A Simplified Definition of Histologic Improvement in Ulcerative Colitis and its Association With Disease Outcomes up to 30 Weeks from Initiation of Therapy: Post Hoc Analysis of Three Clinical Trials

• Published in: Journal of Crohn's and colitis 2019-08, Vol.13 (8), p.1025-1035
• Main Authors: Li, Katherine, Strauss, Richard, Marano, Colleen, Greenbaum, Linda E, Friedman, Joshua R, Peyrin-Biroulet, Laurent, Brodmerkel, Carrie, De Hertogh, Gert
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Biopsy - methods; Biopsy - standards; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Colonoscopy - methods; Drug Monitoring - methods; Female; Humans; Intestinal Mucosa - pathology; Male; Outcome Assessment, Health Care - methods; Outcome Assessment, Health Care - standards; Quality Improvement; Remission Induction - methods; Reproducibility of Results; Severity of Illness Index; Tumor Necrosis Factor Inhibitors - administration & dosage; Tumor Necrosis Factor Inhibitors - adverse effects
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjz022

Histologic evaluation is a meaningful complement to endoscopic and clinical measures in ulcerative colitis [UC]. There is a need for a definition of histologic improvement that can be used in clinical trials, and any such definition must be predictive of disease outcomes. Biopsies were collected from clinical trials (PURSUIT-SC [n = 98], JAK-UC [n = 219], and PROgECT [n = 103]) in patients with moderate-to-severe UC. A pathologist assessed biopsies in a blinded fashion using the Geboes score. A dichotomous histologic improvement end point was defined by selecting Geboes score elements according to their association strength with endoscopic healing. Fisher's exact test and Cramer's V assessed the association of histology with other measures. Using PURSUIT-SC biopsies, histologic improvement was defined as absence of erosion or ulceration, absence of crypt destruction, and 90% of those with endoscopic healing in JAK-UC [Week 8] and PROgECT [Week 30] achieved histologic improvement. In JAK-UC, patients with histologic improvement had lower disease activity than patients without histologic improvement' [Mayo score = 3.8 vs 7.5] at Week 8. Week 4 histologic improvement was a strong indicator of histologic improvement, endoscopic healing, and clinical response or remission at Week 8 [all p < 0.005]. In PROgECT, 73% of patients with histologic improvement at Week 6 achieved histologic improvement at Week 30 [p = 0.0013]. Histologic improvement based on a simplified, dichotomous Geboes score is associated with favourable endoscopic and clinical outcomes across multiple clinical studies and two therapeutic mechanisms of action.ClinicalTrials.gov number: NCT00487539 [PURSUIT-SC]; NCT01959282 [JAK-UC]; NCT01988961 [PROgECT].