Upadacitinib Offers Effective Induction for Pediatric Crohn Disease, Safety Profile Requires Scrutiny

For children battling severe Crohn disease, upadacitinib offers an effective induction therapy but its benefits must be carefully weighed against potential adverse events. | Image Credit: mandm. - stock.adobe.com

Upadacitinib shows promise as an effective induction therapy for children with refractory Crohn disease, but its efficacy must be carefully balanced against potential adverse events (AEs), according to a study published in Alimentary Pharmacology & Therapeutics.1

When children with active Crohn disease don't achieve or maintain remission with steroids, exclusive enteral nutrition (EEN), and an immunomodulator, or face a high risk of a complicated disease course, current guidelines recommend anti-tumor necrosis factor (TNF)-α agents. Real-world data also support using other biologics like vedolizumab and ustekinumab, and Janus kinase (JAK) inhibitors such as tofacitinib, for children with refractory disease, even though these treatments have adult approvals but not pediatric indications.

Ustekinumab, a monoclonal antibody, targets the p40 subunit of interleukin (IL)-12 and IL-23.2 In 2009, the FDA and European Medicines Agency first approved its reference product, Stelara. Both agencies later approved ustekinumab in 2016 to treat Crohn disease.

"This study aimed to evaluate upadacitinib's effectiveness, safety, and dosing for inducing remission in pediatric Crohn's disease,” study authors stated.1

A retrospective cohort study was conducted by researchers at 30 centers in Europe, the Middle East, and North America. These centers are part of the Paediatric Inflammatory Bowel Disease Interest and Porto group of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.

This study investigated 100 children, all with active Crohn disease, who started upadacitinib therapy. Their median age at the initiation of upadacitinib was 15.8 years, and they had experienced the disease for a median of 4.4 years. Before receiving upadacitinib, all participants had undergone treatment with various biologic agents: 97 children received anti-TNFα agents, 83 received ustekinumab, 31 received vedolizumab, and 5 received risankizumab. Additionally, 11 patients had previously received tofacitinib.

A total of 86 patients received a 45 mg daily induction dose, with other patients receiving lower doses. The median daily dose for children weighing 30 kg to 40 kg was 1.2 mg/kg (35.8 mg/m2 BSA), and for those weighing 20 kg to 30 kg, it was 1.3 mg/kg (33.2 mg/m2 BSA).

Researchers administered upadacitinib to 47 children at baseline, combining it with other ongoing treatments. These concomitant therapies included biologic agents, which 22 children received (ustekinumab, 17; risankizumab, 3; vedolizumab, 2). Additionally, 21 children received corticosteroids, 4 received EEN, 2 received 5-aminosalicylic acid, and 1 received azathioprine. In all instances where upadacitinib was combined with steroids or a biologic agent, researchers added upadacitinib to the patient's existing steroid or biologic regimen.

By the end of the induction period, 89% of children continued upadacitinib therapy through the end of the induction period. At week 8, clinicians observed a clinical response in 75% of children, clinical remission in 56%, and clinical free remission (CFR) in 52%. By week 8, 62% of children who began upadacitinib therapy on corticosteroids were steroid-free.

Induction therapy successfully normalized C-reactive protein in 68% of patients, and 58% achieved fecal calprotectin (FC) levels below 150 mcg/g. We observed combined C-reactive protein and FC remission in 42% of the children whose data was available. For patients with available data, 44% demonstrated a clinical response, 33% reached clinical remission, and 24% achieved combined CFR and FC remission.

Upadacitinib therapy was associated with potential AEs in 24 children, with acne being the most common (n = 12). Physicians discontinued upadacitinib in 2 cases due to severe acne and elevated serum triglycerides (233 mg/dL). Patients did not experience any thromboembolic events, severe infections, or malignancies. Furthermore, no one received Pneumocystis jirovecii pneumonia prophylaxis.

The study has several limitations, the authors noted. The retrospective nature prevented structured data follow-up, specifically lacking organized reporting of week 4 outcomes, complete laboratory data, and systematic adverse event monitoring. It also lacked endoscopic follow-up data for most patients during induction. The small patient number prevented multivariate analysis for all outcomes, and we included few young children. Finally, the short-term follow-up highlights a clear need for long-term efficacy and safety data on upadacitinib in children.

“While the safety profile was generally favorable, the efficacy of upadacitinib should be weighed against the potential risk of AEs,” study authors concluded.

References

1. Cohen S, Spencer EA, Dolinger MT, et al. Upadacitinib for induction of remission in paediatric Crohn's disease: an international multicentre retrospective study. Aliment Pharmacol Ther. 2025;61(8):1372-1380. doi:10.1111/apt.70016

2. Ferreri D. Future directions for ustekinumab biosimilars in Crohn disease. The Center for Biosimilars®. May 3, 2025. Accessed June 12, 2025. https://www.centerforbiosimilars.com/view/future-directions-for-ustekinumab-biosimilars-in-crohn-disease