Désirée van der Heijde

Oregon Health and Science University, Portland, Oregon, United States

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Publications (624)3551.91 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: Background: Little is known on how well targeted treatment, for instance targeting towards low DAS, is implemented in clinical practice. Our aim was to evaluate treatment adjustments in response to DAS in RA patients in clinical practice. Methods: We used data from one referral centre, multiple rheumatologists, from the METEOR database. Generalized Estimating Equations (GEE) were used to assess whether in case of non-low disease activity (DAS > 2.4) treatment intensifications in DMARD therapy occurred ((change or increase in dose or number of DMARDs, including synthetic (s)DMARDs, biologic (b)DMARDs and corticosteroids compared to the visit before)). Determinants of not intensifying the treatment when DAS > 2.4 were investigated using GEE. Results: Five thousand one hundred fifty-seven registered visits of 1202 patients were available for the analyses. A DAS > 2.4 was weakly (OR: 1.19; 95 % CI 1.07-1.33) associated with a treatment intensification. In 69 % (n = 3577) of the visits patients were in low disease activity. In 66 % (n = 1028) of the visits with DAS > 2.4 treatment was not intensified. These patients had a higher tender joint count and received more often methotrexate plus a bDMARD, or csDMARD monotherapy, as compared to patients that received treatment intensification. Conclusion: In the majority of visits in the METEOR database patients were already in a state of low disease activity, reflecting appropriate treatment intensity. When DAS was greater than 2.4, treatment was often not intensified due to high tender joint count or specific treatment combinations. This data suggest that while aiming for low DAS, physicians per patient weigh whether all DAS elements indicate disease activity or will respond to DMARD adjustment or not, and make treatment decisions accordingly.
    Full-text · Article · Dec 2016 · BMC Musculoskeletal Disorders
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: The Social Role Participation Questionnaire (SRPQ) assesses the influence of health on 11 specific roles and 1 general role along 4 dimensions. In this study, a shortened version of the SRPQ (s-SRPQ) was developed in patients with ankylosing spondylitis (AS) to facilitate data collection in clinical studies and practice. Methods: Using data from 246 patients with AS and population controls, the fit of each role to the different participation dimensions, the contribution of each role to the measurement precision, and the correlation between dimensions were evaluated using item response theory. Representation of the 3 participation chapters of the International Classification of Functioning, Disability, and Health was ensured. Reliability of each dimension of both versions of the SRPQ was compared by correlating scores to the Medical Outcomes Study Short Form-36 (SF-36) and the Satisfaction With Life Scale (SWLS), and by comparing ability to discriminate between patients and controls and between patients with low and high disease activity (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4). Results: The s-SRPQ, which assesses participation across 6 social roles along 2 dimensions (physical difficulty and satisfaction with performance), was proposed. Both dimensions of the s-SRPQ were highly reliable (r ≥ 0.86) and were shown to have construct validity as indicated by a similar pattern of correlations with the SF-36 and SWLS as the original SRPQ dimensions. Both versions discriminated well between patients and controls and between patients with high versus low disease activity (relative validity ≥ 0.72). Conclusion: The s-SRPQ retains the measurement properties of the original SRPQ and seems useful for measuring the effect of AS on participation.
    No preview · Article · May 2016 · The Journal of Rheumatology
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives To compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-naïve patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. Methods All patients had symptom duration from first swollen joint <2 years and were DMARD naïve with an indication for DMARD treatment. Patients were stratified as seropositive (positive rheumatoid factor (RF)+ and/or anticitrullinated peptide antibody (ACPA)+) or seronegative (RF− and ACPA−), and disease characteristics were compared between groups. Results A total of 234 patients were included, and 36 (15.4%) were seronegative. Ultrasonography (US) scores for joints (median 55 vs 25, p<0.001) and tendons (median 3 vs 0, p<0.001), number of swollen joints (median 17 vs 8, p<0.001), disease activity score (DAS; mean 3.9 vs 3.4, p=0.03) and physician global assessment (mean 49.1 vs 38.9, p=0.006) were significantly higher in seronegative patients compared with seropositive. Total van der Heijde-modified Sharp score, Richie Articular Index and patient-reported outcome measures were similar between groups. Conclusions Seronegative patients had higher levels of inflammation, assessed both clinically and by US, than seropositive patients. These differences may reflect the high number of involved joints required for seronegative patients to fulfil the 2010 ACR/EULAR classification criteria for RA. Trial registration number NCT01205854; Pre-results.
