Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [ doi:10.1016/j.cgh.2013.09.006 ]).

“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.

Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.

Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.


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