Management of Exacerbations and Rescue Therapy in the Phase 3 Myasthenia Gravis Inebilizumab Trial
Richard J. Nowak, Kimiaki Utsugisawa, Michael Benatar, Emma Ciafaloni, M. Isabel Leite, John Vissing, Fengming Tang, Yanping Wu, Catherine Najem, Sue Cheng, James F. Howard, , Conrado Estol, Marcelo Rugiero, Florencia Aguirre, Halina Navumava, Ruslan Yakubtsevich, Yury Holets, Marcelo V. Raffo, Alexandre Guerreiro, Daniel T Pereira Lopes, Eduardo Estephan, Wilson Marques Júnior, Vera Bril, Xinghu Zhang, Fudong Shi, Dian He, Lan Chu, Chongbo Zhao, Yuwei Da, Qi Fang, Jing Li, Ting Chang, Sabrina Sacconi, Aleksandra Nadaj-Pakleza, Tim Hagenacker, Anirudha Apte, Rahul Baviskar, Arvind N. N. Prabhu, Praveen Kumar S, Jayantee Kalita, Ruhal Kulkarni, Surya Prabha Turaga, Rukmini Kandadai, Neeharika L. Mathukumalli, Sanjay Ramteke, Raffaele Iorio, Renato E. Mantegazza, Carlo G. Antozzi, Akiyuki Uzawa, Kimiaki Utsugisawa, Genya Watanabe, Yasushi Suzuki, Masako Suzuki, Takayuki Kondo, Andrej Szczudlik, Anetta Lasek-Bal, Joanna Siuda, Małgorzata Zajda, Karolina Piasecka-Stryczynska, Elena Parshina, Denis Korobko, Irina E Poverennova, Evgeny Evdoshenko, Zoya Goncharova, Yury Trinitatskiy, Klara Bakhtiyarova, Inna Smagina, Byoung Joon Kim, Ha Young Shin, Jeeyoung Oh, Alicia Martínez Piñeiro, Eduardo Agüera Morales, Long-Sun Ro, Jiann-Horng Yeh, Hsuah-Wen Hseuh, Nai-Wen Tsai, Yuan-Ting Sun, Yi-Chung Lee, Chen-Chih Chung, Ayse Nur Yuceyar, Ihsan Sukru Sengun, Olga Shulga, Oleksandr Doroshenko, Sergii Moskovko, Oleksandr Kalbus, Richard J. Nowak, Aziz Shaibani, Waqar Waheed, Tuan Vu, Kelly G. Gwathmey, George A. Small, Ratna K Bhavaraju-Sanka, Ali A. Habib, Urvi Desai, Yessar M. Hussain, Nicholas S. Streicher, Ryan DrakeImportance
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: