105 Ruxolitinib Therapy in Medically Refractory Pediatric IBD

Background: Pediatric onset inflammatory bowel disease (PIBD) is often more aggressive than adult-onset disease with higher rates of biologic use. Anti-TNF therapy is effective but carries notable risks including secondary loss of response, intolerance, and immunogenicity. Absence of other approved advanced therapies significantly complicates care. Janus Kinase (JAK) inhibition has become an important mainstay of salvage therapy in refractory adult IBD. Upadacitinib is a selective JAK1 inhibitor approved for use after anti-TNF exposure in adult patients with moderate to severe IBD. Real-world evidence for upadacitinib in children with IBD is emerging, however its use is limited to patients who can successfully swallow pills as the extended-release formulation prevents administration of a crushed tablet. Ruxolitinib is a selective JAK1/JAK2 inhibitor approved for use in pediatrics age ≥12 years for gastrointestinal graft versus host disease. Ruxolitinib has been shown to be effective in a small case series of patients with refractory very early onset IBD. Methods: We performed a retrospective chart review of all PIBD patients at Cohen Children’s Medical Center treated with ruxolitinib. Patient demographics and clinical outcomes were recorded. Clinical response was defined as a decrease of >20 points in the Pediatric Ulcerative Colitis Index (PUCAI) score and clinical remission as a PUCAI <10. Results: From February 2024 to September 2025, 8 children received ruxolitinib at the PIBD Center at Cohen Children’s (75%) male; age at drug initiation 2–10 years; mean 6.3. The mean age at diagnosis was 4.9 years (range 1–10 years). All had pancolitis, history of previous hospitalization(s), steroid exposure and an inadequate response to anti-TNF therapy (adalimumab, n = 2 and infliximab, n = 6). One had previous tofacitinib exposure. Ruxolitinib was started in 3/8 (37%) as salvage therapy during hospitalization for acute severe colitis and 3/8 (37%) received ruxolitinib as part of advanced combination therapy (vedolizumab, n = 1; risankizumab, n = 2). Mean baseline PUCAI was 50 (range 15–85). Seven (87%) of the 8 achieved steroid free clinical remission within 6 weeks of ruxolitinib therapy. The remaining patient achieved clinical response by 2 weeks and ultimately achieved steroid free clinical remission. Five subjects were followed with intestinal ultrasound and all demonstrated sonographic improvement characterized by decreased bowel wall thickness and hyperemia. There were 2 serious adverse events (SAEs): a complicated pneumococcal pneumonia requiring ICU admission 5 weeks after starting ruxolitinib without an anti-TNF washout and a case of severe colitis secondary to Salmonella infection requiring hospitalization. Both SAEs responded to antibiotic therapy and resolved without sequelae with subsequent continuation of ruxolitinib as maintenance therapy. Conclusions: Ruxolitinib monotherapy or as part of advanced combination therapy can be an effective therapeutic option for pediatric patients with refractory severe inflammatory bowel disease. Careful monitoring for infectious complications seems warranted.