Introduction: Ravulizumab, a monoclonal antibody targeting C5, was recently approved for the treatment of anti-AChR positive generalized myasthenia gravis (gMG) patients. The objective of this study is to present the Italian multicenter real-world experience evaluating the safety and efficacy of ravulizumab in gMG within the context of the Expanded Early Access Program (EAP). Methods: We conducted a retrospective study in 7 gMG referral centres in Italy. Demographic and clinical characteristics were recorded at baseline and during follow-up through clinical scale changes including Myasthenia Gravis-Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Composite (MGC). Frequency of minimal symptom expression (MSE) and changes in concomitant medications were also evaluated. Results: Twenty-four gMG patients (10/24 females) aged between 24 and 82 years (Median 60.5, IQR 52.5–67.5), were included. Fifteen patients had undergone thymectomy, and 14 had a thymoma. Median follow-up duration was 26 weeks (range 10–74, IQR 26–42). MG-ADL and QMG scores showed a significant decrease with respect to baseline (p < 0.001). MSE was achieved by 37.5% patients at the last available follow-up. Tapering of prednisone daily dosage was possible in 76% of patients. Thymoma was significantly associated with QMG score reduction and the frequency of QMG responders at week 2 (p = 0.03). Three patients discontinued treatment. One patient experienced a myasthenic exacerbation and needed rescue therapy. Infectious adverse events were reported in 5/24 patients, and a Stevens-Johnson syndrome in one patient. Conclusions: Real-world data confirm the effectiveness, safety, and prednisone-sparing effect of ravulizumab in patients with gMG, especially in those with thymoma.

We report the case of a 32-year-old woman with an 11-year history of thymomatous AChR antibody-positive generalized myasthenia gravis (gMG, MGFA IIIb) who experienced a myasthenic crisis (MC) during the postpartum period, requiring mechanical ventilation (MV). Initial treatment with therapeutic plasma exchange (TPE) and high-dose prednisone was ineffective, and pyridostigmine worsened airway secretions. Due to contraindications for IVIg, she was treated with the complement inhibitor eculizumab, following prophylactic meningococcal vaccination and antibiotic therapy. Six days after starting eculizumab, the patient showed marked improvement in muscle strength, respiratory function, and was successfully extubated. She was discharged from the intensive care unit (ICU) and continued bi-weekly Eculizumab infusions without adverse events. A systematic literature review identified 19 additional cases of MC treated with eculizumab, examining response timing, treatment efficacy, adverse events, and follow-up data. This case, along with the literature review, supports the possibility of using anti-complement therapy in patients unresponsive to conventional therapies in MC setting.

Background: Generalized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies. Objective: This review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes. Methods: A narrative review was conducted, integrating recent findings from clinical trials, immunogenetic studies, and preclinical research to describe subtype-specific immune mechanisms and corresponding therapeutic innovations. Results: gMG subtypes—characterized by autoantibody profiles (AChR, MuSK, LRP4, or seronegative), thymic histopathology, and age of onset—demonstrate distinct immunological pathways. Early-onset MG is associated with thymic hyperplasia and Th17-driven inflammation; thymoma-associated MG involves central tolerance breakdown; late-onset MG shows immune senescence and altered T-cell regulation. MuSK- and LRP4-positive MG exhibit unique cytokine and antibody signatures. Novel therapeutic strategies include B cell- and T cell-targeted therapies (e.g., anti-CD19, anti-CD38, JAK inhibitors), cytokine inhibitors (IL-6, IL-17, IL-23), FcRn antagonists, complement inhibitors, and gene- or cell-based therapies such as CAR-T and CAAR-T cells. Conclusion: The evolving landscape of gMG treatment reflects a shift toward immunopathology-based precision medicine. Better characterization of subtype-specific molecular signatures and immune dysfunctions is essential to guide clinical decision-making and improve outcomes for treatment-refractory patients.