    No preview · Article · Apr 2016 · Annals of the Rheumatic Diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: Social role participation of persons with a chronic disease is important for their lives, but interpretation of data on participation is difficult in the absence of a benchmark. This study aimed to compare social role participation in patients with ankylosing spondylitis (AS) to population controls using the social role participation questionnaire (SRPQ). Methods: 246 AS patients and 510 population controls completed the SRPQ which assesses participation in eleven roles (score range 1-5) across four dimensions (importance, satisfaction with performance, satisfaction with time, and difficulty), and additionally ranked their three most important roles. The ranking of role-importance, the SRPQ dimension scores, and the gap between 'importance' and 'satisfaction with performance' of roles were compared between patients and controls. Results: Patients (62% male; 51±12 year,) and controls (70% male;42±15 year,)ranked 'intimate relationships', 'relationship with (grand/step-) children' and 'employment' as most important roles. Compared to controls, patients gave higher scores on the SRPQ to 'importance' (3.75 vs 3.43), but reported lower 'satisfaction with performance' (3.19 vs 3.58) and greater 'physical difficulty' (3.87 vs 4.67) (all p≤0.05). The largest difference in gaps between 'importance' and 'satisfaction with performance' for patients compared to controls were seen for physical leisure, hobbies, travelling and vacation, where patients conferred a higher importance but especially lower satisfaction. Conclusion: As society places increasing emphasize on individual's responsibility to participate fully in social roles, the current data suggest that healthcare providers should pay more attention to participation-restrictions experienced by patients with AS. This article is protected by copyright. All rights reserved.
    No preview · Article · Apr 2016
  • Iris M. Markusse · Robert Landewé · Ron Wolterbeek · Meilien Ho · Martin Jenkins · Désirée van der Heijde
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To assess linear extrapolation (LE) and last observation carried forward (LOCF) as imputation methods for radiographic change in patients with RA. Methods: The OSKIRA-1 trial enrolled 918 patients with active RA for studying the efficacy of fostamatinib. Radiographs were scheduled for all patients at baseline and week 12, regardless of early escape, and at weeks 24 and 52 for patients who remained in the study. Complete radiographic data for the 24-week follow-up were available for 623 patients and were assessed according to the Sharp/van der Heijde score. From this complete set of data, a random selection of 10% missingness was generated. This was done 1000 times, and for each replicate the missing radiographic change at week 24 was imputed, first by LE, then by LOCF. The mean of the mean and mean of thes.d.across the 1000 replications was calculated. A similar approach was iterated for different proportions of missingness. Results: The mean (s.d.) observed Sharp/van der Heijde score change from baseline to week 24 was 0.36 (2.39). With LE, the mean (s.d.) change was estimated as 0.36 (2.65), 0.35 (2.88), 0.35 (3.17), 0.34 (3.57) and 0.32 (4.45) with 10/20/30/50/90% missingness, respectively. With LOCF, the mean (s.d.) change was estimated as 0.34 (2.39), 0.32 (2.38), 0.30 (2.37), 0.26 (2.36) and 0.18 (2.34) with 10/20/30/50/90% missingness, respectively. Conclusion: LE led to stable estimates of progression at the group level, but increasing variability with increasing proportions of missingness. In contrast, LOCF imputation systemically underestimated mean progression with increasing proportions of missingness, with artificially reduced variability estimates.
