Marla Dubinsky, MD: Using Off-Label Treatments to Address the Unmet Need in Pediatric IBD

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Marla Dubinsky, MD, discusses the use of off-label upadacitinib in pediatric IBD patients and the importance of this research due to delays in pediatric drug approvals.

Despite the growing armamentarium of new drugs for Crohn disease (CD) and ulcerative colitis (UC) in adults, US Food and Drug Administration (FDA)-approved advanced treatment options for pediatric patients with inflammatory bowel disease (IBD) are few and far between.

Currently, adalimumab and infliximab, both anti-tumor necrosis factor (TNF) agents, are the only advanced therapies available to children with IBD, limiting the scope of what pediatric gastroenterologists are able to offer their patients.

Marla Dubinsky, MD, chief of the division of pediatric gastroenterology at Mount Sinai Kravis Children’s Hospital, explained to HCPLive the limitations posed by the lack of pediatric indications for IBD therapies approved in adults: “Just like somebody who's 18, as opposed to 17, there are other therapies that may be more appropriate for that patient.”

Specifically, she pointed to the growing number of pediatric patients developing skin reactions to anti-TNF therapies with no other treatment options available to them. As a result, clinicians have had to get creative with how they step out of the “TNF bucket,” working around limited FDA indications with off-label utilization of therapies approved for adult patients.

“We're trying to make the lifecycle of suffering much shorter. In peds, we have growth, we have a lot of things that we're working on, and so we will do anything to improve the lives of our pediatric patients,” Dubinsky said.

In an effort to accomplish this, she and a team of investigators from Mount Sinai sought to provide real-world data on the safety and effectiveness of upadacitinib, a novel selective JAK inhibitor approved for adults with UC and with positive phase 3 data for CD, in pediatric patients with IBD. Dubinsky described upadacitinib as having “changed people's lives similar to how I feel infliximab was when it first came out in the 90s,” citing its use in patients refractory to other therapies and what this may offer to pediatric patients who do not respond to anti-TNFs.

The single-center retrospective case series study included 29 adolescent patients 12-17 years of age with IBD (n = 9 for CD; n = 10 for UC) receiving upadacitinib for ≥12 (median 51 [43-63]) weeks. Among the cohort, 55% of patients were female, the median age was 15 years, and 90% were on ≥2 biologics.

The study’s primary outcome was postinduction steroid-free clinical remission (SF-CR), defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes included postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through the last follow-up

Upadacitinib was used as monotherapy in 55% of participants and as combination with ustekinumab and vedolizumab in 35% and 10% of participants, respectively, a practice Dubinsky described as “a lens into the future” as she encourages gastroenterologists to “think outside the gut.”

Results showed week 12 SF-CR was achieved in 75% of patients, and 80% achieved SF-CR with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse events occurred in 2 patients: cytomegalovirus colitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% of participants with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively.

“Earlier utilization of advaced therapies results in better outcomes. So pediatric patients tend to do very well, no matter which therapy we try, on-label or off-label. We don't wait 11 years like the clinical trials wait to actually give these new drugs,” Dubinsky said, explaining how adding or combining effective therapies in pediatric patients, even if they are off-label, before bowel wall damage leads to better outcomes.


Spencer EA, Bergstein S, Dolinger M, et al. Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease, Inflammatory Bowel Diseases, 2023; izad300,