Chronic opioid use and the risk of infections and death in patients with inflammatory bowel disease: a nationwide cohort study based on real-world data

Abstract Background Chronic opioid use (COU) is frequent in inflammatory bowel disease (IBD), but data on its association with infections and mortality are scarce. We examined (1) hospital-diagnosed infections, (2) prescribed systemic antibiotic/antiviral/antifungal agents, and 3) death associated with COU, and assessed these outcomes according to opioid strength. Methods This nationwide cohort study included all prevalent adult patients with Crohn disease (CD) and ulcerative colitis (UC) in Denmark from January 1, 2000, to June 30, 2023. Chronic opioid use (COU) was a time-varying exposure (≥3 opioid prescriptions within 12 months, with ≥ 30 days between each prescription). Cox regression models were used to estimate adjusted hazard ratios (aHRs), including baseline and time-varying covariates (IBD surgery, IBD medications, and psychotropic medications). Results We included 18 897 patients with CD, of whom 3948 (20.9%) had COU. Among those with COU, the aHRs for hospital-diagnosed infections, prescribed antibiotics, and death were 1.91 (95% CI, 1.79-2.04), 1.47 (95% CI, 1.40-1.56), and 1.76 (95% CI, 1.58-1.96), respectively. We included 32 947 patients with UC, of whom 4779 (14.5%) had COU. Among those with COU, the aHRs for hospital-diagnosed infections, prescribed antibiotics, and death were 1.93 (95% CI, 1.80-2.06), 1.56 (95% CI, 1.47-1.65), and 1.74 (95% CI, 1.60-1.90), respectively. Both strong and weak opioids were associated with these adverse outcomes in CD and UC. Conclusions Real-world data have demonstrated an association between COU and increased risks of infections and mortality, independent of opioid strength, affecting users of both strong and weak opioids. Clinicians should be attentive to these risks when prescribing opioids to this population.