Cure in Myasthenia Gravis: An Unmet Need

ABSTRACT

A cure for myasthenia gravis is necessary to achieve “A World Without Myasthenia Gravis”. Current treatments reduce symptom burden and broadly suppress immune activity, but generally need to be administered chronically and are associated with significant risks, incomplete remission rates, infrequent treatment‐free remission, and potential disability. We define a cure for MG as complete remission of MG, without the need for ongoing treatment, plus desirably: a high probability of success; a low risk of later relapse; the possibility of treatment repetition if MG does relapse; low and proportionate treatment toxicity; and cost‐effectiveness. Thymectomy is the only currently available widely applied sometimes curative treatment for ACHR+ antibody MG. The MGTX trial post hoc analysis showed a 52% steroid free remission rate following thymectomy, which is approximately 1/3 of the whole population above the background remission rate. However, thymectomy is not universally applied even in younger ACHR+ patients. Recent regulatory approved and marketed therapies for MG are highly effective but are largely chronic continuous suppressive strategies at significant cost. Non‐selective ablative chemotherapy and transplant or CAR‐T approaches to B or plasma cells in development have toxicity risks and may still require maintenance therapies to prevent relapse. Treatments specific only to the pathogenic antibodies or clones using antigen‐bait, anti‐idiotype, or toleragenic approaches are yet to be demonstrated in humans with spontaneously acquired myasthenia gravis. A cure for myasthenia gravis remains an unmet need.