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Published on: September 12, 2019
Anti-fibrotic therapy in Crohn's disease: hype or reality-can intestinal fibrosis be targeted effectively?
Sailish Honap1,2, Axel Dignass3, Vipul Jairath4,5
1Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.
Introduction:
Fibrostenotic Crohn's disease remains a major unmet clinical need, as currently licensed therapies primarily target inflammation and have not been shown to prevent fibrosis progression or reverse established strictures. Renewed interest in intestinal fibrosis, coupled with an expanding therapeutic pipeline, has prompted renewed debate over whether anti-fibrotic therapy in Crohn's disease represents hype or a realistic therapeutic opportunity.
Areas Covered:
This special report summarizes emerging anti-fibrotic strategies in Crohn's disease, including clinical data for ontunisertib and preclinical evidence for anti-TL1A therapies and obefazimod. It also examines lessons from successful anti-fibrotic drug development in pulmonary and hepatic fibrosis, focusing on pathway selection, patient stratification, endpoint development, and trial design.
Expert Opinion:
Early clinical and translational findings suggest that targeting fibrosis in Crohn's disease may be feasible. In the authors' view, the greater challenge lies in developing the tools and trial frameworks needed to demonstrate that therapies can alter the course of fibrostenotic disease.
Insights
Targeting fibrosis in Crohn's disease (CD) shows promise for treating fibrostenotic strictures, an unmet need. Developing effective anti-fibrotic therapies and robust clinical trial designs are crucial for success.
Area of Science:
- Gastroenterology
- Fibrosis Research
- Drug Development
Background:
- Fibrostenotic Crohn's disease (CD) lacks effective treatments, as current therapies target inflammation but not fibrosis progression.
- Established therapies fail to prevent or reverse fibrotic strictures in CD patients, representing a significant unmet clinical need.
Purpose of the Study:
- To review emerging anti-fibrotic strategies for Crohn's disease.
- To discuss clinical and preclinical data for novel anti-fibrotic agents.
- To examine best practices in anti-fibrotic drug development from other fields.
Main Methods:
- Summary of clinical data for ontunisertib.
- Review of preclinical evidence for anti-TL1A therapies and obefazimod.
- Analysis of lessons learned from pulmonary and hepatic fibrosis drug development.
Main Results:
- Emerging anti-fibrotic strategies show potential feasibility for treating CD fibrosis.
- Clinical and translational findings suggest targeting fibrosis in CD is a viable therapeutic avenue.
Conclusions:
- Anti-fibrotic therapy for Crohn's disease is a realistic opportunity, not just hype.
- The primary challenge is developing appropriate tools and trial frameworks to demonstrate efficacy in altering fibrostenotic disease progression.
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