Browse by author
Lookup NU author(s): Dr John Mansfield
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
ObjectiveEtrolizumab (rhuMAb 7, anti-7, PRO145223) is a humanised monoclonal antibody targeting the 7 subunit of the heterodimeric integrins 47 and E7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10mg/kg intravenous, 3.0mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5mg/kg SC (n=4), 1.5mg/kg SC (n=5), 3.0mg/kg SC (n=4), 4.0mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of 7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.
Author(s): Rutgeerts PJ, Fedorak RN, Hommes DW, Sturm A, Baumgart DC, Bressler B, Schreiber S, Mansfield JC, Williams M, Tang M, Visich J, Wei XH, Keir M, Luca D, Danilenko D, Egen J, O'Byrne S
Publication type: Article
Publication status: Published
Print publication date: 01/08/2013
Online publication date: 20/06/2012
Acceptance date: 12/04/2012
ISSN (print): 0017-5749
ISSN (electronic): 1468-3288
Publisher: BMJ Publishing Group
PubMed id: 22717454
Altmetrics provided by Altmetric