Real world study in Italian public hospital with Efgartigimod in patients affected by generalized myasthenia gravis: influence of clinical and serological factors

Abstract

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder caused by IgG autoantibodies targeting the neuromuscular junction. Recycling of IgG is mediated by the neonatal Fc receptor (FcRn). Efgartigimod, an Fc fragment of human IgG1, has demonstrated efficacy in MG; however, the clinical characteristics of patients with the highest response remain unclear.

Methods: Twelve patients with AChR-positive generalized MG were treated with two cycles of Efgartigimod over 1 year, and nine patients completed a third cycle. Clinical evaluation was conducted using MG-ADL at four time points and QMG at the beginning and end of each cycle. MG-ADL and QMG scores were further subdivided into ocular (O), bulbar (B), and generalized (G) symptom subdomains, and patients were classified as predominantly ocular (pO), bulbar (pB), or generalized (pG) based on symptom prevalence.

Results: Significant improvements were observed in MG-ADL and QMG from baseline across all symptom subdomains. Baseline AChR antibody levels correlated with MG-ADL improvement (p < 0.04). Thymectomized patients demonstrated superior outcomes, with MG-ADL improving by 62% versus 22% (p < 0.01) and QMG by 45% versus 3.5% (p < 0.01) during the first two cycles. Patients with pO symptoms responded less to therapy, with generalized symptoms contributing most to the minor response.

Discussion: Our findings suggest that patients with high baseline AChR antibody titers, previous thymectomy, and non-ocular symptom predominance respond better to Efgartigimod. These results underscore the need for larger studies to validate these observations and optimize patient selection.

Keywords: AChR; Efgartigimod; Myasthenia Gravis; T cells; Thymectomy.

Figure 1

FcRn, Neonatal Fc receptor; IgG, immunoglobulin G. (A) FcRn is widely expressed on endothelial cells. IgG enters the cell via fluid-phase endocytosis. IgG bind to FcRn in acidic conditions (pH 6.0–6.5) to form an IgG-FcRn complex (1). IgG that do not bind to FcRn in the acidified body are degraded in the lysosome (2). Under physiological conditions (extracellular compartment, pH 7.4), the IgG-FcRn complex dissociates at the cell surface and the IgG gets released again into the blood circulation (3). By this mechanism, FcRn efficiently safeguards IgG from lysosomal degradation, thus increasing the half-life of IgG. (B) FcRn inhibitors are monoclonal antibodies with higher affinity and an increased binding capacity to FcRn at neutral and acidic pH (1). Inside the cell, FcRn inhibitors compete with IgG for binding to FcRn, preventing IgG binding to FcRn. The unbound IgG enter the lysosomes where they are degraded (2). The process results in reduced IgG levels in the circulation, including the pathogenic IgG antibodies.

Figure 2

Box plot showing anti-AChR antibody levels, expressed as nmol / L, in patients who underwent (positive, +) or not (negative, −) thymectomy. ** p < 0.01, U-Mann Whitney for indipendent samples.

Figure 3

Percentage change in mean MG-ADL score and standard deviation from baseline (T0 of the 1st cycle) at the time points of the first two EFG cycles in patients who have or have not previously undergone thymectomy.** p < 0.01 with U-Mann–Whitney test.

Figure 4

Percentage change in mean QMG score and standard deviation from baseline (T0 of the 1st cycle) at the time points of the first two EFG cycles in patients who have or have not previously undergone thymectomy.** p < 0.01 with U-Mann–Whitney test.