Patients with Crohn’s disease who were treated with tumor necrosis factor (TNF) inhibitors had a lower mortality risk than those who had prolonged corticosteroid therapy, a large retrospective cohort study found.
Among 1,879 Crohn’s patients initiating anti-TNF therapy, there was a significantly lower risk of death (OR 0.78, 95% CI 0.65-0.93) compared with risks for 7,694 patients treated with long-term steroids, according to James D. Lewis, MD, director of the Gastroenterology and Hepatology Clinical Research Program at the University of Pennsylvania in Philadelphia, and colleagues.
And while the mortality risk was numerically lower for patients with ulcerative colitis receiving anti-TNF treatment (n=459), the difference compared with steroid users (n=3,224) was not statistically significant (OR 0.87, 95% CI 0.63-1.22), the researchers reported in the American Journal of Gastroenterology.
“The reduced mortality rates among patients with Crohn’s disease was potentially a consequence of excess cardiovascular-related mortality and hip fractures and was largely limited to patients with multiple or serious comorbid conditions.”
Corticosteroids and anti-TNF therapies both are widely used in the treatment of inflammatory bowel disease, but both approaches are associated with potentially serious — and even fatal — adverse events, the team explained. Both classes of drugs are associated with serious infections and congestive heart failure, anti-TNFs have been linked with cancer, and corticosteroids are associated with pulmonary embolism and osteoporosis/fractures. Moreover, uncontrolled disease may itself raise the mortality risk.
Previous studies have demonstrated an increased mortality risk among patients with inflammatory bowel disease treated with corticosteroids, but studies assessing anti-TNF therapy have not had clear-cut results. Previous work also has not considered potentially important factors such as comorbid illness and older age in evaluating risk of death.
Lewis and colleagues therefore analyzed outcomes among patients with inflammatory bowel disease enrolled in Medicare from 2006 to 2013 and in Medicaid from 2001 to 2005.
The anti-TNF group included those who had at least one prescription for infliximab (Remicade), adalimumab (Humira), or certolizumab pegol (Cimzia) during the previous year, while the prolonged corticosteroid group included those with at least 3,000 mg prednisone or 600 mg of budesonide exposure within the past 12 months.
The primary outcome was all-cause mortality, and secondary endpoints included major adverse cardiovascular events, cancer, hip fracture, pulmonary embolism, serious infection, and emergency bowel resection. The analysis was conducted using marginal structural models and propensity scoring.
Total follow-up times among the Crohn’s disease patients were 6,222 person-years in the anti-TNF group and 24,625 person-years in the prolonged steroid group, while the corresponding numbers for ulcerative colitis were 1,213 and 9,158 person-years, respectively.
During follow-up, 1,444 patients died, with mean ages at death of 67 for patients with Crohn’s disease and 76.7 for those with ulcerative colitis.
The weighted annual incidence of death among patients with Crohn’s disease was 21.4 per 1,000 patients in the anti-TNF group and 30.1 per 1,000 in the prolonged steroid group. For ulcerative colitis, the corresponding numbers were 23 and 30.9 per 1,000, respectively.
The association between anti-TNF use and mortality risk did not differ according to age, but the lower mortality was seen only among patients with comorbidity scores higher than 3, with odds ratios of 0.65 (95% CI 0.48-0.88) for Crohn’s disease and 0.63 (95% CI 0.36-1.11) for ulcerative colitis.
For secondary endpoints among Crohn’s disease patients, anti-TNF therapy was associated with decreased risks of major adverse cardiovascular events (OR 0.68, 95% CI 0.55-0.85) and hip fracture (OR 0.54, 95% CI 0.34-0.83), although these decreased risks were not seen in patients with ulcerative colitis.
The observation that the risk of major adverse cardiovascular events was not decreased in patients with ulcerative colitis may be explained by the fact that systemic inflammation is more common in Crohn’s disease than in ulcerative colitis, the authors noted.
Hospitalizations for inflammatory bowel disease were somewhat more common in the anti-TNF group for both Crohn’s disease (OR 1.13, 95% CI 1.04-1.23) and ulcerative colitis (OR 1.53, 95% CI 1.29-1.81).
The observation that lower mortality rates seen in this analysis appeared to relate to cardiovascular disease and hip fracture as well as to the presence of serious or multiple comorbidities may have implications for treatment, the team said. Such a patient population, “which is rarely included in clinical trials and for whom some physicians may be reluctant to treat with chronic immunosuppression, may be particularly good candidates for anti-TNF agents such as corticosteroid-sparing therapy.”
Limitations of the study, the researchers said, included its residual confounding and reliance on administrative data.
The study was funded by the Patient Centered Outcomes Research Institute (PCORI).
The authors reported financial relationships with Celgene, Shire, Janssen, AbbVie, Immune Pharmaceuticals, AstraZeneca, Amgen, MedImmune, Merck, Nestle Health Science, Takeda, Pfizer, Ili Lilly, Gilead, Samsung Bioepis, Johnson & Johnson, Lycera, Evidera, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, UCB, and Crescendo.