Maintenance of Minimal Manifestation Status with Individualized-Interval Efgartigimod in Generalized Myasthenia Gravis: Study Protocol for a Single-Arm, Open-Label Clinical Trial

Efgartigimod, a human immunoglobulin G1 Fc fragment targeting the neonatal Fc receptor, improves symptoms in generalized myasthenia gravis (gMG). It remains unknown whether minimal manifestation (MM) status achieved with efgartigimod can be durably maintained over the long term, and whether subcutaneous (SC) self-administration reduces treatment burden and supports quality of life. We designed a prospective study to evaluate maintenance of MM with low-dose oral prednisolone (PSL) ≤ 5 mg/day (MM-5 mg) under interval-adjusted efgartigimod administration. This single-arm, open-label, single-center exploratory study will enroll 24 adults of either sex (aged 18 to < 80 years) with gMG who have achieved MM, defined as a Myasthenia Gravis Activities of Daily Living (MG-ADL) score ≤ 2 or MG Composite score ≤ 4, on efgartigimod with oral PSL ≤ 5 mg/day (commonly with a concomitant calcineurin inhibitor), in a preceding trial or routine care. Efgartigimod (intravenous efgartigimod alfa or SC efgartigimod alfa/vorhyaluronidase alfa) is given once weekly for 4 weeks per cycle. The intercycle interval is individualized from the worst weekly MG-ADL score: shortened by 1 week upon worsening, extended by 1 week after two stable cycles. PSL and permitted background oral immunosuppressants are held constant. Treatment lasts up to 55 weeks, with a 4-week post-observation period. The primary endpoint is the proportion of patients maintaining MM according to prespecified cycle-level criteria throughout the observation period while receiving PSL ≤ 5 mg/day. Secondary endpoints include changes in MG-ADL, MG Composite, the revised 15-item Myasthenia Gravis Quality of Life questionnaire, Japanese version (MG-QOL15r-J), and Quantitative MG (QMG) scores; patient-reported treatment convenience; change in serum immunoglobulin G (IgG); the intercycle-interval distribution; autoantibody titers; and the time from enrollment to protocol discontinuation due to difficulty maintaining MM-5 mg. Safety is also assessed. Graphical Abstract available for this article. Japan Registry of Clinical Trials (jRCT): jRCTs031260127 (prospectively registered on 14 May 2026). Myasthenia gravis is a disease in which the immune system disrupts signals between nerves and muscles, causing weakness of the eyes, swallowing, breathing, and limbs. The prescription medicine efgartigimod lowers harmful antibodies and improves symptoms, and many patients reach a stable state with only very mild symptoms, called “minimal manifestation,” ideally on a low steroid dose (prednisolone, ≤ 5 mg/day). How long this state lasts, and how often treatment must be repeated, are unknown. Efgartigimod is given in cycles of one dose a week for 4 weeks, either as a drip into a vein or as an injection under the skin that some patients self-inject at home. We will enroll adults already in this stable state and follow them for about 1 year. Patients score their symptoms weekly, and the gap between cycles follows those scores: shortened by 1 week if symptoms edge up, lengthened by 1 week when they stay stable, within limits of 2 to 8 weeks. The steroid dose and other tablets stay the same. We will measure how many patients keep this state for 1 year and what gaps between cycles they reach, and will also look at antibody levels, quality of life, and convenience. Because the gap is shortened whenever symptoms worsen, the number of patients staying stable must be read together with how often treatment was needed. This small study has no comparison group, so it can show whether the approach is workable, but a larger trial will be needed.