重症筋無力症の治療～updateと近未来～

抄録

Minimal manifestation (MM) with oral prednisolone 5 mg/day or less (MM–5mg) are recommended as the first goal of treatment for myasthenia gravis (MG) in Japan. To achieve this goal, patients with generalized MG should be treated with low–dose oral corticosteroids and calcineurin inhibitors, but in case that these treatments are not sufficiently effective, intravenous immunoglobulin, plasma pheresis, and intravenous methylprednisolone should be added as early as possible to stabilize the disease. The treatment goals and the EFT strategy have also been followed in the revised Japanese Practical Guideline for Myasthenia Gravis/Lambert–Eaton Myasthenia Syndrome 2022 published in May 2022, and have been recognized more than before. Furthermore, refractory MG was defined as a case in which “treatment with multiple oral immunotherapies” or “treatment with a combination of oral immunotherapies and repeated nonoral fast-acting agents” for a certain period of time “does not result in sufficient improvement” or “it is difficult to continue treatment adequately due to side effects and burden of patients”. In a clinical survey conducted in 2021 at 13 institutions participating in the Japan MG registry study including 1710 MG patients, 50% of the patients had achieved MM–5mg at the time of the survey, and 21% of the patients were refractory. This suggests that even at institutions where the EFT strategy is relatively widespread, the achievement of the treatment goal is not sufficient. On the other hand, the achievement rate of MM–5mg increased from 53% in the 2015 survey to 65% in 2021, indicating that the EFT strategy is effective as a treatment strategy using conventional and feasible methods, although there is room for improvement. Therefore, the EFT strategy seems to be a suitable treatment strategy for patients with generalized MG, but medical problem remains that how to treat patients who fail to achieve and sustain MM–5mg status.

The introduction of molecular–targeted therapies should be considered for these patients, but such therapies should be started after understanding treatment strategies and criteria for refractory cases as described above. In this section, we discuss general treatment strategies for MG and the position of molecular–targeted agents, presenting data from open–label clinical trials and real–world studies.