    No preview · Article · Apr 2016 · Rheumatology
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    [Show abstract] [Hide abstract] ABSTRACT: Introduction The European League Against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) and the treat-to-target (T2T) principles have been developed in order to improve the treatment outcome of patients with RA, and have received broad attention. It is not clear, though, whether these recommendations are indeed followed up in clinical practice. Objective To investigate if rheumatologists that report to agree with existing guidelines indeed follow them up in clinical practice. Methods The International Recommendation Implementation Study (IRIS) included 132 participating rheumatologists from 14 countries. Participating rheumatologists received a questionnaire measuring their awareness/commitment with the EULAR/T2T recommendations and followed a dedicated educational programme. Subsequently, they were asked to enrol 5–10 patients with new-onset RA in the online IRIS database and monitor disease activity and treatment for a period of 1–2 years. Four recommendations (3 from the EULAR recommendations and one from the T2T recommendations) were selected on the basis of testability, and analysed with regard to compliance by participating rheumatologists. Results In total, 72 of the 132 participating rheumatologists contributed 378 patients to the database. Of these participants, 70 (98%) agreed upfront with the recommendation that disease-modifying antirheumatic drug (DMARD) therapy should be started as soon as possible after diagnosis in every patient; 69 (96%) of the rheumatologists agreed with the recommendation that methotrexate (MTX) should be part of the first treatment strategy. When measuring the actual performance, it was found that the recommendation on early DMARD start was met in 253 (67%) of the recorded patients, and the recommendation on MTX in 225 (60%) of the recorded patients. Of the participants, 60 (83%) agreed that composite measures should be recorded regularly, but only in 134(54%) of the patients were composite scores actually recorded in ≥50% of patient visits. Conclusion Reporting to be compliant with EULAR recommendations and T2T principles, even after dedicated education does not mean they actually comply with it in clinical practice.
    Full-text · Article · Apr 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Objective To investigate whether an intensive early rheumatoid arthritis (RA) treat-to-target (T2T) strategy could be improved through the use of musculoskeletal ultrasound (MSUS) assessment of disease activity. Methods 111 newly diagnosed patients with RA or undifferentiated arthritis (symptom duration <1 year) were randomised to strategies that aimed to attain either DAS28-erythrocyte sedimentation rate (ESR)<3.2 (control) or a total power Doppler joint count≤1 during a combined DAS28-ESR/MSUS assessment (intervention). MSUS examination was indicated if: DAS28-ESR<3.2 or DAS28-ESR≥3.2 with two swollen joints. Step-up disease-modifying antirheumatic drug (DMARD) escalation was standardised: methotrexate monotherapy, triple therapy and then etanercept/triple therapy. American College of Rheumatology (ACR) core-set variables were assessed 3 monthly by a metrologist blinded to group allocation. MRI of dominant hand and wrist, and plain radiographs of hands and feet were undertaken at baseline and 18 months for grading by two readers using the Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis MRI Scoring System (RAMRIS) and van der Heijde/Sharp Score, respectively. The coprimary outcomes were mean change from baseline of DAS44 and RAMRIS erosion score. Results Groups were matched for baseline clinical, demographic and radiographic features. The intervention group received more intensive DMARD therapy. Both groups demonstrated significant improvements in DAS44 (mean change: control −2.58, intervention −2.69; 95% CI difference between groups −0.70 to 0.48; p=0.72). There were no significant between-group differences for any ACR core-set variables, except DAS44 remission after 18 months (control 43%, intervention 66%; p=0.03). There was minimal progression of MRI and radiographic erosions and no difference in imaging outcomes or serious adverse event rates. Conclusions In early RA, a MSUS-driven T2T strategy led to more intensive treatment, but was not associated with significantly better clinical or imaging outcomes than a DAS28-driven strategy. Trial registration number NCT00920478.
