Anti-Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease

Abstract

Importance: Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD.

Objective: To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality.

Design, setting, and participants: This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024.

Exposures: Incident use of TNF inhibitors.

Main outcomes and measures: The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality.

Results: Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses.

Conclusions and relevance: In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.

Figure 1.. Study Cohort Enrollment Flowchart

eGFR indicates estimated glomerular filtration rate; ESKD, end-stage kidney disease; and IBD, inflammatory bowel disease. ^aBaseline date was the first date of tumor necrosis factor (TNF) inhibitor prescription (for users), or a randomly assigned data that was computer-generated based on the start dates in the treated group (for nonusers) to mitigate differential start of follow-up bias.

Figure 2.. Kaplan-Meier Cumulative Event Curves for at Least 30% Decline in Estimated Glomerular Filtration Rate (eGFR) and All-Cause Mortality Associated With Incident Use (vs Nonuse) of Tumor Necrosis Factor (TNF) Inhibitors in the Overall Cohort

Log-rank P < .001 for both. Kaplan-Meier curves were demographically adjusted for age, sex, and race.

Figure 3.. Association of Incident Tumor Necrosis Factor (TNF) Inhibitor Use (vs Nonuse) With at Least 30% Decline in Estimated Glomerular Filtration Rate (eGFR) and All-Cause Mortality in Selected Subgroups in the Overall Cohort

Data are adjusted for variables included in model 6 (ie, fully adjusted model). BMI, indicates body mass index (calculated as weight in kilograms divided by height in meters squared); HR, hazard ratio; WBC, white blood cell count (to convert to ×10⁹/L, multiply by 0.001). SI conversion factors: To convert albumin to grams per liter, multiply by 10; white blood cells to ×10⁹/L, multiply by 0.001.