BMJ neurology open · 2025
Exploring the therapeutic potential of IL-17A inhibition in myasthenia gravis: a retrospective study on secukinumab.
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Zhang Zhaoxu, Zhang Shuang Mei, Wang Anrong, Song Xiaodong, Xu Pingbo
Аннотация
OBJECTIVE: Targeting interleukin-17A (IL-17A) represents a potential therapeutic strategy for myasthenia gravis (MG), but its clinical effects and immunomodulatory mechanisms remain incompletely defined. This study investigated the multidimensional efficacy and immune kinetic profile of secukinumab (SEC) in patients with MG.
METHODS: We retrospectively enrolled acetylcholine receptor (AChR) antibody-positive (AChR-Ab+) generalised patients with MG (MG Foundation of America class IIa-IVb) treated at the Department of Neurology, Peking University People's Hospital between February 2023 and November 2024. All patients received SEC therapy (150 mg weekly for 4 weeks, followed by 150 mg every 4 weeks as maintenance for 24 weeks). Stable doses of conventional therapies (pyridostigmine, corticosteroids or immunosuppressive agents) were permitted. Longitudinal assessments were performed to evaluate changes in clinical scores (Quantitative MG (QMG) score, 15-item MG Quality of Life (MG-QOL15) scale, MG Activities of Daily Living (MG-ADL) scale), serum AChR-Ab titres, Th17/Tfh (T helper 17 cell/T follicular helper) cell frequencies and cytokine levels at multiple time points.
RESULTS: A total of 29 patients with MG completed the study and were matched with 29 healthy controls. Following SEC treatment: (a) clinical outcomes: showed that by week 24, significant reductions from baseline were observed in QMG, MG-QOL15 and MG-ADL scores (reductions of 60.7%, 58.3% and 64.1%, respectively; all p<0.01). Significant clinical efficacy emerged by week 8 (25.0% reduction in QMG, p<0.01). (b) Correlations: the reduction in AChR-Ab titres strongly correlated with improvements in clinical scores (r=0.435-0.542, p<0.05). Furthermore, the decrease in Tfh cells showed a significant association with the decline in IL-6 levels (r=0.568-0.591, p<0.001).
INTERPRETATION: In this study, SEC treatment was associated with rapid and sustained clinical improvement, as well as enhanced quality of life in patients with AChR-Ab+ MG. These benefits were correlated with modulation of the Th17/Tfh cell axis, downregulation of the IL-17A/IL-6 pathway and a reduction in autoantibody levels. These preliminary findings highlight the potential of IL-17A inhibition as a therapeutic strategy worthy of further investigation in MG.
METHODS: We retrospectively enrolled acetylcholine receptor (AChR) antibody-positive (AChR-Ab+) generalised patients with MG (MG Foundation of America class IIa-IVb) treated at the Department of Neurology, Peking University People's Hospital between February 2023 and November 2024. All patients received SEC therapy (150 mg weekly for 4 weeks, followed by 150 mg every 4 weeks as maintenance for 24 weeks). Stable doses of conventional therapies (pyridostigmine, corticosteroids or immunosuppressive agents) were permitted. Longitudinal assessments were performed to evaluate changes in clinical scores (Quantitative MG (QMG) score, 15-item MG Quality of Life (MG-QOL15) scale, MG Activities of Daily Living (MG-ADL) scale), serum AChR-Ab titres, Th17/Tfh (T helper 17 cell/T follicular helper) cell frequencies and cytokine levels at multiple time points.
RESULTS: A total of 29 patients with MG completed the study and were matched with 29 healthy controls. Following SEC treatment: (a) clinical outcomes: showed that by week 24, significant reductions from baseline were observed in QMG, MG-QOL15 and MG-ADL scores (reductions of 60.7%, 58.3% and 64.1%, respectively; all p<0.01). Significant clinical efficacy emerged by week 8 (25.0% reduction in QMG, p<0.01). (b) Correlations: the reduction in AChR-Ab titres strongly correlated with improvements in clinical scores (r=0.435-0.542, p<0.05). Furthermore, the decrease in Tfh cells showed a significant association with the decline in IL-6 levels (r=0.568-0.591, p<0.001).
INTERPRETATION: In this study, SEC treatment was associated with rapid and sustained clinical improvement, as well as enhanced quality of life in patients with AChR-Ab+ MG. These benefits were correlated with modulation of the Th17/Tfh cell axis, downregulation of the IL-17A/IL-6 pathway and a reduction in autoantibody levels. These preliminary findings highlight the potential of IL-17A inhibition as a therapeutic strategy worthy of further investigation in MG.