Lauren Collen, MD: Advanced Combination Therapy May Be Effective Option for Pediatric Refractory IBD

A new study presented at the 2024 Annual North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Meeting in Hollywood, Florida, from November 7 to 9, 2024 demonstrated advanced combination therapy may be an effective non-surgical option for children and young adults with refractory inflammatory bowel disease (IBD).

As the incidence and prevalence of pediatric IBD increases, so does the increased number of pediatric patients who do not respond to monotherapy with a biologic or small molecule inhibitor. Investigators sought to examine the efficacy and safety of advanced combination therapy in pediatric patients with IBD. They conducted a single-center, retrospective study of 12 patients aged < 18 years with an IBD diagnosis—either Crohn’s disease (n = 7), ulcerative colitis (n = 3), or IBD unspecified (n = 2)—with a primary outcome of steroid-free clinical remission at 6 months. Participants were included if they failed ≥ 1 biologic agent or molecule inhibitor as monotherapy and continued an advanced combination therapy for ≥ 4 months.

The mean duration of the first trial of advanced combination therapy, a treatment involving TNF-alpha inhibitors, vedolizumab, ustekinumab, dupilumab, and JAK inhibitors, was 27.1 months. Among the 12 patients, 7 (58.3%) achieved steroid-free clinical remission at 6 months of advanced combination therapy.

“The therapeutics that we're using, anti TNF, il 23 blockade il 1223, blockade Jak inhibitors, anti-integrins, there are all, for the most part, targeting specific immune signaling pathways,” said investigator Lauren Collen, MD, from Boston’s Children’s Hospital during an on-site interview with HCPLive. “I think for some patients with IBD, and in particular refractory IBD, there might just be more than one kind of dominant aberrant signaling pathway at play, and I think some of these patients just need to target more than one pathway to get their disease into remission.”

Out of the 5 patients who did not achieve clinical remission at 6 months, 1 patient achieved SFCR at 12 months, 2 patients switched to an alternate advanced combination therapy regimen, and 2 patients discontinued ACT and returned to monotherapy or surgery.

The study also showed 9 patients on advanced combination therapy (75%) demonstrated normal CRP at 6 months. Among the 6 patients who had extraintestinal manifestations of IBD, 4 (66.7%) demonstrated remission of EIMs at 6 months. Investigators observed no adverse events.

Collen recognized the challenge of advanced therapies in pediatric populations. In studies, they often examine off-label use drugs, approved by the US Food and Drug Administration for adult use, for pediatric inflammatory bowel diseases. However, this creates an insurance obstacle since insurance companies are resisting to cover drugs for children that are not FDA-approved, and therefore this can delay treatments for children.

“When you have a patient who has often failed many biologic or small molecule drugs when they're used individually…you really feel like they're a patient that needs 2 drugs to target….2 different mechanisms to get their disease and remission,” Collen said. “It is an even added burden because often you're requesting multiple drugs that aren't FDA approved, and it makes for challenges getting approval and getting insurance companies to buy in. The pediatric IBD community would really benefit from more FDA approvals and better access to the drugs that we know work in adult IBD, and there's tons of retrospective data to show that it works in kids, too. We just need easier access to those drugs.”

References

^{Bachand, J, Ouahed, J, Bousvaros, A, et al. Single-Center Experience Of Advanced Combination Therapy In Pediatric And Young Adult Patients With Inflammatory Bowel Disease. Presented at NASPHGAN 2024 in Hollywood, Florida, from November 7 – November 9, 2024.}