Updated Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Low- Versus High-dose Rituximab for Rheumatoid Arthritis

The purpose of this study is to update a systematic review and meta-analysis comparing low- (2 × 500 or 1 × 1000 mg) and high-dose (2 × 1000 mg) rituximab (RTX) for the treatment of rheumatoid arthritis (RA), considering the recent emergence of new evidence. The systematic literature review searching for randomized controlled trials (RCTs) was updated to November 6, 2014 using the PubMed, EMBASE, Cochrane Library, Web of Science databases, and hand searching. The primary outcomes were the American College of Rheumatology (ACR) criteria for 20 % improvement (ACR20), ACR50, and ACR70 responses and the Disease Activity Score in 28 joints (DAS28) at 24 and 48/52 weeks. The secondary outcomes were change in Health Assessment Questionnaire (HAQ) score, change in the radiographic modified Total Sharp Score (mTSS), levels of immunoglobulin G (IgG), and adverse events. In total, seven RCTs were identified, including two new full publication versions and one abstract of RCTs. There were no significant differences in the primary outcomes and change in HAQ, although the mean change in mTSS was 0.25 units (95 % CI, 0.01 to 0.49; P = 0.04) higher in low-dose group at week 52. Two RCTs did not demonstrate difference between the RTX regimens for maintaining clinical response (obtained initially using high-dose RTX) in anti-TNF-experienced patients. IgG levels were significantly higher (P ≤ 0.02), and first infusion reactions were less frequent in the low-dose group (P = 0.02). Our updated results further support the similar efficacy of both RTX regimens in different subsets of RA patients, demonstrating a better clinical and laboratory safety profile of the low-dose scheme.