denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Bleeding and Clotting, Diseases, thrombocytopenias
The treatment of choice in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) is still controversial due to the unclear mechanism and unpredictable efficacy of available therapies. The small molecule compound iguratimod is widely used as a novel antirheumatic drug to treat several autoimmune diseases. According to studies involving ITP mice, iguratimod may represent a new approach for the prevention and treatment of anti-platelet antibody-mediated ITP by modulating T-cell differentiation. Since iguratimod and danazol share disparate mechanisms in treating ITP, a combination of iguratimod and danazol may work synergistically based on a "double-hit" mechanism targeting both platelet production and destruction. The aim of this study was to evaluate the efficacy and safety of iguratimod and danazol versus danazol alone in patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia.
Methods:
Across seven tertiary medical centers in China, adult ITP patients from this randomized, controlled, multicenter, open-label trial participated. Eligible corticosteroid-resistant or relapsed ITP patients with a platelet count <30×109/L or bleeding symptoms at enrollment were randomly allocated by masked statisticians in a 1:1 ratio to receive oral iguratimod at 25 mg twice daily plus oral danazol at 200 mg twice daily or oral danazol monotherapy at 200 mg twice daily for 12 weeks. The group assignment was not masked for clinicians or patients. Following the first eight weeks of treatment, patients were assessed every two weeks thereafter. The primary endpoint was a 6-month sustained response (SR), defined as a platelet count of 30×109/L or more and at least a doubling of the baseline platelet count (partial response) or a platelet count of 100×109/L or more (complete response) and the absence of bleeding without rescue medication. This trial was registered with ClinicalTrials.gov (NCT05281068).
Results:
From September 1, 2021, to December 31, 2022, a total of 106 patients were screened for eligibility; 35 were excluded, and 71 were randomly assigned: 37 to the iguratimod plus danazol group and 34 to the danazol group. The median age of the patients was 41 years, and 69.0% (49/71) of them were females. All patients enrolled failed to respond to the first-line treatment with corticosteroids, and 21 (29.6%) of all patients had received three or more therapies. The data cutoff for the analyses was July 1, 2023. The median follow-up was 14 months (IQR 11-15) in the iguratimod plus danazol group and 12.5 months (11-15) in the danazol group. Six-month follow-up results showed that iguratimod plus danazol was more likely to produce SR than danazol alone (20 [54.1%] of 37 vs. 9 [26.5%] of 34; odds ratio 1.82, 95% CI 1.22-2.70, p = 0.003). The combination group had 25 (67.6%) patients with at least one response (overall response), and 13 (35.1%) patients had a complete response by the end of the follow-up; whereas 15 (44.1%) of 34 patients in the monotherapy group had an overall response, and three (8.8%) had a complete response. A target platelet count of 30×109/L was achieved in 18 (48.6%) of 37 patients given iguratimod plus danazol after 4 weeks and five (14.7%) of 34 patients given danazol monotherapy, indicating that the combination therapy significantly increased the initial response rate (p = 0.002). Both groups experienced similar serious adverse events (AEs), rescue treatment, and treatment side effects, and all patients tolerated the treatment well, without any grade 4 AEs or treatment-related deaths reported.
Conclusions:
Patients with corticosteroid-resistant or relapsed ITP responds well to iguratimod plus danazol. This regimen achieved a rapid and long-lasting response. It is necessary to conduct further studies to determine the optimal dosage and a variety of combination therapies using several immune-suppressing agents, including iguratimod, to achieve a sustained response in patients with corticosteroid-resistant or relapsed ITP.
Disclosures: No relevant conflicts of interest to declare.
OffLabel Disclosure: Iguratimod is a small molecule compound that is widely used as a novel antirheumatic drug in the treatment of rheumatoid arthritis in China and Japan. Iguratimod inhibits the production of several inflammatory cytokines, including IL-1, IL-6, IL-8, and tumor necrosis factor (TNF), and reduces the production of immunoglobulins. Th1 and Th17 cell counts were significantly reduced in patients with rheumatoid arthritis after treatment with iguratimod. The low long-term remission rate of ITP makes the investigation of its pathogenesis and the search for new treatments important clinical problems to be solved. Abnormal T-cell function and anti-platelet antibody production play important roles in the pathogenesis of ITP, and iguratimod is a therapeutic agent that could potentially be used to treat ITP. Previous clinical studies have shown that iguratimod can increase platelet levels in patients with dry syndrome. The potential of iguratimod for treating anti-platelet antibody-mediated thrombocytopenia in mice with ITP by modulating T-cell differentiation suggests that iguratimod may be a new approach for the prevention and treatment of ITP.