Concomitant Immunosuppressive Therapy Use in Eculizumab-Treated Adults With Generalized Myasthenia Gravis During the REGAIN Open-Label Extension Study

Abstract

Introduction: Chronic, broad-spectrum immunosuppressive therapy (IST) can be associated with side effects in many people with generalized myasthenia gravis (gMG), and treatment guidelines recommend that the IST dose be tapered once patients achieve a stable treatment response. We therefore examined IST use in eculizumab-treated patients with refractory gMG. Methods: The REGAIN open-label extension (OLE) enrolled 117 adults with refractory anti-acetylcholine receptor antibody-positive gMG who had completed the 6-month, randomized, double-blind, placebo-controlled REGAIN study of eculizumab. Eligible patients had received ≥2 ISTs for ≥1 year or ≥1 IST with intravenous immunoglobulin or plasma exchange ≥4 times in 1 year, without symptom control. During REGAIN, changes in concomitant MG therapies were not permitted; during the OLE, they were permitted at the investigators' discretion. Participants received eculizumab 1,200 mg every 2 weeks for up to 4 years; concomitant prednisone and related corticosteroids (PRED), azathioprine (AZA), and mycophenolate mofetil (MMF) use was recorded. Changes in MG Activities of Daily Living and Quantitative MG total scores, MG exacerbations, and adverse events were also recorded. Results: At last OLE assessment, 88.0% (103/117) of participants were using ≥1 IST vs. 98.3% (115/117) at OLE baseline. During the OLE, 76.9% (90/117) of patients experienced a total of 719 IST changes. Almost half of participants [48.7% (57/117)] stopped or decreased ≥1 IST owing to MG symptom improvement, representing 38.9% (280/719) of all changes. In patients who decreased and/or stopped ≥1 IST, mean daily doses of PRED, AZA, and MMF decreased between OLE baseline and last assessment by 60.8% [standard deviation (SD), 28.07; P < 0.0001], 89.1% (SD, 25.77; P < 0.0001), and 56.0% (SD, 32.99; P < 0.0001), respectively. Improved clinical outcomes were observed with eculizumab regardless of IST changes during the OLE, and eculizumab's safety profile was similar in patients who used PRED, AZA, and MMF. Conclusions: Use of ISTs by patients with previously refractory gMG decreased during eculizumab treatment in the REGAIN OLE. Clinical improvements with eculizumab were maintained by patients in all groups, including those who decreased and/or stopped concomitant ISTs. Trial registration: www.clinicaltrials.gov: NCT01997229, NCT02301624.

Keywords: acetylcholine receptor; eculizumab; immunosuppressive therapy; myasthenia gravis; refractory.

Copyright © 2020 Nowak, Muppidi, Beydoun, O'Brien, Yountz, Howard and for the REGAIN study group.

Figures

Figure 1

Overall changes to immunosuppressive therapy (IST) at any time during the open-label extension (OLE) in patients using prednisone and related corticosteroids (PRED), azathioprine (AZA), or mycophenolate mofetil (MMF). During the OLE, 94 patients used PRED (90 patients at OLE baseline), 39 patients used AZA (39 patients at OLE baseline), and 34 patients used MMF (30 patients at OLE baseline). aIncreases/decreases were calculated from the starting dose and the dose at the last assessment.

Figure 2

Immunosuppressive therapy (IST) doses at open-label extension (OLE) baseline and last assessment in patients using (A) prednisone and related corticosteroids (PRED; n = 90), (B) azathioprine (AZA; n = 39), or (C) mycophenolate mofetil (MMF; n = 30) at OLE baseline. A total of 90 patients were using PRED at OLE baseline, 39 were using AZA, and 30 were using MMF. The distribution of IST doses at OLE baseline and last assessment, mean and median daily doses at OLE baseline and last assessment, and mean and median dose reductions from OLE baseline to last assessment are shown for these patients. P-values for mean percentage changes were calculated using the one-sample t-test; P-values for median percentage changes were calculated using the Wilcoxon signed-rank test. SD, standard deviation.