.

Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

Article

Jan 2016

Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). Conclusions The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

Article

Jan 2016
BRIT J SPORT MED

Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (=9/10). Conclusions The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: Implications for the use of ultrasound within a treatment-to-target strategy

Article

Mar 2016

Objective: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early RA, achieved with treat-to-target management in clinical practice. Methods: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by DAS28-CRP < 2.6. Twelve-month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on US of 26 joints (total PDA score = 0 or ⩽1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes. Results: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Among patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42, 44 and 40%, respectively; absent/minimal PDA was detected in 62, 66 and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of OA predicted absence of PDA, and lower total baseline PDA predicted absent/minimal PDA. Conclusion: DAS28-CRP remission and absence of PDA were observed in almost half of the patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target.

Situational but Not Dispositional Pain Catastrophizing Correlates With Early Postoperative Pain in Pain-Free Patients Before Surgery

Article

Jan 2016

Unlabelled: Pain catastrophizing may be assessed as a dispositional measure using a previous painful experience as a reference or as a situational measure using an actual ongoing pain as a reference. The latter has shown more robust correlations with pain-related outcomes; the relative influence of dispositional and situational pain catastrophizing remains unknown in relation to populations with no pain before surgery. Forty-two consecutive patients who underwent corrective surgery for funnel chest were asked to complete the Pain Catastrophizing Scale with reference to 1) a previous painful experience (dispositional pain catastrophizing), 2) experimental pain during a 2-minute cold pressor test (situational experimental pain catastrophizing), and 3) clinical pain 3 days after surgery (situational clinical pain catastrophizing) to investigate whether these measures predicted immediate pain intensity and unpleasantness in the early postoperative period. Thirty-four patients were available for analyses. Dispositional pain catastrophizing was unrelated to situational experimental and situational clinical pain catastrophizing and to postoperative pain and unpleasantness (P > .05). In contrast, the 2 situation-specific pain catastrophizing measures were strongly associated (ρ = .59, P = .0002). In analyses adjusted for preoperative anxiety, depression, and cold pressor pain sensitivity, situational experimental and situational clinical pain catastrophizing correlated with postoperative movement-evoked pain (β = 1.36, P = .01 and β = 1.24, P = .02, respectively) and unpleasantness (β = 1.32, P = .01 and β = 1.36, P = .01, respectively). Perspective: Pain catastrophizing should be captured in relation to specific painful events in otherwise healthy patients. Future studies might benefit from assessing situational pain catastrophizing to identify patients at risk for increased postoperative pain to optimize stratified pain treatment.

Editorial Review (Thematic Issue: An Update on Central Sensitivity Syndromes and the Issues of Nosology and Psychobiology)

Article

Aug 2015
Curr Rheumatol Rev

Muhammad B Yunus

Central sensitization (CS), simply defined as an amplified response of the central nervous system to peripheral input, is a concept of great importance in clinical medicine. It has helped to explain aspects of the pathophysiology of common diseases, e.g. fibromyalgia syndrome (FMS), irritable bowel syndrome, vulvodynia, headaches, chronic pelvic pain and other overlapping conditions (collectively called central sensitivity syndromes, or CSS). It also applies to pain of complex regional pain syndrome, osteoarthritis (OA), rheumatoid arthritis (RA) and post-operative pain. The pathology-pain gap in CSS is readily explained by CS. Many FMS and other CSS patients have peripheral pathology, e.g. nociceptive areas in the muscles, arthritis, small fiber neuropathy and inflammation. Pro-inflammatory cytokines are elevated in some patients. Identification of CS in patients with structural pathology, e.g. OA and RA, has helped to explain why not all patients benefit from nonsteroidal anti-inflammatory drugs or joint replacement surgery, and require therapy directed at CS. Glial cells are important in pain processing. Remarkable advances have been achieved in neuroimaging, including visualization of grey matter and white matter, not only during provoked pain but also pain at rest. Based on CS mechanisms, targeted individual therapy may now be possible. Appropriate nosology is important particularly for effective patient care. Dichotomy of neurochemical-structural ("functional") and structural ("organic") pathology should be abandoned; many patients have both. Psychobiology is also biology. Patient-blaming terms like somatization, somatizer and catastrophizing should be avoided. For therapy, both pharmacological and non- pharmacological approaches are important, including recognition of subgroups and person/patient-centered care.

