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At 14 week, 33% of patients in the 210 mg induction etrolizumab group were in clinical remission, compared to 29% of the placebo induction group.
New data shows etrolizumab increases the likelihood of clinical remission and endoscopic improvements for patients with Crohn’s disease.
A team, led by William J. Sandborn, MD, Department of Gastroenterology, University of California San Diego, compared the safety and efficacy of 2 doses of etrolizumab with placebo in patients with Crohn’s disease.
Etrolizumab is a gut-targeted anti-β7 monoclonal antibody targeting α4β7 and αEβ7 integrins.
In the randomized, placebo-controlled, double-blind, phase 3 trial dubbed BERGAMOT, the investigators examined patients aged 18-80 years with moderately to severely active Crohn’s disease who had intolerance, inadequate response, or no response to 1 more corticosteroids, immunosuppressants, or anti-TNF therapy within the previous 5 years at 326 treatment centers around the world between March 20, 2015 and September 7, 2021.
Each participant had a Crohn’s Disease Activity Index (CDAI) score of 220-480 and a mean daily stool frequency score of at least 6 or a mean daily stool frequency score greater than 3 and a mean daily abdominal pain score greater than 1.
The participants also had the presence of active inflammation on screening ileocolonoscopy.
The study included 3 induction cohorts—a placebo-controlled double-blind exploratory cohort, an active treatment cohort not containing a placebo control, and a placebo-controlled, double-blind pivotal cohort. There was also 1 maintenance cohort.
In cohort 3, patients were randomly assigned at a 2:3:3 ratio over the 14 week induction period to receive matched placebo (n = 97), 105 mg etrolizumab subcutaneously every 4 weeks (n = 143), or 210 mg etrolizumab subcutaneously at weeks 0, 2, 4,8, and 12 (n = 145).
The patients were stratified by concomitant treatment with oral corticosteroids, concomitant treatment with immunosuppressants, baseline disease activity, and previous exposure to anti-TNF therapy.
At week 14, the etrolizumab responders were randomly assigned to receive either 105 mg etrolizumab or placebo every 4 weeks for 52 weeks in the maintenance study.
Patients in the induction placebo group then underwent a sham re-randomization.
In the maintenance study, randomization was stratified by CDAI remission status, concomitant treatment with oral corticosteroids, induction dose regimen, and previous exposure to anti-TNF therapy.
The investigators sought co-primary induction endpoints at week 14 of clinical remission, defined as a mean stool frequency ≤3 and mean abdominal pain ≤1, with no worsening and endoscopic improvement, defined as a ≥50% reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD).
The team also sought co-primary maintenance endpoints at week 66 of clinical remission and endoscopic improvement.
A total of 487 patients had a CDAI-70 response in any of the 3 induction cohorts and were included in the maintenance cohort. Of this group, 434 had a response to etrolizumab and were randomly assigned to placebo (n = 217) or 105 mg etrolizumab (n = 217).
At the 14 week mark, 33% (n = 48) of patients in the 210 mg induction etrolizumab group were in clinical remission, compared to 29% (n = 28) of the placebo induction group (adjusted treatment difference, 3.8%; 95% CI, –8.3 to 15.3%; P = 0.52).
In addition, 27% (n = 40) of the 210 mg etrolizumab group showed endoscopic improvement, compared to 22% (n = 21) of the placebo group (adjusted treatment difference, 5.8%; 95% CI, -5.4 to 17.1%; P = 0.32).
Then at week 66 the investigators found a significantly higher proportion of the etrolizumab group had clinical remission (35%; n = 76) compared to placebo (24%; n = 52) (adjustment treatment difference, 11.3%; 95% CI, 2.7-19.7%; P = 0.0088), as well as for endoscopic improvement (etrolizumab: 24%; n = 51; placebo: 12; n = 26; adjusted treatment difference, 11.5%; 95% CI, 4.1-18.8%; P = 0.0026).
For safety, there were similar proportions of participants reporting 1 or more adverse events during induction (66%; n = 95 of the 105 mg etrolizumab group, 59%; n = 85 of the 210 mg etrolizumab group, and 53%; n = 51 of the placebo group) and maintenance (87%; n = 189 of the etrolizumab group and 88%; n = 190 of the placebo group).
The most common treatment-related adverse events during induction were injection site erythema (4%; n = 6 in the 105 mg etrolizumab group, 3%; n = 4 in the 210 mg etrolizumab group, and 0% in the placebo group), and arthralgia (1%; n = 2 in the 105 mg etrolizumab group, 1%; n = 1 in the 210 mg etrolizumab group, and 4%; n = 4 in the placebo group).
For the maintenance cohort, the most common treatment-related adverse events were injection site erythema (3%; n = 6 in the etrolizumab group; 6%; n = 14 in the placebo: group), arthralgia (2%; n = 5 in the etrolizumab group; 4%; n = 8 in the placebo group), and headache (2%; n = 5 in the etrolizumab group; 3%; n = 7 in the placebo group).
For serious adverse events, the most common was the exacerbation of Crohn’s disease (6%; n = 14 in the placebo group; 2%; n = 4 in patients taking 105 mg etrolizumab).
“A significantly higher proportion of patients with moderately to severely active Crohn's disease achieved clinical remission and endoscopic improvement with etrolizumab than placebo during maintenance, but not during induction,” the authors wrote.
The study, “Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (BERGAMOT): a randomized, placebo-controlled, double-blind, phase 3 trial,” was published online in The Lancet Gastroenterology & Hepatology.