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Etrolizumab superior to placebo for UC remission
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Compared with placebo, the humanized monoclonal antibody etrolizumab appears to be effective in inducing clinical remission in patients with ulcerative colitis who are not responsive to conventional treatment, according to recent findings.
These data suggest that inhibition of the heterodimeric integrins alpha4beta7 and alphaEbeta7 may represent a novel therapeutic approach to treating ulcerative colitis (UC), the researchers wrote.
In the double blind, placebo-controlled, randomized phase 2 study researchers evaluated 124 patients, between the ages of 18 and 75 years, with moderate-to-severe treatment-resistant UC. Study participants were enrolled from 40 referral centers in 11 countries. Participants identified for inclusion had Mayo Clinic Scores (MCS) ≥5 (≥6 in the US) and disease that was evident at 25 cm or more from the anal verge. Participants were randomly assigned to two different dose levels of etrolizumab or placebo.
After the researchers made exclusions, the groups consisted of 39 patients in the etrolizumab 100-mg group; 39 patients in the etrolizumab 300-mg plus loading dose group; and 41 patients in the placebo group.
The study’s primary endpoint was clinical remission at 10 weeks, classified as an MCS of ≤2 evaluated in the modified intent-to-treat population (mITT). The mITT population included all patients who had received at least one dose of study drug, had at least one disease-activity follow-up and had a screening endoscopic subscore of ≥2.
The researchers reported none of the patients in the placebo group achieved clinical remission at week 10 vs. eight patients in the etrolizumab 100-mg cohort (21%; 95% CI, 7-36) and four patients in the 300 mg plus LD group (10%; 95% CI, 0.2-24).
Of those in the etrolizumab 100-mg group, 61% experienced adverse events, and five of which were considered serious. Nearly half of the patients in the etrolizumab 300-mg plus LD group (48%) experienced adverse effects, with two of these events deemed serious. In the placebo group, 72% of patients had side effects, with five deemed serious.
The researchers noted that phase 3 trials are being planned to further understand the mechanism of etrolizumab in UC treatment.
“Additional prospective studies involving larger groups of patients are necessary to confirm these findings,” the researchers wrote. “If validated, these results suggest two possible hypotheses: [alphaE-positive] cells themselves contribute to the pathogenesis of ulcerative colitis; or [alphaE] expression is correlated with the activity of a pathogenic pathway that is inhibited by etrolizumab treatment.”
Disclosure: This study was funded by Genentech. Please see the full study for a complete list of relevant financial disclosures.
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