Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study. Issue 10 (5th October 2017)

• Record Type: Journal Article
• Authors: Sandborn, William J; Lee, Scott D; Tarabar, Dino; Louis, Edouard; Klopocka, Maria; Klaus, Jochen; Reinisch, Walter; Hébuterne, Xavier; Park, Dong-Il; Schreiber, Stefan; Nayak, Satyaprakash; Ahmad, Alaa; Banerjee, Anindita; Brown, Lisa S; Cataldi, Fabio; Gorelick, Kenneth J; Cheng, John B; Hassan-Zahraee, Mina; Clare, Robert; D'Haens, Geert R
• Is Part Of: Gut. Volume 67:Issue 10(2018)
• Page Start: 1824
• Page End: 1835
• Publication Date: 2017-10-05
• Subjects: crohn's disease -- pharmacotherapy -- integrins -- inflammatory bowel disease; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2016-313457
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: This phase II, randomised, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PF-00547659, a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule (MAdCAM) to selectively reduce lymphocyte homing to the intestinal tract, in patients with moderate-to-severe Crohn's disease (CD). Design: Eligible adults were aged 18–75 years, with active moderate-to-severe CD (Crohn's Disease Activity Index (CDAI) 220–450), a history of failure or intolerance to antitumour necrosis factor and/or immunosuppressive agents, high-sensitivity C reactive protein >3.0 mg/L and ulcers on colonoscopy. Patients were randomised to PF-00547659 22.5 mg, 75 mg or 225 mg or placebo. The primary endpoint was CDAI 70-point decrease from baseline (CDAI-70) at week 8 or 12. Results: In all, 265 patients were eligible for study entry. Although CDAI-70 response was not significantly different with placebo versus PF-00547659 treatment at weeks 8 or 12, remission rate was greater in patients with higher baseline C reactive protein (>5 mg/L vs >18.8 mg/L, respectively). Soluble MAdCAM decreased significantly from baseline to week 2 in a dose-related manner and remained low during the study in PF-00547659-treated patients. Circulating β7 + CD4+ central memory T-lymphocytes increased at weeks 8 and 12 with PF-00547659 treatment. No safety signal was seen. Conclusions: Clinical endpoint differences between PF-00547659 and placebo did not reach statistical significance in patients with moderate-to-severe CD. PF-00547659 was pharmacologically active, as shown by a sustained dose-related decrease in soluble MAdCAM and a dose-related increase in circulating β7 + central memory T cells. Trial registration number: NCT01276509 ; Results.