重症筋無力症治療の現況と展望―免疫抑制・調節薬の観点から

Immunosuppressive / Immunomodulating Therapies in Myasthenia Gravis-at Present and in the Near Future

はじめに

　重症筋無力症（myasthenia gravis：MG）は，神経筋接合部を標的とした自己抗体により発症する自己免疫疾患と理解されており，かつて死亡率が30％近いとされた予後は免疫治療の導入により著明に改善した。現在までに多くのエビデンスが積み重ねられるとともに，新規の免疫治療も登場してきており，本稿では免疫抑制・調節薬による治療について概説する。

　MGは血清学的に，①神経筋接合部の後シナプス膜上にあるアセチルコリン受容体（acetylcholine receptor：AChR）に対する抗体が存在する抗AChR抗体陽性MG，②筋特異的チロシンキナーゼ（muscle specific tyrosine kinase：MuSK）に対する抗体が存在する抗MuSK抗体陽性MG，③いずれの抗体も認められないdouble seronegative MG，に分類される。また，眼筋型MGでは抗コリンエステラーゼ薬や低用量ステロイド薬で対処されることが多い。以下に，全身型MG治療に使用される免疫抑制・調節薬治療の現状と展望について述べる。

Abstract

　Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission that is primarily caused autoantibodies specific to the neuromuscular junction and is characterized by fatigability and weakness of the striated muscles.　Immunosuppression is the mainstay of treatment for MG,and patients with MG are currently treated with immunomodulating or immunosuppressive agents.　This review summarizes the current situation and perspective of medical therapy for MG,focusing on mechanisms of action and clinical application of corticosteroids and different classes of immunomodulating or immunosuppressive drugs used for MG.　Immunosuppressive treatment is indicated for patients with disabling weakness,not sufficiently managed with cholinesterase inhibitors.　Prednisolone (PSL) is used in the great majority of patients.　Tacrolimus and cyclosporine are the first-line immunosuppressants,whereas azathioprine is a conventional but less frequently used medication in Japan.　The incidence of late- and elderly-onset MG is reported to be increasing.　The risk of complications in corticosteroid treatment appears to depend on drug dosage,treatment duration,and patients' characteristics,and the serious side effects should be increased in late- and elderly- onset MG.　Although nonspecific,current immunosuppressive treatment is highly effective in most MG patients,the need for prolonged administration and unwanted effects are still relevant limitations to its use.