title: Low- versus high-dose rituximab for rheumatoid arthritis: a systematic review and meta-analysis.
abstract: OBJECTIVE
  The approved dose of rituximab (RTX) for rheumatoid arthritis (RA) is 2 × 1,000 mg infusions given 2 weeks apart. There is contradictory evidence regarding the effectiveness of a lower-dose regimen (2 × 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Low-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.
authors: Hospital Nossa Senhora da Conceição, Grupo Hospitalar Conceição, Porto Alegre, Rio Grande do Sul, Brazil.
authors: Markus
authors: M
authors: Bredemeier
authors: Fernando K
authors: FK
authors: de Oliveira
authors: Cláudia M
authors: CM
authors: Rocha
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab