Concomitant Corticosteroid Use Decreased in Myasthenia Gravis Through Ravulizumab
Long-term use of ravulizumab in patients with generalized myasthenia gravis led to a significant reduction in corticosteroid dependence, highlighting its potential steroid-sparing benefits.
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
Led by senior investigator
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
In a similar
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.
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.
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