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.

BACKGROUND AND 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 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.

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 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].

CONCLUSIONS

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].