Inebilizumab Reduces Exacerbations, Rescue Therapy use in Generalized Myasthenia Gravis

A prespecified analysis of the phase 3 Myasthenia Gravis Inebilizumab Trial (MINT) found that inebilizumab (Uplinza; Amgen) reduced the risk of exacerbations and rescue therapy (RT) use in adults with generalized myasthenia gravis (gMG) who were positive for anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibodies.¹

The analysis, published August 10, 2026, in JAMA Neurology, included 238 participants from MINT, an international, randomized, placebo-controlled phase 3 trial conducted at 81 academic and nonacademic sites across 18 countries. In the trial, participants were randomly assigned 1:1 to intravenous inebilizumab or placebo and underwent a protocol-specified corticosteroid taper to 5 mg/d or less.¹

Led by Richard Nowak, MD, MS, associate professor of neurology at Yale School of Medicine and director of the Yale Myasthenia Gravis Clinic, and colleagues, the mean age of participants was 47.5 (SD, 15.3) years, 61% (n = 144) were female, and the mean baseline Myasthenia Gravis Activities of Daily Living (MG-ADL) score was 9.1 (SD, 2.8). All told, the analysis included 188 participants with AChR-positive gMG and 48 with MuSK-positive gMG. Approximately half of participants had been hospitalized because of MG within the previous 2 years, while 31.4% had a history of RT use during that period.

Inebilizumab Effect on Exacerbation Risk

By week 26, 16% of participants treated with inebilizumab experienced an exacerbation compared with 35% of those receiving placebo. In the AChR-positive subgroup, exacerbations occurred in 16.8% and 32.3% of participants, respectively, while rates in the MuSK-positive subgroup were 12.5% and 45.8%.¹

Overall, inebilizumab treatment reduced the hazard of exacerbation by week 26 in the combined population (HR, 0.41; 95% CI, 0.24-0.70; P = .001). The treatment was also associated with a reduced hazard of exacerbation in the AChR-positive population through week 52 (HR, 0.39; 95% CI, 0.23-0.68; P < .001) and in the MuSK-positive population through week 26 (HR, 0.21; 95% CI, 0.06-0.79; P = .02).

The investigators also observed lower annualized exacerbation rates with inebilizumab. In the combined population, the annualized rate through week 26 was 0.40 with inebilizumab compared with 1.17 with placebo, corresponding to a rate difference of −0.77 (95% CI, −1.20 to −0.33). Similar trends were observed across the AChR-positive and MuSK-positive subgroups.

Lowered Rescue Therapy Use

The reduction in exacerbations was accompanied by less use of RT, which consisted of intravenous immunoglobulin (IVIG) or plasma exchange (PLEX).¹

By week 26, 8.4% of participants in the inebilizumab group received RT compared with 23.9% of those in the placebo group. Among participants with AChR-positive gMG, RT use occurred in 9.5% and 23.7% of participants, respectively. In the MuSK-positive subgroup, RT use was 4.2% with inebilizumab and 25% with placebo.

Inebilizumab reduced the hazard of RT use in the combined population through week 26 (HR, 0.34; 95% CI, 0.16-0.70; P = .003) and in the AChR-positive population through week 52 (HR, 0.30; 95% CI, 0.15-0.59; P < .001). Although the hazard of RT use was numerically lower with inebilizumab in the MuSK-positive subgroup, the difference was not statistically significant (HR, 0.17; 95% CI, 0.02-1.45; P = .11).¹

Among participants with AChR-positive gMG, the reductions remained evident through week 52. Exacerbations occurred in 20% of participants treated with inebilizumab compared with 45.2% of those receiving placebo, while RT use occurred in 11.6% and 35.5%, respectively.

Exacerbations Did Not Cluster With Steroid Taper

The MINT protocol included a corticosteroid taper beginning at week 4 for participants receiving more than 5 mg/d of corticosteroids, with a target dose of 5 mg/d or less by week 24. Most participants reached the target, including 87.4% of those receiving inebilizumab and 84.6% of those receiving placebo.¹

The investigators found few exacerbations during the initiation of the steroid taper, with events also occurring among participants whose corticosteroid dose remained unchanged or increased. Overall, the timing of exacerbations did not indicate a pattern related to the steroid taper.

The analysis defined exacerbations as RT use, myasthenic crisis, or significant symptomatic worsening. Only 3 participants experienced exacerbations involving myasthenic crisis and RT use, and no participants experienced myasthenic crisis independently of either RT use or significant symptomatic worsening. The investigators noted that additional studies may be warranted to specifically evaluate the effect of inebilizumab on myasthenic crisis.

The authors acknowledged several limitations, including the lack of standardization for RT use across gMG trials and the role of investigator discretion in determining when RT was administered. Additionally, the MINT definition of exacerbation incorporated symptomatic worsening and RT use, making it broader than definitions focused specifically on myasthenic crisis. The protocol-specified corticosteroid taper may also differ from steroid management in clinical practice.

Overall, the investigators concluded that the findings support the efficacy of inebilizumab in reducing exacerbation risk and RT use among patients with AChR- or MuSK-positive gMG, adding to evidence on the clinical effects of CD19-positive B-cell depletion in the disease.

REFERENCES
1. Nowak RJ, Utsugisawa K, Benatar M, et al. 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.