Early Initiation of Biologics and Disease Outcomes in Adults and Children with Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort

Review by Prof. Jonathan O'Donnell (Australia)

Study Summary 

Biologic use in inflammatory bowel disease has been steadily increasing, with arguments that early initiation or a “top down” approach will positively impact natural history of disease. The true effect of timing to initiation of biologics is still contentious.

This study examined rates of steroid dependency and IBD related surgery for those on biologics <3 months, 3-12 months, 1-2 years and 2-3 years from diagnosis in 9,477 patients. 93% of CD and 75% of UC initiated anti-TNF as a first biologic.

The only significant difference in CD related surgeries was seen between <3 month initiation and >2-3 year initiation (13% absolute risk reduction, NNT 7.7). A similar effect size was seen with steroid dependency with biologics earlier than 12 months associated with reduced rates of dependence (NNT with biologics <3 months compared to 2-3 years - 8.3). No effect was seen in UC.

This study has shown a clear advantage to biologic initiation earlier than 2 years for CD, but challenges benefit for very early biologic initiation in CD. It provides a statistical framework for future studies via a target trial emulation approach rather than propensity matching.

A major strength of this study is the including of children – a group with known more severe disease course and who are expected to live longer with a diagnosis – therefore with the largest benefit to gain from earlier initiation of therapies that can delay or prevent complications.

Overall, those with CD likely benefit from biologic initiation prior to two years from diagnosis – however those with UC do not, favoring a “step-up” approach in UC prior to biologic initiation.

A real world study randomizing patients at diagnosis to different time-to biologic periods, inclusive of children, with long term follow-up is required moving forward.

Citation

Lujan R, Buchuk R, Focht G, Yogev D, Greenfeld S, Ben-Tov A, Weisband YL, Lederman N, Matz E, Ben Horin S, Dotan I, Nevo D, Turner D. Gastroenterology. 2024 May;166(5):815-825.e22. doi: 10.1053/j.gastro.2024.01.041. Epub 2024 Feb 6. PMID: 38331205.

Link

https://pubmed.ncbi.nlm.nih.gov/38331205/

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