Postmarketing Surveillance of the Safety and Effectiveness of Metreleptin in Patients with Lipodystrophy in Japan.

Purpose: The long-term safety and effectiveness of metreleptin in patients with lipodystrophy were evaluated. Methods: We conducted postmarketing surveillance of all patients administered metreleptin at least once from July 2013 at its launch through July 2021 in Japan. Data were collected through July 2022. The safety analysis set included all patients with Case Report Forms (CRFs) retrieved, including those who transitioned from premarketing clinical trials and those who newly initiated metreleptin after its launch. Only the latter cases were eligible for the effectiveness analysis set. Effectiveness was evaluated by changes in glycated hemoglobin (HbA1c) and triglyceride levels. Results: CRFs were collected from 48 patients. Thirty-six were new cases, and 12 were transitioned cases. Twenty-six types of adverse drug reactions (ADRs) were reported in 15 patients. The most reported ADRs were "decreased appetite" and "neutralizing antibodies positive," reported in 3 patients each. However, there were no safety concerns overall. Mean levels of HbA1c and triglycerides decreased at 2 or 4 months of treatment. Values thereafter remained stable for up to 7 years for HbA1c and triglycerides. Mean levels of HbA1c and triglycerides improved after 1, 2, and 3 years, although the change was not as great in partial lipodystrophy patients as in generalized lipodystrophy patients. Conclusion: Metreleptin treatment was generally well tolerated in patients with generalized and partial lipodystrophy and lowered HbA1c and triglycerides in those with generalized lipodystrophy. This surveillance demonstrated for the first time the long-term safety in the real world and the effectiveness in patients who used the medication correctly.