免疫介在性下痢および大腸炎（炎症所見なし）：後ろ向き研究
Malek Shatila1, Sharada Wali1, Carolina Colli Cruz1
1The University of Texas MD Anderson Cancer Center, Department of Gastroenterology, Hepatology, and Nutrition, Houston, TX (Malek Shatila, Sharada Wali*, Carolina Colli Cruz*, Krishnavathana Varatharajalu, Anusha Shirwaiker Thomas, Yinghong Wang).
Insights
炎症マーカーを伴わない免疫介在性下痢および大腸炎（IMDC）は、PD-1/PD-L1阻害薬と関連している。これらの患者は、より軽度の症状と入院率の低下を経験するが、一部は免疫抑制療法を必要とする。
科学分野:
- 腫瘍学; 消化器病学; 免疫学
背景:
- 免疫介在性下痢および大腸炎（IMDC）は、免疫チェックポイント阻害薬で発生する可能性がある。患者の一部はIMDCを発症するが、便生検マーカー、内視鏡検査、または組織学的炎症所見を欠いている。この特定のIMDC群の治療と転帰の理解は限られている。
研究 の 目的:
- 炎症所見のないIMDC患者の特徴を記述する。このIMDCサブセットの管理における免疫抑制療法の役割を明確にする。PD-1/PD-L1阻害薬とこの特定のIMDC発症との関連を調査する。
主な方法:
- 単一施設の後ろ向き研究。適格基準：臨床的IMDC症状を炎症所見（便中カルプロテクチン、内視鏡検査、組織学）なしに発症した免疫チェックポイント阻害薬で治療された患者。研究期間：2010年1月～2024年2月。
主要な成果:
- IMDC患者の11.4%（131/1151）が炎症を認めなかった。これらの患者はPD-1/L1製剤への曝露が多く、下痢の重症度が低く、入院率も低かった。約40%が免疫抑制療法を必要としたが、治療の有無による症状や重症度の有意な差はなかった。
結論:
- 炎症マーカーが正常なIMDCに関する初の研究である。PD-1/PD-L1阻害は、より軽度の転帰と関連するこのIMDC形態を誘発する可能性がある。軽度の発症にもかかわらず、免疫抑制療法が必要となることが多く、一部の患者は後に大腸炎を発症する可能性がある。
Background:
Immune-mediated diarrhea and colitis (IMDC) due to checkpoint inhibition infrequently presents with normal stool biomarkers and no endoscopic or histologic evidence of inflammation. Little is known about the treatment needs and outcomes of this subset of patients. We aimed to describe this entity and clarify the role of immunosuppressive treatments in its management.
Method:
This was a single-center, retrospective study of patients treated with immune checkpoint inhibitors who developed clinical symptoms of IMDC, with no evidence of inflammation based on fecal calprotectin or endoscopic/histologic evaluation, between January 2010 and February 2024.
Results:
Of 1151 patients with IMDC, 131 (11.4%) had no evidence of inflammation. These patients more frequently had PD-1/L1 agent exposure (P=0.019) and presented with less severe diarrhea than patients with evidence of inflammation (P<0.001). This group had a lower rate of hospitalization (P=0.003). Around 40% of patients with no evidence of inflammation required immunosuppressive treatment. There was no difference in clinical symptoms or severity between patients requiring immunosuppression and those who did not.
Conclusions:
Our study is the first to explore IMDC with no elevations in calprotectin and normal endoscopic/histologic findings. We found that PD-1/PD-L1 inhibition may predispose patients to developing this form of IMDC, which is associated with a lower severity of diarrhea, fewer hospitalizations and lower recurrence rates. Many patients still require immunosuppressive treatment, and a small subset later develop colonic inflammation. Future studies are needed to further elucidate the treatment needs and outcomes of this patient population.
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