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A randomised phase I study of etrolizumab (rhuMAb {beta}7) in moderate to severe ulcerative colitis
Gut, 07/03/2012
Clinical Article
Rutgeerts PJ et al. – Etrolizumab is well tolerated in moderate to severe ulcerative colitis (UC).
Methods- In the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/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 (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/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).
- In 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 β7 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.
