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Objective The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Methods Sixty-two RA patients were treated with rituximab in three different centres. Structural damage was assessed on radiographs of hands and feet before and 1 year after therapy using the Sharp-van der Heijde scoring method (SHS). Patients were divided into progressors vs non-progressors based on different cut-off values. Rituximab serum levels were measured by sandwich ELISA after 4 and 12 weeks (Leiden University Medical Center and University Medical Centre, Utrecht cohorts) or 4 and 16 weeks (Academic Medical Center/University of Amsterdam cohort). Results There was no difference in rituximab levels between progressors and non-progressors 4 weeks and 12 or 16 weeks after initiation of treatment in the different cohorts. There was also no correlation between rituximab levels at week 4 or week 12 or 16 and change in SHS score after 1 year. Conclusion Low rituximab serum levels are not associated with progression of structural damage in RA patients. The results do not support the use of dosages higher than 2 × 1000 mg rituximab to inhibit progression of joint destruction.

Objective The protective effect of HLA–DRB1 alleles on the development of rheumatoid arthritis (RA) is poorly understood. The aim of this study was to perform a meta-analysis of 4 European populations to investigate which HLA–DRB1 alleles are associated with protection in anti–citrullinated protein antibody (ACPA)–positive RA and ACPA-negative RA. Methods Data for >2,800 patients and >3,000 control subjects for whom information on HLA–DRB1 typing and ACPA status was available were collected from 4 European countries: Norway, Sweden, The Netherlands, and Spain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the different HLA–DRB1 alleles were analyzed in a combined meta-analysis focused on protective alleles and classifications. The analysis of ACPA-positive RA was stratified for the shared epitope (SE) alleles, to correct for skewing due to this association. Results In ACPA-positive RA, the only alleles that conveyed protection after stratification for SE were HLA–DRB1*13 alleles (OR 0.54 [95% CI 0.38–0.77]). The protective effect of the allele classifications based on the DERAA and D70 sequences was no longer present after exclusion of DRB1*13 (for D70, OR 0.97 [95% CI 0.75–1.25]), indicating that DRB1*13, rather than the DERAA or D70 sequence as such, is associated with protection. Among the DRB1*13 alleles, only DRB1*1301 was associated with protection (OR 0.24 [95% CI 0.09–0.59]). Protection appeared to follow a north-to-south gradient, with the strongest association in northern European countries. In ACPA-negative RA, there were no robust associations with HLA–DRB1 alleles. Conclusion Our data do not support any of the classifications of protective alleles and indicate that protection against ACPA-positive RA is predominantly associated with HLA–DRB1*1301.

Background Joint destruction in rheumatoid arthritis (RA) was until recently seen as an irreversible state. Lately, it was found that repair of bone erosions occurs; however, little is known about its prevalence. Objective To investigate the frequency of repair and patients9 characteristics associated with repair in an inception cohort. Patients and methods 250 patients with RA, included in the Leiden Early Arthritis Clinic between 1993 and 2000 and treated with conventional disease-modifying antirheumatic drugs, were studied (mean follow-up 10.1 years). Radiographs obtained annually were scored using the Sharp–van der Heijde method, initially aware of the chronology. Patients with a negative change in erosion scores on subsequent radiographs were selected and their series of radiographs were rescored with concealed time sequence by three readers. Repair was defined as agreement between two readers of a negative change in erosion scores that persisted for at least 2 years. Results Repair was identified in 32 joints in 18 patients (7.2%). Patients with repair had a greater prevalence of autoantibodies (rheumatoid arthritis, anti-citrullinated protein antibody) and a higher level of joint destruction. In the joints with repair, arthritis was absent in the 2 years preceding repair. Conclusions Repair occurred in 7.2% of the patients with RA, particularly in clinically inactive joints in patients with severe destructive disease.

Objective: In vitro models for joint diseases often focus on a single cell type, such as chondrocytes in osteoarthritis (OA) or fibroblast-like synoviocytes (synoviocytes) in rheumatoid arthritis (RA). However, these joint diseases affect the whole joint and interaction between chondrocytes and synoviocytes may play an important role in disease pathology. The current study was designed to study the use of the alginate recovered chondrocyte method as a model for cartilage degradation and to study interaction between chondrocytes and synoviocytes. Methods: Bovine chondrocytes were cultured in alginate beads for 1 week, subsequently chondrons were retrieved and seeded into transwells. Every two days cartilage-slices were analysed for proteoglycan content (colorimetric, Blyscan GAG kit), collagen content (HPLC) and collagen HP and LP crosslinking (HPLC). For degradation experiments, monocultures of cartilage-slices labelled with 35S and cocultures with synoviocytes were stimulated with IL-1β or TNF-α. After 7 days, 35S release was measured taken as a measure of cartilage degradation. Results: After biochemical analysis, three week old cartilage-like slices were chosen to perform cartilage-degradation experiments. Synoviocytes were able to induce cartilage degradation only in the presence of living chondrocytes. In addition, the cytokines interleukin 1 (IL-1β) and tumor necrosis factor (TNF-α) were only able to induce cartilage degradation by chondrocytes, not by synoviocytes. Conclusion: These data indicate that the alginate recovered chondrocyte method provides a novel model for cartilage degradation in which the interaction between synoviocytes and chondrocytes can be studied. © Copyright Clinical and Experimental Rheumatology 2007.

To determine the usefulness of a prediction model for making treatment decisions in early rheumatoid arthritis (RA).In 152 patients with early RA, progression of radiological damage during the first year [Sharp-van der Heijde (SH) score0] was assessed and used to define actual disease outcome. Available variables at baseline were entered in a multivariate regression analysis with progression score as dependent variable. This model was used to predict disease outcome in every patient. Using the standard deviations of the predicted disease outcome, patients were divided into 3 groups: (1) severe disease: high probability (or = 0.8) for progression0, (2) mild disease: high probability (or =0.8) for progressionor = 0, and (3) not classified: no high probability for either option. It was determined how many patients could be classified by using this model.One hundred nine patients (71.7%) showed joint damage progression during the first year. Baseline variables available were: age, sex, duration of symptoms, duration of morning stiffness, patient's global assessment of disease activity, Health Assessment Questionnaire score, swollen and painful joint count, bilateral compression pain in metatarsophalangeals, rheumatoid factor positivity, erythrocyte sedimentation rate, shared epitope positivity, SH-score, and the presence of erosions. The R2 value (approximately variation explained) of the prediction model was 0.36. By using this model 46.3% of patients could be classified as having severe disease, 0% as having mild disease, and 53.7% could not be classified.To be able to make treatment decisions in early RA based on predicted disease outcome, a better prediction of disease outcome is needed, making the search for better prognostic variables urgent.

Uit recent onderzoek blijkt dat vroege opsporing van ongedifferentieerde artritis zinvol is. Vroegtijdige behandeling met methotrexaat kan het krijgen van reumatoide artritis enkele jaren uitstellen of zelfs voorkomen.