Rituximab, an anti-CD20 monoclonal antibody, has been approved for treatment in patients with rheumatoid arthritis (RA) who have failed treatment with tumour necrosis factor (TNF) blocking agents.1 Previous studies have demonstrated its safety, efficacy and prevention of radiographic progression;2 3 however few studies have yet addressed the timing of repeated courses of rituximab. A study in 22 patients with RA showed that treatment with repeated courses of rituximab over a 5-year follow-up period was safe and well tolerated4 and additionally an open-label extension study of 3 large randomised, double-blind studies in patients with RA showed that clinical efficacy was maintained with subsequent courses of rituximab, comparable to the first rituximab course, without increased additional safety concerns.5 Interestingly, one study reported that rituximab retreatment was more effective; however, this was in patients whose disease activity had not completely returned to baseline levels.6 Therefore, the preferred timing of repeated treatment courses of rituximab is still a matter of debate and thus far has not been prospectively investigated.

The present study compared the efficacy and safety of 2 B cell depleting strategies in 48 patients with refractory RA failing disease-modifying antirheumatic drugs (DMARD) combination therapy and/or at least 1 TNF blocking agent. In a prospective, two-centre, non-randomised, open-label pilot study, after initial treatment with 2×1000 mg rituximab, one group (n = 28) in one centre received fixed retreatment (FR) at 24 weeks with 1×1000 mg rituximab, while the other group (n = 20) in the other centre received retreatment with the same dose at disease relapse as on-demand retreatment (ODR). Clinical efficacy, safety and immunological outcomes were evaluated every 12 weeks for a period of 1 year. Patients were allowed to continue their daily or weekly dosages of DMARDs and corticosteroids, however TNF blocking agents required an 8-week wash-out period. The study was approved by the local ethics committees of both centres.

Patients in both treatment arms were comparable with respect to baseline characteristics, as shown in table 1. After 1 year of follow-up, no significant differences were observed between both treatment arms regarding change in 28-joint Disease Activity Score (DAS28) results, change in Health Assessment Questionnaire (HAQ) scores and radiographic progression. Additionally, American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response rates were comparable (table 1). Additionally, we found that both treatments were equally safe: 86% of the patients in the FR group compared to 95% in the ODR group had reported an adverse event (p = 0.30). One patient died 8 weeks after initiation of rituximab treatment from respiratory insufficiency due to progression of pre-existent lung fibrosis. Infusion-related events were seen in 14% of patients in the FR group and 30% in the ODR group (p = 0.19), of which all reported symptoms were mild with a common toxicity criteria (CTC) grade of 1 or 2.

We demonstrated that over a 1-year follow-up period fixed retreatment and on-demand retreatment with rituximab resulted in comparable efficacy as measured by ACR response, EULAR response, change in DAS28 results and HAQ scores and radiographic progression. With respect to the safety profile, both treatment strategies were comparable. The present study warrants further randomised studies with longer follow-up of repetitive retreatment courses with rituximab, which are needed to evaluate different B cell depleting strategies.