Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis

Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Arthritis & Rheumatology (Impact Factor: 7.76). 10/2005; 52(9):2616-24. DOI: 10.1002/art.21259
Source: PubMed


Based on comparisons of short-term cohort studies or cross-sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years.
We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985-1990, 1990-1995, 1995-2000, 2000-2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts.
The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease-modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy.
The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.

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Available from: Jaap Fransen, Jan 13, 2014
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    • "The treatment possibilities for patients with RA have improved recently with the emergence of several new disease-modifying antirheumatic drugs (DMARDs) and a focus on early intervention and tight inflammatory control [1]. Over time, a decrease in the numbers of swollen and tender joints, joint damage, disease activity, disability [2,3], and rates for most types of interventions of orthopaedic surgery have also been observed [4-6]. "
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    ABSTRACT: Background The aim of the present study was to evaluate the accuracy of two approaches using magnetic resonance imaging (MRI) or combined ultrasonography (US) and anti-cyclic citrullinated peptide antibody (ACPA) for diagnosis and classification of individuals with established rheumatoid arthritis (RA). Methods In 53 individuals from a population-based, cross-sectional study, historic fulfilment of the American College of Rheumatology (ACR) 1987 criteria (“classification”) or RA diagnosed by a rheumatologist (“diagnosis”) were used as standard references. The sensitivity, specificity and Area under Curve for Receiver Operating Characteristics curves (ROC-area: (sensitivity + specificity)/2) were calculated for “current fulfilment of the ACR 1987 criteria” (list format), “adapted ACR 1987 criteria” (list format, substituting IgM rheumatoid factor with ACPA and clinical joint swelling and erosions on radiography with synovitis and erosions detected by US on a semi-quantitative scale), and RA MRI scoring System (RAMRIS) scores on low-field MRI in the unilateral hand. Results For the ACR 1987 criteria the ROC-area was 75% (sensitivity/specificity = 50%/100%) (with “classification” as standard reference) and 69% (44%/94%) (with “diagnosis” as standard reference), while for the adapted ACR 1987 criteria it was 86% (75%/97%) (classification) and 82% (72%/91%) (diagnosis). For RAMRIS synovitis score in metacarpophalangeal (MCP) joints only (cut-off ≥5), the ROC-area (sensitivity/specificity) was 78% (62%/94%) (classification) and 85% (69%/100%) (diagnosis), while for the total synovitis score of MCP joints plus wrist (cut-off ≥10) it was 78% (62%/94%) (both classification and diagnosis). Conclusions Compared with the ACR 1987 criteria, low-field MRI alone or adapted criteria incorporating US and ACPA increased the correct classification and diagnosis of RA.
    Full-text · Article · Aug 2014 · BMC Musculoskeletal Disorders
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    • "RA is a chronic systemic autoimmune disease characterized by inflammatory polyarthritis which affects approximately 0.5 -1% of the population worldwide (Hochberg et al., 2007). Although the currently favored treatment regime using disease-modifying anti-rheumatic drugs (DMARD's) in an early stage of RA is believed to have a favorable result on disease course by influencing inflammation, patients assessment of disease activity and functional disability do not always support this result (Welsing et al., 2005). Even 30% of the RA patients initiating the most effective treatment option available, anti-TNFα therapy, fail to respond (Smolen, 2005). "
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    ABSTRACT: Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information about the various roles that metabolites have in rheumatoid arthritis. An extensive PubMed search is conducted to collect the relevant manuscripts. The metabolites are discussed in relation to rheumatoid arthritis. Subsequently, the metabolites are organized according to levels of system organization. In the last section an integrated pathway analysis of the metabolites conducted with Ingenuity Pathway Analysis software is presented. Literature search resulted in information about vitamins, eicosanoids, fatty acids, lipids, hormones and peptides. The metabolites could be related to metabolic processes, oxidative stress processes and inflammatory processes. Cell death, lipid metabolism and small molecule biochemistry were found by the pathway analysis to be the top functions, characterized by the metabolites arachidonic acid, ascorbic acid, beta-carotene, cholecalciferol, hydrocortisone, keratan sulfate, melatonin, palmitic acid and stearic acid. These nine metabolites are highly connected to a number of canonical pathways related to immune functions, the production of nitric oxygen and reactive oxygen species in macrophages and pathways involved in arthritis. This review indicates groups of metabolites that could be interesting for metabolomics studies related to rheumatoid arthritis. Circadian rhythms of metabolite levels are found to be important for understanding and treating rheumatoid arthritis. In addition, some key processes and pathways are found by integrating the metabolite data. This might offer new ideas for studies into the mechanism of and possible treatment options for rheumatoid arthritis.
    Full-text · Article · Jul 2012
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    • "With the earlier initiation of disease-modifying therapies and the development of targeted immunomodulating agents [2], an increasing number of RA patients are able to achieve minimal disease activity, and some are able to achieve complete disease remission [3-5]. However, on a population level, mean pain ratings have remained the same over the past 20-year period [6], and 82% of RA patients who consider their disease to be "somewhat to completely controlled" continue to report moderate to severe pain levels [7]. "
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    ABSTRACT: 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.
    Full-text · Article · Jun 2011 · Arthritis research & therapy
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