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

Abstract

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.

Case report: Recovery from refractory myasthenic crisis to minimal symptom expression after add-on treatment with efgartigimod

“…A recent study described excellent results regarding MG complicated by SPSs successfully treated with efgartigimod; these patients experienced very large reductions in MG-ADL scores ( 19 ). This evidence opens the possibility of treating patients affected by anti-GAD antibody-related diseases, which are also often found in SPS.…”

Physical Activity in Patients with Neuromuscular Disease Three Years after COVID-19, a Longitudinal Survey: The After-Effects of the Quarantine and the Benefits of a Return to a Healthier Life-Style

“…These findings suggest that the abrupt interruption of usual physical activities during the pandemic might have favored a worsening of such subtypes of NMD; among disease groups, PN and ND patients might be more prone to clinical progression compared to autoimmune conditions like NJ and CIDP that are treatable with effective drugs that reduce disease progression [ 49 ]. Considering the progressive nature of the former conditions, the restoration of previous PA levels may be difficult.…”

Clinical Features and Prognostic Analysis of MuSK-Antibody-Positive Myasthenia Gravis versus Double-Seropositive Myasthenia Gravis: A Single-Center Study from Central South China

“…For instance, anti-CD19 monoclonal antibodies such as inebilizumab depleting a wider range of B cells and antibody-producing cells, 40 neonatal Fc receptor (FcRn) blockers such as efgartigimod clearing IgG of multiple subclasses, 41 and telitacicept suppressing the activities of both B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) that sustain B cell development and survival, 42 could all be promising agents for treating DSP-MG or even MG complicating other B-cell-mediated autoimmune disorders like stiff-person syndrome. 43 Overall, the similarities between MuSK-MG and DSP-MG led to the notion that DSP-MG may be a subtype of MuSK-MG, 30 though the low prevalence of DSP-MG and potential selection bias may render it plausibly arbitrary.…”

“…B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) that sustain B cell development and survival, 42 could all be promising agents for treating DSP-MG or even MG complicating other B-cell-mediated autoimmune disorders like stiff-person syndrome. 43 Overall, the similarities between MuSK-MG and DSP-MG led to the notion that DSP-MG may be a subtype of MuSK-MG, 30 though the low prevalence of DSP-MG and potential selection bias may render it plausibly arbitrary.…”