Children who developed inflammatory bowel disease before the age of 18 had a three- to fivefold increase in risk of death, compared with others in a large, retrospective registry study.
The study, which spanned a recent 50-year period, found “no evidence that [these] hazard ratios have changed since the introduction of immunomodulators and biologics,” wrote Ola Olén, MD, PhD, of Karolinska University Hospital in Sola, Sweden, together with her associates. Malignancy was the most frequent cause of death among patients with childhood-onset inflammatory bowel disease, followed by digestive diseases and infections. Absolute numbers of premature deaths were low, but the increase in relative risk was highest among patients with childhood-onset ulcerative colitis with primary sclerosing cholangitis and patients who had a first-degree relative with ulcerative colitis. The findings were published in the February issue of.
Inflammatory bowel disease is thought to be more severe when it begins in childhood, but data on mortality for these patients are lacking. Using national Swedish health registries, Dr. Olén and her associates compared deaths among 9,442 children and adolescents with inflammatory bowel disease with those among 93,180 others matched by sex, age, and place of residence. Both groups were typically followed through age 30 years, and the study covered 1964 through 2014.
In all, there were 294 deaths among patients with childhood-onset inflammatory bowel disease (2.1 deaths per 1,000 person-years) and 940 deaths among matched individuals (0.7 deaths per 1,000 person-years), for a statistically significant adjusted hazard ratio of 3.2 (95% confidence interval, 2.8-3.7). For every 694 patients with childhood-onset inflammatory bowel disease who were followed through adulthood, there was one additional death per year, compared with a demographically similar population, the researchers determined.
Among the 294 deaths, 133 were because of cancer. Consequently, individuals with childhood-onset inflammatory bowel disease had a more than sixfold greater risk of dying from cancer than the general population (HR, 6.6; 95% CI, 5.3-8.2). The risk of death from malignancy was higher among individuals with ulcerative colitis (HR, 9.7) than among those with Crohn’s disease (HR, 3.1). Deaths from conditions of the digestive system were next most common, and these included deaths from liver failure.
In all, 27 individuals with childhood-onset inflammatory bowel disease died before their 18th birthday, for a fivefold increase in the adjusted hazard of death, compared with the general population of children and adolescents (HR, 4.9; 95% CI, 3.0-7.7). There was no significant trend in hazard of death according to calendar period, either among children and adolescents, or young adults (followed through age 25 years), the researchers said.
Additionally, childhood-onset inflammatory bowel disease was associated with a 2.2-year shorter life expectancy in patients followed through age 65 years, they reported. Thus, a diagnosis of childhood-onset inflammatory bowel disease merits careful follow-up, especially if patients have ulcerative colitis and primary sclerosing cholangitis, which was the strongest correlate of fatal intestinal cancer in this study.
Funders included the Swedish Medical Society, the Swedish Cancer Society, the Swedish Research Council, the Swedish Foundation for Strategic Research, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, and the Karolinska Institutet Foundation. Dr. Olén disclosed investigator-initiated grants from Janssen and Pfizer. Other investigators also disclosed ties to Janssen, Pfizer, AstraZeneca, Ferring, Celgene, and Takeda.
SOURCE: Olén O et al. Gastroenterology. 2018 Oct 17..