PT - JOURNAL ARTICLE AU - William J Sandborn AU - Scott D Lee AU - Dino Tarabar AU - Edouard Louis AU - Maria Klopocka AU - Jochen Klaus AU - Walter Reinisch AU - Xavier Hébuterne AU - Dong-Il Park AU - Stefan Schreiber AU - Satyaprakash Nayak AU - Alaa Ahmad AU - Anindita Banerjee AU - Lisa S Brown AU - Fabio Cataldi AU - Kenneth J Gorelick AU - John B Cheng AU - Mina Hassan-Zahraee AU - Robert Clare AU - Geert R D’Haens TI - Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn’s disease: report of the OPERA study AID - 10.1136/gutjnl-2016-313457 DP - 2017 Oct 05 TA - Gut PG - gutjnl-2016-313457 4099 - http://gut.bmj.com/content/early/2017/10/05/gutjnl-2016-313457.short 4100 - http://gut.bmj.com/content/early/2017/10/05/gutjnl-2016-313457.full AB - 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.