One- and two-item measures of pain beliefs and coping strategies

Article

Aug 2003

Pain-related beliefs and pain coping strategies are central components of current cognitive-behavioral models of chronic pain, and have been found in numerous studies to be associated significantly with psychosocial and physical disability. However, the length of most measures of pain-related beliefs and coping restricts the ability of clinicians and researchers to perform a thorough assessment of these variables in many Situations. The availability of very brief versions of existing scales would make possible the assessment of a range of important pain beliefs and coping strategies in settings where Subject or patient assessment burden is an issue. In this study, one- and two- item versions of the subscales of several commonly used measures of pain beliefs and coping strategies were developed using both rational and empirical procedures. The findings support the validity of these brief subscales. The appropriate use and limitations of these measures are discussed.

Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

Article

May 2015
ANN RHEUM DIS

José Luis Andreu

Background Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). Conclusions The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis

Article

Mar 1988
ARTHRIT RHEUM-ARTHR

The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a “classification tree” schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91–94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

Subgrouping of Patients With Rheumatoid Arthritis Based on Pain, Fatigue, Inflammation, and Psychosocial Factors

Article

Aug 2014

Objective: Among patients with rheumatoid arthritis (RA), pain may be attributed to peripheral inflammation or other causes, such as central pain mechanisms. The aim of this study was to use self-report measures and physical examination findings to identify clusters of RA patients who may have different causes of pain as well as different prognoses and treatment options. Methods: Data from 169 RA patients with pain scores of >0 (on a 10-point numeric rating scale) in the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study were analyzed. The patients completed questionnaires on pain, fatigue, and psychosocial factors. A hierarchical agglomerative clustering procedure with Ward's method was used to obtain subgroups. Multivariate analysis of variance was used to determine the contribution of each variable in a cluster. General linear regression models were used to examine differences in clinical characteristics across subgroups. Discriminant analyses were performed to determine coefficients for linear combinations of variables that assigned cluster membership to individual cases. Results: Three clusters best fit these data. Cluster 1 consisted of 89 individuals with low levels of inflammation, pain, fatigue, and psychosocial distress. Cluster 2 consisted of 57 individuals with minimal inflammation but high levels of pain, fatigue, and psychosocial distress. Cluster 3 consisted of 23 individuals with active inflammatory disease, manifested by high swollen joint counts, high C-reactive protein levels, and high levels of pain and fatigue. Conclusion: Although most patients had low levels of inflammation, pain, and fatigue, 47.3% continued to report having moderate to high levels of pain and fatigue. Most of these patients had minimal signs of inflammation but high levels of fatigue, pain catastrophizing, and sleep disturbance, indicative of a chronic widespread pain syndrome.

High pain catastrophizing scores in one-fourth of patients on biotherapy for spondylarthritis or rheumatoid arthritis

Article

Dec 2013

To measure catastrophizing scores in patients on biotherapy for spondyloarthritis (SpA) or rheumatoid arthritis (RA). The first 140 outpatients or day-hospital patients seen at a teaching hospital rheumatology department for biotherapy administration completed the validated French version of the Pain Catastrophizing Scale (PCS, total score ranging from 0 to 52); a questionnaire on perceived support and past, current, and future disease activity; and a questionnaire on perceived understanding of their disease by family and co-workers. PCS scores were significantly higher in the 54 SpA patients than in the 86 RA patients (20.8±12.1 versus 17.0±13.6; P=0.08), as a result of a higher helplessness subscore (10.0±6.2 versus 7.8±6.2; P=0.046). The PCS score was ≥30 in 14/54 (26%) SpA patients and in 19/86 (22%) RA patients; physicians identified catastrophizing in only 17 of these 33 patients. PCS scores showed moderate correlations with the AS-DAS and DAS-28 and slightly stronger correlations with the overall pain score (Pearson, +0.431; P=0.0001). SpA patients reported significantly worse understanding by their co-workers than did RA patients (33.9±33.4 versus 53.9±36.3; P=0.007). One-fourth of patients with SpA or RA had very high pain catastrophizing scores despite biotherapy. Pain catastrophizing was missed by the physicians in half the cases and was relatively independent from other follow-up parameters. Pain catastrophizing can jeopardize treatment outcomes and deserves specific management.

Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis

Article

Jan 1995
ARTHRIT RHEUM-ARTHR

Objective. The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts. Methods. These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated. Results. No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists). Conclusion. The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.

Coping with rheumatoid arthritis pain: Catastrophizing as a maladaptive strategy

Article

May 1989

The present study examined catastrophizing in rheumatoid arthritis (RA) patients. Subjects were 223 RA patients who were participants in a longitudinal study. Each patient completed the Catastrophizing scale of the Coping Strategies Questionnaire (CSQ) on 2 occasions separated by 6 months (time 1, time 2). The Catastrophizing scale is designed to measure negative self-statements, castastrophizing thoughts and ideation (sample items = ‘I worry all the time about whether it will end,’ ‘It is awful and I feel that it overwhelms me’). Data analysis revealed that the Catastrophizing scale was internally reliable (alpha = 0.91) and had high test-retest reliability (r = 0.81) over a 6 month period. Correlational analyses revealed that catastrophizing recorded at time 1 was related to pain intensity ratings, functional impairment on the Arthritis Impact Measurement scale (AIMS), and depression at time 2. Predictive findings regarding catastrophizing while modest were obtained after controlling for initial scores on the dependent variables, demographic variables (age, sex, socioeconomic status), duration of pain, and disability support status. Taken together, these findings suggest that catastrophizing is a maladaptive coping strategy in RA patients. Further research is needed to determine whether cognitive-behavioral interventions designed to decrease catastrophizing can reduce pain and improve the physical and psychological functioning of RA patients.

Analyzing pain in rheumatoid arthritis patients. Pain coping strategies in patients who have had knee replacement surgery

Article

Sep 1991

This study used the Coping Strategies Questionnaire (CSQ) to investigate pain coping strategies in 52 rheumatoid arthritis patients who reported having knee pain 1 year or more following knee replacement surgery. Data analysis revealed that, as a group, these patients were active copers in that they reported frequent use of a variety of pain coping strategies. Pain coping strategies were found to be related to measures of pain and adjustment. Patients who rated their ability to control and decrease pain high and who rarely engaged in catastrophizing (i.e., who scored high on the Pain Control and Rational Thinking factor of the CSQ) had much lower levels of pain and psychological disability than patients who did not. Coping strategies were not found to relate to age, gender, obesity status or disability/compensation status. Taken together, these results suggest that an analysis of pain coping strategies may be helpful in understanding pain in arthritis patients who have pain following joint replacement surgery.

The Use of Coping Strategies in Chronic Low-Back-Pain Patients - Relationship to Patient Characteristics and Current Adjustment

Article

Oct 1983

Cognitive and behavioral pain coping strategies were assessed by means of questionnaire in a sample of 61 chronic low back pain patients. Data analysis indicated that the questionnaire was internally reliable. While patients reported using a variety of coping strategies, certain strategies were used frequently whereas others were rarely used. Three factors: (a) Cognitive Coping and Suppression, (b) Helplessness and (c) Diverting Attention or Praying, accounted for a large proportion of variance in questionnaire responses. These 3 factors were found to be predictive of measures of behavioral and emotional adjustment to chronic pain above and beyond what may be predicted on the basis of patient history variables (length of continuous pain, disability status and number of pain surgeries) and the tendency of patients to somaticize. Each of the 3 coping factors was related to specific measures of adjustment to chronic pain.

