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P224 Responder definitions for the ulcerative colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) tool using patients with ulcerative colitis treated with etrolizumab

P. Higgins*1, A. Matsui2, K. DeBusk2, J. Pulley3, A. Scalori3, Y. S. Oh2, U. Arulmani2

1University of Michigan, Ann Arbor, USA, 2Genentech, South San Francisco, USA, 3Roche, Burgess Hill, UK

Background

Patient-reported outcomes (PROs) are important for evaluating treatment efficacy; there is a need to define what is a clinically meaningful change in PROs. The UC-PRO/SS is the first PRO to undergo a rigorous development process outlined by health authorities, with input from patients and clinical experts.1 Responder definitions for the UC-PRO/SS may allow for it to be a valuable tool for use in clinical trials and practice. We propose responder definitions for the UC-PRO/SS using patients treated with etrolizumab from the Phase 3 open-label induction cohorts of HICKORY (NCT02100696) and LAUREL (NCT02165215).

Methods

Analysis included patients with moderate to severe ulcerative colitis (UC) who were treated with etrolizumab 105 mg every 4 weeks during a 10- or 14-week induction period. The UC-PRO/SS consists of 2 separately scored scales: a 3-item functional symptoms domain and 6-item bowel signs and symptoms domain (Table 1). The domain score is equal to the sum of the items (0–12 for functional and 0–27 for bowel; no combined total score). Item scores were calculated as an average of 4–7 days during a 9-day window before follow-up. Minimum clinically meaningful differences were calculated using distributional- and anchor-based methods. Responder definitions were triangulated from the anchor-based thresholds based on a reduction of ≥ 16 points in the inflammatory bowel disease Questionnaire and > 3 points in the full Mayo Clinic Score at Week 10 or 14.

Table 1. The UC-PRO/SS. BM, bowel movement; UC-PRO/SS, ulcerative colitis Patient-Reported Outcomes Signs and Symptoms.

Results

As of May 2018, 218 patients (38% aTNF-experienced) provided a baseline UC-PRO/SS response (Table 2). The anchor methodology provided a range for the minimum clinically meaningful change of 1.48–2.07 for the functional domain and a range of 4.85–6.31 for the bowel domain. From these ranges, responder definitions of a reduction ≥ 1.5 points in the functional domain and ≥5 points in the bowel domain were determined through triangulation. Using these cut-offs, 56% of patients were responders according to the functional domain and 62% according to the bowel domain.

Table 2. Baseline, Week 10/14 and Change from Baseline in UC-PRO/SS Scores by Domain. UC-PRO/SS, ulcerative colitis Patient-Reported Outcomes Signs and Symptoms.

Conclusion

Preliminary definitions for response to treatment using the UC-PRO/SS are a reduction of ≥ 1.5 points in the functional domain or ≥5 points in the bowel domain. These cut-offs will be confirmed in the ongoing Phase 3 UC placebo-controlled studies.

References

1 Higgins PDR, Harding G, Revicki DA, et al., (2017), Development and validation of the ulcerative colitis patient-reported outcomes signs and symptoms (UC-pro/SS) diary, J Patient Rep Outcomes, 26