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P077 Histological remission in ulcerative colitis: an analysis of two independent cohorts

Li K.*1, Strauss R.1, Marano C.1, Greenbaum L.1, Brodmerkel C.1, De Hertogh G.2

1Janssen Research & Development, LLC, Spring House, United States 2University Hospitals Leuven, Pathology, Leuven, Belgium

Background

The relationship of histological and clinical or endoscopic measures of ulcerative colitis (UC) is not well-described. Based on prior analysis1, we proposed a definition of Histological remission (HR) using selected features of the Geboes score (neutrophils in <5% of the crypts, no crypt destruction, ulceration, or erosion). Here we validate the definition in two additional independent UC cohorts.

Methods

Biopsies were collected during endoscopies at screening and post-treatment in two phase 2 clinical trials targeting patients (pts) with moderate to severe UC defined as a Mayo score of 6–12 inclusive, including endoscopy score ≥2 (Table 1). All endoscopies were videoed and centrally read using Mayo endoscopy subscore. A Mayo endoscopic score ≤1 defined endoscopic healing (EH). A single, blinded histopathologist assessed 453 biopsies from 219 pts in 54781532UCO2001 and 526 biopsies from 103 pts in PROgECT. Association of dichotomous endpoints was assessed by Fisher's exact test. Clinical differences between histological remitters and non-remitters were evaluated by t-test. P-values <0.05 were considered significant.

Results

Performance of the histological endpoint was highly reproducible in 54781532UCO2001 and PROgECT. Histological remission was significantly associated with endoscopic healing in both studies across all the time points. 92% and 90% of pts who achieved endoscopic healing at wk 8 in 54781532UCO2001 and wk 30 in PROgECT, respectively, also achieved histological remission. Furthermore, pts with histological remission had significantly lower disease activity including lower stool frequency and rectal bleeding scores compared to histological non-remitters (e.g. mean Mayo=3.78 vs. 7.52 at wk 8 in 54781532UCO2001). Early (wk 4) HR was also a strong indicator of wk 8 HR, EH, and clinical response/remission in 54781532UCO2001 (all p<0.005). In PROgECT, 73% of wk 6 HR achieved long-term (wk 30) HR (p=0.0013).

Table 1. Trial characteristics of 54781532UCO2001 and PROgECT

54781532UCO2001PROgECT
StudyPlacebo-controlledOpen-label
Study agentPeficitinib, a Janus kinase inhibitorGolimumab, an anti-TNFa therapy
Dosing regimenWks 0–8: placebo, JNJ-54781532 25 mg once daily (QD),Wk 0: 200 mg SC Wk 2: 100 mg SC Wks 6–50:
75 mg QD, 150 mg QD, or 75 mg twice daily by 1:1:1:1:1 randomization ratio100 mg per 4 wks or country approved maintenance dose
Endoscopy with biopsiesWks 0, 4 (optional) & 8Wks 0, 6 & 30

Conclusion

Histological remission defined as minimal residual microscopic disease and absence of epithelial damage is highly reproducible in multiple UC cohorts. Histological remitters are more likely to achieve endoscopic and clinical response/remission.

References:

[1] Strauss R, et al, (2015), OP235 UEGW