    No preview · Article · Mar 2016 · Annals of the rheumatic diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Methods: In this phase III, double-blind, placebo-controlled study, 606 patients with psoriatic arthritis were randomised to intravenous (IV) secukinumab 10 mg/kg (weeks 0, 2, 4) followed by subcutaneous secukinumab 150 mg (IV→150 mg) or 75 mg (IV→75 mg), or placebo. Patients were stratified by prior anti-TNF (tumour necrosis factor) exposure (71% anti-TNF-naïve). At week 16, placebo-treated patients who had ≥20% reduction in tender and swollen joint count (responders) remained on placebo until week 24; non-responders were re-randomised to secukinumab 150 or 75 mg. The van der Heijde modified total Sharp score (mTSS) was determined at baseline, week 16/24 and week 52. Results: In the overall population, radiographic progression was inhibited through 52 weeks; efficacy was demonstrated for both erosion and joint space narrowing scores and in patients who switched from placebo to secukinumab at week 24. Subgroup analyses showed secukinumab reduced progression at week 24, regardless of prior anti-TNF use; mean change from baseline to week 24 in mTSS in the secukinumab pooled and placebo groups was 0.05 and 0.57, respectively for anti-TNF-naïve patients and 0.16 and 0.58, respectively in anti-TNF-IR patients. Anti-TNF-naïve patients showed negligible progression through week 52. Inhibition of structural damage was observed through week 52, irrespective of concomitant methotrexate use. A high proportion of patients showed no progression (≤0.5) with secukinumab from baseline to week 24 (IV→150 mg, 82.3%; IV→75 mg, 92.3%) and from week 24 to week 52 (IV→150 mg, 85.7%; IV→75 mg, 85.8%). Conclusion: Secukinumab inhibited radiographic progression in patients with active psoriatic arthritis through 52 weeks of therapy. This article is protected by copyright. All rights reserved.
    No preview · Article · Mar 2016 · Arthritis and Rheumatology
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: To explore whether age, gender or education influence the time until initiation of the first bDMARD in patients with RA. Methods: Data from the Norwegian Register of DMARDs collected between 2000 and 2012 were used. Only DMARD-naïve patients with RA starting their first conventional synthetic DMARD were included in the analyses. The start of the first bDMARD was the main outcome of interest. Cox regression analyses were used to explore the impact of education, age and gender on the start of a first bDMARD, adjusting for confounders, either at baseline or varying over time (time-varying model). Results: Of 1946 eligible patients [mean (s.d.) age: 55 (14) years, 68% females], 368 (19%) received a bDMARD during follow-up (mean 2.6 years). In the baseline prediction model, older age [Hazard Ratio (HR) 0.97, 95% CI: 0.96, 0.98], lower education [HR = 0.76 and 0.68 for low and intermediate education levelsvscollege/university education, respectively (P = 0.01)] and female gender [only in the period 2000-03, HR = 0.61 (95% CI: 0.41, 0.91)] were associated with a lower hazard ratio to start a bDMARD. The time-varying model provided overall consistent results, but the effect of education was only relevant for older patients (>57 years) and became more pronounced by the end of the decade. Conclusions: Less educated and older patients have disadvantages with regard to access to costly treatments, even in a country with highly developed welfare like Norway. Females had lower access in the beginning of the 2000s, but access had improved by the end of the decade.
    Full-text · Article · Mar 2016 · Rheumatology
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives: to evaluate in radiographic (r) and non-radiographic (nr) axial (ax) spondyloarthritis (SpA) 1) the rate of radiographic sacroiliac joints (SIJ) structural progression 2) to evaluate the predisposing factors of such progression over 2 years. Methods: Patients:Recent onset axial SpA(DESIR cohort). Outcome measures: Radiographic SIJ score according to the mNew-York criteria (mNY). Potential predisposing factors: Demographics, smoking status, HLAB27 positivity, inflammation at MRI of the SIJ, disease activity and treatment intake . Analysis: The main analysis consisted in the evaluation of the switch from nr-to r-axSpA but also other definitions of radiographic progression. Results: of the 708 enrolled patients, 449 had baseline and 2-year pelvic radiographs(males: 47%, age: 34±9 years old, B27 positive: 61%, MRI-SIJ positive: 29%) . The % of switch from nr-to-r-axSpA (16/326: 4.9%) and from r-to-nr-axSpA: 7/123 (5.7%) was low. The mean changes in the total SIJ score (o-8) was small 0.1± 0.8 but highly statistically significant (p<0.001). The potential baseline predisposing factors for developing mNY criteria in the multivariate analysis were current smokers, HLAB27 positivity and MRI-SIJ positivity with the following respective odds-ratio: 3.3 [1.0 - 11.5], 12.6 [2.3 - 274] and 498 [9.3 - 904]. Conclusion: Our study suggest that in early SpA: a)The structural progression does exist but is quite small and observed in a small number of patients b) Both environmental (smoking status), genetic (HLAB27 positivity) and inflammatory (MRI-SIJ) markers might be independent predisposing factors of progression. This article is protected by copyright. All rights reserved.
