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Amsterdam-Zuidoost, Netherlands

Van Kuijk A.W.R.,Jan Van Breemen Institute | Van Kuijk A.W.R.,University of Amsterdam | Tak P.P.,University of Amsterdam
Current Rheumatology Reports | Year: 2011

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis that affects the peripheral joints, spine, and entheses. Most patients with PsA present with peripheral synovitis of the oligoarticular or polyarticular subtype. As one of the targets of this disease, studies on the synovium may provide insight into the mechanisms involved in this condition. Key findings from the available studies comparing synovial tissue of PsA and rheumatoid arthritis patients are discussed in this review. Also, changes in the synovial infiltrate, expression of proinflammatory cytokines and adhesion molecules, and vascularity in synovial tissue after treatment with various medications are addressed. Finally, a model for proof-of-principle study design using serial synovial biopsies is described, which could be used to predict clinical (in)efficacy in early clinical trial design in PsA. © 2011 The Author(s).


Van Baarsen L.G.M.,Medical Center | Bos W.H.,Jan Van Breemen Institute | Rustenburg F.,Medical Center | Van Der Pouw Kraan T.C.T.M.,Medical Center | And 4 more authors.
Arthritis and Rheumatism | Year: 2010

Objective. To identify molecular features associated with the development of rheumatoid arthritis (RA), to understand the pathophysiology of preclinical development of RA, and to assign predictive biomarkers. Methods. The study group comprised 109 anti-citrullinated protein antibody (ACPA)- and/or rheumatoid factor-positive patients with arthralgia who did not have arthritis but were at risk of RA, and 25 patients with RA. The gene expression profiles of blood samples obtained from these patients were determined by DNA microarray analysis and quantitative polymerase chain reaction. Results. In 20 of the 109 patients with arthralgia who were at risk of RA, arthritis developed after a median of 7 months. Gene expression profiling of blood cells revealed heterogeneity among the at-risk patients, based on differential expression of immune-related genes. This report is the first to describe gene signatures relevant to the development of arthritis. Signatures significantly associated with arthritis development were involved in interferon (IFN)-mediated immunity, hematopoiesis, and chemokine/cytokine activity. Logistic regression analysis revealed that the odds ratio (OR) for developing arthritis within 12 months was 21.0 (95% confidence interval [95% CI] 2.8-156.1 [P = 0.003]) for the subgroup characterized by increased expression of genes involved in IFN-mediated immunity and/or cytokine/chemokine-activity. Genes involved in B cell immunology were associated with protection against progression to arthritis (OR 0.38, 95% CI 0.21-0.70 [P = 0.002]). These processes were reminiscent of those in patients with RA, implying that the preclinical phase of disease is associated with features of established disease. Conclusion. The results of this study indicate that IFN-mediated immunity, hematopoiesis, and cell trafficking specify processes relevant to the progression of arthritis independent of ACPA positivity. These findings strongly suggest that certain gene signatures have value for predicting the progression to arthritis, which will pave the way to preventive medicine. © 2010, American College of Rheumatology.


Van Den Broek M.,Leiden University | Huizinga T.W.J.,Leiden University | Dijkmans B.A.C.,Jan Van Breemen Institute | Dijkmans B.A.C.,VU University Amsterdam | Allaart C.F.,Leiden University
Current Opinion in Rheumatology | Year: 2011

