Etrolizumab outperforms placebo in achieving clinical remission for Crohn's disease

A recent trial found that using etrolizumab has provided good clinical remission and endoscopic improvement than a placebo in a significantly greater proportion of patients with moderately to severely active Crohn's disease during the maintenance phase. The trial results were published in the journal The Lancet Gastroenterology and Hepatology.

Crohn's disease is an autoimmune disorder of the gastrointestinal tract affecting many people worldwide. There are many therapeutic options available presently including alpha-4 integrin inhibitors and several TNF-alpha inhibitors. Among these etrolizumab is a gut-targeted anti-β7 monoclonal antibody targeting α4β7 and αEβ7 integrins. Researchers compared the safety and efficacy of two doses of etrolizumab with a placebo in patients with Crohn's disease.

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About BERGAMOT trial:

• BERGAMOT was a randomized, placebo-controlled, double-blind, phase 3 study done at 326 treatment centers worldwide.
• Patients aged 18–80 years with moderately to severely active Crohn's disease with the following were included:

• BERGAMOT consisted of three induction cohorts and one maintenance cohort. They are:

• In induction cohort 3, during the 14-week induction, patients were randomly assigned (2:3:3) to receive matched placebo and the following:

105 mg etrolizumab subcutaneously every 4 weeks given at weeks 0, 4, 8, and 12

or 210 mg etrolizumab subcutaneously given at weeks 0, 2, 4, 8, and 12.

• This was stratified by concomitant treatment with oral corticosteroids, concomitant treatment with immunosuppressants, baseline disease activity, and previous exposure to anti-TNF therapy. To preserve masking, all patients received two injections at weeks 0, 4, 8, and 12 and one injections at week 2.
• Week 14 etrolizumab responders from all cohorts were re-randomly assigned (1:1) to receive 105 mg etrolizumab called the etrolizumab maintenance group or placebo called the placebo maintenance group every 4 weeks for 52 weeks.
• Patients in the induction placebo group underwent a sham re-randomization to preserve masking.
• During maintenance, randomization was stratified by CDAI remission status, concomitant treatment with oral corticosteroids, induction dose regimen, and previous exposure to anti-TNF therapy.
• All participants and study site personnel were masked to treatment assignment for both induction and maintenance.
• Co-primary induction endpoints at week 14 (placebo vs 210 mg etrolizumab) were clinical remission measured by mean stool frequency of ≤3 and mean abdominal pain ≤1, with no worsening and endoscopic improvement of ≥50% reduction in Simple Endoscopic Score for Crohn's Disease [SES-CD].
• Co-primary maintenance endpoints at week 66 (placebo vs etrolizumab) were clinical remission and endoscopic improvement.
• Efficacy was analyzed using a modified intention-to-treat (mITT) population, defined as all randomized patients who received at least one dose of the study drug (induction) and as all patients re-randomized into maintenance who received at least one dose of the study drug in the maintenance phase (maintenance).
• Safety analyses included all patients who received at least one dose of the study drug.
• Maintenance safety analyses include all adverse events occurring in both induction and maintenance.

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Results:

• Out of 385 patients who were randomly assigned to induction cohort 3 97 received a placebo, 143 received105 mg etrolizumab, and 145 received 210 mg etrolizumab.
• 487 patients had a CDAI-70 response in any of the induction cohorts and were enrolled into the maintenance cohort, of whom 434 had a response to etrolizumab and were randomly assigned to placebo (n=217) or 105 mg etrolizumab (n=217).
• At week 14, 48 (33%) of 145 patients in the 210 mg induction etrolizumab group versus 28 (29%) of 96 patients in the placebo induction group were in clinical remission and 40 (27%) versus 21 (22%) showed endoscopic improvement.
• At week 66, a significantly higher proportion of patients receiving etrolizumab than those receiving placebo had clinical remission (35% vs 24%) and endoscopic improvement (24% vs 12%).
• One or more adverse events were reported during induction by 95 [66%] of 143 in the 105 mg etrolizumab group, 85 [59%] of 145 in the 210 mg etrolizumab group, and 51 [53%] of 96 in the placebo group
• During the maintenance phase, 189 [87%] of 217 in the etrolizumab group and 190 [88%] of 217 in the placebo group showed one or more adverse events.