—薬剤関連消化管病変の臨床的特徴—免疫チェックポイント阻害薬関連消化管病変

Clinical and Colonoscopic Features of Immune Checkpoint Inhibitor-associated Colitis

要旨●当院における免疫チェックポイント阻害薬の使用状況と下痢および大腸炎の頻度を遡及的に解析した．ニボルマブ（NIV）単剤治療が218例で施行され（単独群），他の32例ではNIVとイピリムマブ（IPI）の併用療法ないしスイッチ療法が施行されていた（併用・スイッチ群）．全250例のうち下痢は27例（10.8%）に認められ，そのうち9例（3.6%）が大腸炎と診断された．下痢および大腸炎の頻度は，単独群で9.2%および1.4%であったのに対し，併用・スイッチ群ではそれぞれ21.9%と18.8%であり，大腸炎の頻度は単独群よりも併用・スイッチ群で有意に高かった（p＝0.0002）．併用・スイッチ群における大腸炎6例のうち4例が併用療法，2例がスイッチ療法を受けており，後者はいずれもNIVからIPIへのスイッチ症例であった．大腸炎の内視鏡所見は，9例中5例で潰瘍性大腸炎に類似していた．NIVとIPIの併用療法ないしスイッチ療法は，大腸炎のリスクを上昇させる可能性が示唆された．

　We compared the prevalence of diarrhea and colitis in patients with cancer who were under an ICI（immune checkpoint inhibitor）monotherapy and those who were under a combination or a sequential therapy using two ICIs. Confirmation of marked apoptosis in the biopsy specimens was the basis for the diagnosis of ICI-associated colitis. There were 218 patients under ICI monotherapy and 32 patients under a combined or sequential therapy of two ICIs. In total, 27 patients（10.8%）complained of diarrhea and 9 patients（3.6%）were diagnosed with ICI-associated colitis. The prevalence of ICI-associated colitis was significantly higher in patients under combined or sequential ICIs（18.8%）than in those under monotherapy（1.4%, p＝0.0002）. Six patients were under combined or sequential ICIs and four of them belonged to the combined therapy group. Of the nine patients diagnosed with ICI-associated colitis, the endoscopic findings of ICI colitis mimicked those of ulcerative colitis in 5 patients, while the colonoscopic findings were nonspecific in the remaining four patients. These findings suggest that the risk of ICI-associated colitis is higher in patients under combined or sequential ICIs as compared to those under ICI monotherapy.