Inebilizumab Reduces Exacerbations in gMG: MINT Trial Analysis

Inebilizumab, a CD19+ B-cell–depleting monoclonal antibody, significantly reduced the risk of exacerbations and the need for rescue therapy in patients with generalized myasthenia gravis (gMG), even as participants underwent a protocol-specified corticosteroid taper, according to a prespecified analysis of the phase 3 MINT trial published in JAMA Neurology.¹

The results build on the trial's primary efficacy findings, reported earlier in the New England Journal of Medicine,² and offer a more clinically detailed look at how the therapy performs as corticosteroids are withdrawn in a disease that remains a significant driver of hospitalization, intensive care unit (ICU) admission, and health care resource utilization.¹

gMG is a rare, antibody-mediated autoimmune disease in which pathogenic autoantibodies, most often targeting the acetylcholine receptor (AChR+, roughly 80% of cases) or, less commonly, muscle-specific kinase (MuSK+, 7% to 10% of cases), disrupt neuromuscular signaling and cause fatigable muscle weakness. When left uncontrolled, the disease can escalate into exacerbations or myasthenic crisis, requiring hospitalization, ICU admission, and ventilatory support. Rescue therapy is typically intravenous immunoglobulin or plasma exchange and is used to manage exacerbations and myasthenic crisis.

"Particularly moderate to severe disease exacerbations require hospitalization, and not uncommonly, those hospitalizations can be prolonged as we wait for rescue therapy," Richard J. Nowak, MD, MS, associate professor of neurology at Yale School of Medicine and global principal investigator of the MINT trial, said in an interview with The American Journal of Managed Care ^®.

That burden was evident at baseline in MINT as more than half of enrolled participants (51.7%) had a history of MG-related hospitalization in the prior 2 years, and nearly 1 in 4 (22.9%) had experienced a prior myasthenic crisis. Even with standard immunosuppressive therapy, 10% to 20% of patients remain refractory. Inebilizumab (Uplizna; Amgen), a monoclonal antibody that depletes CD19+ B cells, including the plasmablasts and plasma cells producing pathogenic AChR and MuSK antibodies, is already approved in the US and Europe for AChR+ and MuSK+ gMG.³

Phase 3 MINT Trial of Inebilizumab in AChR+ and MuSK+ Myasthenia Gravis

The prespecified analysis stems from MINT, a phase 3, international, randomized, double-blind, placebo-controlled trial conducted at 81 sites across 18 countries between August 2020 and November 2023. Researchers randomized 238 patients (190 AChR+, 48 MuSK+) with baseline MG Activities of Daily Living (MG-ADL) scores of 6 to 10—the higher the score, the greater the functional impairment—in a 1:1 ratio to receive either inebilizumab 300 mg IV or placebo, administered on days 1, 15, and 183 for AChR+ participants and days 1 and 15 for MuSK+ participants. All underwent a protocol-specified corticosteroid taper to 5 mg/day or less. The randomized controlled period ran 52 weeks for AChR+ patients and 26 weeks for MuSK+ patients.

The results favored inebilizumab across every measure. By week 26, 16.0% of inebilizumab-treated patients experienced an exacerbation versus 35.0% on placebo (HR, 0.41; 95% CI, 0.24-0.70; P = .001). Among AChR+ patients followed to week 52, rates were 20.0% versus 45.2% (HR, 0.39; 95% CI, 0.23-0.68; P < .001); among MuSK+ patients at week 26, 12.5% versus 45.8% (HR, 0.21; 95% CI, 0.06-0.79; P = .02). Rescue therapy use was also lower with inebilizumab (8.4% vs 23.9%; HR, 0.34; 95% CI, 0.16-0.70; P = .003), and the annualized exacerbation rate fell from 1.17 to 0.40 (rate difference, −0.77; 95% CI, −1.20 to −0.33).

"We are observing that the probability of rescue therapy use, the probability of exacerbation, is lower in the inebilizumab group despite lowering of prednisone as compared to placebo," Nowak said.

Notably, the benefit held despite the concurrent steroid taper in both arms: 87.4% of inebilizumab-treated patients and 84.6% of placebo-treated patients reached the ≤5 mg/day target by week 24, and taper timing did not appear to drive clustering of exacerbations. Additionally, only 3 participants in the entire trial (2 on inebilizumab, 1 on placebo) experienced an exacerbation meeting the myasthenic crisis definition by week 26. The majority of events were driven by rescue therapy use or MG-ADL worsening rather than crisis itself.

"If we can mitigate risk of exacerbation, mitigate risk of hospitalization, mitigate risk of rescue therapy use, that's not only beneficial to the health system, but also reduces costs spent in caring for patients that aren't doing well," Nowak added.

Broad Exacerbation Definition a Key Caveat to Findings

There are several limitations to the findings. As gMG trials lack standardized definitions for rescue therapy use, limiting cross-trial comparisons, and rescue therapy administration in MINT was partially left to researchers’ discretion. The trial's exacerbation definition was also broader than myasthenic crisis or the more restrictive Myasthenia Gravis Foundation of America worsening criteria used elsewhere in the literature. As true crisis events were rare, the analysis was underpowered to assess that outcome independently, a gap the authors flag for future study.

In the MuSK+ subgroup, a history of myasthenic crisis was more common among placebo-treated participants at baseline than among those on inebilizumab. A sensitivity analysis adjusting for this imbalance produced hazard ratios consistent with the primary results, suggesting it did not drive the treatment effect. Finally, MINT used a protocol-specified steroid taper schedule that may not reflect the variability of steroid tapering in routine clinical practice.

"We do expect additional learnings in terms of efficacy, safety, and long-term durability from our open-label extension...likely available in the coming year or so," Nowak concluded.

References

1. Nowak RJ, Utsugisawa K, Benatar M, Ciafaloni E, Leite MI, Vissing J, Tang F, Wu Y, Najem C, Cheng S, Howard JF Jr; for the MINT investigators. Management of exacerbations and rescue therapy in the phase 3 myasthenia gravis inebilizumab trial: a prespecified analysis of a randomized clinical trial. JAMA Neurol. Published online August 10, 2026. doi:10.1001/jamaneurol.2026.2558
2. Nowak RJ, Benatar M, Ciafaloni E, et al; MINT Investigators. A phase 3 trial of inebilizumab in generalized myasthenia gravis. N Engl J Med. 2025;392(23):2309-2320. doi:10.1056/NEJMoa2501561
3. Shaw ML. FDA approves inebilizumab for generalized myasthenia gravis. AJMC^®. December 12, 2025. Accessed August 26, 2026. https://www.ajmc.com/view/fda-approves-inebilizumab-for-generalized-myasthenia-gravis