Crohn’s Patients Treated With Anti-TNFs Have Lower Risk for Death Than Those Treated With Corticosteroids

Issue: July 2017

CHICAGO — Patients with Crohn’s disease who were treated with anti-TNF agents showed significantly lower risks for death, cardiovascular events and hip fracture compared with patients treated with long-term corticosteroids, according to research presented at Digestive Disease Week.

Perspective from Stephen B. Hanauer, MD

These risks were not significantly different between patients with ulcerative colitis treated with either therapy.

James D. Lewis

“Prolonged corticosteroid use for IBD remains common. Compared to further corticosteroid use, initiating anti-TNF therapy was associated with lower mortality, major adverse cardiac events, and hip fracture rates among patients with Crohn’s disease, and the magnitude of this benefit appeared to be greatest in those with more comorbid illnesses,” James D. Lewis, MD, of the University of Pennsylvania in Philadelphia, said during his presentation.

Lewis and colleagues used Medicaid and Medicare data from 2006 to 2013 to identify patients with IBD who received corticosteroids within the previous year, and then either began anti-TNF therapy or received a total of 3,000 mg or more of prednisone or an equivalent within the next year. These included 7,694 Crohn’s patients who received prolonged corticosteroids vs. 1,879 Crohn’s patients who began anti-TNFs, and, among ulcerative colitis patients, 3,224 corticosteroid users vs. 459 new anti-TNF users.

Then they compared the risks for all-cause mortality and common causes of death between treatment groups, adjusting for “57 potential confounder variables including demographic characteristics, medications, diagnostic tests, comorbidities and health care utilization,” Lewis said. They also performed a number of sensitivity analyses.

They found that the weighted annual incidence of death was 21.4 per 1,000 in anti-TNF-treated Crohn’s patients vs. 30.1 per 1,000 in Crohn’s patients treated with long-term corticosteroids. In patients with ulcerative colitis, it was 23 per 1,000 in anti-TNF-treated patients vs. 30.9 per 1,000, patients treated with long-term corticosteroids.

All-cause mortality risk was significantly lower in anti-TNF-treated Crohn’s patients vs. those treated with corticosteroids (OR = 0.78; 95% CI, 0.65-0.93), but the risk was not significantly lower in anti-TNF-treated ulcerative colitis patients.

Further, anti-TNF-treated Crohn’s patients showed a significantly lower risk for major adverse cardiovascular events (OR = 0.68; 95% CI, 0.55-0.85), a significantly lower risk for hip fracture (OR = 0.54; 95% CI, 0.34-0.83), and a lower risk for stroke that was nearly statistically significant.

Conversely, there was a nearly statistically significant increase in the incidence of cancer among Crohn’s patients treated with anti-TNFs (OR = 1.27; 95% CI, 0.98-1.65). Lewis acknowledged that there may be insufficient follow-up for this outcome, but that 25% of the patients had more than 4 years follow up.

Lewis noted that while they did not see the same statistically significant pattern of mortality risk in ulcerative colitis patients, the change (OR = 0.87, 95% CI 0.63-1.22) “was in the same direction.” – by Adam Leitenberger

Reference:

Lewis JD, et al. Abstract #247. Presented at: Digestive Disease Week; May 6-9, 2017; Chicago.

Disclosures: Lewis reports financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie and Dark Canyon Laboratories.

Perspective

Stephen B. Hanauer, MD

Corticosteroids are the drugs we love to hate. While effective at improving short-term clinical signs and symptoms in IBD, steroids are merely a “band-aid” or bridge to long-term treatment with immune suppressants or biologic agents.

Further, the known metabolic effects of corticosteroids likely contribute to the long-term morbidity and mortality in IBD as has been demonstrated by the TREAT registry for infliximab as well as the DDW presentation by Lewis where both cardiovascular events and hip fractures contributed to the excess mortality associated with corticosteroid therapy in contrast to anti-TNF therapy.

In my opinion the biggest therapeutic opportunity or gap in IBD is to replace corticosteroids in the short-term and certainly long-term management strategies.

Stephen B. Hanauer, MD

Clifford Joseph Barborka Professor of Medicine

Northwestern University Feinberg School of Medicine

Medical Director, Digestive Health Center

Disclosures: Hanauer reports financial relationships with AbbVie, Janssen, Takeda, Pfizer, Celgene, Shire, Salix, Hospira, Merck, Boehringer Ingelheim, Amgen, Samsung Bioepis, Arena, Lilly, Seres Health, Tigenex, VHsquared and UCB.