By David Douglas
NEW YORK (Reuters Health) - Patients being treated with anti-TNF alpha agents, particularly etanercept, for autoimmune diseases such as rheumatoid arthritis (RA) are at increased risk of developing inflammatory bowel disease (IBD), according to a Danish population-based study.
As lead author Dr. Joshua Korzenik, told Reuters Health by email, "For the clinician it is important to recognize the development of IBD as a potential complication of etanercept therapy as the discontinuation might improve the IBD."
In a paper online July 3 in Alimentary Pharmacology and Therapeutics, Dr. Korzenik of Brigham and Women's Hospital, in Boston, and colleagues note that in Denmark anti-TNF alpha therapy is administered only in hospitals or hospital-based out-patient settings. This system, they explain, "permits a complete assessment of individuals receiving an anti-TNF alpha and its associated consequences."
The team studied data on more than 17,000 patients who had a diagnosis calling for such agents for non-IBD indications including RA, psoriatic arthritis and ankylosing spondylitis between 2004 and 2017. Most received infliximab, etanercept or adalimumab. They compared these with more than 63,000 patients with autoimmune diseases who had not been exposed to the drugs.
Patients treated with etanercept had significantly increased risks of being diagnosed with Crohn's disease (adjusted hazard ratio, 2.0) and ulcerative colitis (aHR, 2.0) while under treatment. Corresponding hazard ratios for infliximab were 1.3 and 1.0, and for adalimumab, 1.2 and 0.6 - none of which represented significant risk increases.
"The data from the Danish health registries have a very high completeness and validity," the researchers observe, adding that "as in other observational studies confounding can never be ruled out."
Dr. Korzenik noted, "This study also raises a number of important research questions: what is the natural history of the IBD which develops in this setting; what are the risk factors which increase the possibility of this occurring and what are the pathologic mechanisms underlying this process? These questions may be relevant more broadly to the development of IBD as well as other autoimmune diseases."
Dr. Arthur Kavanaugh of the UC San Diego School of Medicine, in La Jolla, who was not involved in the study but has conducted similar research, called it "an interesting report" in an email to Reuters Health.
But Dr. Kavanaugh also point out that "the numbers of cases are quite small; with the strong potential for bias, one would have to interpret carefully."
Aliment Pharmacol Ther 2019.