Crohn病経過例における免疫抑制剤の効果

The Effect of Immunosuppressants on the Longtime Clinical Course of Crohn's Disease

要旨　Crohn病に対する少量の免疫抑制剤の治療効果を検討した．対象は当院において免疫抑制剤を投与したCrohn病患者の109例であり，治療効果の判定は長期経過が追跡可能な76例で行った．治療目的別では緩解維持37.3％，ステロイド減量・離脱目的では63.6％の有効率を示した．さらに，腸切除術後に緩解維持療法を目的に免疫抑制剤を投与した症例19例と非投与症例32例の比較では，再手術率，1年以内・2年以内の早期再燃率はともに免疫抑制剤投与群で低かった．投与量は6-mercaptopurine30mg/日，azathioprine50mg/日の少量投与であるが，有効性は欧米からの報告と遜色はないと思われた．副作用は109例中14例(12.8％)にみられた．内訳は骨髄抑制7例，消化器症状3例，脱毛3例，頭痛1例であり，いずれも投与中止により症状の改善，検査値の正常化が得られ，重篤なものはなかった．免疫抑制剤の少量投与の緩解維持およびステロイド減量・離脱における有用性と安全性が確認された．

　To assess the effectiveness of low dose immunosuppressants (6-mercaptopurine : 6-MP, 30mg/day ; azathioprine : AZA, 50mg/day) on the long term outcome of Crohn's disease, we analyzed 109 Crohn's disease cases who were treated with 6-MP/AZA and who were followed up between 1973 and 2003 at Keio University Hospital. Of these, adequate records that could be analyzed for assessment of the long-term course were available in 76 cases.

　Immunosuppressants were used mainly in order to stop or reduce the dosage of corticosteroids and maintain remission. The time to relapse and to re-surgery in the group receiving 6-MP/AZA after intestinal resection was significantly longer than in the group who had not received it. In 19 patients who received 6-MP/AZA after surgery, probabilities of relapse at 1 and 2 years were 26.3％ and 46.9％, respectively. On the other hands, in 32 patients who did not receive therapy, probabilities of relapse at 1 and 2 years were 36.9％ and5 6.3％, respectively. Therefore, cumulative probabilities of re-surgery at 5 years were 26.3％ and 46.9％, respectively. Furthermore, low dose immunosuppressants had a steroid-sparing effect in this study.

　Adverse-effects possibly attributable to 6-MP/AZA and requiring discontinuation of treatment were seen in 12.8％ of patients. Seven had leukopenia associated in one case with thrombocytopenia, three had alopecia, threehad GI symptoms and another had headache. None of the patients died due to toxicity of the immunosuppressants and all complications were reversible.

　Our data indicate that a low dose of 6-MP/AZA is safe and well-tolerated and has long-term benefits in maintaining remission and minimizing re-surgery.

　1) Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo

　2) Center for Comprehensive and Progressive Medicine, Keio University School of Medicine, Tokyo