P035 Defining Responders for the Crohn’s Disease Patient-Reported Outcomes Signs and Symptoms (CD-PRO/SS) Tool Using Data From Patients Treated With Etrolizumab
Authors: Higgins Peter , DeBusk Kendra , Jacob Rhian , Hassanali Azra , Sharafali Zaineb , Oh Young , Kadva Alysha , Matsui Alison 
Published: December 2019

BACKGROUND:
Clinically relevant patient-reported outcome (PRO) tools are important for assessing the effect of a treatment on the clinical course of Crohn’s disease (CD). Available PRO instruments used for CD have limitations in evaluating the full extent of disease components, appropriately quantifying clinical symptoms, and adequately capturing the patient perspective. The Crohn’s Disease Patient-Reported Outcomes Signs and Symptoms (CD-PRO/SS) is the first Crohn’s disease–specific PRO tool developed with input from health authorities, patients, and clinical experts and is under review by the US Food and Drug Administration for validation as a clinical outcome measure. In April 2019, the European Medicines Agency released a letter of support for use of the CD-PRO/SS as an endpoint in inflammatory bowel disease clinical trials. The aim of this study was to define responder definitions for the CD-PRO/SS using data from patients with moderate-to-severe CD treated with etrolizumab in the BERGAMOT Phase 3 trial (NCT02394028).

METHODS:
In BERGAMOT, anti-tumor necrosis factor (aTNF)–naive and aTNF-experienced patients with CD were treated with etrolizumab 105 mg, 210 mg, or placebo subcutaneously every 4 weeks during a 14-week induction phase. Cohort 1 (blinded) and cohort 2 (open-label etrolizumab) were analyzed independently; those cohorts included all treatments. Data presented are from all patients regardless of treatment. The CD-PRO/SS consists of 2 separately scored scales: a 3-item functional domain and a 3-item bowel domain. The domain score was calculated as the sum of the item scores, which were derived using the average of ≥4 out of 7 days before week 0 (baseline) and week 14. Minimum clinically important differences (MCIDs) were calculated using distributional- and anchor-based methods on a reduction of ≥16 points in the Inflammatory Bowel Disease Questionnaire and ≥100 points in the Crohn’s Disease Activity Index (CDAI) at week 14.

RESULTS:
As of September 2018, the CD-PRO/SS scores from 479 patients (67.4% aTNF-experienced; cohort 1, n = 215; cohort 2, n = 264) with nonmissing data were analyzed. Mean changes from baseline at week 14 were −2.28 (standard deviation, 2.55) and −2.45 (2.89) for the functional domain and the bowel domain, respectively. Based on a reduction of ≥100 CDAI, the MCIDs from anchor-based method were 2.7 for the functional domain and 3.1 for the bowel domain regardless of treatment arm. Responder definitions for the CD-PRO/SS were a reduction ≥2.5 for the functional domain and ≥3.0 for the bowel domain that were determined through triangulation. According to these cutoffs, 44% and 40% of patients were responders by week 14 based on the functional domain and the bowel domain, respectively.

CONCLUSION(S):
In the pooled analysis, the proposed responder definitions demonstrate that a clinically meaningful response on the CD-PRO/SS are a reduction of ≥2.5 in the functional domain or ≥3.0 in the bowel domain. Similar to the responders defined by the Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms tool, these preliminary definitions for the CD-PRO/SS will be validated in the ongoing etrolizumab Phase 3 clinical trials for use in both clinical trials and practice to assess a clinically meaningful improvement.