Dual targeting complement C5 and BAFF/APRIL in highly active myasthenia gravis: A prospective case series
Yibin Zhang, Dingxian He, Lei Jin, Lu Qi, Hong Jin, Huahua Zhong, Jialin Chen, Jianing Ou, Jie Song, Chong Yan, Jianying Xi, Chongbo Zhao, Zhiguo Lv, Sushan LuoBackground
Highly active Generalised myasthenia gravis (gMG) represents a group of patients with substantial disability and recurrent, life-threatening exacerbations. The recent emergence of targeted biologics has created new therapeutic opportunities, yet the potential of dual targeting complement C5 and B-cell signaling, such as B cell activating factor (BAFF)/proliferation-inducing ligand (APRIL), has not been thoroughly explored in these patients.
Objectives
To explore the efficacy and safety of combined therapies with eculizumab (C5 complement inhibitor) and telitacicept (BAFF/APRIL inhibitor) in acetylcholine receptor antibody (AChR-ab)+ gMG patients who had high disease activity.
Design
Single-centre, prospective, observational case series.
Methods
Patients with highly active gMG despite advanced immunotherapies were enrolled in a neuromuscular reference centre for treatment with eculizumab and telitacicept. The primary endpoint was the change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Minimal Symptom Expression (MSE), Clinically Meaningful Improvement (CMI), oral corticosteroid dose, serum IgG, and the incidence of treatment-emergent adverse events (TEAEs) were assessed.
Results
Among the 22 patients ultimately enrolled, 16 (72.7%) had a history of myasthenic crisis (MC). Previously administered immunomodulatory therapies included intravenous immunoglobulin (IVIG) (16/22, 72.7%), efgartigimod (14/22, 63.6%), and plasma exchange (PE) (13/22, 59.1%). At Week 12 after initiation of eculizumab and telitacicept, significant improvements were observed: the MG-ADL score decreased substantially from a baseline value of 8.0 (IQR 5.0–10.0) to 1.0 (IQR 0.0–2.8) (p < 0.001), with all participants achieving CMI and 54.5% (12/22, 95% CI 32.2–75.6) achieving MSE. Concurrently, the daily oral prednisone dose was significantly reduced by 33% (from 22.5 mg to 15.0 mg; p < 0.001), and serum IgG levels declined markedly from 11.86 g/L to 7.14 g/L (p < 0.001). Notably, no meningococcal infections or other serious adverse events were reported.
Conclusion
In highly active AChR-ab+ gMG requiring rapid disease control, simultaneous targeting of complement C5 and B cell activating pathway achieved clinical improvement, corticosteroid sparing, and reduced serum IgG, with an acceptable short-term safety profile. These proof-of-concept findings require confirmation in controlled trials with a mono-targeting therapy regimen and longer follow-up.