    No preview · Article · Mar 2016 · Arthritis and Rheumatology
  • Désirée van der Heijde · Robert Landewé
    [Show abstract] [Hide abstract] ABSTRACT: Purpose ofreview: To describe the most recent randomized-controlled trials (RCTs) and long-term observational studies (LOS) of RCTs with regard to radiological endpoints, and to interpret the results in the context of methodology. Recent findings: Many RCTs include radiological endpoints, sometimes as primary endpoints, usually as secondary endpoints. The results of these RCTs prove that radiological assessment can still detect meaningful differences in the progression of structural RA-related damage between treatment arms. In addition, LOS provide the opportunity to investigate if radiological progression is stable over time in patients on treatment. Improvements in the selection of appropriate patients (enrichment) and in the analysis of radiological data allow a more meaningful interpretation of radiological data in RA clinical trials and LOS. Summary: Radiological evaluation in RA clinical trials and observational studies is still valuable. Although subtle progression scores observed in clinical trials have limited direct clinical relevance, radiological treatment effects in trials may reflect subtle differences in clinical efficacy between treatment arms, and radiological progression may be considered a reflection of historic disease activity.
    No preview · Article · Mar 2016 · Current opinion in rheumatology
  • Robert Landewé · Désirée van der Heijde
    [Show abstract] [Hide abstract] ABSTRACT: Purpose of review: The purpose is to describe the most recent randomized controlled trials (RCT) in patients with rheumatoid arthritis that had a noninferiority design, and to focus on methodological aspects of noninferiority. Recent findings: In 2014 and 2015 10 different RCTs with a noninferiority-design could be identified, in comparison to only a few in the decade before. Most RCTs had a rather small sample size, and had ill-defined noninferiority-margins, or noninferiority-margins without comprehensible clinical meaning. Six of the 10 trials indeed arrived at a conclusion of 'noninferiority'; four did not. Interestingly, many of the RCTs were pragmatic studies comparing strategies, and the investigators were neither blind to the treatment nor to the outcome. In addition, the treatments were often adaptive (e.g. treat-to-target approach). These characteristics are considered built-in incentives for noninferiority. Summary: In the competitive pharmaceutical landscape of rheumatoid arthritis, with many effective drugs and strategies, it is no surprise that the number of noninferiority-trial (sharply) rises. But noninferiority trials are difficult to design, conduct, and interpret, and many principles of noninferiority-trial designs are currently ignored, which may jeopardise their conclusions to some extent.
    No preview · Article · Mar 2016 · Current opinion in rheumatology
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    [Show abstract] [Hide abstract] ABSTRACT: In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in patients with chronic inflammatory rheumatic diseases. We also aimed to develop a pragmatic reporting form to foster the implementation of the points to consider. In accordance with the EULAR Standardised Operating Procedures, the process comprised (1) a systematic literature review of existing recommendations on reporting, screening for or preventing six selected comorbidities: ischaemic cardiovascular diseases, malignancies, infections, gastrointestinal diseases, osteoporosis and depression and (2) a consensus process involving 21 experts (ie, rheumatologists, patients, health professionals). Recommendations on how to treat the comorbidities were not included in the document as they vary across countries. The literature review retrieved 42 articles, most of which were recommendations for reporting or screening for comorbidities in the general population. The consensus process led to three overarching principles and 15 points to consider, related to the six comorbidities, with three sections: (1) reporting (ie, occurrence of the comorbidity and current treatments); (2) screening for disease (eg, mammography) or for risk factors (eg, smoking) and (3) prevention (eg, vaccination). A reporting form (93 questions) corresponding to a practical application of the points to consider was developed. Using an evidence-based approach followed by expert consensus, this EULAR initiative aims to improve the reporting and prevention of comorbidities in chronic inflammatory rheumatic diseases. Next steps include dissemination and implementation.
