To describe a patient with refractory AChR-positive generalized MG who required multiple biologic transitions and achieved significant clinical improvement with concurrent zilucoplan and rozanolixizumab therapy.

Zilucoplan, a complement C5 inhibitor, and rozanolixizumab, an FcRn (neonatal Fc receptor) antagonist, are novel targeted agents approved for generalized myasthenia gravis (MG). Both have demonstrated efficacy in reducing disease activity through their distinct mechanisms. However, the concurrent use of these agents has not been systematically studied, and data on potential synergistic effects are lacking.

A 70-year-old female patient developed ocular myasthenia gravis in June 2023, confirmed as AChR-positive and initially responsive to prednisone and pyridostigmine. She progressed to generalized disease with bulbar involvement and respiratory failure in July 2024, requiring intubation. Despite multiple courses of IVIG and plasma exchange, she experienced recurrent relapses and was transferred to our facility. 

On initial evaluation, patient had stage V MG by MGFA criteria. She was started on eculizumab, achieving marked clinical improvement. She was later transitioned to ravulizumab with initial stability but relapsed in early 2025 despite high-dose steroids, necessitating additional plasma exchange. Zilucoplan was initiated. Due to ongoing disease activity and difficulty tapering steroids, rozanolixizumab was added.

Following initiation of zilucoplan, the patient showed gradual improvement but remained steroid-dependent with limited tolerance for tapering. Due to refractoriness, rozanolixizumab was added, which allowed successful steroid tapering, reaching minimal symptoms expression (Myasthenia Gravis Activities of Daily Living Scale=0) within 4 months, which persisted till her last evaluation in September 2025.

This case highlights the potential synergistic benefit of dual-pathway inhibition. This combination may be feasible as zilucoplan (a macrocyclic peptide) and rozanolixizumab (a monoclonal antibody) have distinct mechanisms and no known pharmacologic interaction. Further research is needed to evaluate the safety, efficacy, and immunologic rationale of concurrent use in larger controlled studies.