Advancements in Targeted Therapies for Generalized Acetylcholine Receptor Antibody Positive Myasthenia Gravis: Beginnings of a Paradigm Shift.

In recent years, a new era of biologic therapeutics has emerged for the treatment of generalized myasthenia gravis (gMG). Compared to traditional immune modulatory therapies (steroids, non-steroidal immunosuppressive agents), these agents have more specific target engagement via inhibition of complement activation (eculizumab, ravulizumab, zilucoplan) or blockade of IgG recycling via the neonatal Fc receptor (FcRn; efgartigimod, rozanolixizumab). Phase 3 trials with each of these agents have shown rapid clinical improvement and good safety and tolerability. B-cell targeting with rituximab was safe and well-tolerated but with less impressive efficacy in two phase 2 studies. As a result, four new therapies are now approved for use (eculizumab, ravulizumab, efgartigimod, rozanolixizumab), another (zilucoplan) is in regulatory approval process and several others are in pivotal trials. A paradigm shift is afoot. The challenge is figuring out where these therapies may fit in gMG treatment algorithms.