Role of Azathioprine in the Management of ITP in the TPO-RA Era: A Single Centre Retrospective Study

• Azathioprine remains a viable and safe treatment in relapsed/refractory ITP in the TPO-RA era.

• Azathioprine offers clinicians a comparable drug response irrespective of prior TPO-RA exposure or splenectomy.

Immune thrombocytopenia (ITP) is an autoimmune disease associated with low platelets and risk of bleeding. Standard-of-care treatment now includes the novel thrombopoietin-receptor agonists (TPO-RA). However, access to these modern therapeutics remains a challenge, limiting clinicians’ options. We investigated azathioprine in relapsed/refractory ITP to determine its efficacy and safety, focusing on evaluating its utility in post-TPO-RA patients.

We retrospectively reviewed all adult patients, age 18 years and older, who were worked up for thrombocytopenia between 2009 and 2022 at a tertiary care centre in Ontario, Canada. Only ITP patients treated with azathioprine were included.

We identified 92 ITP patients who received azathioprine, mean age 55.6 ± 22.3 years, 53 females and 39 males, with 64 having primary ITP. The overall response rate (ORR) was 47.8% (44/92), with a sustained response rate of 77.3% (34/44) at 6 months. Median time to response was 6 weeks. Fourteen patients (31.8%) relapsed with a median duration of response of 10 weeks. Most patients (73.9%) had documented side effects, with nausea/vomiting, infections and myelosuppression being the most common. The majority of patients received azathioprine as third-line; 6 patients were post-TPO-RA and 27 post-splenectomy. ORR was 50.0% (3/6) and 40.7% (11/27) in each group respectively.

This is the largest retrospective study demonstrating benefit with azathioprine in relapsed/refractory ITP. Its efficacy remains consistent both post-TPO-RA (p=0.948) and post-splenectomy (p=0.259), offering clinicians a comparable drug response irrespective of prior TPO-RA exposure or splenectomy. We propose that azathioprine remains a viable option for relapsed/refractory ITP in the TPO-RA era.