Study Identifies Predictors of Anti-TNF Nonresponse in Pediatric IBD

A recent study identified 1 predictor of primary nonresponse to infliximab in children with Crohn’s disease (erythrocyte sedimentation rate > 55 mm/h on infliximab) and 2 predictors of nonresponse in ulcerative colitis/ unclassified inflammatory bowel disease (UC/IBD-U) (baseline albumin <4 g/dL and <15.6 years at diagnosis).1

“This study lends support for the long-term durability of anti-TNF therapies for pediatric IBD, while keeping in mind predictive factors of nonresponse,” wrote investigators, led by Nicole Davidson, MD, from the division of pediatric gastroenterology, hepatology, and nutrition at Nationwide Children's Hospital in Ohio.

First-line treatment options for children with IBD, ulcerative colitis, and IBD-unclassified include antitumor necrosis factor (anti-TNF) therapies. Yet, limited studies have evaluated the durability of anti-TNF therapies or the proportion of children who experience a loss of response. Investigators sought to assess predictors of primary nonresponse to anti-TNF therapies, including infliximab or adalimumab, and the 3-year drug durability in children with IBD.

The team conducted a single-center retrospective review of 456 patients with IBD ≤ 18 years who initiated an anti-TNF therapy, either infliximab (n= 273) or adalimumab (n = 183), from 2014 to 2019. Clinical and laboratory data were collected at the time of anti-TNF initiation, 14 weeks, 12 months, and 3 years. Investigators assessed predictors of primary nonresponse, indicated by a discontinuation within 14 weeks, and durability.

Among the sample, 8% (n = 37) were primary non-responders (3% with Crohn’s disease and 25% with UC/IBD-U). The 3-year durability for both infliximab and adalimumab was> 70%. Patients with Crohn’s disease had a 3-year durability of > 75% for both therapies (81% for infliximab and 77% for adalimumab). As for patients with UC/IBD-U, the study showed that the 3-year durability was 56% for infliximab and 37% for adalimumab.

“While our study evaluated loss of response as well as other indications for drug discontinuation, we found overall higher drug durability rates at 3 years compared to prior studies,” investigators wrote.

For instance, an adult Crohn’s disease study reported a 72% and 62% 3-year durability of adalimumab on combination and monotherapy, respectively.2 A pediatric study examining 1-year drug durability rates of adalimumab and infliximab had similar findings to this recent study.3 Another study found 90% of the children with Crohn’s disease remained on their first biologic at 1 year and 73% by 3 years, though this study included all biologics, and not just anti-TNF therapies, and participants were only eligible within 90 days of their Crohn’s disease diagnosis.4

In Davidson and colleagues’ study, patients with less active Crohn’s disease post-induction (Week 14 albumin > 3.9 g/dL, week 14 hemoglobin > 11.8 g/dL, week 14 CRP < 1.2 mg/dL, and Week 14 calprotectin < 650 µg/g) were more likely to remain on medication at 1 year than patients with evidence of active disease.1 The use of infliximab vs adalimumab was the only significant factor impacting long-term durability at 1 year in UC/IBD-U.

“This may be attributed to the use of infliximab in the treatment of acute severe colitis, and that adalimumab was not approved for pediatric UC until 2021, which limited drug availability in our study population,” investigators noted.

The research found that an erythrocyte sedimentation rate > 55 mm/h in Crohn’s disease was a predictor of primary nonresponse to infliximab. Primary nonresponse predictors for UC/IBD-U included baseline albumin of <4 g/dL, being younger at diagnosis (< 15.6 years), and not being on combination therapy.

“The 3-year drug durability in CD was similar for adalimumab (77%) and infliximab (81%), and it is higher than in adults on anti-TNFs,” investigators wrote. “…the infliximab long-term durability was higher compared to adalimumab in UC/IBD-U.”

Reference

1. Davidson N, Morris GA, Wright MA, et al. Predictors of antitumor necrosis factor primary nonresponse and drug durability in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. Published online July 21, 2025. doi:10.1002/jpn3.70160

2. Atia O, Friss C, Focht G, et al. Durability of the First Biologic in Patients with Crohn's Disease: A Nationwide Study from the epi-IIRN. J Crohns Colitis. 2024;18(1):38-46. doi:10.1093/ecco-jcc/jjad121

3. deBruyn JC, Huynh HQ, Griffiths AM, et al. Adalimumab vs Infliximab in Luminal Pediatric Crohn's Disease: Comparable Outcomes in a Prospective Multicenter Cohort Study. Am J Gastroenterol. 2024;119(3):565-575. doi:10.14309/ajg.0000000000002552

4. Ali S, Pasternak B, Moses J, et al. Characterization of Biologic Discontinuation Among Pediatric Patients With Crohn's Disease. Clin Gastroenterol Hepatol. 2024;22(10):2075-2083.e1. doi:10.1016/j.cgh.2024.03.043