OBJECTIVES: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA) and are present years before onset of symptoms. Avidity of (auto) antibodies can have a... Show moreOBJECTIVES: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA) and are present years before onset of symptoms. Avidity of (auto) antibodies can have a strong impact on their effector potency. Here, we analyzed the avidity of ACPA in pre-disease, early-disease and established RA samples as well as avidity maturation in time in samples of healthy subjects that later developed RA. METHODS: We measured ACPA avidity in samples from ACPA-positive healthy individuals, symptomatic individuals and patients with established RA derived from five collections from The Netherlands, Canada and Austria. Furthermore, we determined the dynamics of avidity maturation of ACPA from the stage of pre-disease to established disease in one case from the native North American population and 10 cases from a Dutch blood donor cohort. RESULTS: The overall ACPA response was characterized by low avidity antibodies. Individuals with higher avidity ACPA were confined to symptomatic patients, while low avidity ACPA were observed in both healthy subjects and patients. In longitudinal samples obtained from subjects prior to disease onset, the ACPA avidity increased over time until disease onset. Following onset of disease no further avidity maturation was observed. CONCLUSIONS: Avidity maturation of the ACPA response takes place prior to disease onset. Show less
Broek, M. van den; Klarenbeek, N.B.; Dirven, L.; Schaardenburg, D. van; Hulsmans, H.M.J.; Kerstens, P.J.S.M.; ... ; Allaart, C.F. 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... Show moreObjective 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 infl iximab, of whom 77 had received infl iximab plus methotrexate as initial treatment. Mean DAS at the time of infl iximab 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 infl iximab, 84% of these patients again achieved a DAS = 2.4. In the multivariable model, smoking, infl iximab treatment duration = 18 months and shared epitope (SE) were independently associated with the re-introduction of infl iximab: 6% of the non-smoking, SE-negative patients treated < 18 months needed infl iximab re-introduction. Conclusion Cessation of infl iximab was successful in 52%, with numerically higher success rates in patients initially treated with infl iximab. 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 infl iximab treatment duration and SE were independently associated with re-introduction of infl iximab. Show less
