Anti-Tumor Necrosis Factor Therapy Associated with Reduced Mortality in IBD

Among veterans with Crohn disease (CD), anti-tumor necrosis factor (TNF) therapy was associated with reduced mortality compared with long-term corticosteroid use. These findings were published in JAMA Network Open.

Anti-TNF drugs and corticosteroids are commonly used to treat inflammatory bowel disease (IBD). However, these medications are known to have adverse effects, such as infections (both), osteoporosis (corticosteroids), and congestive heart failure (both). Previous research has suggested that anti-TNF therapy may be associated with reduce mortality compared with prolonged corticosteroid use among Medicare and Medicaid beneficiaries with IBD.

A group of researchers therefore aimed to examine the association of anti-TNF with reduced mortality relative to prolonged corticosteroid use in a cohort of veterans with IBD.

From January 1, 2006 to October 1, 2015, a well-established Veteran’s Health Administration (VHA) cohort of 2997 patients with IBD were treated with prolonged corticosteroids (>3000 mg prednosone equivalent and/or >600 mg of budesonide within a 12-month period) and/or new anti-TNF therapy. These data were then analyzed from July 1, 2019 to December 31, 2020.

Exclusion criteria included patients aged 90 years and older, patients with IBD diagnosed before 2006, and patients with a diagnosis of HIV, rheumatoid arthritis, psoriatic arthritis, psoriasis, or ankylosing spondylitis. The primary end point was all-cause mortality, which was defined by the Veterans Health Association (VHA) vital status file. 

The study participants were mostly men 2725 (90.9%), mean (standardized difference [SD]) age was approximately 50.0 (17.4) years, 1734 (57.9%) were diagnosed with CD and 1263 (42.1%) with ulcerative colitis (UC).

The overall mortality in the study population was 8.5% (n= 256) over a mean (SD) of 3.9 (2.3) years of follow-up. Upon cohort entry, 1836 patients (61.3%) were new anti-TNF therapy users and 1161 (38.7%) were prolonged corticosteroid users.

After controlling for covariates, the adjusted mortality odds ratio (aOR) for the commencement of anti-TNF therapy compared with receiving corticosteroids was 0.54 (95% CI, 0.31-0.93) in the CD cohort and 0.33 (95% CI, 0.10-1.10) in the UC cohort.

In a sensitivity analysis adjusted for prolonged corticosteroid users to include patients receiving corticosteroids within 90 to 270 days after commencement of anti-TNF therapy, the OR for UC was statistically significant at 0.33 (95% CI, 0.13-0.84), and the OR for CD was 0.55 (95% CI, 0.33-0.92).

This study is not without limitations. Residual and unmeasured confounding are possible and data on smoking were not included. The study population was limited to veterans receiving care within the VHA, thus these findings may not be generalizable to all patients with IBD. The investigators noted that limited sample size may have contributed to the lack of a significant mortality reduction seen in the group of patients with UC.

According to the data, anti-TNF therapy was associated with a lower likelihood of mortality compared with long-term corticosteroid use among veterans with CD. Though, it should be noted that the reduction in mortality among anti-TNF agent users with UC was not considered statistically significant during the primary analysis.

According to the study authors, “Given the observation that older patients with more comorbidities do not seem to receive anti-TNF agents to the same degree as their younger, healthier counterparts, there is an urgent need to recognize the benefit associated with anti-TNF therapy vs corticosteroid use in such populations.”

Disclosure: Some study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.

Disclosure: This research was supported by the Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety. Please see the original reference for a full list of disclosures.

Reference

Cohen-Mekelburg S, Wallace BI, Van T, et al. Association of anti-tumor necrosis factor therapy with mortality among veterans with inflammatory bowel disease. JAMA Netw Open. Published online March 1, 2021. doi:10.1001/jamanetworkopen.2021.0313