Treatment Challenges in Triple Seronegative Myasthenia Gravis: A Single‐Center Experience and Narrative Review of the Literature

Introduction Triple seronegative myasthenia gravis (tSNMG) constitutes a distinct subgroup of MG that, despite the absence of recognized pathogenetic antibodies directed against the acetylcholine receptor (AChR), muscle‐specific tyrosine kinase (MuSK), or low‐density lipoprotein receptor–related protein 4 (LRP4), is considered to have an autoimmune origin and is frequently treated with immunosuppressive medications. Limited data exist regarding long‐term prognosis and treatment response in tSNMG patients. Methods We conducted a single‐center, retrospective study to investigate the clinical profile and responsiveness to conventional treatment in tSNMG patients, with particular focus on refractory tSNMG patients, compared with nonrefractory tSNMG patients, based on predefined criteria. We also present a narrative overview of therapeutic approaches and treatment response in SNMG in the past decade. Results Twenty‐six out of the 196 (13.3%) MG patients were identified as tSN, and nine of the tSN patients (34.6%) met criteria for refractory MG. Refractoriness in tSNMG patients was associated with female sex and thymic abnormalities ( p ≤ 0.005) for both). Less than half of tSNMG patients reached an optimal outcome, defined as minimum manifestation status or better. Prednisone more commonly resulted in a favorable outcome (76.9%), followed by azathioprine (50%). In the subgroup analysis, azathioprine showed a similar response rate ( p = 0.193), while significantly lower favorable response rates were achieved with other conventional immunosuppressants in refractory compared to nonrefractory tSNMG patients ( p ≤ 0.034 for all). Discussion Treatment challenges in tSNMG are closely linked to the fact that a high proportion of patients in this subgroup exhibit a suboptimal response to conventional immunosuppressants.