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. 2025 May 30:18:17562864251332037.
doi: 10.1177/17562864251332037. eCollection 2025.

Complement inhibitor therapy as a steroid-sparing strategy in generalized myasthenia gravis

Sofia Marini  1 , Silvia Falso  1 , Federico Habetswallner  1 , Martina Marini  1 , Raffaele Iorio  2   3
Affiliations

Complement inhibitor therapy as a steroid-sparing strategy in generalized myasthenia gravis

Sofia Marini et al. Ther Adv Neurol Disord. .

Abstract

Background: Standard management of generalized myasthenia gravis associated with anti-acetylcholine receptor autoantibodies (AChR-gMG) includes corticosteroids and nonsteroidal immunosuppressants. Complement inhibitors (CI) represent a more tailored therapeutic strategy. Real-world data on the steroid-sparing efficacy of CI remain limited.

Objective: To investigate the steroid-sparing efficacy of CI in AChR-gMG.

Design: We identified 69 AChR-gMG patients on corticosteroids treated with azathioprine (AZA), mycophenolate mofetil (MMF), or CI.

Methods: Steroid tapering was assessed by comparing corticosteroid dosage at several time-points to baseline.

Results: Steroids reductions were statistically significant for all therapies at every time point compared to baseline (all p < 0.001). Pairwise comparisons using the Mann-Whitney U test revealed significant differences between CI and MMF at 3 months (p = 0.0372), 6 months (p = 0.0193), and 9 months (p = 0.0321) and between CI and AZA at 6 months (p = 0.0415).

Conclusion: CI rapidly and effectively reduced corticosteroid dosage in most AChR-gMG patients, suggesting their potential role as steroid-sparing therapeutic options.

Keywords: acetylcholine receptor antibodies; complement inhibitors; corticosteroids; myasthenia gravis; steroid-sparing agents.

Plain language summary

Using complement inhibitor therapy to reduce steroid doses in patients with generalized myasthenia gravis This study evaluated the effectiveness of complement inhibitor therapy in reducing steroid use in patients with generalized myasthenia gravis (gMG), an autoimmune disease associated with autoantibodies targeting the neuromuscular junction, leading to muscle weakness and fatigability. Standard treatment for gMG involves corticosteroids and non-steroidal immunosuppressants such as azathioprine and mycophenolate mofetil. However, long-term steroid use can lead to significant systemic adverse effects. Recently approved targeted therapies, including complement inhibitors such as eculizumab and ravulizumab, offer a promising approach by inhibiting the complement C5 protein. However, there is limited real-world data on their ability to reduce steroid use. In this study, we enrolled 69 gMG patients who were receiving steroids at baseline, in addition to either azathioprine, mycophenolate mofetil, or complement inhibitors. We assessed changes in steroid dosage at different time points. Our results showed a significant reduction in steroid use across all treatment groups. Notably, patients treated with complement inhibitors experienced a more significant reduction in steroid dosage at earlier time points, compared to those receiving azathioprine or mycophenolate mofetil. These findings suggest that complement inhibitors may be effective in reducing steroid use in gMG patients, making them a promising treatment option for minimizing steroid doses and their associated side effects.

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Conflict of interest statement

R.I. has received consultancy fees and speaker honoraria from Alexion, Argenx, UCB, and Dianthus Therapeutics. Other authors declare no potential conflict of interest.

Figures

Figure 1.
Figure 1.
(a) MGFA classification distribution by therapy group. (b) Comparison of steroid dose categories across therapy groups at baseline and at 6 months. (c) Density plots showing the distribution of steroid doses for patients receiving AZA, MMF, or CI at baseline, 3, 6, 9, and 12 months. CI therapy shows a marked shift toward lower steroid doses over time compared to MMF and AZA. Density reflects the probability distribution of doses in each group. (d) The colored lines represent the mean steroid reduction at each follow-up time point for each therapy group. The shaded bands around each line indicates the interquartile range (25th–75th percentile), illustrating the central spread of values. Different colors distinguish the therapy groups (CI in blue, AZA in green, MMF in red). AZA, azathioprine; CI, complement inhibitor; MGFA, Maximum Myasthenia Gravis Foundation of America; MMF, mycophenolate mofetil.
See this image and copyright information in PMC

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