Among patients with inflammatory bowel disease (IBD), opioid prescriptions tripled during a recent 20-year period, and heavy use of strong opioids was a significant predictor of all-cause mortality, according to a large cohort study reported in the April issue of Clinical Gastroenterology and Hepatology.

Because this study was retrospective, it could not establish causality, said Nicholas E. Burr, MD, of the University of Leeds (England) and his associates. But “[de]signing and conducting a large-scale randomized controlled trial may not be feasible,” they wrote. “Despite the limitations of observational data, population data sets may be the best method to investigate a potential effect.”

The gastrointestinal side effects of many analgesics complicate pain management for patients with IBD, who not only live with chronic abdominal pain but also can develop arthropathy-related musculoskeletal pain, chronic widespread pain, and fibromyalgia. In addition to the risk of narcotic bowel associated with opioid use in IBD, opioids can mask flares in IBD or can cause toxic dilatation if administered during acute flares, the researchers noted. Because few studies had examined opioid use in IBD, the investigators retrospectively studied 3,517 individuals with Crohn’s disease and 5,349 patients with ulcerative colitis from ResearchOne, a primary care electronic health records database that covers about 10% of patients in England. The data set excluded patients with indeterminate colitis or who underwent colectomy for ulcerative colitis.From 1990 through 1993, only 10% of patients with IBD were prescribed opioids, vs. 30% from 2010 through 2013 (P less than .005). After the investigators controlled for numerous demographic and clinical variables, being prescribed a strong opioid (morphine, oxycodone, fentanyl, buprenorphine, methadone, hydromorphone, or pethidine) more than three times per year significantly correlated with all-cause mortality in both Crohn’s disease (hazard ratio, 2.2; 95% confidence interval, 1.2-4.0) and ulcerative colitis (HR, 3.3; 95% CI, 1.8-6.2), the researchers reported .Among patients with ulcerative colitis, more moderate use of strong opioids (one to three prescriptions annually) also significantly correlated with all-cause mortality (HR, 2.4; 95% CI, 1.2-5.2), as did heavy use of codeine (HR, 1.8; 95% CI, 1.1-3.1), but these associations did not reach statistical significance among patients with Crohn’s disease. Tramadol was not linked to mortality in either IBD subtype when used alone or in combination with codeine.

Dr. Burr and his associates said they could not control for several important potential confounders, including fistulating disease, quality of life, mental illness, substance abuse, and history of abuse, all of which have been linked to opioid use in IBD. Nonetheless, they found dose-dependent correlations with mortality that highlight a need for pharmacovigilance of opioids in IBD, particularly given dramatic increases in prescriptions, they said. These were primary care data, which tend to accurately reflect long-term medication use, they noted.

Crohn’s and Colitis U.K. and the Leeds Teaching Hospitals NHS Trust Charitable Foundation provided funding. The investigators reported having no conflicts of interest.

SOURCE: Burr NE et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2017.10.022.


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