10.1001/TESTjama.2012.4607

Vollständiger Abstract

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IMPORTANCE: Uncontrolled generalized myasthenia gravis (gMG) can lead to exacerbations that often warrant rescue therapy (RT) use, especially in moderate to severe cases. Inebilizumab, a monoclonal antibody that depletes cluster of differentiation 19+ B cells, demonstrated efficacy and safety in patients with gMG enrolled in the Myasthenia Gravis Inebilizumab Trial (MINT); the present analysis evaluated its effect on exacerbations and RT use. OBJECTIVE: To examine the effect of inebilizumab on exacerbations, including RT use, in participants enrolled in MINT. DESIGN, SETTING, AND PARTICIPANTS: MINT was a phase 3, international, randomized, placebo-controlled trial that enrolled participants between August 2020 and November 2023. The randomized controlled period was 52 weeks for the anti-acetylcholine receptor antibody positive (AChR+) subpopulation and 26 weeks for the anti-muscle-specific kinase antibody positive (MuSK+) subpopulation with an optional 3-year open-label extension. Participants were enrolled at 81 academic and nonacademic sites in 18 countries. MINT screened 485 patients with gMG (AChR+ or MuSK+) and enrolled adult participants with Myasthenia Gravis Activities of Daily Life (MG-ADL) scores of 6-10. This prespecified analysis was conducted between September 2024 and March 2025. INTERVENTIONS: Participants were randomized 1:1 to either inebilizumab or placebo and underwent a protocol-specified corticosteroid taper to 5 mg per day or less. MAIN OUTCOMES AND MEASURES: The frequency of exacerbations, defined as myasthenic crisis, worsening of individual MG-ADL scores, or RT use (intravenous immunoglobulin or plasma exchange). RESULTS: MINT enrolled 238 participants. The mean (SD) age at baseline was 47.5 (15.3) years, 144 (61%) were female, and the mean (SD) MG-ADL score was 9.1 (2.8). Inebilizumab reduced the risk of exacerbations compared with placebo in the combined population by week 26 (hazard ratio [HR], 0.41; 95% CI, 0.24-0.70), in the AChR+ subpopulation by week 52 (HR, 0.39; 95% CI, 0.23-0.68), and in the MuSK+ subpopulation by week 26 (HR, 0.21; 95% CI, 0.06-0.79). CONCLUSIONS AND RELEVANCE: In this prespecified analysis of a randomized clinical trial, inebilizumab treatment reduced exacerbation rate, including RT use, in participants with gMG who underwent a protocol-specified corticosteroid taper during MINT. These findings further support the clinical benefits of inebilizumab in AChR+ and MuSK+ gMG. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04524273.

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