Role of complement, anti-complement therapeutics, and other targeted immunotherapies in myasthenia gravis

Introduction Several patients with myasthenia gravis (MG) do not adequately respond to available drugs or exhibit poor tolerance, necessitating the need for new therapies. Areas covered The paper discusses the rapidly evolving target-specific immunotherapies that promise long-standing remissions in the management of MG. It is specifically focused on the role of complement, anti-complement therapeutics, and the anti-FcRn and B cell monoclonals. Expert opinion Anti-AChR antibodies cause internalization of the receptors and activate complement leading to in situ MAC formation that damages the post-synaptic membrane of the neuromuscular junction. Inhibiting MAC formation by antibodies targeting key complements subcomponents is a reasonable therapeutic goal. Indeed, the anti-C5 monoclonal antibodies, Eculizumab, Ravulizumab, and Zilucoplan, have been successfully tested in MG with Eculizumab first and now Ravulizumab FDA-approved for refractory MG based on sustained long-term benefits. Among the biologics that inhibit FcRn, Efgartigimod caused rapid reduction of the circulating IgG in the lysosomes, and induced sustained clinical remission with good safety profile leading to FDA-approved indication. Anti-B cell agents, like Rituximab, can induce sustained long-term remissions, especially in IgG4 antibody-mediated Musk-MG, by targeting short-lived antibody-secreting plasmablasts. These biologics offer effective targeted immunotherapies with good tolerance promising to change the therapeutic algorithm in the chronic MG management.