    Full-text · Article · Mar 2016 · Annals of the Rheumatic Diseases
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    Ana Maria Gherghe · Sofia Ramiro · Robert Landewé · Carina Mihai · Désirée van der Heijde
    [Show abstract] [Hide abstract] ABSTRACT: Objectives To evaluate the separate effects of erosions (E) (bone damage), joint space narrowing (JSN) (cartilage loss) and (sub)luxation (SLUX) (soft tissue damage) in four different joint groups on physical disability in rheumatoid arthritis (RA). Methods 3-year follow-up data from the Rheumatoid Arthritis PreventIon of structural Damage (RAPID) 1 and 2 trials were used. These randomised controlled trials compared certolizumab plus methotrexate (MTX) versus MTX in patients with RA. Physical function was measured by Health Assessment Questionnaire (HAQ). Radiographic damage was measured by the van der Heijde-modified Sharp score; separate scores for E, JSN and SLUX were available. Generalised estimating equations were performed to assess the relationship between HAQ and E, JSN and SLUX scores, separately and in all joint groups. Results In separate models for each type of damage and after adjusting for age, gender, baseline disease activity and treatment group, E and JSN were more strongly associated with HAQ than with SLUX. In combined models, JSN was the only type of lesion associated with HAQ when all joints were included together. When separate joint groups were analysed, E in the wrist and JSN in the metacarpophalangeal joints (MCPs) were most strongly associated with function. Conclusions Among RA-related joint damage, cartilage loss quantified by JSN is an important determinant of physical function. However, when analysing joint groups separately, erosive damage in the wrist and JSN in the MCPs had the most important influence on disability. These data indicate that the comprehensive assessment of joint damage is needed to reliably reflect disease-related damage.
    Full-text · Article · Mar 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Objective The Social Role Participation Questionnaire (SRPQ) assesses the influence of health on participation in 11 specific and one general participation role across 4 participation dimensions: ‘importance’, ‘satisfaction with time’, ‘satisfaction with performance’ and ‘physical difficulty’. This study aimed to translate the SRPQ into Dutch, and assess the clinimetric properties and aspects of its validity among patients with ankylosing spondylitis (AS). Methods Translation was performed using the dual panel approach. For each participation dimension, internal consistency, test-retest reliability (n=31), and construct validity were assessed in 246 patients with AS. Results The translation required only minor adaptations. Cronbach αs were α≥0.7. A strong correlation was present between satisfaction with ‘time’ and ‘performance’(r=0.85). Test-retest reliability was satisfactory (κ=0.79–0.95). Correlations with participation domains of the Short-Form Health Survey 36 (SF-36), the WHO Disease Assessment Score II, and generic as well as disease-specific health outcomes (Physical and Mental component scale of the SF-36, Satisfaction With Life Scale, Bath Ankylosing Spondylitis Disease Index (BASDAI), Bath Ankylosing Spondylitis Functioning Index (BASFI)) were at least moderate (r=−0.41 to 0.75) for all dimensions except for ‘role importance’ where correlations were weak (r≤40). Discriminative ability across 5 self-reported health states was good for all dimensions (p<0.01). The ‘general participation’ role showed similar reliability and validity for each dimension, as the average of the all 11 roles. Conclusions The Dutch version of the SRPQ is available to help understand social role participation of patients with AS. The dimension ‘role importance’ measures a distinct aspect of participation. The general participation item was a good global measure of participation.
