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Visman I.M.,Jan Van Breemen Instituut | Bartelds G.M.,Jan Van Breemen Instituut | Ouwerkerk W.,Jan Van Breemen Instituut | Peelen L.M.,Julius Center for Health science and Primary Care | And 5 more authors.
Journal of Rheumatology | Year: 2011

Objective. To evaluate the influence of inclusion criteria used in rheumatoid arthritis (RA) trials with adalimumab on clinical outcome and response. Methods. The different inclusion criteria of published trials of adalimumab in RA were separately applied to a large prospective cohort of patients with RA treated with adalimumab (AdRA cohort), thereby mimicking patient selection for a clinical trial. Clinical response and outcome in the resulting 11 projection groups were compared using the 28-joint Disease Activity Score (DAS28) and time-averaged DAS28 as outcome measures of efficacy. Results. Thirteen trials (n = 54-799) with 11 different sets of entry criteria were identified, resulting in 11 projection groups (n = 22-168). The DAS28 at baseline was similar in the original trial and each projection group based on this trial (5.1-6.4, total AdRA cohort 5.1). After 28 weeks, the efficacy varied substantially among the 11 projected groups (change from baseline DAS28: -1.65 to -2.65, time-averaged DAS28 3.67-4.53). Expressed as outcome (DAS28 at 28 weeks), the efficacy was much more similar for almost all projection groups (3.5-4.0) and thus appeared to be mostly independent of disease activity at baseline. Conclusion. We observed that different inclusion criteria for clinical trials can have a marked effect on the expected response, i.e., improvement from baseline. A novel finding is that final disease activity appeared much less dependent on initial disease activity. Our study suggests that for daily practice, one can assume that adalimumab treatment will on average result in a DAS28 between 3.5 and 4.0 after 28 weeks of treatment, regardless of baseline disease activity. The Journal of Rheumatology Copyright © 2011. All rights reserved.


Turkstra F.,Jan Van Breemen Instituut | Piskin G.,BovenIJ Ziekenhuis | Stoof T.,VU Medisch Centrum | Van Vugt R.,VU Medisch Centrum
Nederlands Tijdschrift voor Dermatologie en Venereologie | Year: 2010

Behçet syndrome is an auto-infammatory disease. For purpose of research the disease is diagnosed with international criteria. Some of the dilemma's with these criteria are discussed. Treatment of skin problems according to the EULAR evidence based guidelines are discussed.


Van De Sande M.G.H.,University of Amsterdam | De Hair M.J.H.,University of Amsterdam | Van Der Leij C.,University of Amsterdam | Klarenbeek P.L.,University of Amsterdam | And 8 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Background: The aetiology of rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disorder, is poorly understood. It is currently unknown whether the disease process starts in the synovium, the primary target of RA, or at other sites in the body. Objective: To examine, in a prospective study, the presence of synovitis in people with an increased risk of developing RA. Methods: Thirteen people without evidence of arthritis, who were positive for IgM rheumatoid factor and/or anticitrullinated protein antibodies, were included in the study. To evaluate synovial inflammatory changes, all participants underwent dynamic contrast-enhanced MRI and arthroscopic synovial biopsy sampling of a knee joint at inclusion. Results were compared with knee MRI data and synovial biopsy data of 6 and 10 healthy controls, respectively. Results: MRI findings evaluated by measurement of maximal enhancement, rate of enhancement, synovial volume and enhancement shape curve distribution were similar between the autoantibody-positive subjects and the healthy controls. Consistent with these findings, all but one autoantibody-positive subject showed very low scores for phenotypic markers, adhesion molecules and vascularity, all in the same range as those in normal controls. The one person with higher scores had patellofemoral joint space narrowing. Conclusion: Subclinical inflammation of the synovium does not coincide with the appearance of serum autoantibodies during the pre-RA stage. Thus, systemic autoimmunity precedes the development of synovitis, suggesting that a 'second hit' is involved. This study supports the rationale for exploring preventive strategies aimed at interfering with the humoral immune response before synovial inflammation develops.


Bos W.H.,Jan Van Breemen Instituut | Wolbink G.J.,Jan Van Breemen Instituut | Wolbink G.J.,Sanquin Research | Boers M.,Jan Van Breemen Instituut | And 12 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Background: Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. Objective: To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia. Methods: Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development. Results: 147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR=6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p=0.004), but not of IgM-RF (HR=1.4, 95% CI 0.6 to 3.1) nor the SE (HR=1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR=3.0; 95% CI 1.4 to 6.9; p=0.01) and high ACPA levels (HR=1.7; 95% CI 1.1 to 2.5; p=0.008), but not the SE (HR=1.0; 95% CI 0.5 to 2.1; p=1.0). Conclusion: In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.


Bos W.H.,Jan Van Breemen Instituut | Dijkmans B.A.C.,Jan Van Breemen Instituut | Dijkmans B.A.C.,VU University Amsterdam | Boers M.,Jan Van Breemen Instituut | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Background: Rheumatoid arthritis is characterised by antibodies to citrullinated proteins (ACPA) and rheumatoid factor (RF) in the preclinical phase. Objective: To determine whether an intervention aimed at decreasing autoantibody levels in people at risk may be effective in preventing progression to arthritis. Methods: 83 patients with arthralgia positive for ACPA or IgM-RF were randomly allocated to intramuscular injections of 100 mg dexamethasone or placebo at baseline and 6 weeks. The primary end point was a 50% antibody reduction or normalisation at 6 months. Results: The primary end point was reached in one patient in each group. Patients treated with dexamethasone had reductions of antibody levels after 1 month (ACPA -22% and IgM-RF -14%), which persisted at 6 months for ACPA. During a median follow-up of 26 months, arthritis development in both groups was similar (20% vs 21%). Conclusion: In autoantibody-positive patients with arthralgia, dexamethasone treatment decreases ACPA and IgM-RF levels, but does not prevent arthritis development.


PubMed | Jan van Breemen Instituut
Type: Journal Article | Journal: Annals of the rheumatic diseases | Year: 2010

Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis.To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia.Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development.147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0).In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.

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