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Mechanisms And Management Of Loss Of Response To Anti-tnf Therapy For Patients With Crohn's Disease: 3-year Data From The Prospective, Multicentre Pants Cohort Study.

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Mechanisms And Management Of Loss Of Response To Anti-tnf Therapy For Patients With Crohn's Disease: 3-year Data From The Prospective, Multicentre Pants Cohort Study.

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Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from

Neil Chanchlani¹, Simeng Lin¹, Claire Bewshea²

¹Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK; Exeter IBD and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.

The Lancet. Gastroenterology & Hepatology

|April 19, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

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Only about a third of Crohn's disease patients achieve remission after 3 years of anti-TNF therapy. Maintaining optimal drug levels and using immunomodulators can improve long-term outcomes and prevent treatment failure.

Area of Science:

Gastroenterology
Immunology
Pharmacology

Background:

Crohn's disease (CD) management often involves anti-tumor necrosis factor (anti-TNF) therapies like infliximab and adalimumab.
Treatment effectiveness and factors influencing loss of response (LOR) require further investigation for personalized therapeutic strategies.

Purpose of the Study:

To evaluate the 3-year effectiveness of infliximab and adalimumab in anti-TNF-naive Crohn's disease patients.
To identify predictors of anti-TNF treatment failure and strategies to mitigate loss of response.

Main Methods:

Prospective observational cohort study (PANTS) including anti-TNF-naive patients with active luminal CD.
Assessed remission rates at years 1, 2, and 3 using modified survival analysis.
Utilized multivariable regression and survival analyses to identify factors associated with LOR and immunogenicity.

Main Results:

Remission rates at year 3 were 34.7% for infliximab and 28.9% for adalimumab.
Low drug concentrations at week 14 predicted LOR by year 3 for both agents.
Female sex, obesity, and higher baseline white cell count predicted LOR for infliximab; HLA-DQA1*05 carriage predicted LOR for adalimumab.
Concomitant immunomodulator use reduced anti-drug antibody development and LOR for both infliximab and adalimumab.

Conclusions:

Long-term remission rates for infliximab and adalimumab in Crohn's disease remain suboptimal.
Optimizing drug concentrations early in treatment and utilizing concomitant immunomodulator therapy are crucial for sustained response.
Identifying genetic and clinical predictors can guide personalized anti-TNF therapy selection and management.