Key Points：

1. Hormone-resistant/relapsed immune thrombocytopenia (ITP) severely endangers patients’ life, health, and quality of life, and the JAK/STAT signaling pathway may be involved in its pathogenesis in various ways. There has been no previous international research exploring the use of JAK inhibitors for ITP treatment.
2. This study is a single-center, single-arm, open-label phase 2 clinical trial (NCT05446831), including 35 adult patients with primary ITP, all of whom were diagnosed with hormone-resistant/relapsed ITP and had failed at least one recommended second-line treatment. The treatment plan was baricitinib 4 mg/day orally for 26 weeks, with the primary endpoint being the 6-month sustained response.
3. The study showed that baricitinib was well-tolerated in patients with hormone-resistant/relapsed ITP, with a 6-month sustained response rate of 57.1% and a platelet sustained response rate of 54.3%.
4. The 2023 European Hematology Association Annual Meeting invited poster exchange, and the article was published in the form of an Article in the American Journal of Hematology (IF=10.1).

In patients with hormone-resistant/relapsed immune thrombocytopenia (ITP), the regulatory role of the JAK/STAT signaling pathway is of interest, especially the JAK2/STAT5 signaling pathway as the main signal transduction pathway downstream of TPO. Although the application of most JAK inhibitors in ITP treatment is limited due to the side effect of causing thrombocytopenia, the JAK1/2 inhibitor baricitinib (baricitinib) has shown an effect of increasing platelet count in clinical studies, and there are few reports of drug-related thrombocytopenia adverse events. Based on these findings, we conducted a single-center, single-arm, open-label phase 2 clinical trial (NCT05446831) to preliminarily explore the efficacy and safety of baricitinib in ITP patients.

The study included 35 adult patients with primary ITP, all of whom were diagnosed with hormone-resistant/relapsed ITP and had failed at least one recommended second-line treatment. Patients received baricitinib 4 mg/day orally for 26 weeks, with the primary endpoint being the 6-month sustained response. The results showed that 57.1% of patients achieved a sustained response, 54.3% achieved a platelet sustained response, 31.4% achieved a complete response, and 65.7% achieved an initial response, with an average response time of 12 days and an average platelet count peak of 94×109/L. Extended observation after discontinuation of treatment showed that 44.4% of patients still had a sustained response after the end of baricitinib treatment. Adverse events were mainly mild, and no serious adverse events such as thromboembolic events or major cardiac adverse events were observed.

These results preliminarily confirm the safety of baricitinib in adult primary ITP and suggest that it may be a new option for the treatment of hormone-resistant/relapsed ITP.

Reference

Zhao P, An ZY, Fu HX, Liu HX, Feng CJ, Huang QS, Wu J, Wu YJ, Yang LP, Qu QY, Chen YX, Li ML, Wang CC, Chen Q, Zhu XL, He Y, Zhang YY, Jiang Q, Jiang H, Lu J, Chang YJ, Zhao XS, Zhao XY, Huang XJ, Zhang XH. Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study. Am J Hematol. 2024 Jul 9. doi: 10.1002/ajh.27433. Epub ahead of print. PMID: 38980207.