Examine effect of JAKi therapy in MS patients.

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.

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.