Achievement of Improved Post-Intervention Status in Patients with Generalized Myasthenia Gravis Treated with Ravulizumab during the CHAMPION MG Study
Srikanth Muppidi1, Pushpa Narayanaswami2, Andreas Meisel3, Tuan Vu4, Kimiaki Utsugisawa5, Renato Mantegazza6, Kathleen Beasley7, Serena Liao7, James Howard8
1Stanford University School of Medicine, 2Beth Israel Deaconess Medical Center, 3Charité Universitätsmedizin Berlin, 4University of South Florida, 5Hanamaki General Hospital, 6Fondazione IRCCS Istituto Neurologico Carlo Besta, 7Alexion, AstraZeneca Rare Disease, 8The University of North Carolina
Objective:
To determine whether ravulizumab treatment enables patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR Ab+ gMG) to achieve the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) of “improved”, with or without achieving minimal manifestation status (MMS).
Background:
The 26-week, phase 3, randomized, double-blind, placebo-controlled CHAMPION MG study demonstrated the efficacy and safety of ravulizumab in patients with AChR Ab+ gMG. Patients who completed the randomized controlled period (RCP) could receive ravulizumab in an open-label extension (OLE); blinding to original treatment was maintained.
Design/Methods:
In a prespecified exploratory analysis, modified MGFA-PIS (improved and achieved MMS, improved without MMS, unchanged, worsened) was assessed at Week 26 (patients who completed the RCP with Week 26 MGFA-PIS data) and Week 60 (patients who received ≥1 ravulizumab dose during the OLE with Week 60 MGFA-PIS data) relative to RCP baseline. A proportional-odds cumulative logit model (cumulated across categories starting from best outcome) was used to analyze outcomes at Week 26, with treatment as a fixed categorical effect and adjusting for geographic region (estimated odds ratio [OR] >1 indicates beneficial treatment effect).
Results:
At Week 26, improved status with and without MMS, respectively, was achieved by 25.6% (20/78) and 21.8% (17/78) of ravulizumab-treated patients, and by 9.9% (8/81) and 22.2% (18/81) of patients who received placebo (adjusted OR: 2.236, 95% confidence interval: 1.210, 4.130; p=0.01). At Week 60, improved status, with/without MMS, was achieved by 33.9% (19/56)/32.1% (18/56) of patients who continued ravulizumab treatment and 31.6% (18/57)/42.1% (24/57) of patients who switched from placebo to ravulizumab.
Conclusions:
Ravulizumab-treated patients were more likely than those receiving placebo to achieve MGFA-PIS of improved, with or without MMS. The increase in the proportion of patients achieving MGFA-PIS of improved, with or without MMS, with continued treatment, suggests that longer-term treatment may be needed for some patients to achieve this status.