Purpose of Review: To give an overview of recently published articles covering drug-free remission in rheumatoid arthritis (RA). Recent Findings: Recent studies covering drug-free remission showed differences in numbers studied, remission definition, disease duration and medication used. Drug-free remission was reported in 9-29%. Only two out of four studies reported on patients who restarted medication due to a disease flare or loss of remission, which occurred in 45-46%. In the BeSt study, remission or low disease activity was achieved again after retreatment within 6 months in 96%. In the Finnish Early Rheumatoid Arthritis study, none of the patients achieved remission after retreatment; their mean Disease Activity Score (DAS28) was 3.68. Joint damage progression was not higher in patients who restarted medication when compared to patients in sustained drug-free remission or patients with continued treatment. Anticitrullinated protein antibody, rheumatoid factor or shared epitope negativity and short symptom duration were independent predictors of successful drug-free remission in more than one cohort. Summary: Drug-free remission can be achieved and sustained in a small group of RA patients. In early RA, retreatment is successful in the majority of patients. Disease flare after cessation of medication does not seem to increase joint damage progression. Sustained drug-free remission is predicted by autoantibody and shared epitope negativity and short disease duration before treatment initiation. © 2011 Wolters Kluwer Health | Lippincott Williams and Wilkins.


INTRODUCTION: To investigate whether baseline levels of anti-citrullinated protein antibody (ACPA) or IgM rheumatoid factor (IgM-RF) and changes in the year thereafter are associated with disease activity, functional and radiographic outcome in early arthritis patients, and provide additional information over baseline autoantibody status. METHODS: In 545 early arthritis patients ACPA and IgM-RF levels, disease activity (DAS28), the Health Assessment Questionnaire (HAQ) and Sharp/Van der Heijde Score (SHS) were assessed annually. Baseline status, levels and first-year changes of the autoantibodies were associated with these measures at the two-year follow-up and sub-analysed according to autoantibody status. RESULTS: The mean age was 52.7 years, 69% was female, at baseline 56% was ACPA positive, 47% IgM-RF positive. At the two-year follow-up the mean DAS28 was 2.88, and the median HAQ and SHS were 0.38 and 1, respectively. At one year, ACPA and IgM-RF levels had decreased by 31% and 56%, respectively. A switch from negative to positive occurred in 2% for ACPA and 3% for IgM-RF. Positive ACPA and RF status were both associated with SHS at two years (P < 0.001), but baseline levels only showed a minor correlation of ACPA with DAS28 and HAQ at two years. Level changes were not associated with the outcome parameters. CONCLUSIONS: Baseline levels and first-year changes of ACPA and IgM-RF are hardly associated with outcome after two years. Seroconversion seldom occurs. Therefore, it does not appear useful to repeat ACPA or IgM-RF measurements.


Van Den Broek M.,Leiden University | Klarenbeek N.B.,Leiden University | Dirven L.,Leiden University | Van Schaardenburg D.,Jan Van Breemen Institute | And 6 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective: To describe the disease course after the cessation of infliximab in early rheumatoid arthritis patients with disease activity score (DAS)-steered treatment and to identify predictors of persistent low disease activity. Methods: In a post-hoc analysis of the BeSt study, disease activity and joint damage progression were observed in patients treated with methotrexate plus infliximab, who discontinued infliximab after achieving low disease activity (DAS ≤2.4) for 6 months. Predictors were identified using Cox regression analysis. Results: 104 patients discontinued infliximab, of whom 77 had received infliximab plus methotrexate as initial treatment. Mean DAS at the time of infliximab cessation was 1.3, median symptom duration was 23 months and median Sharp/van derHeijde score was 5.5. The median follow-up was 7.2 years. Infliximab was re-introduced after loss of low disease activity in 48%, after a median of 17 months. The joint damage progression rate did not increase in the year after cessation, regardless of flare. After re-introduction of infliximab, 84% of these patients again achieved a DAS ≤2.4. In the multivariable model, smoking, infliximab treatment duration ≥18 months and shared epitope (SE) were independently associated with the re-introduction of infliximab: 6% of the non-smoking, SE-negative patients treated <18 months needed infliximab re-introduction. Conclusion: Cessation of infliximab was successful in 52%, with numerically higher success rates in patients initially treated with infliximab. Of the 48% who flared, 84% regained low disease activity. The joint damage progression rate did not increase in the year after cessation. Smoking, long infliximab treatment duration and SE were independently associated with re-introduction of infliximab.

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