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.
J Crohns Colitis. 2019 Feb 04;:
Authors: Li K, Strauss R, Marano C, Greenbaum LE, Friedman JR, Peyrin-Biroulet L, Brodmerkel C, De Hertogh G
Background & Aims: 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.
Methods: 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 endpoint 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.
Results: Using PURSUIT-SC biopsies, histologic improvement was defined as absence of erosion or ulceration, absence of crypt destruction, and <5% of crypts with epithelial neutrophil infiltration. Histologic improvement was associated with endoscopic healing, as >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 non-healers (Mayo score=3.8 versus 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).
Conclusions: Histologic improvement based on a simplified, dichotomous Geboes score is associated with favorable 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).
PMID: 30721964 [PubMed – as supplied by publisher]