Sequential efgartigimod and ofatumumab for stiff-person syndrome: a case report illustrating a pathophysiology-informed strategy and literature review.

Background: Stiff-person syndrome (SPS) is a rare, antibody-mediated autoimmune disorder of the central nervous system, most frequently associated with antibodies against glutamic acid decarboxylase 65 (GAD65). Management of patients with an insufficient response to conventional immunotherapy remains a clinical challenge. Case presentation: We report a 40-year-old woman with anti-GAD65 antibody-positive SPS. She experienced severe relapse and functional disability (modified Rankin Scale [mRS] score 4) despite plasma exchange and maintenance immunosuppression. We designed a sequential, mechanism-base regimen: the neonatal Fc receptor antagonist efgartigimod (3 cycles) was administered to rapidly reduce pathogenic IgG, followed by the anti-CD20 monoclonal antibody ofatumumab (2 cycles) to deplete B-cells and provide sustained immunomodulation. Results: This sequential strategy resulted in substantial and sustained clinical improvement (mRS score 4 to 1, Barthel Index 75 to 100) and a reduced clonazepam requirement despite persistently high anti-GAD65 antibody titers, demonstrating efficacy beyond mere antibody reduction. The regimen was well-tolerated with no significant adverse events. Conclusion: This case provides preliminary clinical experience with a sequential efgartigimod-ofatumumab strategy in treatment-resistant SPS. This approach, which combines rapid antibody clearance with sustained B-cell suppression, not only affirms the role of ofatumumab in long-term immunomodulation but also highlights the potential synergy of sequential administration, warranting further investigation.