Eculizumab for adult patients with atypical haemolytic-uraemic syndrome: full dataset analysis of Japanese post-marketing surveillance.

Background: Eculizumab has been approved for atypical haemolytic-uraemic syndrome (aHUS) in Japan since 2013. Post-marketing surveillance enrolled patients with aHUS who received ≥ 1 dose of eculizumab to assess eculizumab safety and effectiveness.
Methods: We evaluated serious adverse events and effectiveness endpoints, i.e., haematologic normalization, a decrease of ≥ 25% in serum creatinine (sCr) levels, and complete thrombotic microangiopathy (TMA) response in adult patients with aHUS without other underlying diseases. In addition, the difference of baseline characteristics between patients who did and did not meet effectiveness endpoints was examined.
Results: In this safety and effectiveness analysis, 79 adult patients were included; median age was 54.0 years, median treatment duration was 30 weeks. Total exposure time of eculizumab was 75.51 patient-years, and 94 serious adverse events were reported in 39 patients. No unexpected safety signals were identified in this population. Mean platelet count, lactate dehydrogenase and estimated glomerular filtration rate significantly improved after 7 days of treatment. Complete TMA response, haematologic normalization and the improvement of sCr levels were met by 35.3%, 40.4% and 51.3% of patients, respectively. Median treatment duration was shorter in patients who did not achieve complete TMA response (6 weeks) than in patients who did (114 weeks). Multivariate analysis suggested that the time from the most recent TMA episode to start of eculizumab treatment was negatively associated with kidney function improvement.
Conclusions: No unexpected safety signals of eculizumab were identified in Japanese patients with aHUS in a real-world setting. Renal outcomes were negatively associated with the time from the most recent TMA episode to the initiation of eculizumab treatment.
Competing Interests: Declarations. Conflict of interest: S. Maruyama received honoraria for lectures and participation on advisory board from Alexion Pharma GK. S. Kaname received honoraria for lectures and participation on advisory board from Alexion Pharma GK. M. Matsumoto received honoraria for lectures and participation on advisory board from Alexion Pharma GK. Y. Miyakawa received research grant, clinical trials, and honoraria for participation on advisory board from Alexion Pharma GK. Y. Ishikawa. and A. Shimono are employees of Alexion Pharma GK and shareholders of Alexion Pharmaceutical Inc. All other authors have nothing to disclose. Ethical approval: Post-marketing surveillance was mandated by the Japanese government as part of the regulatory approval of eculizumab for aHUS in Japan. Post-marketing surveillance was conducted in accordance with Good Post-Marketing Study Practice (Ministry of Health, Labour and Welfare, Ministerial Ordinance No. 171 of 2004) to evaluate the safety and effectiveness of eculizumab in clinical practice. Ethical approval by an institutional review board is not mandatory for post-marketing surveillance. Human and animal rights: All procedures followed were in accordance with the Helsinki Declaration of 1964 and later versions. This article does not contain any studies with animal subjects performed by any of the authors. Infomed consent: Informed consent from individual patients is not mandatory for post-marketing surveillance.
(© 2024. The Author(s).)