Abstract
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.
Keywords
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Article Info
Publication History
Published online: February 01, 2022
Accepted:
January 25,
2022
Received in revised form:
December 20,
2021
Received:
May 17,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
