Systematic review of rituximab for autoimmune diseases: a potential alternative to intravenous immune globulin

摘要

BACKGROUND The anti‐CD20 monoclonal antibody rituximab has immune‐modulatory effects similar to intravenous immunoglobulin (IVIG). We performed a systematic review and meta‐analysis to determine the efficacy and safety of rituximab in autoimmune diseases that are also treated with IVIG. STUDY DESIGN AND METHODS The most common indications for immune modulation with IVIG, as identified from a 2012 regional audit in Canada, were chronic inflammatory demyelinating polyneuropathy (CIDP), immune thrombocytopenia (ITP), myasthenia gravis, multifocal motor neuropathy, Guillain‐Barré syndrome, systemic lupus erythematosus (SLE), Sjogren's syndrome, and pemphigus vulgaris. We searched MEDLINE, EMBASE, and the Cochrane Library until July 2016 for studies evaluating rituximab in each of these conditions. The primary outcome in our meta‐analysis was clinical response at 6 months as defined by disease‐specific criteria in randomized trials. We also calculated pooled proportions of responders within disease types from observational studies. RESULTS Ninety‐five rituximab studies were identified: 86 were observational studies in patients with ITP (n = 1746), SLE (n = 1047), pemphigus vulgaris (n = 564), Sjogren's syndrome (n = 138), myasthenia gravis (n = 66), and CIDP (n = 31) and nine were randomized controlled trials (n = 992) in patients with ITP, SLE, and Sjogren's syndrome that compared rituximab with placebo plus standard of care. Among randomized trials, response rates were higher with rituximab (relative risk, 1.38; 95% confidence interval [CI], 1.05‐1.83). The pooled proportion of rituximab responses ranged from 94% (95% CI, 88%‐98%) for pemphigus vulgaris to 48% (95% CI, 30%‐66%) for CIDP. Rituximab was generally well tolerated in observational studies although in the randomized trials, adverse events were more common in the rituximab group. CONCLUSION Rituximab is an immune‐modulating agent with biologic activity across many autoimmune conditions. Our data support the use of comparative trials with broad eligibility criteria to evaluate rituximab as an alternative to IVIG in autoimmune diseases.