In:
Gut, BMJ, Vol. 67, No. 10 ( 2018-10), p. 1824-1835
Abstract:
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 β 7 + 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 β 7 + central memory T cells. Trial registration number NCT01276509 ; Results.
Type of Medium:
Online Resource
ISSN:
0017-5749
,
1468-3288
DOI:
10.1136/gutjnl-2016-313457
DOI:
10.1136/gutjnl-2016-313457.supp1
DOI:
10.1136/gutjnl-2016-313457.supp2
DOI:
10.1136/gutjnl-2016-313457.supp3
Language:
English
Publisher:
BMJ
Publication Date:
2018
detail.hit.zdb_id:
1492637-4
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