TNF inhibitors prevent complications in kids with Crohn’s disease, recommended as first-line therapies

Early treatment of pediatric Crohn’s disease with anti-tumor necrosis factor medications can substantially reduce the risk of perianal fistulas, a particularly debilitating complication of Crohn’s disease.

Michigan Medicine researchers confirmed this finding using prospective data.

The resulting paper, “Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohn’s disease: Post-hoc analysis of the RISK study,” appeared in Gut.

A previous retrospective study from the same team had established a link between early treatment and reduced likelihood of perianal fistulas.

That research, however, was unable to confirm that anti-TNF drugs, specifically, caused the reduced risk of complication. 

“Previously, you could just say there was an association between early treatment and reduced risk of perianal fistulas, but now we have an actual time frame,” said Jeremy Adler, M.D., M.Sc., clinical professor of pediatric gastroenterology at the University of Michigan Health C.S. Mott Children’s Hospital and lead author on the paper.

“Last time we also lumped together a bunch of different medications. This time we separated them out and found it's the anti-TNF medicines specifically that prevent perianal fistulas.”

Around 40,000 children in the United States suffer from Crohn’s Disease.

Among those patients, around 1 in 3 will develop perianal fistulas.

Perianal fistulas are tunnels that develop near the anus.

They can cause pain and drainage and make the patient more likely to require an ostomy, a device that diverts stool into a pouch on the abdomen instead of having a bowel movement in a toilet.

They also come with an increased risk of morbidity as patients can develop infections or organ damage.

These debilitating and painful complications are more likely to occur in children and can be hard to successfully treat—making their prevention a priority for doctors and researchers.

Standard treatment for perianal fistulas involves anti-TNF drugs at higher doses than would be prescribed before complications begin.

There’s also no guarantee that treatment can completely solve the problem.

Around 70% of such patients require at least one surgical procedure.

“If we can prevent these disease complications, that’s way better than trying to address them once they develop, because they’re so hard to treat,” Adler said.

Earlier research by the same group had found that starting anti-TNF drugs as a first line of treatment reduced the likelihood of the patient developing a perianal fistula by about 60%. (And among those children who did develop fistulas anyway, they were significantly less likely to require an ostomy bag.)

This latest study found that anti-TNF therapy was associated with an 82% decrease in the likelihood of perianal fistula complications—and a 94% decrease for patients with perianal lesions such as large skin tags and fissures, which commonly develop in people with Crohn’s disease who don’t yet have perianal fistulas.

The data comes from the Pediatric RISK Stratification study, which followed 913 children across the United States and Canada who had been recently diagnosed with Crohn’s Disease.

Anti-TNF medications used to treat pediatric Crohn’s Disease include infliximab and adalimumab.

They have fewer side effects to the other classes of drugs typically prescribed at the beginning of Crohn’s disease treatment, namely immunomodulators such as azathioprine and methotrexate.

Beyond their superior ability to prevent perianal fistulas, however, the anti-TNF drugs are distinguished by the higher costs.

Researchers hope that given the suffering associated with perianal fistulas—and the much higher cost of treating them versus preventing them—insurers, doctors, and parents will see the benefit of opting for anti-TNF therapies as a first-line treatment.

“I think this study should really help all three groups make a decision,” Adler said.

“For the insurance companies, you prevent the fistulas and all the downstream complications those cost. For the physician, it shows this is really the more efficacious treatment. For the families, it’s a question of which drug. And this group of medicines is so effective at preventing complications."

Additional authors: Samir K. Gadepalli, Moshiur Rahman and Sandra C. Kim.

Funding/disclosures: Funding provided by the Shaevsky Family Research Fund for Crohn’s Disease. Adler has received consulting fees from Janssen Research & Development not relevant to this study.

Paper cited: “Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohn’s disease: Post-hoc analysis of the RISK study,” Gut. DOI: 10.1136/gutjnl-2024-333280

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