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Clinical Trial
. 2025 Jan;71(1):43-54.
doi: 10.1002/mus.28289. Epub 2024 Nov 7.

Efficacy and safety of maintenance intravenous immunoglobulin in generalized myasthenia gravis patients with acetylcholine receptor antibodies: A multicenter, double-blind, placebo-controlled trial

Vera Bril  1 , Tomasz Berkowicz  2 , Andrzej Szczudlik  3 , Michael W Nicolle  4 , Josef Bednarik  5 , Petr Hon  6 , Antanas Vaitkus  7 , Tuan Vu  8 , Csilla Rozsa  9 , Tim Magnus  10 , Gyula Panczel  11 , Toomas Toomsoo  12 , Mamatha Pasnoor  13 , Tahseen Mozaffar  14 , Miriam Freimer  15 , Ulrike Reuner  16 , László Vécsei  17 , Nizar Souayah  18 , Todd Levine  19 , Robert M Pascuzzi  20 , Marinos C Dalakas  21   22 , Michael Rivner  23 , Rhonda Griffin  24 , Montse Querolt Coll  25 , Elsa Mondou  24
Affiliations
Clinical Trial

Efficacy and safety of maintenance intravenous immunoglobulin in generalized myasthenia gravis patients with acetylcholine receptor antibodies: A multicenter, double-blind, placebo-controlled trial

Vera Bril et al. Muscle Nerve. 2025 Jan.

Abstract

Introduction/aims: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care.

Methods: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs).

Results: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death.

Discussion: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

Keywords: autoimmune disease; intravenous immunoglobulin; myasthenia gravis; neuromuscular disease.

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Conflict of interest statement

V. Bril, T. Berkowicz, A. Szczudlik, J. Bednarik, M.W. Nicolle, P. Hon, A. Vaitkus, C. Rozsa, T. Magnus, G. Panczel, T. Toomsoo, M. Pasnoor, T. Mozaffar, M. Freimer, U. Reuner, L. Vécsei, N. Souayah, T. Levine, and R.M. Pascuzzi report no potential conflicts of interest. M. Querolt Coll, R. Griffin, and E. Mondou are employees of Grifols, which financially supported this study and manufactures human immune globulin 10%, caprylate/chromatography purified (Gamunex‐C®). T. Vu served as a site principal investigator for myasthenia gravis trials sponsored by Alexion, argenx, Ra Pharma/UCB, Horizon/Viela Bio, Janssen/Momenta, Regeneron, and Cartesian Therapeutics and as a consultant and/or speaker for UCB, Alexion, and argenx. M. Dalakas is an Associate Editor for Neurology: Neuroimmunology & Neuroinflammation, Neurodiem, and Therapeutic Advances in Neurology; is on the editorial board for Acta Myologica, Acta Neurologica Scandinavica, and Neuro‐Therapeutics; is a commentator for Clinical Practice Elsevier; serves on the CIPD DSMB for Octapharma; has consulted for Grifols, Octapharma, Dysimmune Diseases Foundation, Takeda, Alexion, and argenx; and has received institutional support for Thomas Jefferson University Neurology Department or for the Neuroimmunology Unit, University of Athens Medical School for research and education from Merck‐Serono, Novartis, Guillain–Barre/CIDP Foundation, Dysimmune Diseases Foundation, InfuCare, and Nufactor. M. Rivner has served as a consultant and received research support from Alexion, argenx, and Allergan and received research support from UCB, Momenta, Shire Takeda, Orion, Biohaven, Catalyst, Seikagaku, Viela Bio, Apellis Pharmaceuticals, MediciNova, Millennium Pharmaceuticals, Anelixis Therapeutics, and RA Pharmaceutical.

Figures

FIGURE 1
FIGURE 1
Disposition of subjects in a multicenter, randomized, double‐blind, placebo‐controlled study of the efficacy and safety of intravenous immunoglobulin (10%, caprylate/chromatography‐purified; IGIV‐C) in patients with symptomatic myasthenia gravis. ITT, intent to treat; mITT, modified intent to treat; PP, per protocol.
FIGURE 2
FIGURE 2
(A) Percentage of patients showing improvement in Quantitative Myasthenia Gravis (QMG) score in patients treated with caprylate/chromatography‐purified IVIG (IGIV‐C) or placebo (LOCF). Improvement was defined as at least a three‐point decrease in QMG total score. For IGIV‐C, n = 30 patients, and for placebo, n = 32 patients.*p < .05 (p = .029 at week 9 and p = .005 at week 21). (B) Change from baseline in Quantitative Myasthenia Gravis (QMG) score in patients treated with caprylate/chromatography‐purified IVIG (IGIV‐C) or placebo. For IGIV‐C, n = 30 patients, and for placebo, n = 32 patients. Data shown are mean ± standard deviation. Treatment group comparisons showed significant differences between the groups at week 9 and week 21 (p < .05: p = .023 at week 9 and p = .025 at week 21).
FIGURE 3
FIGURE 3
(A) Percentage of patients showing improvement in myasthenia gravis (MG) composite score in patients treated with caprylate/chromatography‐purified IVIG (IGIV‐C) or placebo (LOCF). Improvement was defined as at least a three‐point decrease in MG Composite score. For IGIV‐C, n = 30 patients, and for placebo, n = 32 patients. (B) Change from baseline in Myasthenia Gravis (MG) Composite score in patients treated with caprylate/chromatography‐purified IVIG (IGIV‐C) or placebo. For IGIV‐C, n = 30 patients, and for placebo, n = 32 patients. Data shown are mean ± standard deviation. Treatment group comparisons showed a significant difference only at week 9 (p = .042).
FIGURE 4
FIGURE 4
Change from baseline in Quantitative Myasthenia Gravis (QMG) score in patients treated with caprylate/chromatography‐purified IVIG (IGIV‐C) or placebo (LOCF). For this analysis, patients were analyzed as a priori stratified by baseline treatment regimen: cholinesterase inhibitor (ChEI) only, corticosteroid (CS) as the only immunosuppressant/immunomodulator (I/I), or non‐CS I/I. For the ChEI‐only subgroup: IGIV‐C n = 8 and placebo n = 10; for the CS‐only I/I subgroup: IGIV‐C n = 6 and placebo n = 4; and for the non‐CS I/I subgroup: IGIV‐C n = 16 and placebo n = 18.
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References

    1. Gamunex‐C [Immune Globulin Injection (Human) 10% Caprylate/Chromatography Purified]‐Package Insert. Grifols Therapeutics LLC. 2020. https://www.gamunex‐c.com/documents/27482625/27482925/Gamunex‐C+Prescrib.... Accessed 22 March 2024.
    1. Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011;76(23):2017‐2023. - PMC - PubMed
    1. Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis. Neurology. 2007;68(11):837‐841. - PubMed
    1. Gajdos P, Tranchant C, Clair B, et al. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double‐blind clinical trial. Arch Neurol. 2005;62(11):1689‐1693. - PubMed
    1. Karelis G, Balasa R, De Bleecker JL, et al. A phase 3 multicenter, prospective, open‐label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations. Eur Neurol. 2019;81(5–6):223‐230. - PubMed

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