Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

Abstract

Objective: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension.

Methods: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.

Results: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.

Conclusion: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.

Clinicaltrialsgov identifier: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624.

Classification of evidence: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.

Figure 1. Study Design

^aDuring the blinded induction phase of the open-label study, patients received eculizumab (1,200 mg; 4 vials) on day 1 and at week 2 and placebo (4 vials) at weeks 1 and 3 (eculizumab/eculizumab group), or placebo (1 vial) plus eculizumab (900 mg; 3 vials) each week (placebo/eculizumab group). ^bPatients who withdrew from or discontinued participation in the study after receiving any amount of eculizumab were required to complete a safety follow-up visit 8 weeks after their last eculizumab dose. REGAIN = Safety and Efficacy of Eculizumab in Anti-acetylcholine Receptor-Positive Refractory Generalized Myasthenia Gravis; SOC = standard of care. Figure reproduced with permission (creativecommons.org/licenses/by-nc/4.0/) from Muppidi et al.

Figure 2. Patient Disposition in REGAIN (Safety and Efficacy of Eculizumab in Anti-acetylcholine Receptor-Positive Refractory Generalized Myasthenia Gravis) and the Open-Label Study

ECU = eculizumab; PLC = placebo. Figure reproduced with permission (creativecommons.org/licenses/by/4.0/) from Vissing et al.

Figure 3. Patients Who Achieved Myasthenia Gravis Foundation of America Post-intervention Status of Improved or Minimal Manifestations at REGAIN (Safety and Efficacy of Eculizumab in Anti-acetylcholine Receptor-Positive Refractory Generalized Myasthenia Gravis) Weeks 4, 12, and 26, and Open-Label Study Weeks 26, 52, 78, 104, and 130

^aWeeks are numbered separately for REGAIN (0–26) and the open-label study (0–130). ^bAt the time of study completion, patients had participated for different periods of time. The numbers of patients at each time point reflect this and also account for discontinuations and for patients who did not complete the assessment at the specified time point.