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. 2024 Nov 4;30(11):2057-2063.
doi: 10.1093/ibd/izad300.

Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease

Elizabeth A Spencer  1 , Suzannah Bergstein  1 , Michael Dolinger  1 , Nanci Pittman  1 , Amelia Kellar  1 , David Dunkin  1 , Marla C Dubinsky  1
Affiliations

Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease

Elizabeth A Spencer et al. Inflamm Bowel Dis. .

Abstract

Background: Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD.

Methods: This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The 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 include 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 last follow-up.

Results: Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegalovirus colitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively.

Conclusion: While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile.

Keywords: Crohn’s disease; adolescent; inflammatory bowel disease; pediatric; ulcerative colitis; upadacitinib.

Plain language summary

This case series presents novel data on the effectiveness and safety of upadacitinib in adolescent patients with IBD.

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Conflict of interest statement

S.B.: Support from the Digestive Disease Research Foundation (DDRF) Fellowship Program. M.C.D.: Consulting fees from Abbvie, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer -Ingelheim, Celgene, Ferring, Genentech, Gilead, Hoffmann-La Roche, Janssen, Pfizer, Prometheus Biosciences, Takeda, and Target PharmaSolutions. Research funding from Abbvie, Janssen, Pfizer, Prometheus Biosciences, and Takeda. Cofounder and CEO of Trellus Health. M.T.D.: Consulting fees from Neurologica Corp., a subsidiary of Samsung Electronics Co., Ltd. A.K.: No conflict of interest. N.P.: No conflict of interest. D.D.: No conflict of interest. E.A.S.: Grant support from the NIH (K23DK125760-01).

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Postinduction and 6-month clinical outcomes in adolescents with IBD on upadacitinib.
Figure 2.
Figure 2.
Survival of steroid-free clinical remission on upadacitinib in adolescents with IBD in all comers (left) and by IBD type (right).
See this image and copyright information in PMC

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