Dataset Information

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance.

ABSTRACT: BACKGROUND:Eculizumab has been available for the treatment of atypical hemolytic-uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations. METHODS:This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based on Japanese clinical guide published in 2013 as inclusion criteria and treated with eculizumab. Although the term aHUS was redefined to denote only complement-mediated HUS in the guide revised in 2016, the patients with TMA caused by other causes (secondary TMA) were included. Patient outcomes and safety were evaluated at 6 months, 12 months, and annually thereafter. RESULTS:Thirty-three patients with aHUS and 27 patients with secondary TMA were enrolled. Median treatment duration of aHUS was 24weeks. Complement genes variants were detected in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine (SCr) improved within 1-month after eculizumab initiation. TMA event-free status, complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9% (19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients, respectively. Thirty-three and 11 adverse reactions were observed in patients with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively. CONCLUSIONS:This interim analysis confirmed the acceptable safety profile and effectiveness of eculizumab for Japanese adult aHUS patients in real-world settings.

SUBMITTER: Kato H

PROVIDER: S-EPMC6344388 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance.

Kato Hideki H Miyakawa Yoshitaka Y Hidaka Yoshihiko Y Inoue Norimitsu N Ito Shuichi S Kagami Shoji S Kaname Shinya S Matsumoto Masanori M Mizuno Masashi M Matsuda Takahisa T Shimono Akihiko A Maruyama Shoichi S Fujimura Yoshihiro Y Nangaku Masaomi M Okada Hirokazu H

Clinical and experimental nephrology 20180629 1

<h4>Background</h4>Eculizumab has been available for the treatment of atypical hemolytic-uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations.<h4>Methods</h4>This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based ...[more]

PMID: 29959568

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Project description:BackgroundEculizumab, a humanized monoclonal antibody targeted to terminal complement protein C5, is approved in Japan for treatment of patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (gMG) whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIg) therapy or plasmapheresis.MethodsThis interim analysis of mandatory post-marketing surveillance in Japan assessed the safety and effectiveness of eculizumab at 26 weeks after treatment initiation in patients with AChR+ gMG.ResultsData were available for 40 adult patients in Japan [62.5% (25/40) female; mean age at eculizumab initiation, 51.0 years]. Fifteen patients had a history of thymoma. Six patients were excluded from the effectiveness analysis set due to participation in the open-label extension part of the phase III, randomized, double-blind, placebo-controlled REGAIN study [ClinicalTrials.gov identifier: NCT02301624]. After 26 weeks' follow up, 32 patients (80%) were continuing eculizumab treatment. Adverse drug reactions were reported by seven patients [most frequently headache (n = 3)]. One death was reported during eculizumab treatment (relationship unclear as determined by the treating physician) and there was one death 45 days after the last dose (considered unrelated). No meningococcal infections were reported. Mean (standard deviation) changes from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores were -3.7 (2.61) (n = 27) and -5.6 (3.50) (n = 26), respectively, at 12 weeks, and -4.3 (2.72) (n = 26) and -5.6 (4.02) (n = 24), respectively, at 26 weeks. Improvements in MG-ADL and QMG scores were generally similar in patients with/without a history of thymoma. Frequency of IVIg use decreased following eculizumab initiation.ConclusionIn a real-world setting, eculizumab was effective and well tolerated for the treatment of AChR+ gMG in adult Japanese patients whose disease was refractory to IVIg or plasmapheresis. These findings are consistent with the efficacy and safety results from the global phase III REGAIN study of eculizumab.

Project description:BackgroundThe terminal complement C5 inhibitor eculizumab is approved in Japan for relapse prevention in aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and is undergoing mandatory post-marketing surveillance (PMS) of clinical use.ObjectivesThe objective of the study is to assess the real-world, long-term safety and effectiveness of eculizumab in Japanese patients with AQP4+ NMOSD.DesignRegulatory-mandated PMS analysis implemented as an all-case surveillance of all patients with AQP4+ NMOSD who have been treated with eculizumab in Japan since its approval in November 2019.MethodsThis PMS interim analysis assessed the safety and effectiveness of eculizumab in Japanese patients with AQP4+ NMOSD from November 2019 to April 2022.ResultsOf 147 patients treated with eculizumab who consented to publication, 71 had at least one case report form collected and locked at the interim analysis data cut-off, constituting the safety analysis set; three patients from PREVENT (NCT01892345) were excluded from the effectiveness analysis set. Twelve and 10 patients in the safety and effectiveness analysis sets discontinued, respectively. In the safety analysis set, 67/71 patients (94.4%) were female, mean illness duration was 6.8 [standard deviation (SD): 6.2] years, mean age at eculizumab initiation was 50.7 (SD: 13.3) years, and mean eculizumab treatment duration was 44.6 (SD: 23.7) weeks. At diagnosis of NMOSD, 34/71 patients (47.9%) and 35/71 patients (49.3%) in the safety analysis set had symptoms of optic neuritis and transverse myelitis, respectively. In the safety analysis set, 19/71 patients (26.8%) reported adverse events, 10/71 (14.1%) reported adverse drug reactions (ADRs), and 7/71 (9.9%) reported serious ADRs; no meningococcal infections were observed. In the effectiveness analysis set, 64/68 patients (94.1%) were female, mean disease duration was 6.9 (SD: 6.3) years, mean age at eculizumab initiation was 50.6 (SD: 13.2) years, and 27/68 (39.7%) were tested for C5 genetic polymorphism (all negative). In the 2 years before eculizumab, 51/68 patients (75.0%) experienced relapse. Relapse rate was 0.02/patient-year after eculizumab initiation versus 0.74/patient-year in the 2 years before eculizumab. Overall, 37/68 patients (54.4%) were prescribed immunosuppressants in the 6 months before and 19/40 (47.5%) in the 6-12 months after starting eculizumab treatment. The proportion of patients taking >10 mg/day of prednisolone decreased from 45.6% at 24-20 weeks before to 23.1% and 0% at 48-52 and 100-104 weeks after eculizumab, respectively.ConclusionThis article reports interim PMS data for Japanese patients and provides updated real-world evidence for the safety of eculizumab and its effectiveness at preventing relapses in patients with AQP4+ NMOSD. Safety and effectiveness results are consistent with those from PREVENT.

Dataset Information

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance.

Publications

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance.

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