111 Loss of Response to Anti-TNF Infusion Treatment in Pediatric Inflammatory Bowel Disease (IBD) Patients

Background: Pediatric patients with moderate-to-severe inflammatory bowel disease (IBD) frequently require anti-TNF infusions which are typically the first line biologic agents used, as they are considered efficacious for inducing long-term remission. A challenge of their use is loss of response; either due to initial failure that manifests early in the treatment course, referred to as primary non-response (PNR); or a subsequent failure after an initial response, referred to as secondary loss of response (sLOR). There is limited published data on the incidence of PNR and sLOR in the pediatric age group. Data from our diverse IBD population provides an opportunity to better understand these. Methods: By retrospective chart review we identified patients with IBD seen at the University of Maryland Pediatric Infusion Center from January 2019 to May 2025 who received infliximab or biosimilar infusions as their first biologic treatment and were subsequently transitioned to another biologic treatment. Results: We identified 195 patients who received infusions of infliximab or its biosimilars) as their initial biologic treatment. One hundred fifty (77%) had Crohn’s disease (CD), 42 (22%) had ulcerative colitis (UC), and 3 (2%) had an indeterminate diagnosis; 76 (39%) were female. The median age at their first infusion was 13 years. The median BMI at therapy initiation was 18.8 kg/m2. Thirty-one patients (16%) switched therapy due to treatment failure (TF), including the presence of symptoms and/or endoscopic evidence of mucosal disease. The median time to decide to switch treatment was 57 weeks. Prevalence of TF was not significantly different between females and males (18% vs 14%; P = 0.44). PNR was defined by the decision to switch within 16 weeks of starting treatment; sLOR was defined by the decision to switch after 16 weeks. Four patients (2.0%) had PNR; 27 patients (14%) had sLOR. Three patients with CD (2%) and 1 patient with UC (2%) had PNR. Twenty patients with CD (13%) and 7 patients with UC (17%) had sLOR. Therapeutic drug level monitoring was performed. Of the TF patients, prior to the transition 7 had low or non-detectable infliximab levels, 6 of which had sLOR. Eight TF patients had detectable antibodies to infliximab, all of which were sLOR. There were no statistically significant differences in TF, PNR, or sLOR between CD and UC patients. Medications switched to included ustekinumab (n = 10; 32%), vedolizumab (n = 10; 32%), adalimumab (n = 9; 29%), ozanimod (n = 1; 3%), and risankizumab-rzaa (n = 1; 4%). Conclusions: Anti-TNF infusion treatment failure in pediatric IBD is common. TF was more frequently due to sLOR than PNR. There was no difference between CD and UC patients for TF occurrence. By studying those seen at an infusion center, we were able to study patients in a controlled environment which permitted close monitoring of clinical symptoms and biochemical markers. This could possibly lead to earlier detection of treatment failure. This may however limit the generalizability of our observations to other IBD patients. Knowledge of the likelihood of success of treatment with infliximab and biosimilars is important in helping patients, caregivers and clinicians to navigate long-term IBD care.