Romiplostim for the treatment of chronic immune thrombocytopenia in adult Japanese patients: a double-blind, randomized Phase III clinical trial

Abstract

The efficacy and safety of romiplostim, a thrombopoietin-mimetic peptibody, were evaluated in a double-blind, placebo-controlled, randomized trial of Japanese patients with chronic immune thrombocytopenia (ITP). Thirty-four ITP patients received romiplostim (n = 22) or placebo (n = 12) for 12 weeks, with a starting romiplostim dose of 3 μg/kg weekly. The primary end point was the number of weeks with platelet response, defined as a platelet count ≥50 × 10(9)/L (not including the 4 weeks after rescue medication administration). Patients received a median of 4 (range 1-19) prior ITP therapies including splenectomy in 44%. On study, 68% also received concomitant ITP therapy. Weekly responses occurred for a median of 11 weeks with romiplostim as compared to 0 weeks with placebo (p < 0.0001). Most romiplostim-treated patients (95%) achieved platelet responses; two showed extended responses after the treatment period. The use of rescue medication was required in 9% of romiplostim-treated patients as compared with 17% of placebo-treated patients. Both treatment groups had similar incidences of adverse events (91% romiplostim, 92% placebo). Adverse events that occurred more frequently (>10%) in romiplostim-treated patients included nasopharyngitis, headache, peripheral edema, back pain, and extremity pain. In conclusion, romiplostim significantly increased and maintained platelet counts and was well tolerated in Japanese patients with ITP.

Evaluation of the safety, pharmacokinetics, and efficacy of recombinant factor VIII fc fusion protein in Japanese subjects with severe haemophilia A: analysis from the A-LONG study

“…[23][24][25] Japanese subjects when compared with previous studies of these agents in non-Japanese populations. [17][18][19]26) Haemophilia A is a relatively rare disease. 27) Although the A-LONG study is one of the largest global studies conducted in haemophilia A, there were 14 Japanese subjects included.…”

“…15,16) In addition, studies evaluating other approved Fc fusion proteins have not reported differences in safety and efficacy between Japanese and non-Japanese subjects. [17][18][19] However because of pharmacokinetic differences found in other drug categories, it is Deerfield, Illinois, USA), followed by pharmacokinetic assessment (up to 72 hours). Then, after a washout period (≥96 hours), a 50-IU/kg dose of rFVIIIFc was administered, followed by a second pharmacokinetic assessment (up to 120 hours).…”

Highly Fluctuating Thrombocytopenia Developing in a Patient with Immune Thrombocytopenia (ITP) while Administering Romiplostim

“…Rebound thrombocytopenia, is defined as a platelet count at least less than 10×10 9 /L below the baseline platelet count during the first 4 weeks following the discontinuation of these TPO receptor agonists (1,3,5). Rebound thrombocytopenia reportedly occurred in approximately 8 to 10% of patients and was associated with an increased risk of bleeding (1, 3, 5, 7), while, in a report of a Phase III clinical trial of romiplostim involving a small number of 22 adult Japanese patients, no such cases were reported (8). A proposed mechanism for rebound thrombocytopenia is the increased clearance of endogenous TPO by the expanded megakaryocytes and platelets induced by the thrombopoietin receptor agonists (5).…”

“…Two thrombopoietin (TPO) receptor agonists that stimulate platelet production, romiplostim and eltrombopag, are now approved for the treatment of adult chronic immune thrombocytopenia (ITP) for patients at risk of bleeding who show a relapse after splenectomy or do not respond to at least one immunosuppressive therapy (1)(2)(3)(4)(5)(6)(7)(8)(9). Post-treatment worsening of thrombocytopenia after administration of TPO receptor agonists has been reported after the withdrawal of administration, termed rebound thrombocytopenia (1,3,5,7).…”

Risk of Thromboembolism in Patients with Immune Thrombocytopenia

“…They promote megakaryocyte differentiation, proliferation, and platelet production [50]. In these patients with ITP treated with TPO-R agonists, a significant number of TEEs has been reported (0 to 6.7%) [51][52][53][54][55][56][57][58][59][60][61][62][63] ( Table 2). Arterial and/or venous TEEs occurred in these patients.…”