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Secukinumab versus conventional immunotherapy in myasthenia gravis: A single-Center 24-week retrospective comparative
Shuangmei Zhang1, Anrong Wang2, Xiaodong Song3
1Department of Pain Rehabilitation, Zhejiang Cancer Hospital, Hangzhou 310022, China.
Background:
Myasthenia gravis (MG) management remains challenged by the delayed onset of conventional immunosuppressants. While B-cell and complement pathways are established therapeutic targets, the role of IL-17 A in human MG is underexplored, and its potential as a target represents a novel therapeutic avenue.
Objectives:
This study aimed to evaluate, for the first time in a clinical setting, the efficacy and safety of the anti-IL-17 A monoclonal antibody secukinumab compared to conventional immunotherapy in patients with acetylcholine receptor-positive generalized MG (AChR+ gMG).
Methods:
In this single-center, retrospective cohort study, 35 patients received subcutaneous secukinumab (150 mg/week for 4 weeks, then monthly) plus standard care, while 32 matched controls received conventional immunosuppressants alone. Outcomes included clinical scores (QMG, MG-ADL, MG-QOL15), AChR antibody (AChR-Ab) titers, and immunologic parameters (Th17/Tfh cells, cytokines) assessed at baseline, week 4, 12, and 24.
Results:
Secukinumab demonstrated significantly superior and rapid efficacy. By week 24, improvement rates in QMG, MG-ADL, and MG-QOL15 scores were significantly greater with secukinumab (44.7%, 45.7%, 46.7%) than controls (27.5%, 25.8%, 32.0%; all p < 0.01). AChR-Ab levels decreased rapidly by 61.1% as early as week 4, achieving a 68.9% reduction at week 24, significantly surpassing the control group's response (21.6%). Immunologically, secukinumab induced rapid and profound suppression of IL-17 A (-84.1% at week 4), Th17 cells (-68.3%), and Tfh cells (-71.7%) over 24 weeks, effects strongly correlated with each other and with AChR-Ab decline. Reductions in key cytokines (IL-6, IL-21) were also more pronounced.
Conclusion:
This first clinical investigation of IL-17 A inhibition in AChR+ gMG demonstrates that secukinumab provides rapid, superior clinical and serological efficacy alongside broad immunomodulation, targeting the Th17/Tfh-B cell axis.Further prospective studies are needed to validate these results.
