Efgartigimod in generalized myasthenia gravis: A real-life experience at a national reference center

Abstract

Background and purpose: Inhibition of the neonatal Fc receptor (FcRn) for IgG is a promising new therapeutic strategy for antibody-mediated disorders. We report our real-life experience with efgartigimod (EFG) in 19 patients with generalized myasthenia gravis (gMG) along a clinical follow-up of 14 months.

Methods: EFG was administered according to the GENERATIVE protocol (consisting of a Fixed period of two treatment cycles [given 1 month apart] of four infusions at weekly intervals, followed by a Flexible period of re-cycling in case of worsening). Eight patients were positive for acetylcholine receptor antibody, four for muscle-specific tyrosine kinase antibody, and two for lipoprotein-related protein 4 antibody, and five were classified as triple negative. Efficacy of EFG was assessed by the Myasthenia Gravis Activities of Daily Living, Myasthenia Gravis Composite, and Quantitative Myasthenia Gravis scales.

Results: Fifty-three percent of patients needed three treatment cycles, 26% needed four, and 21% needed five along the 14-month clinical follow-up. Meaningful improvement was observed at the end of each cycle with the clinical scores adopted. EFG had a dramatic effect on disease course, as during the year before treatment eight of 19 patients (42%) were hospitalized, and 15 of 19 (79%) needed treatment with plasma exchange or immunoglobulins; three of 19 (16%) were admitted to the intensive care unit. During EFG, none of the patients was hospitalized and only one patient required plasma exchange and intravenous immunoglobulins. No major side effects or infusion-related reactions occurred.

Conclusions: We observed that EFG was safe and modified significantly the course of the disease along a 14-month follow-up. Our experience strengthens the role of FcRn inhibition as an effective new tool for long-term treatment of gMG.

Keywords: MuSK; acetylcholine receptor; efgartigimod; myasthenia gravis; neonatal Fc receptor.

FIGURE 1

Myasthenia Gravis Activity of Daily Living (MG‐ADL) and Myasthenia Gravis Composite (MGC) mean score changes recorded during the Fixed period (a) and the Flexible Period (b) in generalized myasthenia gravis patients treated with efgartigimod (EFG). Changes in MG‐ADL and MGC (expressed as reduction of the score values, mean ± SEM) were calculated comparing each time point to the score recorded at the first infusion of each cycle. The time interval between EFG cycles during the Flexible period are reported as weeks (mean ± SD). *p < 0.05, **p < 0.01 ***p < 0.001.

FIGURE 2

Myasthenia Gravis Activity of Daily Living (MG‐ADL) changes in acetylcholine receptor (AChR) antibody‐positive MG(a) and triple‐negative MG patients (b) treated with efgartigimod. MG‐ADL changes (expressed as reduction of the score values, mean ± SEM) were calculated comparing each time point to the score recorded at the first infusion of each cycle.

FIGURE 3

Myasthenia Gravis Activity of Daily Living (MG‐ADL) changes in muscle‐specific tyrosine kinase (MuSK; n = 4) and lipoprotein‐related protein 4 (LRP4; n = 2) generalized myasthenia gravis (MG) patients treated with efgartigimod (EFG). (a) MG‐ADL changes in an MuSK‐MG patient showing a rapid and considerable response to EFG. (b) MG‐ADL changes in the remaining three MuSK‐MG patients. (c) MG‐ADL changes in two LRP4‐MG patients. MG‐ADL changes were calculated comparing each time point to the score recorded at the first infusion of each cycle.

FIGURE 4

Total IgG changes (mean ± SEM) expressed as percentage reduction in blood samples collected at the first and fourth infusion of each efgartigimod cycle, and at each follow‐up visit 30 days after the end of each cycle.

FIGURE 5

Revised 15‐item Myasthenia Gravis Quality of Life (MG‐QoL‐15r) changes in generalized myasthenia gravis patients treated with efgartigimod along the Fixed period (a) and Flexible period (b). MG‐QoL‐15r changes (expressed as reduction of the score values, mean ± SEM) were calculated comparing each time point to the score recorded at the first infusion of each cycle.