A new study presented at the 2024 Annual North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Meeting indicates that advanced combination therapy may be an effective non-surgical approach for children and young adults suffering from refractory inflammatory bowel disease (IBD). The single-center, retrospective study, which included TNF-alpha inhibitors, vedolizumab, ustekinumab, dupilumab, and JAK inhibitors, offers hope for patients who have not responded to monotherapy with biologic or small molecule inhibitors.
Efficacy of Advanced Combination Therapy
The study involved 12 patients under 18 years of age diagnosed with Crohn’s disease (n = 7), ulcerative colitis (n = 3), or IBD unspecified (n = 2). All participants had previously failed at least one biologic agent or molecule inhibitor as monotherapy and continued advanced combination therapy for at least 4 months. The primary outcome assessed was steroid-free clinical remission (SFCR) at 6 months. The mean duration of the first trial of advanced combination therapy was 27.1 months. Results showed that 7 out of 12 patients (58.3%) achieved SFCR at 6 months.
According to Lauren Collen, MD, from Boston’s Children’s Hospital, the therapeutics used in these combinations target specific immune signaling pathways. "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," she stated.
Additional Outcomes and Observations
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 reported that 9 patients on advanced combination therapy (75%) demonstrated normal CRP levels at 6 months. Among the 6 patients who had extraintestinal manifestations of IBD, 4 (66.7%) demonstrated remission of these manifestations at 6 months. Notably, no adverse events were observed during the study period.
Challenges and Future Directions
Dr. Collen highlighted the challenges associated with using advanced therapies in pediatric populations, particularly the off-label use of drugs approved by the FDA for adults. This often leads to insurance coverage issues, delaying necessary 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 explained. "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."