Examination of intra and interrater reliability with a new ultrasonographic reference atlas for scoring of synovitis in patients with rheumatoid arthritis

Article

Jul 2011
ANN RHEUM DIS

Synovitis in patients with rheumatoid arthritis (RA) may be scored semiquantitatively (0-3) for B-mode (BM) and power Doppler (PD) ultrasonography. The objective was to assess the reliability of BM and PD examinations with a novel ultrasonographic atlas as reference. Representative ultrasound images (including scores 0-3) of BM and PD from 24 different joints were collected to develop an ultrasonographic atlas. Ten RA patients were assessed twice by five rheumatologists performing BM and PD scoring (0-3) of 16 joints bilaterally (metacarpophalangeal 1-5, wrist (radiocarpal, intercarpal, radioulnar), elbow, knee, talocrural and metatarsophalangeal 1-5), with the novel ultrasonographic atlas as a reference. The median (range) percentages of exact agreements for BM/PD assessments were 73.1 (70.3-80.6)/83.7 (76.7-87.6) and for close agreement 98.1 (96.2-99.7)/98.0 (96.8-98.4) with weighted κ values of median (range) 0.77 (0.70-0.83) for BM and 0.83 (0.73-0.86) for PD. The intrarater intraclass correlation coefficients (ICC) for BM/PD scores were 0.95 (0.93-0.99)/0.97 (0.95-0.99) and interrater ICC were 0.95 (0.86-0.99)/0.97 (0.94-1.00). Scoring of 32 joints was completed in median 15 min (range 12-20). With the use of an ultrasonographic atlas as reference high intra and interrater reliability was found for BM and PD scoring. This novel atlas may be a useful resource in clinical practice and research.

Pain, catastrophizing, and depression in the rheumatic diseases

Article

Jun 2011
NAT REV RHEUMATOL

Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: A EULAR initiative

Article

Jun 2011
ANN RHEUM DIS

A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. 570 patients (79% women, mean ± SD age 56 ± 13 years, disease duration 12.5 ± 10.3 years, disease activity score (DAS28) 4.1 ± 1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical -0.59 and mental -0.55, p<0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.

Performance of the Rheumatoid Arthritis Impact of Disease (RAID) score in relation to other patient-reported outcomes in a register of patients with rheumatoid arthritis

Article

Mar 2011
ANN RHEUM DIS

Delegates at the Outcome Measures in Rheumatology (OMERACT) 10 conference (Borneo, 4-8 May 2010) questioned how the new seven-domain Rheumatoid Arthritis Impact of Disease (RAID) score performs as a global measure. Score distributions and associations between the RAID score and patient-reported outcomes (PROs) and demographic variables were examined in a large sample of rheumatoid arthritis (RA) patients. 1086 patients in the Oslo RA Register responded to a postal survey with commonly used PROs. Bivariate associations between the RAID score and other measures are reported as Pearson correlation coefficients. The mean RAID was 3.37 ± 2.17. The distribution of the RAID score showed a slight floor effect: 17.5% had a score between 0 and 1, and 14.4% between 1 and 2, whereas only 1.0% and 0.3% had scores between 8 and 9, and 9 and 10, respectively. Correlations between the RAID score and the patient global assessment, Rheumatoid Arthritis Disease Activity Index, Short-Form (SF)-6D and EQ-5D were 0.82, 0.82, -0.77 and -0.73, respectively. Strong correlation was also seen between RAID and pain, the domain with highest weight, whereas correlations to measures of other RAID domains were moderate. The RAID score was higher in women than men (3.49 vs 2.95, p=0.001). The RAID score was correlated more strongly to other global measures than to PROs, reflecting single health domains.