    Full-text · Article · Feb 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To establish the predictive validity of the Assessment of SpondyloArthritis international Society (ASAS) spondyloarthritis (SpA) classification criteria. Methods: 22 centres (N=909 patients) from the initial 29 ASAS centres (N=975) participated in the ASAS-cohort follow-up study. Patients had either chronic (>3 months) back pain of unknown origin and age of onset below 45 years (N=658) or peripheral arthritis and/or enthesitis and/or dactylitis (N=251). At follow-up, information was obtained at a clinic visit or by telephone. The positive predictive value (PPV) of the baseline classification by the ASAS criteria was calculated using rheumatologist's diagnosis at follow-up as external standard. Results: In total, 564 patients were assessed at follow-up (345 visits; 219 telephone) with a mean follow-up of 4.4 years (range: 1.9; 6.8) and 70.2% received a SpA diagnosis by the rheumatologist. 335 patients fulfilled the axial SpA (axSpA) or peripheral SpA (pSpA) criteria at baseline and of these, 309 were diagnosed SpA after follow-up (PPV SpA criteria: 92.2%). The PPV of the axSpA and pSpA criteria was 93.3% and 89.5%, respectively. The PPV for the 'clinical arm only' was 88.0% and for the 'clinical arm'±'imaging arm' 96.0%, for the 'imaging arm only' 86.2% and for the 'imaging arm'+/-'clinical arm' 94.7%. A series of sensitivity analyses yielded similar results (range: 85.1-98.2%). Conclusions: The PPV of the axSpA and pSpA criteria to forecast an expert's diagnosis of 'SpA' after more than 4 years is excellent. The 'imaging arm' and 'clinical arm' of the axSpA criteria have similar predictive validity and are truly complementary.
    No preview · Article · Feb 2016 · Annals of the Rheumatic Diseases
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    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Flares may be used as outcomes in axial spondyloarthritis (axSpA) trials or observational studies. The objective was to develop a definition for 'flare' (or worsening) in axSpA, based on validated composite indices, to be used in the context of clinical trial design. Methods: (1) Systematic literature review of definitions of 'flare' in published randomised controlled trials in axSpA. (2) Vignette exercise: 140 scenarios were constructed for a typical patient with axSpA seen at two consecutive visits. Each scenario included a change in one of the following outcomes: pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI plus C-reactive protein (CRP) or Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP. Each Assessment of Spondyloarthritis (ASAS) expert determined if every scenario from a random sample of 46 scenarios was considered a flare (yes/no). Receiver-operating characteristic (ROC) analyses were applied to derive optimal cut-off values. (3) ASAS consensus was reached. Results: (1) The literature review yielded 38 studies using some definition of 'flare', with 27 different definitions indicating important heterogeneity. The most frequent definitions were based on BASDAI changes or pain changes. (2) 121 ASAS experts completed 4999 flare assessments. The areas under the ROC curves were high (range: 0.88-0.89). Preliminary cut-offs for pain (N=3), BASDAI (N=5) and ASDAS-CRP (N=4) were chosen, with a range of sensitivity 0.60-0.99 and range of specificity 0.40-0.94 against the expert's opinions. Conclusions: This data-driven ASAS consensus process has led to 12 preliminary draft definitions of 'flare' in axSpA, based on widely used indices. These preliminary definitions will need validation in real patient data.
