Search

Objectives: Rheumatoid arthritis (RA) patients show an earlier circadian rhythm (i.e. serum melatonin peaks earlier during the night, indicating an earlier timing of the internal circadian pacemaker). In the current study, we examined whether the chronotype, which is influenced by the circadian rhythm, is also earlier. In addition, we explored whether chronotype is related to disease activity and patient-reported outcomes. Methods: The chronotype (Munich Chronotype Questionnaire) of patients with RA (n = 121; mean age 60 years, 73% female) was compared with that of subjects from the general population (norm group; n = 1695) with a one-sample t test. In addition, we investigated chronotype in relation to disease activity (Disease Activity Score; DAS), reported morning stiffness, fatigue (Checklist Individual Strength), and health-related quality of life (RAND-36). Results: The chronotype of patients with RA was, on average, 23 min (95% CI, 15 to 31 min) earlier than that of the norm group (t(115) = − 5.901, p < 0.001, d = 0.55). Chronotype was not related to disease activity or patient-reported outcomes (p > 0.05). Conclusion: As expected, chronotype was earlier in RA patients. However, in this correlational study, chronotype was not related to disease activity or patient-reported outcomes. An experimental study is needed to examine whether delaying the circadian rhythm has a positive influence on these outcomes. This insight could improve our understanding of the pathophysiology of RA and contribute to exploring new treatment possibilities.• This is the first study examining chronotype in patients with rheumatoid arthritis, and how chronotype relates to disease activity and patient-reported outcomes.• We found an earlier chronotype in patients with rheumatoid arthritis than in subjects from the general population.• In this correlational s more...

Objectives: To study the impact of treatment strategy on achieving and sustaining disease-modifying antirheumatic drug (DMARD)-free remission in patients with rheumatoid arthritis (RA). Methods: Two hundred seventy-nine RA patients (median follow-up 7.8 years) were studied. Of these, 155 patients participated in a disease activity score (DAS) < 1.6 steered trial aimed at DMARD-free remission. Initial treatment comprised methotrexate with high-dose prednisone (60 mg/day) and a possibility to start biologicals after 4 months. In the same period and hospital, 124 patients were treated according to routine care, comprising DAS < 2.4 steered treatment. Percentages of DMARD-free remission (absence of synovitis for ≥ 1 year after DMARD cessation), late flares (recurrence of clinical synovitis ≥ 1 year after DMARD cessation), and DMARD-free sustained remission (DMARD-free remission sustained during complete follow-up) were compared between both treatment strategies. Results: Patients receiving intensive treatment were younger and more often ACPA-positive. On a group level, there was no significant association between intensive treatment and DMARD-free remission (35% vs 29%, corrected hazard ratio (HR) 1.4, 95%CI 0.9–2.2), nor in ACPA-negative RA (49% versus 44%). In ACPA-positive RA intensive treatment resulted in more DMARD-free remission (25% vs 6%, corrected HR 4.9, 95%CI 1.4–17). Intensive treatment was associated with more late flares (20% versus 8%, HR 2.3, 95%CI 0.6–8.3). Subsequently, there was no difference in DMARD-free sustained remission on a group level (28% versus 27%), nor in the ACPA-negative (43% versus 42%) or ACPA-positive stratum (17% versus 6%, corrected HR 3.1, 95%CI 0.9–11). Conclusions: Intensive treatment did not result in more DMARD-free sustained remission, compared to routine up-todate care. The data showed a tendency towards an effect of intensive treatment in ACPA-positive RA; this needs further investigation. more...

