A higher adalimumab dosage during induction and maintenance may increase the likelihood of clinical remission in ulcerative colitis (UC), according to study data published in Gastroenterology.
Researchers conducted a phase 3, double-blind, randomized controlled trial, called Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis (SERENE UC; ClinicalTrials.gov Identifier: NCT002209456). The trial comprised 2 studies: a main study conducted at 120 clinical sites across 19 countries in the West and a substudy conducted at 22 clinical centers across Japan. Eligible patients were aged 18 to 75 years and had a full Mayo Clinic score of 6 to 12 with a centrally read endoscopy subscore of 2 to 3. Patients were randomly assigned 3:2 to either higher adalimumab induction (160 mg at weeks 0, 1, 2, and 3) or standard adalimumab induction (160 mg at week 0 and 80 mg at week 2).
All patients received 40 mg of adalimumab at weeks 4 and 6. At week 8, patients in the main cohort were once again randomly assigned 2:2:1 to the following maintenance regimens: 40 mg every week, 40 mg every other week, or exploratory therapeutic drug monitoring. Patients in the Japan substudy were randomly assigned 1:1 to 40 mg every week or 40 mg every other week. The primary efficacy endpoint was the proportion of patients who achieved clinical remission, defined by a full Mayo score of 2 or lower, with no subscore higher than 1. Remission rates were compared across induction and maintenance regimens.
The main cohort enrolled 852 patients, among whom 606 entered the maintenance phase. The Japan induction cohort included 100 patients, among whom 89 were once again randomly assigned to a maintenance dosage. Demographic characteristics were comparable within cohorts. Disease duration and severity were also similar across induction and maintenance regimens.
The proportion of patients who achieved clinical remission at week 8 in the main study cohort was not significantly different in the high vs standard induction regimens (13.3% vs 10.9%; P =.265). After integrating data from the Japan trial, the respective rates were 13.8% and 11.6% (P =.297). Among week 8 responders in the main cohort, clinical remission was achieved by 39.5% of the every-week and 29.0% of the every-other-week dosing groups (P =.069). In the integrated cohort, these rates were 41.1% and 30.1%, respectively, reaching borderline significance (P =.45).
Adverse events occurred at similar rates between the high and standard induction groups in the main cohort, although patients with the high regimen were more likely to experience injection site reactions (12.1% vs 3.8%). Adverse events of special interest were rare and experienced at comparable rates between the high and standard induction regimens (13.5% vs 17.1%). In the Japan cohort, 50% of patients reported 1 or more adverse events. Adverse events were more common with the high induction regimen (55.7% vs 41.0%) but did not differ significantly across maintenance doses.
While results were not statistically significant, the higher maintenance dose was associated with a greater than 10% absolute difference in clinical remission rates. A higher dosage was generally well tolerated, with no unexpected safety events observed.
Study limitations included the lack of a placebo control group and potential methodological differences across study sites.
“[Our trial] confirms the approved adalimumab induction dosing regimen is appropriate,” the investigators wrote. “Clinical remission was [at least] 10% higher with weekly vs every-other-week maintenance dosing. Safety was consistent with the known safety profile.”
Disclosure: This research was supported by AbbVie, Inc. Please see the original reference for a full list of disclosures.
Panés J, Colombel JF, D’Haens GR, et al. Higher vs standard adalimumab induction and maintenance dosing regimens for treatment of ulcerative colitis: SERENE UC trial results. Gastroenterology. 2022;162(7):1891-1910. doi:10.1053/j.gastro.2022.02.033