{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:00:34Z","timestamp":1790096434022,"version":"4.0.1"},"reference-count":85,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Refractory acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab-positive gMG) is clinically heterogeneous, and evidence on how to select a therapeutic mechanism after incomplete response to a previous targeted class remains limited. This narrative review synthesizes guidelines, randomized trials, extension studies, meta-analyses, observational evidence, and emerging translational data identified through targeted searches updated to 21 June 2026, with a final bibliographic check through 10 August 2026. We examine conventional immunosuppression, rescue therapy, B-cell and B-lineage depletion, terminal complement inhibition, and neonatal Fc receptor (FcRn) inhibition as interventions acting at different levels of the pathogenic cascade. We propose a framework in which prior response, nonresponse, intolerance, corticosteroid dependence, respiratory vulnerability, and rescue-therapy dependence are interpreted as mechanistic clues rather than as a fixed treatment ladder. An illustrative case of severe refractory AChR-Ab-positive gMG showed incomplete control after conventional immunosuppression, rituximab, thymectomy, and terminal complement inhibition, with reproducible but transient benefit from plasma exchange. This pattern supported a mechanistic rationale for FcRn inhibition, although overlapping treatments and single-case design preclude causal attribution. Mechanism-based sequencing should be viewed as structured decision support rather than a validated algorithm. Prospective switching studies and predictive biomarkers are needed to optimize individualized treatment sequencing.<\/jats:p>","DOI":"10.3390\/jcm15197369","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:28:43Z","timestamp":1790090923000},"page":"7369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Rescue Therapy to Mechanism-Based Sequencing in Refractory Myasthenia Gravis: A Narrative Review with an Illustrative Clinical Case"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-5982","authenticated-orcid":false,"given":"Aleksandr","family":"Ilves","sequence":"first","affiliation":[{"name":"Department of Neurology, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6399-9068","authenticated-orcid":false,"given":"Vera","family":"Nikitin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41572-019-0079-y","article-title":"Myasthenia gravis","volume":"5","author":"Gilhus","year":"2019","journal-title":"Nat. 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