Development of interim patient‐reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials. Issue 10 (21st September 2015)

• Record Type: Journal Article
• Authors: Jairath, V.; Khanna, R.; Zou, G. Y.; Stitt, L.; Mosli, M.; Vandervoort, M. K.; D'Haens, G.; Sandborn, W. J.; Feagan, B. G.; Levesque, B. G.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 42:Issue 10(2015)
• Page Start: 1200
• Page End: 1210
• Publication Date: 2015-09-21
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.13408
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt13408-abs-0001"> <title>Summary</title> <sec id="apt13408-sec-0001" sec-type="section"> <title>Background</title> <p>Patient‐reported outcomes (PROs) have an increasingly important role in the evaluation of new therapies for inflammatory bowel disease. The US Food and Drug Administration has issued formal guidance to describe the role of PRO instruments in evaluation of claims for product labelling. However, no validated PRO exists for ulcerative colitis.</p> </sec> <sec id="apt13408-sec-0002" sec-type="section"> <title>Aim</title> <p>To investigate whether the PROs from the Mayo Clinic Score (MCS) for UC can be modified, to develop an interim PRO for use in clinical trials, alone or in combination with endoscopy.</p> </sec> <sec id="apt13408-sec-0003" sec-type="section"> <title>Methods</title> <p>Data from an induction trial of a mesalazine (mesalamine) formulation were used to compare effect sizes between mesalazine and placebo for PRO items (stool frequency and rectal bleeding) alone and in combination with endoscopy. The operating properties of the PRO were validated using data from a phase 2 trial of MLN02, a humanised antibody to the <italic>α</italic>4<italic>β</italic>7 integrin in patients with UC.</p> </sec> <sec id="apt13408-sec-0004" sec-type="section"> <title>Results</title> <p>A two‐item PRO (PRO2) consisting of rectal bleeding = 0 and stool frequency ≤1 or ≤2, combined with an endoscopy subscore ≤1 yielded statistically significant differences between active drug and placebo. This combination yielded the most similar effect sizes and placebo rates for remission, compared to the primary trials. Use of PRO items alone yielded high placebo remission rates in both data sets, although rates were lower when the items were combined and remission defined as PRO2 = 0.</p> </sec> <sec id="apt13408-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Patient‐reported outcomes items derived from the Mayo Clinic Score combined with endoscopy as a co‐primary endpoint may be an appropriate interim outcome measure for ulcerative colitis trials.</p> </sec> </abstract>