Etrolizumab Maintenance, but not Induction, Superior to Placebo in Crohn Disease

Patients with moderate to severe Crohn disease (CD) achieve clinical remission and endoscopic improvement with etrolizumab compared with placebo during maintenance therapy, according to study findings published in The Lancet Gastroenterology & Hepatology.

The BERGAMOT trial (ClinicalTrials.gov Identifier: NCT02394028) was 1 of 6 pivotal phase 3 trials that evaluated etrolizumab for the treatment of inflammatory bowel disease (IBD). In BERGAMOT, patients with moderate to severe CD were enrolled at 326 sites worldwide between 2015 and 2021. The trial comprised 3 induction cohorts: cohort 1 (n=300) was a placebo-controlled, double-blind, proof-of-concept arm; cohort 2 (n=350) was an active treatment arm; and cohort 3 (n=385) was a placebo-controlled, double-blind pivotal arm. The patients (n=487) who achieved at least a 70-point decrease in Crohn’s Disease Activity Index (CDAI) after 14 weeks of induction with 105 mg subcutaneous etrolizumab every 4 weeks; 210 mg subcutaneous etrolizumab at weeks 0, 2, 4, 8, and 12; or placebo were eligible to enter the 52-week maintenance phase, which rerandomly assigned participants to receive 105 mg etrolizumab (n=217), placebo (n=217), or sham placebo (n=53; eg, responders to placebo induction).

The co-primary endpoints were clinical remission and endoscopic improvement, defined as mean daily stool frequency less than or equal to 3 with mean daily abdominal pain score less than or equal to 1 and at least a 50% reduction in the Simple Endoscopic Score for Crohn’s Disease (SES-CD) from baseline, respectively.

Among the maintenance cohort, the median duration of disease was 7.2 (IQR, 2.8-13.0) years and mean (SD) CDAI score at baseline was 325.0[62.2] points.

For induction cohort 3, 33% of the 210 mg etrolizumab cohort and 29% of the placebo group exhibited a clinical response (P =.52) and 27% and 22% endoscopic improvement (P =.32) at week 14, respectively.

Among the patients who progressed to maintenance therapy, 35% of the etrolizumab recipients and 24% of the placebo recipients achieved clinical remission (P =.0088), and 24% and 12% had endoscopic improvement (P =.0026) at week 66, respectively. Due to the fact that the co-primary endpoints were not met during the induction phase of this trial, the group differences reported for the maintenance phase were not considered statistically significant.

Nonetheless, etrolizumab was also favored over placebo for the secondary endpoints of endoscopic remission (12% vs 6%; P =.048) and corticosteroid-free clinical remission (29% vs 11%; P =.048) at week 66, respectively.

The adverse event rate was 53% for placebo induction, 59% to 66% for etrolizumab induction, 88% for placebo maintenance, and 87% for etrolizumab maintenance. The serious adverse events occurring among over 1% of the groups included gastrointestinal disorder (5%-9%), CD (2%-6%), abdominal pain (0%-1%), and anal fistula (0%-1%).

During the trial, the most common reason for discontinuation was lack of efficacy (induction: 9%; maintenance: 36%).

The major limitations of this study include the high placebo response rate and the long study duration.

“Etrolizumab did not achieve co-primary induction endpoints at week 14 but did achieve co-primary maintenance endpoints at week 66,” the study authors noted.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.