Steroid-Sparing Effect of Efgartigimod in Generalized Myasthenia Gravis: Study Protocol for a Single-Arm, Open-Label Clinical Trial.

introductionOral corticosteroids remain a cornerstone of therapy for generalized myasthenia gravis (gMG) but are associated with substantial long-term toxicity. Efgartigimod, a human immunoglobulin G1 (IgG1) antibody Fc fragment targeting the neonatal Fc receptor (FcRn), has demonstrated efficacy in gMG; however, no prospective trial has evaluated whether regularly scheduled efgartigimod administration can safely reduce oral prednisolone (PSL) dosage. We designed a prospective clinical study to evaluate the steroid-sparing effect of efgartigimod in patients with gMG who remain dependent on ≥ 6 mg/day of oral PSL.

methodsThis is a single-arm, open-label, single-center clinical study. Patients with gMG who are receiving ≥ 6 mg/day of oral PSL on a stable dose for at least 4 weeks prior to enrollment, with any concomitant oral immunosuppressants also at stable doses for at least 4 weeks, and scoring ≥ 5 on the MG Activities of Daily Living (MG-ADL) scale will be enrolled. Efgartigimod will be intravenously administered at 10 mg/kg once weekly for 4 consecutive weeks (one cycle), repeated for four cycles with a 28-day interval between cycles. On the fourth administration day of each cycle, oral PSL will be tapered if MG symptoms have not worsened, defined as no ≥ 1-point increase in the MG-ADL score from both baseline and the first administration day of that cycle. PLANNED OUTCOMES: The primary endpoint is the change in PSL dosage from baseline at the end of the study. Secondary endpoints include the proportion of patients achieving minimal manifestations (MM) or better status with PSL ≤ 5 mg/day (MM-5 mg), the time to reach ≤ 5 mg/day, the cumulative PSL dose over the study period, the proportion of patients completing the protocol, changes in MG-ADL and other clinical scales, responder rate to efgartigimod, comparison of clinical course between MG subtypes (anti-acetylcholine receptor (AChR) antibody-positive, anti-muscle-specific kinase (MuSK) antibody-positive, and double-seronegative cases) and between patients who are anti-AChR antibody positive, with and without thymoma, changes in indicators of steroid toxicity (HbA1c, lumbar spine bone mineral density, and blood pressure), and the safety profile. The study will also explore biomarkers predictive of efgartigimod response through proteomic and immunologic analyses of serially collected blood samples.  Graphical abstract available for this article. 

trial registrationJapan Registry of Clinical Trials (jRCT), CRB3180028; registered on 1 October 2024 (prospectively registered).