Management of Exacerbations and Rescue Therapy: A Prespecified Analysis of the Phase 3 Myasthenia Gravis Inebilizumab Randomized Clinical Trial.

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.