Low- Versus High-Dose Rituximab for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

ObjectiveThe approved dose of rituximab (RTX) for rheumatoid arthritis (RA) is 2 x 1,000 mg infusions given 2 weeks apart. There is contradictory evidence regarding the effectiveness of a lower-dose regimen (2 x 500 mg) of RTX. Our aim was to compare the efficacy and safety of low- and high-dose RTX and to test the noninferiority of the low-dose regimen. MethodsA systematic literature review searching for randomized controlled trials (RCTs) and cohort studies comparing low- and high-dose RTX for RA was conducted using the Embase, PubMed, Cochrane Library, and Web of Science databases. The primary end points were the American College of Rheumatology criteria for 20% improvement (ACR20), ACR50, and ACR70 responses and the Disease Activity Score in 28 joints (DAS28) at 24 and 48 weeks. The secondary end points were patient-reported outcomes (PROs; Health Assessment Questionnaire, Short Form 36, and Functional Assessment of Chronic Illness Therapy-Fatigue scores) and adverse events. Noninferiority of low-dose RTX was tested using different approaches, one of which was based on the fixed margin method. ResultsIn total, 6 RCTs and 2 cohort studies were identified. Four RCTs were included in the meta-analysis of efficacy outcomes, which showed no significant differences in the primary outcomes between low- and high-dose RTX. Noninferiority criteria of low-dose RTX were met for the ACR20, ACR50, DAS28, and PROs (at 24 and 48 weeks). Serious adverse events did not differ significantly. The results of 2 additional RCTs and a meta-analysis of 2 cohort studies corroborated the results of the meta-analysis of RCTs. ConclusionLow-dose RTX has similar effectiveness and met noninferiority criteria for most primary outcomes. Considering the lower cost, it should be the standard RTX regimen for RA.