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.
Highlights
Chronic, broad-spectrum immunosuppressive therapy (IST) can be associated with side effects in many people with generalized myasthenia gravis, and treatment guidelines recommend that the IST dose be tapered once patients achieve a stable treatment response
During eculizumab treatment in REGAIN and its open-label extension (OLE), improvements were observed in both patient-reported activities of daily living (MG-ADL total score) and physician-evaluated neurologic function related to myasthenia gravis (MG) (QMG total score) [14, 22]
This study presents data on concomitant IST use with eculizumab in a strictly defined population of patients with refractory acetylcholine receptor (AChR)+ Generalized myasthenia gravis (gMG) who were recruited for REGAIN
Summary
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. The current guidelines for the management of MG recommend that immunosuppressive therapy (IST), including prednisone and related corticosteroids (PRED), should be used in all patients with MG who have not met treatment goals after an adequate trial of pyridostigmine [15]. 10–15% of patients with MG have refractory disease on the basis that they do not respond adequately to ISTs, they require maintenance intravenous immunoglobulin or plasma exchange treatment, or they experience intolerable adverse events associated with ISTs [15, 20, 21]
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