難治性潰瘍性大腸炎に対するタクロリムス急速導入療法の治療効果と安全性

The Safety and Efficacy of Rapid Induction Therapy Using Tacrolimus for Severe Ulcerative Colitis Refractory to Steroid Therapy

要旨　タクロリムスは難治性潰瘍性大腸炎（UC）に対する新たな治療法として寛解導入効果など有効性が実証された薬剤である．しかしながら，その使用法に関して血中トラフ濃度コントロールや用量調節方法など課題点が存在する．今回，筆者らは難治性UCに対するタクロリムスの短期治療効果について，さらにタクロリムス急速導入療法（RI）の有用性と安全性について検討した．RIにより，短期奏効率は83.3％（25/30）と非常に高い有効性を示していた．また重篤な有害事象も認めず，安全性が確認された．早期トラフ到達性は投与4日以内に93.3％の症例で至適トラフ値に到達した．また，4週後の改善度（CAI減少度）は2～3週間目の中期平均トラフ値と相関を認めた．さらに安定した中期トラフ値をもたらすのは，タクロリムス投与後5日以内の初期トラフを上昇させることが有用であると考えられ，RIが4週後の症状改善に有効であると考えられた．以上のように，タクロリムスは難治性UCの寛解導入・維持において有効な薬剤であるが，症例の選択や導入時期投与期間，および併用薬剤などの問題，また重篤な副作用もあるため慎重に適応症例を検討し，厳重な管理のうえでの投与が必要であると考えた．

　Tacrolimus is the medicine whose the effectiveness including the induction of remission was demonstrated as a new therapy for intractable UC（ulcerative colitis）. However, there are problems involved including blood trough level control and dose control methods. In this study, we examined the usefulness and safety of Tacrolimus rapid induction therapy for the short-term treatment effect of Tacrolimus on refractory ulcerative colitis The short-term response rate of the RI（rapid induction）therapy showed 83.3％（25/30）and very high effectiveness. Also, safety was confirmed without any serious adverse effects. It arrived at the optimal trough value in 93.3％ of cases within its administration for four days. Also, the percent improvement〔CAI（clinical activity index）rate of decline in mortality〕four weeks later correlated with intermediary mean trough value of eyes for 2～3 weeks. Furthermore, what the primitive trough raised within five days after the administration was thought to be useful for symptom improvement so that a Middle trough value brought a stable value. FK506 is a medicine which induces remission, and brings about maintenance of refractory UC. However, there are problems involved in the dosing period and combined drug selection and the induction time of each case. Because there can be serious adverse effects, we examine and accommodate each case carefully, and it is necessary to treat severe cases based on a strict controls.