Pain, catastrophizing, and depression in the rheumatic diseases

Article

Feb 2011
NAT REV RHEUMATOL

Persistent and disabling pain is the hallmark of osteoarthritis, rheumatoid arthritis, fibromyalgia, and various other rheumatologic conditions. However, disease severity (as measured by 'objective' indices such as those that employ radiography or serology) is only marginally related to patients' reports of pain severity, and pain-related presentation can differ widely between individuals with ostensibly similar conditions (for example, grade 4 osteoarthritis of the knee). Increasing evidence in support of the biopsychosocial model of pain suggests that cognitive and emotional processes are crucial contributors to inter-individual differences in the perception and impact of pain. This Review describes the growing body of literature relating depression and catastrophizing to the experience of pain and pain-related sequelae across a number of rheumatic diseases. Depression and catastrophizing are consistently associated with the reported severity of pain, sensitivity to pain, physical disability, poor treatment outcomes, and inflammatory disease activity, and potentially with early mortality. A variety of pathways, from cognitive to behavioral to neurophysiological, seem to mediate these deleterious effects. Collectively, depression and catastrophizing are critically important variables in understanding the experience of pain in patients with rheumatologic disorders. Pain, depression, and catastrophizing might all be uniquely important therapeutic targets in the multimodal management of a range of such conditions.

Ultrasonography shows significant improvement in wrist and ankle tenosynovitis in rheumatoid arthritis patients treated with adalimumab

Article

Nov 2010
SCAND J RHEUMATOL

Tenosynovitis is common in rheumatoid arthritis (RA) but knowledge is limited regarding its response to anti-inflammatory treatment. This study used ultrasonography (US) to examine the distribution and responsiveness of tenosynovitis to anti-tumour necrosis factor (anti-TNF) treatment in RA patients. Twenty patients with RA were examined at baseline and 1, 3, 6, and 12 months after starting adalimumab treatment, and grey-scale (GS) and power Doppler (PD) US scoring (semi-quantitative range 0-3) of wrist and ankle tendons was performed in addition to assessment of the 28-joint Disease Activity Score (DAS28), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The extensor carpi ulnaris (ECU) tendon in the wrists and the closely related tendons tibialis posterior (TB) and flexor digitorum longus (FDL) in the ankles were most often inflamed. Median sum scores for this reduced number of tendons at baseline/12-month follow-up were 5/0.5 for GS (p < 0.001) and 4/0 for PD (p < 0.05), with reductions in the US scores during follow-up as large as those found for sum scores of all tendons. The standardized response means (SRMs) for sum GS or PD scores of the reduced number of tendons were higher (range -0.53 to -0.93) than for the sum scores of all tendons (-0.23 to -0.74), and showed larger responsiveness than CRP (-0.10 to -0.43) and ESR (-0.03 to -0.71). Bilateral assessments of ECU, TB, and FDL tendons were as sensitive to change as the sum scores of all tendons, and scoring of this reduced number of tendons is suggested to be included in US scorings for follow-up of RA patients.

Does Pain Catastrophizing Moderate the Relationship Between Spinal Nociceptive Processes and Pain Sensitivity?

Article

Sep 2009

Unlabelled: Existing evidence indicates that pain catastrophizing is associated with enhanced pain reports and lower pain threshold/tolerance levels, but is not significantly related to nociceptive flexion reflex (NFR) threshold in healthy and clinical pain samples. This suggests pain catastrophizing may modulate pain threshold at a supraspinal level without influencing descending modulation of spinal nociceptive inputs. To examine this issue further, the present study assessed NFR threshold, electrocutaneous pain threshold, and electrocutaneous pain tolerance, as well as subjective ratings of noxious stimuli in a sample of 105 healthy adults. Pain catastrophizing was assessed prior to testing using traditional instructions and after pain testing with instructions to report on cognitions during testing (situation-specific catastrophizing). As expected, NFR threshold was correlated with pain sensitivity measures, but uncorrelated with both measures of catastrophizing. Although situation-specific catastrophizing was correlated with some pain outcomes, neither catastrophizing measure (traditional or situation specific) moderated the relationship between NFR and pain sensitivity. These findings confirm and extend existing evidence that catastrophizing influences pain reports through supraspinal mechanisms (eg, memory, report bias, attention) without altering transmission of spinal nociceptive signals. Perspective: Assessing catastrophic thoughts related to a specific painful event (situation-specific catastrophizing) provides important additional information regarding the negative cognitions that influence pain-related processes. However, neither situation-specific nor traditionally measured pain catastrophizing appear to enhance pain by engaging descending controls to influence spinal nociceptive processes.

