[Pubmed] From Rescue Therapy to Mechanism-Based Sequencing in Refractory Myasthenia Gravis: A Narrative Review with an I

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J Clin Med. 2026 Sep 22;15(19):7369. doi: 10.3390/jcm15197369.

ABSTRACT

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.

PMID:42881831 | DOI:10.3390/jcm15197369


Source: https://pubmed.ncbi.nlm.nih.gov/4288183 ... 1&v=2.20.1