TNF Inhibitors Do Not Up Risk of Serious Infection in Kids With IBD

By Will Boggs MD

September 13, 2019

NEW YORK (Reuters Health) - The use of tumor necrosis factor (TNF)-alpha inhibitors is not associated with an increased risk of serious infection in children with inflammatory bowel disease (IBD), according to data from Denmark.

"The result was unexpected since previous studies in adults have shown risk increases following anti-TNF treatment of 40-70%," Viktor Wintzell of Karolinska Institutet, in Stockholm, Sweden, told Reuters Health by email.

TNF-alpha inhibitors are highly effective for inducing and maintaining remission in pediatric inflammatory bowel disease (IBD), but there are limited data in children with IBD regarding the risk of serious infection associated with use of TNF-alpha inhibitors.

Wintzell and colleagues used data from nationwide registers in Denmark to investigate whether there is an association between TNF-alpha inhibitor use and the risk of serious infection in children with IBD. They defined serious infection as an inpatient hospital admission with a physician-assigned diagnosis code for any infection.

Among 2,817 children with IBD (618 treated with TNF-alpha inhibitors and 2,925 treated without TNF-alpha inhibitors), the incidence of serious infection events per 1,000 patient-years did not differ significantly between patients on TNF-alpha inhibitors (54.6) and those not on such drugs (45.7).

After propensity-score weighting to adjust for potential confounding, the incidences per 1,000 patient-years remained similar (54.6 vs. 61.9, respectively), the researchers report in The Lancet Gastroenterology and Hepatology, online September 4.

There was no association between TNF-alpha-inhibitor use and the risk of serious infections in any of the five specific sites evaluated (respiratory tract, gastrointestinal tract, urinary tract, skin and subcutaneous tissue, and other infections).

Results were similar in a post-hoc analysis restricted to TNF-alpha-inhibitor episodes with and without previous thiopurine and corticosteroid use and in a supplementary analysis of pediatric patients with IBD in Sweden.

"That we found no risk increase is reassuring and supports the current use of anti-TNF treatment in children with IBD," Wintzell said. "The results can be used when deciding on optimal treatment strategy, including the timing of anti-TNF initiation."

"Since our findings were unexpected and contrasted by previous findings in adults, future pediatric studies on this topic will be important to support treatment decisions," he said. "Studies from other health care settings and based on larger cohorts are needed to confirm and help explain the potential risk differences between children and adults."

Dr. Claudio Romano of the University of Messina, in Italy, who recently reviewed the risks of infections and malignancies associated with TNF-alpha-blocking agents in pediatric IBD, told Reuters Health by email, "The data are in line with what is evident in the literature. Anti-TNF therapies in children are not associated with increased risk of opportunistic infections. Biological therapies are safe if the immunization status is checked before starting therapy."

He added that early introduction of biologics in pediatric IBD patients is associated with greater efficacy and a lower infection risk compared with the prolonged use of steroids and azathioprine.

Dr. Jin Soo Moon of Seoul National University, Children's Hospital, in South Korea, recently reviewed the clinical aspects and treatments for pediatric IBD. While he agreed that for "most pediatric IBD patients, anti-TNF-alpha blockers can be applied safely," he worried that the new study could have missed some serious infections by restricting the definition to include only hospital admissions.

Moreover, he told Reuters Health by email, some life-threatening serious infections might have been underweighted due to their rarity (such as disseminated tuberculosis and encephalitis).

The study had no commercial funding. Some of Wintzell's coauthors declare ties to companies selling TNF inhibitors.


Lancet Gastroenterol Hepatol 2019.