Ruxolitinib duration of treatment and effect on phlebotomy use among 2369 patients with polycythemia vera: A real-world analysis of the Medicare fee-for-service claims database

Abstract Background: Ruxolitinib (RUX) is approved for the treatment of adults with polycythemia vera (PV) have inadequate response to or are intolerant of hydroxyurea (HU). The median duration of RUX treatment in the RESPONSE trial was approximately 5 years. This study examined RUX treatment duration in patients with PV based on long-term follow-up in a real-world setting. Methods:This retrospective analysis used Medicare Fee-For-Service Parts A/B claims data and Part D Prescription Drug Event data to identify adults with PV, defined as ≥2 claims for PV by International Classification of Diseases 10th Revision (ICD-10) Code D45, from January 2016 to December 2023; RUX treatment was defined by ≥1 claim from January 2017 to December 2021 (index date was the first RUX claim on or after the first PV claim). Eligible patients were required to have continuous enrollment in medical and pharmacy benefits for ≥12 months before (baseline period) and ≥24 months after index (follow-up period). Patients with claims of primary or secondary myelofibrosis, essential thrombocythemia, acute myeloid leukemia, or myelodysplastic syndrome before index were excluded. Duration of RUX treatment was analyzed using the Kaplan-Meier method; clinical characteristics, PV-related treatments before and after RUX, and RUX doses were assessed descriptively. Results:Among 2369 included patients, median (IQR) age was 75 (70–81) years, 60% (n=1411) were female, and 89% (n=2104) were White. Nearly all patients (98%; n=2311) were high-risk, with 97% (n=2300) aged ≥60 years, 16% (n=372) having a history of thrombotic events, and 15% (n=361) having both risk factors. Additionally, 27% of patients (n=633) had splenomegaly. The most common comorbidities were peripheral vascular disease (27%; n=646), chronic pulmonary disease (23%; n=552), diabetes without complication (23%; n=548), renal disease (21%; n=506), and cerebrovascular disease (20%; n=471). The median (IQR) follow-up duration was 51 (36–71) months. Median (IQR) time from PV diagnosis to RUX initiation was 15 (11–33) months, with 75% of patients (n=1773) starting RUX ≥12 months after diagnosis. The most common treatments during the baseline period prior to RUX initiation were HU (59%; n=1387) and anagrelide (7%; n=170); 29% of patients (n=691) received phlebotomy during the 6 months before index, with a median (IQR) of 2 (1–7) phlebotomy claims. The mean (SD) RUX dose was 20.3 (9.3) mg daily or 10 mg twice daily (bid) at initiation and 19.4 (10.6) mg daily (10 mg bid) at the last recorded dose. Initial dose adjustments occurred at a median of 5 (2–15) months, with 41% of patients (n=970) undergoing a dose reduction and 40% (n=944) a dose escalation. Median (95% CI) RUX treatment duration was 42 (40–44) months, and 38% of patients (n=909) remained on RUX at the end of follow-up. Among the 691 patients who received phlebotomy at baseline, 60% (n=415) did not receive any phlebotomy during the first 6 months post-index, and 73% (n=506) did not receive any phlebotomy during months 7–12 post-index. After RUX discontinuation, the most common treatments among all 2369 patients were HU (17%; n=410) and phlebotomy (14%; n=323), followed by fedratinib (3%, n=66), anagrelide (3%; n=64), pacritinib (2%; n=41), and interferon (n<11).Conclusions: In this large retrospective real-world study with over 4 years of follow-up, older patients with PV continued RUX treatment for a median of 3.6 years, and more than one-third of patients remained on RUX treatment at the end of the study period. Mean RUX dose used was 10 mg bid. Most patients who required phlebotomy at baseline became phlebotomy-free within 6 months after starting RUX. Nearly 4 years of continuous RUX use observed here is indicative of sustained clinical benefit and tolerability over a longer time frame, supporting its role as an effective long-term treatment option for patients with PV.