Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study

Abstract

Background: In the phase III eculizumab for refractory generalized myasthenia gravis REGAIN study [ClinicalTrials.gov identifier: NCT01997229] and its open-label extension (OLE) [ClinicalTrials.gov identifier: NCT02301624], patients with treatment-refractory antiacetylcholine receptor antibody-positive generalized myasthenia gravis had clinically meaningful improvements with eculizumab versus placebo. This subgroup analysis evaluated data from patients with a recent history of chronic intravenous immunoglobulin (IVIg) use before study entry.

Methods: The subgroup comprised patients who had received IVIg at least four times in 1 year, with at least one IVIg treatment cycle during the 6 months before the first REGAIN study dose. Data from REGAIN and the OLE were analyzed. Response to eculizumab versus placebo was assessed using four validated, disease-specific measures. Incidences of exacerbations and safety endpoints were recorded.

Results: The subgroup had similar patient and disease characteristics as the overall REGAIN population. Clinical assessments showed sustained eculizumab efficacy during REGAIN and the OLE over 18 months. Patients receiving placebo in REGAIN experienced rapid improvements in assessment scores when treated with eculizumab in the OLE. There was a lower rate of disease exacerbations with eculizumab than with placebo during REGAIN, and eculizumab was well tolerated.

Conclusion: Eculizumab treatment, compared with placebo, results in meaningful clinical improvements and fewer disease exacerbations for patients who previously received chronic IVIg.

Trial registration: REGAIN [ClinicalTrials.gov identifier: NCT01997229]; REGAIN open-label extension [ClinicalTrials.gov identifier: NCT02301624].

Keywords: IVIg; REGAIN; eculizumab; intravenous immunoglobulin; myasthenia gravis.

Conflict of interest statement

Conflict of interest statement: Saiju Jacob has served as a paid consultant for Alnylam Pharmaceuticals and Alexion Pharmaceuticals, and has received speaker honoraria from Bio Products Laboratory, UK, Eisai Ltd and Terumo BCT. Hiroyuki Murai has served as a paid consultant for Alexion Pharmaceuticals, argenx and Ra Pharma, and has received speaker honoraria from the Japan Blood Products Organization and research support from the Ministry of Health, Labor and Welfare, Japan. Kimiaki Utsugisawa has served as a paid consultant for Alexion Pharmaceuticals, argenx, Ra Pharma and UCB Pharma. Richard Nowak has received research support from Alexion Pharmaceuticals, Genentech, Grifols, Momenta, the Myasthenia Gravis Foundation of America, the National Institutes of Health (including the National Institute of Allergy and Infectious Diseases and the National Institute of Neurological Disorders and Stroke) and Ra Pharma, and has served as a paid consultant for Alexion Pharmaceuticals, CSL Behring, Grifols, Momenta, Ra Pharma, Roivant Sciences and Shire, a Takeda company. Heinz Wiendl received honoraria for participation in scientific advisory boards and consultation for Biogen, Evgen Pharma, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG and Sanofi-Genzyme, and speaker honoraria and travel support from Alexion Pharmaceuticals, Biogen, Cognomed, F. Hoffmann-La Roche Ltd, Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, Teva and WebMD Global. He has been a paid consultant for AbbVie, Actelion, Biogen, IGES, Novartis, Roche Pharma AG, Sanofi-Genzyme and the Swiss Multiple Sclerosis Society. His research is funded by Biogen GmbH, Deutsche Forschungsgesellschaft (DFG), Else Kröner-Fresenius Foundation, the German Federal Ministry of Education and Research (BMBF), GlaxoSmithKline GmbH, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Münster, NRW Ministry of Education and Research, RE Children’s Foundation, Roche Pharma AG and Sanofi-Genzyme. Kenji Fujita was an employee of, and owns stock in, Alexion Pharmaceuticals and is employed by Alnylam Pharmaceuticals. Fanny O’Brien is an employee of, and owns stock in, Alexion Pharmaceuticals. James Howard Jr reports research support from Alexion Pharmaceuticals, argenx, the Centers for Disease Control and Prevention (Atlanta, GA, USA), the Muscular Dystrophy Association, the National Institutes of Health (including the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of Neurological Disorders and Stroke) and Ra Pharma; he has received consulting fees from Alexion Pharmaceuticals, argenx, Ra Pharma and VielaBio; and nonfinancial support from Alexion Pharmaceuticals, argenx and Ra Pharma.

© The Author(s), 2020.

Figures

Figure 1.

Clinical response in REGAIN and the open-label extension study, versus REGAIN baseline. aA clinical response was defined as at least a 3-point improvement in MG-ADL total score or at least a 5-point improvement in QMG total score at the evaluation time point compared with REGAIN baseline. ECU, eculizumab; MG-ADL, Myasthenia Gravis Activities of Daily Living; PLC, placebo; QMG, Quantitative Myasthenia Gravis test; REGAIN, eculizumab for refractory generalized myasthenia gravis study.