    Full-text · Article · Feb 2016 · Annals of the rheumatic diseases
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    [Show abstract] [Hide abstract] ABSTRACT: Objectives: To assess in patients with ankylosing spondylitis (AS) whether extra-articular manifestations (EAMs) are associated with worse functioning, worse quality of life (QoL), and more radiographic damage over time. Methods: 12-year follow-up data from the Outcome in Ankylosing Spondylitis International Study were used, complemented with data on EAMs extracted from medical charts. Functioning was assessed by the BASFI and physical component of the SF-36, QoL by ASQoL and EuroQoL, and radiographic damage by the mSASSS. Generalised estimating equations analyses were made to assess whether EAMs were associated with these outcomes over time. Results: 216 patients were included (154 (71%) men, mean age 43.6 years (SD 12.7), mean symptom duration 20.5 years (SD 11.7), and mean follow-up 8.3 years (SD 4.3). In total, 58 (26.9%) patients had acute anterior uveitis (AAU), 24 (11.1%) inflammatory bowel disease (IBD), and 14 (6.5%) psoriasis. Univariably, IBD was associated with worse BASFI over time (B=1.26, 95%-CI 0.13 to 2.39, p=0.03), but not in a multivariable model. Furthermore, in a multivariable model, IBD was associated with EuroQoL over time (B=2.93, 95%-CI 0.14 to 5.72, p=0.04). Univariably, psoriasis was associated with radiographic damage (B=-7.25, 95%-CI -14.38 to -0.12, p=0.05) and ASQoL (B= -1.94, 95%-CI -3.32 to -0.57, p<0.01) over time, but not in a multivariable model. AAU was not associated with any outcome over time. Conclusions: In this longstanding AS cohort, the presence of EAMs was not associated with functional disability, QoL or radiographic damage over time, except for IBD, which was associated with a better EuroQoL.
    Full-text · Article · Feb 2016 · Clinical and experimental rheumatology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To determine the benefits and harms of nonsteroidal antiinflammatory drugs (NSAID) in axial spondyloarthritis (axSpA). Methods: Systematic review using Cochrane Collaboration methodology. Inclusion criteria: randomized controlled trials (RCT) and quasi-RCT (to June 2014), investigating NSAID versus any control for axSpA, and observational studies of longterm effects (≥ 6 mos) of NSAID on radiographic progression or adverse events. Main outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, radiographic progression, number of withdrawals because of adverse events, and number of serious adverse events. Risk of bias was assessed. Results: Thirty-five RCT, 2 quasi-RCT, and 2 cohort studies were included. Twenty-nine RCT and 2 quasi-RCT (n = 4356) were included in pooled analyses [traditional NSAID vs placebo (n = 5), cyclooxygenase-2 (COX-2) vs placebo (n = 3), COX-2 vs traditional NSAID (n = 4), NSAID vs NSAID (n = 24), naproxen vs other NSAID (n = 3), and low- vs high-dose NSAID (n = 5)]. Compared with placebo, both traditional and COX-2 NSAID were consistently more efficacious at 6 weeks and equally safe after 12 weeks. No significant differences in benefits or harms between the 2 NSAID classes and no important differences in benefits or withdrawals because of adverse events between different NSAID were found, especially if studies with high risk of bias were excluded. Single studies suggest NSAID may retard radiographic progression, especially by continuous rather than on-demand NSAID use. Conclusion: High-quality evidence indicates that both traditional and COX-2 NSAID are efficacious for treating axSpA, and harms are not different from placebo in the short term. Various NSAID are equally effective.
    No preview · Article · Feb 2016 · The Journal of Rheumatology
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    [Show abstract] [Hide abstract] ABSTRACT: Objectives To explore the effects of tofacitinib—an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)—with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. Methods In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant. Results In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were −1.55 (90% CI −2.52 to −0.58) for tofacitinib + MTX and −1.74 (−2.72 to −0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were −0.63 (−1.58 to 0.31) for tofacitinib + MTX and −0.52 (−1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy. Conclusions These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage. Trial registration number NCT01164579.
    Preview · Article · Jan 2016 · Annals of the Rheumatic Diseases

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  • 2014
    • Oregon Health and Science University
      Portland, Oregon, United States
    • Centre Hospitalier Universitaire de Liège
      Luik, Wallonia, Belgium
  • 2012
    • University of Leeds
      • Section of Clinical Musculoskeletal Disease
      Leeds, England, United Kingdom
  • 2009
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2008
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2000-2008
    • Maastricht University
      • Department of Internal Medicine
      Maestricht, Limburg, Netherlands
  • 2004
    • Carol Davila University of Medicine and Pharmacy
      • Department of Internal Medicine and Rheumatology
      Bucharest, Bucuresti, Romania