Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome

Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by high titers of antibodies against glutamic acid decarboxylase (GAD) causing impaired GABAergic inhibitory neurotransmission. To date, there is not a defined therapy for such condition, but immunomodulating therapies, such as plasma exchange, intravenous immunoglobulins, and rituximab, have been widely used in clinical practice. However, the efficacy and tolerability of these treatments is not well established. Efgartigimod, a new neonatal Fc receptor (FcRn) blocker, is a human IgG1 antibody Fc fragment engineered with increased affinity for FcRn binding, leading to a reduction in IgGs levels, including pathogenic IgG autoantibody showing promising results in neurological autoimmune disorders and has been approved for the treatment of AChR-seropositive generalized myasthenia gravis (MG). In this study, we report and describe the first data on treatment with efgartigimod in three patients affected by both AChR-seropositive generalized MG and anti-GAD-seropositive SPS. Patients were followed since the start of efgartigimod and for the whole treatment period (12 weeks). MG symptoms were assessed with the MG activity of daily living score and the Quantitative Myasthenia Gravis score, while SPS ones were assessed with the SPS activity of daily living score; muscle strength was assessed with the Medical Research Council Sum score; the overall disability from MG and SPS was assessed by the modified Rankin Scale. All patients showed an improvement in symptoms of both SPS and MG after 2 cycles of treatment. Our data suggest that efgartigimod may be considered as a candidate drug for SPS and other autoantibody-mediated neurological disorders.

Automated summary

Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by high levels of antibodies against glutamic acid decarboxylase (GAD), leading to impaired inhibitory neurotransmission. Efgartigimod, a new Fc receptor blocker, has shown promising results in neurological autoimmune disorders and has been approved for the treatment of AChR-seropositive generalized myasthenia gravis (MG). In this study, three patients with both MG and anti-GAD-seropositive SPS showed improvement in symptoms of both conditions after treatment with efgartigimod.