Sub-Analysis of CHAMPION MG Study Reveals No Differences in Ravulizumab Treatment Based on Prior Immunoglobulin Use

In a new post hoc sub-analysis of the phase 3 CHAMPION MG study (NCT03920293), findings showed no statistically significantly differences in outcomes among patients with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) who on intravenous immunoglobulin (IVIg) after starting treatment with ravulizumab (Ultomiris; AstraZeneca), an FDA-approved agent.¹

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). In this cohort, 46 of the patients had received only chronic IVIg (placebo, n = 22; ravulizumab, n = 24), and all of the groups had comparable baseline characteristics and demographics.

These findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held November 1-4, in Phoenix, Arizona, by lead author Vera Bril, MD, FRCPC, the professor of medicine/neurology and director of the neuromuscular section in the division of neurology at the University of Toronto, and colleagues. In this study analysis, the investigators assessed patients' response to ravulizumab, according to prior IVIg treatment.

READ MORE: Zilucoplan Shows Reduction in MG Worsening in Phase 3 RAISE Study for Generalized Myasthenia Gravis

In the original CHAMPION MG study, changes from baseline to week 26 in Myasthenia Gravis Activities of Daily Living (MG-ADL) were the primary end point while change in Quantitative Myasthenia Gravis (QMG) total scores acted as a secondary end point. Although IVIg treatment was only allowed as rescue therapy during the study, many patients with AChR Ab+ gMG had received IVIg before entry of the trial.

In comparison with placebo, ravulizumab-treated patients with no, any, or previous chronic IVIg use demonstrated least square (LS) mean changes of -2.1 (95% CI, -3.6 to -0.5), -1.3 (95% CI, -2.8 to -0.6), and -1.1 (95% CI -2.6 to 0.0), respectively, for MG-ADL total scores, at week 26. At the same time point, the between-group changes in QMG total scores were -2.4 (95% CI, -4.2 to -0.7), -1.6 (95% CI, -3.2 to -0.0), and -2.3 (95% CI, -4.6 to 0.1), respectively, for the same groups.

At the 9th Congress of the European Academy of Neurology, held July 1-4, in Budapest, Hungary, a post-hoc analysis from CHAMPION MG revealed that ravulizumab had a higher benefit in reducing symptom severity compared with placebo in patients gMG after 26 weeks of treatment.² Among 175 patients with gMG, 160 had score-shift data at week 26. Overall, in comparison with placebo, investigators observed a greater number of ravulizumab-treated patients who achieved improved scores in at least 7 of the 8 MG-ADL items and completed resolution.

The previous post-hoc analysis investigated changes in impairment severity for the 8 MG-ADL items. Impairment, assessed through MG-ADL, was scored between 0-3, with higher scores indicating more severe impairment. Proportions of patients who improved in MG-ADL item scores during the randomized control period were analyzed in the post-hoc analysis. Patients with an MG-ADL score of 3 in the ravulizumab-treated group were reduced from after 26 weeks in those with eyelid droop (23.1% to 14.1%) and double vision (11.5% and 10.3%). In contrast, the placebo-treated group, observed increases from baseline to week 26 for both eyelid droop (20.7% to 24.4%) and double vision (6.1% to 12.2%).

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.³ 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.

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. 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.
2. Vissing J, Mozaffar T, Mantegazza R, et al. Ravulizumab in adults with generalised myasthenia gravis: Post hoc analysis of MG-ADL item score change in CHAMPION MG. Presented at: EAN 2023. July 1-4, 2019; Budapest, Hungary. EPR-135.
3. 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.