Etrolizumab, an anti-β7 monoclonal antibody, inhibits both trafficking of immune cells into the gut and their inflammatory effects on the gut lining. Results from the LAUREL trial showed that despite nominally significant benefits with etrolizumab compared with placebo in endoscopic improvement, endoscopic remission and histologic remission at week 62 among week 10-responders was not met in a cohort of TNF-naïve ulcerative colitis patients1.
The phase 3 LAUREL trial evaluated the safety, efficacy, and tolerability of etrolizumab in 359 patients with moderately to severely active ulcerative colitis who were naïve to TNF antagonists. In the induction phase, patients received subcutaneous, open-label etrolizumab. The induction phase to week 10 was completed by 347 participants, of whom 214 clinical responders were randomly assigned at week 12 to etrolizumab or placebo, administered every 4 weeks for a total of 52 weeks in the maintenance phase. At week 62, 74.1% of etrolizumab patients and 39.6% of placebo patients had completed the maintenance phase.
The primary efficacy endpoint was remission (defined as a Mayo Clinic total score ≤2, with individual subscores ≤1 and a rectal bleeding subscore of 0) at week 62 among patients with a clinical response (defined as a Mayo Clinic total score with ≥3-point decrease and 30% reduction from baseline and ≥1-point decrease in rectal bleeding subscore or a score of 0 or 1) at week 10.
At week 62, the remission rate observed in patients assigned to etrolizumab (29.6%) was not significantly different from the placebo group (20.6%; P=0.1942). Most adverse events were non-serious and low grade (grades 1/2). No deaths or cases of progressive multifocal leukoencephalopathy were observed.
Despite nominally significant benefits with etrolizumab versus placebo in endoscopic improvement, endoscopic remission, and histologic remission in this cohort of TNF-naïve patients, the primary endpoint of remission at week 62 among week 10-responders was not met. No new or unexpected safety signals occurred, and most adverse events were grades 1/2.
1. Vermeire S. Etrolizumab versus placebo in tumor necrosis factor antagonist naïve patients with ulcerative colitis: results from a randomized phase 3 LAUREL trial. UEG Week E-congress 2020, abstract LB18.