Concomitant Corticosteroid Use Decreased in Myasthenia Gravis Through Ravulizumab

James F. Howard, MD

In a new analysis of the open-label extension (OLE) of the phase 3 CHAMPION-MG study (NCT03920293), investigators observed that patients with myasthenia gravis (MG) treated with ravulizumab (Ultomiris; AstraZeneca) experienced decrease concomitant corticosteroid (CS) use over the long-term treatment period. Overall, these data suggest a steroid-sparing role for ravulizumab in acetylcholine receptor antibody-positive (AChR+) gMG.¹

In the OLE, patients with AChR+ gMG received intravenous ravulizumab for up to 4 years, with CS use assessed at each study visit. Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, data were available for 161 patients who entered the OLE and received ravulizumab for up to 164 weeks. During the OLE, 113 of these patients were on oral/enteral CS, with 112 receiving CS from the OLE start.

Led by senior investigator James F. Howard, MD, Distinguished Professor of Neuromuscular Disease and professor of neurology and medicine at The University of North Carolina at Chapel Hill School of Medicine, a total of 14 patients (12%) completed discontinued CS by the last visit. Throughout the OLE, the percentage of patients treated with at least 10 mg/day CS decrease from 58% (n = 66) at first OLE dose to 37% (n = 42) at last reported dose. At the last visit, 35 patients (31%) were receiving 5 mg/day or less and 71 (63%) were receiving less than 10 mg/day.

Overall, the mean CS dosage/patient decreased from 17.5 (SD, 11.9) mg/day at first OLE dose to 11.7 (SD, 10.9) mg/day at last assessment. Ravulizumab, a complement C5 inhibitor, was first approved as a treatment for patients with gMG in 2022 based on data from CHAMPION-MG, and later had its indication expanded to include patients with neuromyelitis optica spectrum disorder (NMOSD) in 2024. It is also approved in the US as a treatment for adults and children 1 month and older with paroxysmal nocturnal hemoglobinuria.

CHAMPION-MG, a double-blind study, had results originally published in the New England Journal of Medicine in 2022. In the original trial, patients on ravulizumab received body weight-based doses of 2400 to 3000 mg induction on day 1, then 3000 to 3600 mg every 8 weeks on day 15. Overall, the trial met its primary end point, with statistically significant changes observed on Myasthenia Gravis Activities of Daily Living (MG-ADL) total score relative to placebo (–3.1 vs –1.4; P <.001).²
Ravulizumab also demonstrated statistically significant differences vs placebo on Quantitative Myasthenia Gravis (QMG), a secondary end point (P <.001). All told, the least squares estimate of the mean QMG change was –2.8 (95% CI, –3.7 to –1.9) in the ravulizumab group and –0.8 (95% CI, –1.7 to 0.1) in the placebo group (P <.001). QMG total scores improved by 5 points or more in a significantly greater proportion of ravulizumab-treated patients than of those receiving placebo (30.0% vs 11.3%; P = .005).

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Since its approval in MG, there have been several post hoc sub-study analyses of CHAMPION-MG. In a prior analysis presented at AANEM 2023, results showed that ravulizumab was effective regardless of whether patients were on prior immunoglobulin use. Among 175 patients with AChR Ab+ gMG enrolled in the study, 79 had no previous IVIg use (placebo, n =38; ravulizumab, n = 41) and 96 had received either acute or chronic IVIg (placebo, n = 51; ravulizumab, n = 45).³

In a similar post-hoc analysis of CHAMPION MG, presented at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 19-22, in Dallas, Texas, findings showed that treatment with ravulizumab significantly improves ocular and respiratory muscle domains. This analysis aimed to calculate least-square mean changes in MG-ADL, the primary end point, and QMG total scores, in 4 separate muscle domains (ocular, bulbar, limb, and respiratory) as a percentage of the respective maximum domain scores.⁴

Among 175 enrolled individuals with MG, LS mean MG-ADL score changes at week 26, expressed as a percentage of the maximum domain score, showed greater improvements for ravulizumab versus placebo in ocular (-14.6% vs -3.2%; P = .0028) and respiratory domains (-10.3% vs -4.2%; P = .0484). Outcomes on bulbar (-12.7% vs 8.0%; P = .0603) were also similar, and favored ravulizumab. Ravulizumab-treated patients continued to outperform placebo on QMG in specific domains such as ocular (-13.0% vs -3.1%; P = .0020) and limb (-5.9% vs -1.5%; P = .0134). Notably, investigators found no between-group differences in bulbar (-8.6% vs -5.3%; P = .2171) and respiratory (+6.2% vs +3.0%; P = .3415) domains.

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REFERENCES
1. Nicolle M, Annane D, Meisel A, et al. Concomitant corticosteroid use with ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: phase 3 CHAMPION-MG open-label extension final results. Presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; October 15-18, 2024; Savannah, GA. ABSTRACT 236.
2. Vu T, Meisel A, Mantegazza R, et al. Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. NEJM Evidence. Published online April 26, 2022. doi:10.1056/EVIDoa21000066
3. Bril V, Shin JH, Silvestri N, et al. Ravulizumab in Adults with Generalized Myasthenia Gravis: A Sub-Analysis of the Phase 3 CHAMPION Myasthenia Gravis Study According to Chronic Intravenous Immunoglobulin Use at Study Entry. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; November 1-4, 2023; Phoenix, AZ. Abstract 174.
4. Mozaffar T, Mantegazza R, Attarian S, et al. Ravulizumab in adults with generalized myasthenia gravis: a post-hoc analysis of the phase 3 CHAMPION-MG study by muscle domain. Presented at: MDA 2023; March 19-22; Dallas, TX. Abstract 137.