Anti-acetylcholine receptor antibody overshoot following efgartigimod in myasthenia gravis: Two case reports with literature review.

BACKGROUND

FcRn antagonists have reshaped generalized myasthenia gravis (MG) treatment by enhancing IgG catabolism, complementing traditional antibody-depleting therapy (ADT). However, disrupting IgG homeostasis may paradoxically cause antibody overshoot, potentially worsening MG symptoms. The risk factors and optimal management of antibody overshoot remain inadequately characterized.

METHODS

We report two novel cases of anti-acetylcholine receptor (AChR) antibody overshoot and clinical exacerbation following FcRn antagonist efgartigimod treatment. To contextualize these findings, we performed a literature search in PubMed, identifying 10 previously reported cases of antibody overshoot in MG (2 following efgartigimod and 8 following plasma exchange).

RESULTS

In the efgartigimod cohort (n=4, including our two novel cases), all patients were anti AChR positive, had thymoma associated MG (TAMG, 100%), and had undergone prior thymectomy (100%). Notably, none had received adequate background immunosuppressive therapy before efgartigimod initiation (75% inadequate, 25% none). All patients (100%) experienced severe clinical exacerbation (MGFA class V in the 3 patients with available data). Rescue therapies-including corticosteroids (75%), eculizumab (50%), IVIG (50%), and tacrolimus (50%)-were effective, with all four patients showing significant improvement. Furthermore, analysis of the plasma exchange cohort (n=8) and the combined cohort (n=12) revealed a distinct and shared clinical risk profile for the development of antibody overshoot.

CONCLUSION

Anti AChR antibody overshoot following efgartigimod therapy is a rare but clinically significant adverse event, predominantly affecting patients with TAMG or prior thymectomy who lack adequate baseline immunosuppression. Given the dissociation between total IgG reduction and autoantibody rebound, monitoring should focus specifically on anti-AChR titer rather than total IgG level alone.