Background: Disease-modifying antirheumatic drug (DMARD)-free remission, the sustained absence of synovitis after DMARD cessation, is increasingly achievable, especially in autoantibody-negative rheumatoid arthritis (RA). However, underlying mechanisms are unknown and patient subgroups that achieve this outcome are insufficiently characterized. We evaluated whether serological biomarkers at disease onset, as measured within the multibiomarker disease activity (MBDA) score, are differently expressed in RA patients who achieve sustained DMARDfree remission. Methods: Two hundred ninety-nine RA patients were evaluated for achievement of sustained DMARD-free remission during a median follow-up of 4.3 years. Twelve biomarkers, as included in the MBDA score, were determined from the serum obtained at disease onset. Patients were categorized as having a low (< 30), moderate (30–44) or high (> 44) score. Analyses were stratified for anti-citrullinated protein antibodies (ACPA) based under the assumption that ACPApositive and ACPA-negative RA are different disease entities. Results: Twenty percent achieved sustain more...

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatolog more...

Objectives (1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc). Methods A small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit. Skin biopsies were taken at baseline and month 3. Immunophenotyping of peripheral blood mononuclear cells was performed at every visit, except at months 9 and 18. Adverse events, course of skin and pulmonary involvement and B cell populations in skin and peripheral blood were evaluated. Results In total 16, patients (rituximab n=8, placebo n=8) were included. Twelve patients had diffuse cutaneous SSc more...

Background: Joint space narrowing ( JSN) in rheumatoid arthritis (RA) may be a manifestation of (primary) osteoarthritis becoming more prominent with age. We investigated the severity and predictors of JSN progression among different age groups. Methods: 10-year follow-up data of the BeSt study, a randomised controlled treat-to-target trial in early RA were used. Annual X-rays of hands and feet were scored using the Sharp/van der Heijde score (SHS). Subgroups were defined by age at baseline: 55, 40<55 and <40 years. JSN progression predictors were assessed by Poisson regression. Results: Baseline JSN scores (median (IQR)) were igher in patients 55 (2.0 (0.0-6.0)) compared with the other age groups: 1.0 (0.0-3.0) 40<55 and 0.3 (0.0-3.0) <40, p<0.001. After 10 years, total JSN and SHS were similar in all age groups. In patients 55 the mean erythrocyte sedimentation rate (ESR) over time (relative risk 1.02 (95% CI 1.00 to 1.03)) more...

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on t more...

Introduction: Morning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA). Methods: In arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions. Results: In arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver ope more...

Introduction: Personalized medicine is the holy grail of medicine. The EULAR recommendations for the management of rheumatoid arthritis (RA) support differential treatment between patients with baseline characteristics suggestive of a non-poor prognosis (non-PP) or poor prognosis (PP) (presence of autoantibodies, a high inflammatory activity and damage on radiographs). We aimed to determine which prognostic risk groups benefit more from initial monotherapy or initial combination therapy. Methods: 508 patients were randomized to more...

The Study Group for Risk Factors for Rheumatoid Arthritis was established by the EULAR Standing Committee on Investigative Rheumatology to facilitate research into the preclinical and earliest clinically apparent phases of rheumatoid arthritis (RA). This report describes the recommendation for terminology to be used to define specific subgroups during different phases of disease, and defines the priorities for research in this area. Terminology was discussed by way of a three-stage structured process: A provisional list of descriptors for each of the possible phases preceding the diagnosis of RA were circulated to members of the study group for review and feedback. Anonymised comments from the members on this list were fed back to participants before a 2-day meeting. 18 participants met to discuss these data, agree terminologies and prioritise important research questions. The study group recommended that, in prospective studies, individuals without RA are described as having: genetic risk factors for RA; environmental risk factors for RA; systemic autoimmunity associated with RA; symptoms without clinical arthritis; unclassified arthritis; which may be used in a combinatorial manner. It was recommended that the prefix 'pre-RA with more...

Objective: To investigate the association between weight or Body Mass Index (BMI) and the development of hand osteoarthritis (OA). Methods: Systematic review of observational studies. Medical databases were searched up to April 2008. Articles which presented data on the association between weight and hand OA were selected. The qualities of these studies were then assessed by two independent reviewers using a 19 criteria scoring syste more...

Objective. The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. Methods. Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of "developing RA," complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. Results. The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. Conclusion. The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set. more...

Objective. The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease - this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." Results. In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). Conclusion. This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather th more...