Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial

Background The licensed dose of rituximab in rheumatoid arthritis (RA) is two doses of 1000 mg given 2 weeks apart. A lower dose has never been specifically studied in patients with an inadequate response to anti-tumour necrosis factor (TNF) agents. Objective To compare the efficacy and safety of rituximab repeat treatment with two doses (1000 mgx1 and 1000 mgx2) following initial treatment with 1000 mgx2. Methods We set up an open-label, prospective, multicentre, non-inferiority study comprising a non-controlled period (24 weeks) followed by a randomised controlled period (weeks 24-104) in patients with RA and an inadequate response to anti-TNF agents. All patients received one course of rituximab (1000 mgx2) with methotrexate. At week 24, patients achieving a EULAR response (moderate or good) were randomised to rituximab retreatment at 1000 mgx1 (Arm A) or 1000 mgx2 (Arm B). The primary objective measure was disease activity in 28 joints C-reactive protein (DAS28-CRP) area under the curve (AUC) over 104 weeks with a non-inferiority margin defined by 20% (444) of the mean DAS28-CRP AUC (mean +/- SD 2218 +/- 967) of the reference data. Results The intent-to-treat and per-protocol (PP) populations comprised 143 (A/B: 70/73) and 100 (A/B: 51/49) patients, respectively. The adjusted mean difference in DAS28-CRP AUC (PP) was 51.4 (95% CI -131.2 to 234), demonstrating non-inferiority between arms A and B. The overall rituximab safety profile was similar with both retreatment regimens. Conclusions Following a clinical response to a first course of rituximab in RA at the licensed dose of 1000 mgx2, retreatment with rituximab at 1000 mgx1 results in efficacy outcomes that are non-inferior to those achieved with retreatment at 1000 mgx2.