Why is development of new treatments necessary for myasthenia gravis? Recent advances in clinical trials

Abstract

AbstractDespite the availability of an increasing variety of disease‐modifying therapies, the proportion of patients with generalized myasthenia gravis (MG) who achieved the practical treatment goal remained low at approximately 50%‐60% in our latest survey. Therefore, there is a need for further development of new treatment options based on novel mechanisms of action for MG treatment. Eculizumab and ravulizumab are monoclonal antibodies used to prevent complement‐mediated damage at the endplate of neuromuscular junction in MG with acetylcholine receptor (AChR) antibody. Neonatal Fc receptor (FcRn) antibodies including efgartigimod and rozanolixizumab are currently in different stages of clinical trial. The FcRn antibodies would be rational therapeutic agents for decreasing the levels of pathogenic autoantibodies with IgG isotypes, resulting in reduction in muscle‐specific kinase (MuSK) antibody as well as AChR antibody. Rituximab, a CD20+ B‐cell depleting monoclonal antibody, also results in a significant decrease in autoantibody titers in serum. Several studies indicate that rituximab may have the potential to treat MuSK‐MG. Monarsen, an antisense oligonucleotide, may reduce the production of acetylcholinesterase. A phase 2 study showed improvement in quantitative MG scores while on the drug. Several case reports showed the efficacy of autologous hemopoietic stem cell transplantation in patients with severe MG refractory to conventional therapies. This article introduces the new drugs and their latest development and discusses the evidence for thymectomy in relation to the Japanese clinical guidelines for MG.