@article {Sandborngutjnl-2016-313457, author = {William J Sandborn and Scott D Lee and Dino Tarabar and Edouard Louis and Maria Klopocka and Jochen Klaus and Walter Reinisch and Xavier H{\'e}buterne and Dong-Il Park and Stefan Schreiber and Satyaprakash Nayak and Alaa Ahmad and Anindita Banerjee and Lisa S Brown and Fabio Cataldi and Kenneth J Gorelick and John B Cheng and Mina Hassan-Zahraee and Robert Clare and Geert R D{\textquoteright}Haens}, title = {Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn{\textquoteright}s disease: report of the OPERA study}, elocation-id = {gutjnl-2016-313457}, year = {2017}, doi = {10.1136/gutjnl-2016-313457}, publisher = {BMJ Publishing Group}, 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{\textquoteright}s disease (CD).Design Eligible adults were aged 18{\textendash}75 years, with active moderate-to-severe CD (Crohn{\textquoteright}s Disease Activity Index (CDAI) 220{\textendash}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.}, issn = {0017-5749}, URL = {https://gut.bmj.com/content/early/2017/10/05/gutjnl-2016-313457}, eprint = {https://gut.bmj.com/content/early/2017/10/05/gutjnl-2016-313457.full.pdf}, journal = {Gut} }