Efficacy and safety of azathioprine during remission of immune-mediated thrombotic thrombocytopenic purpura

Acquired immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy, caused by anti-ADAMTS13 autoantibodies. After an acute episode, up to 50% of the patients will experience a clinical relapse. Patients with low ADAMTS13 activity are usually treated with rituximab, but in case of rituximab failure or ineligibility, there is no clear guidance for the second-line choice. The aim of our study was to assess azathioprine safety and efficacy for clinical relapse prevention and attainment of ADAMTS13 remission. We enrolled 43 iTTP patients treated with azathioprine during disease remission between 2002 and 2020. Median employed dosage was 1.3 mg/kg/day. The cumulative incidence of clinical relapse during azathioprine treatment was 22% (95% confidence interval 10 - 43%) at 2 years. Partial ADAMTS13 remission was achieved in 48% of the patients with baseline ADAMTS13 activity <20% after a median time of 3 months (interquartile range [IQR] 3 - 9 months) since azathioprine start, and lasted for a median time of 40 months (IQR 16 - 56 months). Complete ADAMTS13 remission occurred in 33% of the patients, after a median time of 8 months (IQR 3 - 16 months) and lasted for a median time of 16 months (IQR 0 - 53 months). At least one adverse event (AE) occurred in 30% of the patients, usually gastrointestinal toxicity, prompting treatment interruption in 14% of treated patients. Thus, azathioprine proved to be effective in terms of clinical relapse prevention, attainment of a durable ADAMTS13 remission, with infrequent and relatively mild AEs.