Pain catastrophizing: A critical review

Article

Jun 2009

Pain catastrophizing is conceptualized as a negative cognitive-affective response to anticipated or actual pain and has been associated with a number of important pain-related outcomes. In the present review, we first focus our efforts on the conceptualization of pain catastrophizing, highlighting its conceptual history and potential problem areas. We then focus our discussion on a number of theoretical mechanisms of action: appraisal theory, attention bias/information processing, communal coping, CNS pain processing mechanisms, psychophysiological pathways and neural pathways. We then offer evidence to suggest that pain catastrophizing represents an important process factor in pain treatment. We conclude by offering what we believe represents an integrated heuristic model for use by researchers over the next 5 years; a model we believe will advance the field most expediently.

Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis

Article

Feb 1995

The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts. These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated. No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists). The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.

Changes in beliefs, catastrophizing, and coping are associated with improvement in multidisciplinary pain treatment

Article

Sep 2001

To examine the associations between changes in cognitions and coping and multidisciplinary pain treatment outcomes, the authors had 141 patients with chronic pain complete measures of adjustment, beliefs, catastrophizing, and coping; in addition, their significant others rated patient physical functioning at pretreatment, posttreatment, and 6- and 12-month follow-ups. Decreases in guarding and resting and in the belief that pain signals damage were associated with decreases in patient disability. Increases in perceived control over pain and decreases in catastrophizing and in the belief that one is disabled were associated with decreases in self-reported patient disability, pain intensity, and depression. The results are consistent with the hypothesis, derived from cognitive-behavioral models of chronic pain, that the outcomes of multidisciplinary pain treatment are associated with changes in patient cognitions and coping responses.

Power Doppler Ultrasonography for Assessment of Synovitis in the Metacarpophalangeal Joints of Patients with Rheumatoid Arthritis: A Comparison with Dynamic Magnetic Resonance Imaging

Article

Sep 2001

To evaluate the effectiveness of power Doppler ultrasonography (PDUS) for assessing inflammatory activity in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA), using dynamic magnetic resonance imaging (MRI) as a reference method. PDUS and dynamic MRI were performed on 54 MCP joints of 15 patients with active RA and on 12 MCP joints of 3 healthy controls. PDUS was performed with a LOGIQ 500 unit by means of a 7-13-MHz linear array transducer. Later the same day, MRI was performed with a 1.0T MR unit. A series of 24 coronal T1-weighted images of the second through the fifth MCP joints was obtained, with intravenous injection of gadolinium diethylenetriaminepentaacetic acid after the fourth image (dynamic MRI). From the MR images, the rate of early synovial enhancement (RESE; defined as the relative enhancement per second during the first 55 seconds postinjection) was calculated and compared with the flow signal on PDUS, which was scored as present or absent. In RA patients, flow signal on PDUS was detected in 17 of 54 MCP joints examined. Postcontrast MR images revealed an RESE of > or = 1.0%/second in 18 of 54 RA MCP joints. PDUS showed no flow in 47 of 48 MCP joints with an RESE of <1.0%/second and revealed flow in 16 of 18 MCP joints with an RESE of > or = 1.0%/second. Using dynamic MRI as a reference, PDUS had a sensitivity of 88.8% and a specificity of 97.9%. PDUS was reliable for assessing inflammatory activity in the MCP joints of RA patients, using dynamic MRI as the standard. PDUS and clinical assessment of joint swelling/tenderness were only weakly correlated.

