Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura

Abstract

Patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) often experience life-threatening relapses of the disease, and rituximab (RTX) can be used to mitigate relapse risk. However, the predictors of relapse in iTTP and the magnitude and duration of effect of RTX remain key unanswered questions. Using a multi-institutional cohort of consecutive adult patients with iTTP, we used survival analysis to compare relapse rates between patients who received RTX during the index presentation with acute iTTP and those who did not. Of 124 patients, 60 (48%) received RTX and 34 (27%) experienced relapse. Median time to relapse was 3.71 (interquartile range, 1.75-4.9) and 1.33 (interquartile range, 0.43-2.35) years for RTX-treated and untreated patients, respectively. RTX conferred protection from relapse at 1 year of follow-up (P = .01) but not at 5 years of follow-up. Extended Cox regression was then used to identify predictors of relapse and to estimate the protective effect of RTX. The following parameters were independently associated with increased risk for subsequent relapse: presenting in iTTP relapse (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.4-6.4), age younger than 25 years (HR, 2.94; 95% CI, 1.2-7.2), and non-O blood group (HR, 2.15; 95% CI, 1.06-4.39). RTX initially provided protection from relapse (HR, 0.16; 95% CI, 0.04-0.70), but this effect gradually diminished, returning to the baseline risk for untreated patients at approximately 2.6 years. Patients who are young, have non-O blood group, or present with relapsed iTTP are at increased risk for subsequent relapse. RTX appears to confer short-term protection from relapse.

Graphical abstract

Figure 1.

Kaplan-Meier curve for relapse-free survival, entire cohort. Vertical red lines indicate censored patients.

Figure 2.

Relapse-free survival of patients according to treatment with RTX. (A) Unadjusted Kaplan-Meier analysis for relapse-free survival at 1 year, stratified by administration of RTX. Patients begin contributing time to the RTX group starting on the day of RTX administration. The curves were compared using the log-rank test. (B) Unadjusted Kaplan-Meier analysis for relapse-free survival at 5 years, stratified by administration of RTX. Patients begin contributing time to the RTX group starting on the day of RTX administration. The curves were compared using the log-rank test. (C) Graphical representation of increasing hazard ratio of relapse rate over time for patients receiving RTX, derived from the Cox proportional hazards model.