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

@entity1 @entity882 @entity281 @entity3039 @entity288
BACKGROUND: Immune @entity882 is characterised by immune-mediated destruction and suboptimum production of platelets. Despite the absence of supporting evidence, rituximab is frequently used off-label in @entity1 with @entity3039 . We aimed to assess the efficacy of rituximab as compared with placebo as a splenectomy-sparing treatment in @entity1 who were previously treated with @entity288 . METHODS: In this multicentre, randomised, double-masked, placebo-controlled trial, we enrolled corticosteroid unresponsive adult @entity1 (aged >= 18 years) with primary @entity3039 and a platelet count of less than 30   *   10(9) platelets per L. @entity1 were randomly assigned (1:1) to four weekly infusions of 375 mg/m(2) rituximab or placebo. Concurrent treatment with @entity288 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 @entity1 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 @entity1 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 @entity1 . 32 (58%) of 55 @entity1 in the rituximab group and 37 (69%) of 54 @entity1 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 @entity1 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 @entity281 (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. FUNDING: South-East Regional Health Authority and   stfold Hospital, Norway; Roche, France; and Roche, Norway.
