Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial

Background Immune thrombocytopenia is characterised by immune-mediated destruction and suboptimum production of platelets. Despite the absence of supporting evidence, rituximab is frequently used off-label in patients with immune thrombocytopenia. We aimed to assess the efficacy of rituximab as compared with placebo as a splenectomy-sparing treatment in patients who were previously treated with corticosteroids. Methods In this multicentre, randomised, double-masked, placebo-controlled trial, we enrolled corticosteroid unresponsive adult patients (aged >= 18 years) with primary immune thrombocytopenia and a platelet count of less than 30 x 10(9) platelets per L. Patients were randomly assigned (1: 1) to four weekly infusions of 375 mg/m(2) rituximab or placebo. Concurrent treatment with corticosteroids only was allowed during the study. The primary endpoint was rate of treatment failure within 78 weeks-a composite of splenectomy or meeting criteria for splenectomy after week 12 if splenectomy was not done, assessed in all patients who received at least one dose of study treatment. Secondary endpoints were response rates, relapse rates, and duration of response. Efficacy endpoints were assessed with the Kaplan-Meier method. Safety endpoints were assessed in all patients who received at least one dose. This trial is registered with ClinicalTrials.gov, number NCT00344149. Findings Between Aug 17, 2006, and June 30, 2011, we enrolled 112 patients. 32 (58%) of 55 patients in the rituximab group and 37 (69%) of 54 patients in the placebo group had treatment failure within 78 weeks (Kaplan-Meier cumulative incidence 46% for rituximab vs 52% for placebo (hazard ratio [HR] 0.89, 95% CI 0.55-1.45; p=0.65). The cumulative incidence of overall response was 81% in the rituximab group versus 73% in the placebo group (p=0.15) and complete response was 58% in the rituximab group versus 50% in the placebo group (p=0.12). Of those achieving an overall response, 68% relapsed in the rituximab group and 78% relapsed in the placebo group, and of those achieving complete response, 50% relapsed in the rituximab group and 62% relapsed in the placebo group. Time to relapse in the rituximab group was longer in patients who achieved overall response (36 vs 7 weeks; p=0.01) but not complete response (76 vs 49 weeks; p=0.19). Rates of bleeding were similar in the two groups (21 [38%] in the rituximab group vs 27 [50%] in the placebo group; p=0.08) as were rates of infection (22 [40%] vs 13 [24%]; p=0.09). Interpretation Despite no reduction in the rate of long-term treatment failure with rituximab, a small benefit cannot be ruled out, as suggested by an apparently longer duration of response and numerically higher response rates with rituximab.