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. 2024 Sep;271(9):6114-6126.
doi: 10.1007/s00415-024-12569-w. Epub 2024 Jul 25.

United States clinical practice experience with eculizumab in myasthenia gravis: symptoms, function, and immunosuppressant therapy use

Ali A Habib  1 , Andrew J Klink  2 , Srikanth Muppidi  3 , Anju Parthan  4   5 , S Chloe Sader  4 , Alexandrina Balanean  2 , Ajeet Gajra  2   6 , Richard J Nowak  7 , James F Howard Jr  8 ; ELEVATE Study Group
Affiliations

United States clinical practice experience with eculizumab in myasthenia gravis: symptoms, function, and immunosuppressant therapy use

Ali A Habib et al. J Neurol. 2024 Sep.

Abstract

Background/objectives: The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States.

Methods: A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use.

Results: In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p < 0.001). At 24 months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24 months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy.

Discussion: Eculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24 months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab.

Keywords: Activities of daily living; C5; Chart review; Clinical practice; Complement inhibition; Corticosteroid; Eculizumab; Immunosuppression; Myasthenia gravis.

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Conflict of interest statement

Ali A. Habib has served as a medical advisor and speaker on behalf of Alexion, AstraZeneca Rare Disease, and argenx; he has received research support from Alexion, AstraZeneca Rare Disease, and Cabaletta Bio; and has received research support and honoraria from argenx, UCB, Pfizer, Genentech, Viela Bio/Horizon, Sanofi, Immunovant Inc., and Regeneron. Andrew J. Klink is a salaried employee of and owns stock in Cardinal Health, which received funding from Alexion, AstraZeneca Rare Disease for work performed on this study. Srikanth Muppidi has served on advisory board meetings for Alexion, AstraZeneca Rare Disease, argenx, Horizon Therapeutics, and Ra Pharmaceuticals (now UCB). Anju Parthan was an employee of Alexion, AstraZeneca Rare Disease and owned stock in AstraZeneca at the time the study was conducted and analyzed. S. Chloe Sader is an employee of Alexion, AstraZeneca Rare Disease and owns stock in AstraZeneca. Alexandrina Balanean is a salaried employee of Cardinal Health, which received funding from Alexion, AstraZeneca Rare Disease for work performed on this study. Ajeet Gajra was a salaried employee of and owned stock in Cardinal Health (which received funding from Alexion, AstraZeneca Rare Disease for work performed on this study) at the time the study was conducted. Richard J. Nowak has received research support from Alexion, AstraZeneca Rare Disease, argenx, Genentech, Grifols, Immunovant, Inc., Momenta Pharmaceuticals, the Myasthenia Gravis Foundation of America, the National Institutes of Health (National Institute of Neurological Disorders and Stroke and National Institute of Allergy and Infectious Diseases), Ra Pharmaceuticals (now UCB), and Viela Bio Inc. (now Horizon Therapeutics); and consultancy fees from Alexion, AstraZeneca Rare Disease, argenx, Cour Pharmaceuticals, Grifols, Immunovant, Inc., Momenta Pharmaceuticals, Ra Pharmaceuticals (now UCB), Roivant Sciences, and Viela Bio (now Horizon Therapeutics). James F. Howard Jr. has received research support (paid to institution) from Ad Scientiam, Alexion, AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, the Centers for Disease Control and Prevention (Atlanta, GA, USA), the Myasthenia Gravis Foundation of America, the Muscular Dystrophy Association, the National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), NMD Pharma, PCORI, and UCB Pharma; honoraria from Alexion AstraZeneca Rare Disease, argenx, Biohaven Ltd, Biologix Pharma, CheckRare CME, F. Hoffman-LaRoche, Horizon Therapeutics (now Amgen), Medscape CME, Merck EMD Serono, NMD Pharma, Novartis Pharma, PeerView CME, Physicians’ Education Resource (PER) CME, PlatformQ CME, Regeneron Pharmaceuticals, Sanofi US, UCB Pharma, and Zai Labs; and non-financial support from Alexion, AstraZeneca Rare Disease, argenx, Toleranzia AB, UCB Pharma, and Zai Labs.

Figures

Fig. 1
Fig. 1
Eculizumab use: a reasons for initiating eculizumaba (n = 119); b duration of eculizumab treatment at data cut-offb (n = 119). aCategories not mutually exclusive. bOf patients who were alive at the time of data cut-off (n = 109), 88% were receiving eculizumab. cProviders were allowed to specify other reasons, which included patients with an impending crisis. MG myasthenia gravis
Fig. 2
Fig. 2
Mean (±SD) MG-ADL total scores over time in a patients who received eculizumab per the prescribing information in the United States, and b the subset of patients with prednisone dosage reduction and ≥12 months of follow-upa. aStatistical analysis not conducted. bLower scores indicate less severe symptoms. * p < 0.001 versus mean MG-ADL scores before eculizumab initiation (paired t test). MG-ADL Myasthenia Gravis–Activities of Daily Living, SD standard deviation
Fig. 3
Fig. 3
a Minimal symptom expressiona over time in patients in the study population who received eculizumab per the prescribing information; b physicians’ impression of change in patients’ disease; and c minimal manifestation status or betterb before and during eculizumab treatment. aMG-ADL score of 0 or 1. bMinimal manifestation status is based on the percentage of the total patient population with available data; minimal manifestation status was defined as having MG improvement and no symptoms or functional limitations from MG, but some weakness on examination of some muscles. MG-ADL Myasthenia Gravis–Activities of Daily Living, N/A not applicable (includes patients who were no longer receiving eculizumab or did not have data)
Fig. 4
Fig. 4
Concomitant therapies: a use of concomitant therapiesa at eculizumab initiation (n = 119); b prednisone dosage at eculizumab initiation (n = 69); c proportion of patients with changes in prednisone dosage during eculizumab treatment (n = 69); d median (interquartile range) time to change in prednisone dosage during eculizumab treatmentb (n = 69). Cited values may not sum to 100% because of rounding. aPatients may have been receiving more than one concomitant therapy. bTime to discontinuation may be impacted by prednisone dosage—higher dosages may have required more gradual tapering. IVIg intravenous immunoglobulin, PLEX plasma exchange, NSIST nonsteroidal immunosuppressant therapy
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