Comparison of the Effects of the Thrombopoietin (TPO) Receptor Agonist Romiplostim in Patients with Immune Thrombocytopenia (ITP) for ≤1 Year Vs. >1 Year

Background: Romiplostim is an option for second-line use in patients with chronic ITP, but its effects in patients with newly diagnosed or persistent ITP (ie, ITP ≤1 year) are not as well characterized. Aims: We examined patients with ITP for ≤1 year and >1 year at study baseline who had failed first-line treatments and subsequently received romiplostim, placebo (PBO), or standard of care (SOC) in romiplostim ITP studies. Methods: Data were pooled from 13 completed romiplostim ITP studies conducted from 2002-2014. Data from the PBO and SOC arms were pooled. Safety data were adjusted for exposure (ie, to reflect the longer exposure to romiplostim in extension studies). Results: Both patients with ITP ≤1 year (N=311) and >1 year (N=726) were predominantly Caucasian with similar ages (Table). For romiplostim-treated patients, doses were similar and treatment duration longer for patients with ITP >1 year; the proportion of patients receiving romiplostim for longer than a year was 63% for patients with ITP >1 year and 37% for patients with ITP ≤1 year. There were no new or unexpected safety signals seen with romiplostim vs. PBO/SOC. Independent of ITP duration at therapy onset, rates of serious adverse events and bleeding were decreased with romiplostim relative to PBO/SOC. Thrombotic / thromboembolic events in romiplostim-treated patients occurred at a wide range of platelet counts - from 9 /L to ≥400×10 9 /L - independent of ITP duration. There were too few thrombotic events with PBO/SOC to analyze by platelet count. Many patients, independent of treatment assignment, had a platelet response at some point on study. For patients with ITP ≤1 year at baseline, platelet response rates were romiplostim: 86% and PBO/SOC: 62%; for patients with ITP >1 year at baseline, platelet response rates were romiplostim: 87% and PBO/SOC: 33%. Response rates were notably increased with romiplostim for more stringent measures such as responding ≥75% or ≥90% of the time or having a durable platelet response, ie responding ≥6 weeks of weeks 17-24 (Figure; platelet response defined as platelet counts ≥50×10 9 /L, excluding 8 weeks after rescue medication use). Median time to first platelet response for romiplostim-treated patients did not differ appreciably by ITP duration (2 weeks for both ITP ≤1 year and >1 year). Of patients who had ≥9 months on study, some were able to discontinue romiplostim and maintain platelet counts ≥50×10 9 /L without any ITP treatments for ≥6 months. Rates of these treatment-free periods were ITP ≤1 year: 16% (95% CI: 11%, 21%) and ITP >1 year: 6% (95% CI: 4%, 8%). Of the included studies, only one had a forced taper design; the other instances of patients with treatment-free periods were from following standard study dosing rules (eg, reduce dose if platelet counts ≥200×10 9 /L, withhold treatment if platelet counts ≥400×10 9 /L). Nine months on study (not necessarily 9 months of exposure) was chosen as an appropriate duration to assess for these treatment-free periods as it allowed sufficient time to escalate to a stable romiplostim dose and for the effects of romiplostim to be observed - ie, a few months titrating the dose and 6+ months off romiplostim. For romiplostim-treated patients, rescue medications were used by 44% of patients with ITP ≤1 year and 50% of patients with ITP >1 year; rescue medication data for PBO/SOC were recorded differently (as SOC for most of these patients) and so could not be compared. For romiplostim-treated patients, independent of ITP duration, use of corticosteroids (which made up >60% of rescue medication use) decreased after the first few months and then fluctuated, dropping by ~3/4 over time. Conclusion : In this analysis of patients with ITP duration ≤1 year and >1 year at study baseline, the safety profile of romiplostim was similar to PBO/SOC, with lower rates of bleeding and serious adverse events with romiplostim. Thrombotic events happened at comparable rates for romiplostim and PBO/SOC. For romiplostim-treated patients, safety and efficacy (eg, platelet response rates) did not differ noticeably by ITP duration. Treatment-free periods of ≥6 months occurred more frequently in patients with ITP ≤ 1 year (16% vs. 6%). Only one study had a forced taper design, which may have led to an underestimate of how many patients can discontinue ITP medications including romiplostim. Future studies are needed to confirm the risk-benefit profile of romiplostim in patients with ITP ≤1 year. Disclosures Kuter: Shire: Consultancy, Research Funding; 3SBIO: Consultancy; ONO: Consultancy; Dova: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Argenx: Consultancy; Fujifilm: Consultancy; Zafgen: Consultancy; Protalex: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Merck: Consultancy; Genzyme: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Alexion: Consultancy, Research Funding; Rigel: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Syntimmune: Consultancy, Research Funding; Novartis: Consultancy. Newland: Rigel: Consultancy; Argenx: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Angle: Consultancy; Amgen Inc.: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Consultancy; Novartis: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Research Funding. Rodeghiero: MedImmune: Membership on an entity9s Board of Directors or advisory committees; LFB: Membership on an entity9s Board of Directors or advisory committees; GSK/Novartis: Membership on an entity9s Board of Directors or advisory committees; Amgen: Membership on an entity9s Board of Directors or advisory committees; Argenx: Membership on an entity9s Board of Directors or advisory committees; UCB: Membership on an entity9s Board of Directors or advisory committees. Pabinger: Boehringer Ingelheim: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Sobi: Consultancy, Honoraria; Bayer: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau. Chen: Amgen Inc.: Employment, Other: Stock holder. Wang: Amgen Inc.: Employment, Equity Ownership. Mehta: Amgen Inc.: Employment, Equity Ownership. Eisen: Amgen Inc.: Employment, Equity Ownership.