TY - JOUR
T1 - Chronic Use of Proton Pump Inhibitors Is Associated With an Increased Risk of Immune Checkpoint Inhibitor Colitis in Renal Cell Carcinoma
AU - Yin, Jianyi
AU - Elias, Roy
AU - Peng, Lan
AU - Levonyak, Nicholas
AU - Asokan, Annapoorani
AU - Christie, Alana
AU - Kubiliun, Nisa
AU - Brugarolas, James
AU - Hammers, Hans-Joerg
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/6
Y1 - 2022/6
N2 - Introduction: Immune checkpoint inhibitors (ICIs) have become a standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including colitis. Growing evidence suggests proton pump inhibitors (PPIs) increase the risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and ICI colitis, we sought to evaluate the relationship between PPI use and ICI colitis in mRCC patients. Patients and Methods: We performed a retrospective study of adult patients who received ICI therapy for mRCC between 2015 and 2018 at University of Texas Southwestern Medical Center affiliated hospitals. Clinical characteristics, oncological outcomes, ICI colitis details, and PPI use details were collected by manual chart review. The diagnosis of ICI colitis was made via biopsy when available, or by clinical criteria (symptoms and response to immunosuppressive therapy) when biopsy specimens were unavailable or inconclusive. Univariable and multivariable logistic regression analyses were conducted to assess the potential contribution of PPIs to ICI colitis. Results: A total of 176 patients received ICI therapy for mRCC, of which 16 (9.1%) were diagnosed with ICI colitis. Patients with ICI colitis presented with elevated stool lactoferritin and calprotectin and a wide range of endoscopic and histologic findings. There were no significant differences between patients with and without ICI colitis in age, gender, medical comorbidities, RCC history, and overall survival. However, exposure to ipilimumab and PPI use were more frequently observed in patients with ICI colitis than those without. In univariable and multivariable logistic regression analyses, exposure to ipilimumab and chronic use of PPIs > 8 weeks were significantly associated with ICI colitis. Conclusion: In addition to ipilimumab use, chronic use of PPIs may be associated with ICI colitis in patients with mRCC.
AB - Introduction: Immune checkpoint inhibitors (ICIs) have become a standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including colitis. Growing evidence suggests proton pump inhibitors (PPIs) increase the risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and ICI colitis, we sought to evaluate the relationship between PPI use and ICI colitis in mRCC patients. Patients and Methods: We performed a retrospective study of adult patients who received ICI therapy for mRCC between 2015 and 2018 at University of Texas Southwestern Medical Center affiliated hospitals. Clinical characteristics, oncological outcomes, ICI colitis details, and PPI use details were collected by manual chart review. The diagnosis of ICI colitis was made via biopsy when available, or by clinical criteria (symptoms and response to immunosuppressive therapy) when biopsy specimens were unavailable or inconclusive. Univariable and multivariable logistic regression analyses were conducted to assess the potential contribution of PPIs to ICI colitis. Results: A total of 176 patients received ICI therapy for mRCC, of which 16 (9.1%) were diagnosed with ICI colitis. Patients with ICI colitis presented with elevated stool lactoferritin and calprotectin and a wide range of endoscopic and histologic findings. There were no significant differences between patients with and without ICI colitis in age, gender, medical comorbidities, RCC history, and overall survival. However, exposure to ipilimumab and PPI use were more frequently observed in patients with ICI colitis than those without. In univariable and multivariable logistic regression analyses, exposure to ipilimumab and chronic use of PPIs > 8 weeks were significantly associated with ICI colitis. Conclusion: In addition to ipilimumab use, chronic use of PPIs may be associated with ICI colitis in patients with mRCC.
KW - Colitis
KW - Immunotherapy
KW - Kidney Cancer
KW - Proton Pump Inhibitor
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U2 - 10.1016/j.clgc.2022.01.017
DO - 10.1016/j.clgc.2022.01.017
M3 - Article
C2 - 35277350
AN - SCOPUS:85126066257
SN - 1558-7673
VL - 20
SP - 260
EP - 269
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 3
ER -