Among patients with moderately to severely active ulcerative colitis (UC) who had a clinical response at 10 weeks, maintenance etrolizumab, a gut-targeted anti-b7 integrin monoclonal antibody, was no more effective than placebo at week 62. These findings, from a phase 3, randomized, placebo-controlled, double-blind study, were published in The Lancet Gastroenterology & Hepatology.
The LAUREL study was conducted at 111 centers in 15 countries between 2014 and 2020 (ClinicalTrials.gov Identifier: NCT02165215). Patients (N=658) with moderately to severely active UC who were tumor necrosis factor inhibitor naïve received 105 mg subcutaneous injections of etrolizumab every 4 weeks for 10 weeks total.
At 10 weeks, those with a clinical response, defined as ³3-point decrease in Mayo Clinic total score (MCS), ³30% reduction, and ³1-point decrease in the rectal bleeding subscore, were randomly assigned to receive maintenance etrolizumab (n=108) or placebo (n=106) for 52 weeks. Remission rates were assessed at week 62, defined as MCS £2, individual subscores £1, and a rectal bleeding subscore of 0.
The etrolizumab and placebo cohorts were aged median 36 (range, 18-77) and 38 (range, 18-69) years, 44% and 51% were women, body mass index (BMI) was 24 (range, 13-80) and 25 (range, 15-46) kg/m2, duration of disease was 5.4 (range, 0.6-44.0) and 5.9 (range, 0.3-40.4) years, MCS was £9 among 68% and 71% of patients, and 28% and 27% used immunosuppressants at baseline, respectively.
Among the etrolizumab recipients, the serum concentration increased from 4.5 mg/mL at week 4 to 15.4 mg/mL at week 62, corresponding with an 11 times higher concentration than the target. By week 24, placebo recipients had no measurable serum etrolizumab.
Remission at week 62 occurred among 29.6% of etrolizumab and 20.6% of placebo recipients (adjusted treatment difference, 7.7%; 95% CI, -4.2% to 19.2%; P =.19). No effects on remission (40% vs 27%; P =.31) or corticosteroid-free remission (18% vs 8%; P =.14) at week 62 were observed among patients who were in remission at week 10.
Etrolizumab was associated with endoscopic improvement (38% vs 23%; P =.024), endoscopic remission (31% vs 17%; P =.029), and histological remission (42% vs 22%; P =.0075).
Antidrug antibodies were detected among 32% of both groups in the maintenance phase.
Adverse events were reported by more of the placebo recipients (80% vs 65%). Adverse events that were more common among the etrolizumab group included fatigue, headache, and nasopharyngitis. One event of pruritus was considered related to the study drug.
This study may have been limited by the high proportion of patients who developed antidrug antibodies (32%), which was higher than what was observed during phase 1 and 2 studies (~5%).
This study did not identify a benefit of maintenance therapy with etrolizumab for the treatment of moderately to severely active UC.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Vermeire S, Lakatos PL, Ritter T, et al. Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study. Lancet Gastroenterol Hepatol. 2022;7(1):28-37. doi:10.1016/S2468-1253(21)00295-8