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A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis

Lookup NU author(s): Dr John Mansfield


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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.

Publication metadata

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

Journal: Gut

Year: 2013

Volume: 62

Issue: 8

Pages: 1122-1130

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


DOI: 10.1136/gutjnl-2011-301769

PubMed id: 22717454


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