PREDICTORS OF PRIMARY NON-RESPONSE AND DRUG DURABILITY FOR ADALIMUMAB AND INFLIXIMAB IN PEDIATRIC INFLAMMATORY BOWEL DISEASE
Authors: Davidson Nicole , Morris Grant , Wright Molly , Brock Guy , Boyle Brendan , Dotson Jennifer , Michel Hilary , Maltz Ross 
Published: January 2024

Abstract

BACKGROUND
Anti-tumor necrosis factor (anti-TNF) therapies have become first-line therapy for children with inflammatory bowel disease (IBD). Studies describing drug durability and loss of response to anti-TNF therapies are limited in children with IBD. This study evaluates predictors of primary non-response and long-term durability in children with IBD.

METHODS
This was a single-center retrospective review of patients with IBD aged 4-17 years that initiated anti-TNF therapy (infliximab or adalimumab) from January 1, 2014 - December 31, 2019. Clinical and laboratory data were recorded at time of anti-TNF initiation, at 14 weeks, 12 months, and 36 months. Kaplan-Meier analysis and log-rank tests evaluated long-term durability of anti-TNF therapy. Predictors of primary non-response (discontinuation of anti-TNF within 14 weeks) and long-term durability were assessed using Cox regression analysis and time-dependent receiver operating characteristic curves identified cut points.

RESULTS
A total of 456 patients were initiated on anti-TNF therapy (183 adalimumab (86% CD and 14% UC/IC) and 273 infliximab (69% CD and 31% UC/IC)). Eighty one patients were lost to follow up or transferred care.
Thirty seven (8%) patients were considered primary non-responders. Seven of these patients received adalimumab (3 CD, 4 UC/IC) and 30 received infliximab (7 CD, 23 UC/IC). In CD, baseline ESR &gt;31 mm/h was predictive of primary non-response (p&lt;0.05). In UC/IC, mono-therapy at diagnosis, baseline albumin &lt;4 g/dL, and age at diagnosis &lt;15.6 years were significant predictors of primary non-response.
Eighty patients discontinued anti-TNF therapy between 14 weeks and 36 months. Reasons for drug discontinuation included loss of response (56%), drug reaction (24%), low therapeutic level/antibodies (19%), miscellaneous (1%).
Amongst patients with CD that completed induction, week 14 lab values of albumin &gt;3.9 g/dL, hemoglobin &gt;11.8 g/dL, CRP &lt;1.2 mg/dL and calprotectin &lt;650 ug/g were associated with improved drug durability at 1 year. Patients with UC/IC had improved drug durability at 1 year if they received infliximab compared to adalimumab.
The three year drug durability for both adalimumab and infliximab was slightly above 70%. Amongst patients with CD the three year drug durability was nearly 80% for both therapies. The three year drug durability with UC/IC was 37% for adalimumab and 56% for infliximab.

CONCLUSIONS
Less than 10% of patients are primary non-responders to anti-TNF therapies; higher baseline ESR is a predictor in patients with CD, and a lower baseline albumin and younger age are predictors for patients with UC/IC. At 1 year, patients with a lesser inflammatory burden after induction appeared to have improved drug durability. Three-year durability is &gt;75% for patients with CD on either therapy, while the durability is less for patients with UC/IC.