A Simplified Disease Activity Index for rheumatoid arthritis for use in clinical practice

Article

Mar 2003

One- and two-item measures of pain beliefs and coping strategies

Article

Sep 2003

Pain-related beliefs and pain coping strategies are central components of current cognitive-behavioral models of chronic pain, and have been found in numerous studies to be associated significantly with psychosocial and physical disability. However, the length of most measures of pain-related beliefs and coping restricts the ability of clinicians and researchers to perform a thorough assessment of these variables in many situations. The availability of very brief versions of existing scales would make possible the assessment of a range of important pain beliefs and coping strategies in settings where subject or patient assessment burden is an issue. In this study, one- and two-item versions of the subscales of several commonly used measures of pain beliefs and coping strategies were developed using both rational and empirical procedures. The findings support the validity of these brief subscales. The appropriate use and limitations of these measures are discussed.

Validating the Use of Two-Item Measures of Pain Beliefs and Coping Strategies for a Veteran Population

Article

May 2006
J PAIN

Unlabelled: Previous research has demonstrated that 2-item versions of subscales from the Chronic Pain Coping Inventory, Coping Strategy Questionnaire, and the Survey of Pain Attitudes appear adequately reliable and valid for use in studies with large sample sizes. It was suggested that use of the abbreviated scales might help to expand the testing and application of cognitive-behavioral models of pain to new settings and with new populations where assessment burden might be a key issue. This study explored the utility of these brief scales among veterans in a Veterans Affairs setting. Strong associations were found between the 2-item versions and their respective parent scales. In addition, the 2-item scales were found to be associated with other pain-related measures, supporting their predictive validity. The results of this study replicate previous findings and offer support for the use of the 2-item versions for both screening and research purposes in Veterans Affairs settings with a veteran population. Perspective: This article presents the psychometric properties of brief versions of 3 commonly used pain coping and belief questionnaires in a unique population. These measures could be used clinically for initial screening purposes, as well as for treatment monitoring.

Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: Evidence from an imaging study may explain structural progression

Article

Dec 2006

More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.

Beliefs About the Causes and Consequences of Pain in Patients With Chronic Inflammatory or Noninflammatory Low Back Pain and in Pain-Free Individuals

Article

Apr 2008
SPINE

Case control study including 2 groups of patients with low back pain (LBP, inflammatory and noninflammatory) and a pain-free community control group. We explored whether pain beliefs differ between patients with chronic LBP attributed to inflammatory or noninflammatory medical diagnoses, and between patients with chronic LBP and pain-free controls. Beliefs strongly influence patients' engagement in and response to treatments for chronic LBP. It is unclear, however, whether unhelpful beliefs held by patients with chronic LBP are predominantly associated with diagnosis, or with other aspects of the patient's pain experience. Patients and controls completed the pain beliefs questionnaire addressing beliefs about the causes and consequences of pain. Patients also completed questionnaires addressing catastrophizing (Coping Strategies Questionnaire), physical disability and bodily pain (SF-36 Health Survey), and psychological distress (Spielberger State-Trait Anxiety Inventory Short Form and Cognitive Depression Index). Variance analysis and chi2 test were used as appropriate, adjusting for effects of covariates and multiple comparisons. Linear regression and logistic regression were used to adjust for confounding factors. Patients with noninflammatory LBP more strongly endorsed organic pain beliefs (e.g., that pain necessarily indicates damage), and catastrophizing (e.g., that the pain is never going to get better), than did patients with inflammatory LBP (P < 0.01). Patients with inflammatory LBP, in turn, more strongly endorsed organic pain beliefs than did pain-free controls (P < 0.05). Endorsement of organic pain beliefs was associated with catastrophizing. Organic pain beliefs are associated with increased catastrophizing in patients with chronic LBP, and addressing these beliefs may help patients to manage their pain and disability. Meanings attributed to inflammatory and noninflammatory diagnostic labels may contribute to the different pain beliefs held by different patient groups.

Pain catastrophizing is strongly associated with subjective outcomes, but not with inflammatory assessments in rheumatoid arthritis patients

Abstract

No full-text available

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