Long-Term Efficacy and Safety of Romiplostim for the Treatment of Patients with Chronic Immune Thrombocytopenia (ITP): 5-Year Update From An Open-Label Extension Study.
Authors: Bussel James B. , Kuter David J , Newland Adrian , de Wolf Joost TM , Wasser Jeffrey , Chang Paul , Nie Kun , Berger Dietmar 
Published: October 2019

Abstract
Abstract 681
Chronic ITP is characterized by increased platelet destruction and suboptimal platelet production. Immunosuppressive ITP therapies may produce only short-term responses and may have issues with toxicity. Romiplostim is a novel peptibody that increases platelet production by a mechanism similar to thrombopoietin; and is approved for the treatment of chronic ITP. We report data from adult patients with chronic ITP treated with romiplostim in an open-label extension study. Collection of safety and efficacy data from long-term treatment of these patients is ongoing. Eligible patients had completed a prior romiplostim study. Romiplostim was administered once weekly by subcutaneous injection, with dose adjustments to maintain platelet counts in the target range (50 to 200 × 109/L). Patients who achieved a stable dose of romiplostim for 3 consecutive weeks were eligible to administer romiplostim at home (by self-injection or by a caregiver); these patients returned to the clinic every 4 weeks for study evaluations. As of May 2009, 291 adult patients had been treated with romiplostim; most were female (63%) and their median time since diagnosis was 4.9 years (range, 1 to 46 years). Thirty-three percent had previously undergone a splenectomy. Patients were treated with romiplostim for a median of 48 weeks (range, 1 to 244 weeks). Two hundred and nineteen patients (75%) were continuing the study at the data cut-off. Home administration of romiplostim was able to be started by 75% of patients; 8/218 patients (4%) discontinued home administration and resumed study-site injection. The median of the average weekly dose across the overall study population was 4 mcg/kg (interquartile range: 2 to 7 mcg/kg). The weekly dose among individual patients remained stable: after week 12, 79% (228/288) of patients were administered a dose of romiplostim within 2 mcg/kg of their most frequent dose at least 90% of the time. Almost all patients (94%) experienced a platelet count ≥50 × 109/L during the study, and more than 50% of patients had platelet counts ≥50 × 109/L on 95% of all study visits. After the first week, median platelet counts remained within the target range (50 to 200 × 109/L) for the duration of the study. Of patients receiving concurrent ITP medication at baseline, 78% (29/37) were able to discontinue or reduce their dose by >25%. Adverse events were reported in 92% of patients overall; the most common were headache (32%); nasopharyngitis (30%); and contusion and fatigue (each 28%). The frequency of adverse events did not increase with time on study (Table). The patient incidence of bleeding events of moderate or greater severity (≥Grade 2) and of clinical significance (≥Grade 3) did not increase over time (Table). Thrombotic events were experienced by 17 (6%) patients and did not increase in frequency over time (Table). Bone marrow reticulin was present or increased in 9 patients with no evidence of progression to collagen fibrosis or chronic idiopathic myelofibrosis. Two patients developed neutralizing antibodies to romiplostim that were absent on retesting after drug withdrawal, with no cross-reactive antibodies to thrombopoietin. Thirteen patients died; 2 deaths were considered by the investigator as possibly related to treatment (unstable angina, myocardial infarction). In conclusion, romiplostim-treated patients were able to maintain platelet counts within the target range, with minimal dose adjustments for up to almost 5 years. Romiplostim was well-tolerated and adverse events did not increase with longer duration of treatment.Table.Summary of patient incidence of adverse events by study periodStudy periodAdverse eventsAny n (%)Serious n (%)Treatment related n (%)Bleeding n (%)Bleeding ≥Grade 2 n (%)Bleeding ≥Grade 3 n (%)Thrombotic events n (%) <24 wks N = 291245 (84)41 (14)68 (23)93 (32)36 (12)12 (4)7 (2) 24 to <48 wks N = 271215 (79)32 (12)31 (11)66 (24)23 (9)5 (2)5 (2) 48 to <72 wks N = 151113 (75)14 (9)18 (12)41 (27)12 (8)2 (1)3 (2) 72 to <96 wks N = 12498 (79)11 (9)4 (11)38 (31)6 (5)1 (1)2 (2) 96 to <120 wks N = 11283 (74)19 (17)8 (7)31 (28)9 (8)1 (1)4 (4) 120 to <144 wks N = 10176 (75)8 (8)7 (7)21 (21)7 (7)1 (1)1 (1) 144 to <168 wks N = 8151 (63)6 (7)2 (3)15 (19)4 (5)00 68 to <192 wks N = 4726 (55)3 (6)2 (4)9 (19)4 (9)1 (2)1 (2) 192 to <216 wks N = 2619 (73)2 (8)010 (39)2 (8)00 216 to <240 wks N = 2417 (71)2 (8)07 (29)2 (8)1 (4)0 >240 wks N = 61 (17)000000

Disclosures:
Bussel: Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Kuter:Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Esehi: Consultancy; Shionagi: Consultancy, Honoraria, Speakers Bureau; ONO: Consultancy, Honoraria, Speakers Bureau; MGI Pharma: Consultancy, Research Funding; Ligand: Honoraria, Speakers Bureau. Newland:Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pangenetics: Consultancy; Schering Plough: Consultancy; Baxter: Research Funding; Genentech: Research Funding; Gilead: Research Funding. Wasser:Amgen Inc.: Speakers Bureau. Chang:Amgen Inc.: Employment, Equity Ownership. Nie:Amgen Inc.: Employment, Equity Ownership. Berger:Amgen Inc.: Employment, Equity Ownership.