Does 5‑ASA Prevent Colorectal Cancer in TNF‑Treated Ulcerative Colitis? A Real‑World Study.

Abstract

Introduction: Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC). Although 5-aminosalicylic acid (5‑ASA) have long been regarded as chemopreventive, it remains unclear whether 5-ASA therapy still confers this benefit when used concomitantly with tumour necrosis factor (TNF) inhibitors.

Methods: We performed a retrospective cohort study using the nationwide Japanese Medical Data Vision database. Patients with UC who initiated TNF inhibitors were followed from the first TNF-inhibitor prescription until CRC diagnosis or disenrollment. Concomitant 5-ASA use was defined as prescription within 90 days before or after TNF initiation. Cumulative incidence was compared with Kaplan-Meier curves and the log-rank test; hazard ratios (HRs) were estimated with multivariable Cox regression and inverse probability-of-treatment weighting (IPTW), adjusting for age, sex, primary sclerosing cholangitis (PSC), diabetes, obesity, immunomodulator use, type of TNF agent and prior advanced-therapy exposure.

Results: Among 9,919 eligible patients, 8,387 (84.6%) received concomitant 5-ASA. During follow-up (median 3.14 years), 161 CRC events occurred: crude incidence 3.67/1,000 person-years (with 5-ASA use) versus 4.58/1,000 person-years (without 5-ASA use) (P = 0.42). Concomitant 5-ASA was not associated with CRC risk (adjusted HR 1.25, 95% CI 0.76-2.04; IPTW-adjusted HR 1.28, 95% CI 0.78-2.11). Independent risk factors were older age, male sex and PSC.

Conclusions: We found no measurable chemopreventive benefit of concomitant 5-ASA in UC patients receiving TNF inhibitors during this treatment phase. Accordingly, 5-ASA need not be prioritized for colorectal-cancer prevention at this stage. Longer observation is required to clarify any benefit beyond the early years of TNF inhibitors.