A recent retrospective cohort study suggested azathioprine may have utility in relapse prevention for patients with immune-related thrombotic thrombocytopenic purpura (iTTP). The results of the study warrant further research, according to the researchers who performed the analysis. The study was reported in the journal Blood Advances.
Azathioprine is used in treatment of autoimmune diseases, but with limited research on its use in treatment of iTTP. The researchers performed this study to evaluate its efficacy and safety in preventing relapse in patients with iTTP who are in clinical remission.
The study was a single-arm cohort study including patients from the Milan TTP Registry who were retrospectively screened for criteria related to iTTP diagnosis and the use of azathioprine during clinical remission for iTTP. The study had a primary efficacy outcome of cumulative incidence of clinical relapse during azathioprine therapy. Secondary efficacy outcomes included partial and complete ADAMTS13 remission and ADAMTS13 relapse. Safety with azathioprine treatment was also analyzed.
A total of 40 patients were included in the analysis. Rituximab failure had occurred in 25 patients prior to azathioprine treatment. The primary efficacy analysis occurred at a median follow-up of 40 months (95% CI, 14-69). This analysis included 35 patients, of whom 20% experienced clinical relapse. The 1-year cumulative incidence of clinical relapse was 10% (95% CI, 3-27%), and at 2 years it was 22% (95% CI, 10-43%).
A subgroup analysis of patients at higher relapse risk, based on a baseline ADAMTS13 activity of <20%, suggested that 19% of these patients experienced relapse, with a 1-year cumulative incidence of clinical relapse of 6%, and a 2-year cumulative incidence of 21%.
Evaluable patients in the secondary efficacy analysis included 21 patients who had a baseline ADAMTS13 activity of <20% and 4 patients with baseline ADAMTS13 activity of ≥20%. Among patients with <20% ADAMTS13 baseline activity, 10 (48%) reached partial ADAMTS13 remission, with a median duration of remission of 40 months, and 3 patients experienced ADAMTS13 relapse but without clinical relapse. One-third (33%) of patients with <20% baseline ADAMTS13 activity had complete remission, with a median duration of remission of 16 months. Among the 4 patients with baseline ADAMTS13 activity of ≥20%, 3 patients experienced ADAMTS13 relapse but without clinical relapse.
The safety analysis included 40 patients, of whom 28% had 1 or more AEs. Azathioprine was discontinued in 13% of patients. Gastrointestinal and hepatopancreatic AEs were the most common types. Acute myeloid leukemia occurred 5 months after initiating azathioprine in 1 patient, and it was unclear whether this was related to azathioprine treatment or another cause.
“In conclusion azathioprine should be considered as the second-line treatment for iTTP relapse prevention in patients unresponsive or intolerant to rituximab, since a durable ADAMTS13 remission was achieved in half of the patients and with infrequent and relatively mild AEs,” the researchers concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Bichard C, Mancini I, Agosti P, et al. Efficacy and safety of azathioprine during remission of immune-mediated thrombotic thrombocytopenic purpura. Blood Adv. Published online June 30, 2022. doi:10.1182/bloodadvances.2022007632