2026 American Academy of Neurology Abstract Website

Objective:

Examine effect of JAKi therapy in MS patients.

Background:

Janus kinase inhibitors (JAKi) are immunomodulators used to treat autoimmune and myeloproliferative diseases. Preclinical data suggest JAKi may decrease inflammation in multiple sclerosis (MS). However, a recent case study temporally associated JAKi exposure with newly diagnosed MS. Real-world data on clinical effectiveness and safety in MS are lacking.

Design/Methods:

We identified patients at Mass General Brigham (Boston, MA) diagnosed with multiple sclerosis and prescribed a JAKi (with or without concurrent MS-specific treatment). Each JAKi exposure was analyzed as a distinct epoch for MS activity and safety.

Results:

Six patients were identified (5 relapsing-remitting, 1 secondary progressive; 100% female), with a median age of 58 years and disease duration of 18.5 years (IQR 14.2 years). Indications for JAKi use were rheumatologic disorders (4), graft-vs-host disease (1), and hemophagocytic lymphohistiocytosis (1). JAKi medications used were ruxolitinib (3 of 7 epochs), tofacitinib (2 of 7), baricitinib (1 of 7), and upadacitinib (1 of 7). One patient used MS-specific therapy (glatiramer acetate) concurrently. In total, 12.5 patient-years of treatment (median 6 months per patient, IQR 11 months) were analyzed. No new clinical or radiographic MS relapses occurred. One patient experienced disease progression with worsening gait. Another developed increased weakness attributed to deconditioning versus progression. Notably, one patient had a clinical and radiographic relapse 10 months after discontinuation of JAKi. All 3 had relapsing-remitting disease. No serious infections or coagulopathies occurred. Two patients had baseline anemia and lymphocytopenia that did not worsen.

Conclusions:

In this case series of older adults with longstanding MS and co-morbid autoimmune or myeloproliferative disease, JAKi exposure was not associated with MS relapse or serious infections. However, there was clear disease progression in one patient and equivocal progression in another. Larger studies are warranted to evaluate JAKi safety and efficacy in MS to inform treatment strategies.