From the AGA Journals

Complete endoscopic healing tied to better Crohn’s disease outcomes



Patients with Crohn’s disease who experienced complete endoscopic healing with biologic therapy had significantly lower subsequent rates of treatment failure, intestinal resection, and hospitalization, compared with patients who experienced only partial mucosal healing, according to the findings of a two-center retrospective study.

Over a median of 4.8 years of follow-up (interquartile range, 2.1-7.2 years) rates of treatment failure were 25% in patients with complete mucosal healing at baseline (that is, a Crohn’s Disease Endoscopic Index of Severity [CDEIS] score of 0) and 48% in patients with partial healing (CDEIS score greater than 0 but less than 4). The difference was statistically significant (P = .045). No patient with a baseline CDEIS score of 0 required intestinal resection, compared with 11% of patients with scores greater than 0 but less than 4 (P = .031). Rates of hospitalization because of Crohn’s disease were 3.5% versus 18.5%, respectively (P = .013). Clara Yzet, MD, of Amiens (France) University Hospital, Université de Picardie Jules Verne, reported the findings together with her associates in Clinical Gastroenterology and Hepatology.

Mucosal healing is a key therapeutic target in Crohn’s disease that has been linked to desirable outcomes, such as steroid-free remission and a lower rate of intestinal resection. However, prior observational studies have inconsistently defined mucosal healing, and clinical trials of biologics have used any of at least seven different definitions, the researchers wrote. Recently, in patients with ulcerative colitis, a Scandinavian Journal of Gastroenterology and another in the Journal of Crohn’s and Colitis linked a stricter definition of mucosal healing (an endoscopic Mayo score of 0, or histologic healing) with superior long-term clinical outcomes. In patients with Crohn’s disease, however, there has been no established threshold for mucosal healing based on either the CDEIS or the Simplified Endoscopic Score for Crohn’s disease (SES-CD).

Therefore, Dr. Yzet and her associates identified and reviewed the medical records of 84 consecutive adults with clinically remitted Crohn’s disease who received anti–tumor necrosis factor therapies (infliximab and adalimumab) or vedolizumab at two university hospitals in France between 2008 and 2015. All patients received baseline and follow-up colonoscopies, with results scored on the CDEIS. In all cases, the second CDEIS score was less than 4 (the CDEIS ranges from 0 to 44). The primary outcome was treatment failure, defined as the need for biologic optimization (increasing the dose or shortening the dosing interval of the biologic), corticosteroids, or immunosuppressants; a Harvey-Bradshaw score greater than 4 associated with a change in treatment; or the need for intestinal resection or hospitalization because of Crohn’s disease.

At baseline, 57 patients had CDEIS scores of 0 (complete mucosal healing) and 27 patients had scores greater than 0 but less than 4 (partial mucosal healing). The two groups were otherwise similar except that patients with complete mucosal healing had a shorter median duration of Crohn’s disease (10.3 vs. 15.1 years in the partial healing group; P = .029) and a lower prevalence of Crohn’s disease phenotype B2 (stricturing) according to the Vienna classification (1.8% vs. 14.8%; P = .035). In the multivariate analysis, CDEIS score was the only factor associated with treatment failure (hazard ratio, 2.61; 95% confidence interval, 1.16-5.88; P = .02).

“Our findings suggest that we should be more ambitious in clinical practice to change patients’ life and disease course by achieving complete endoscopic healing. However, this strategy could be limited by the ability of current drugs to achieve complete mucosal healing,” the researchers wrote. “Obtaining a complete mucosal healing would require today a significant need for optimization or change of biologics.”

No external funding sources were reported. Two coinvestigators disclosed ties to AbbVie, Amgen, Biogaran, Biogen, Ferring, Janssen, MSD, Pfizer, Takeda, and several other pharmaceutical companies. The remaining investigators reported having no relevant conflicts of interest.

SOURCE: Yzet C et al. Clin Gastroenterol Hepatol. 2019 Nov 16. doi: 10.1016/j.cgh.2019.11.025.

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