Upadacitinib 45 mg once daily (QD) had superior efficacy for symptomatic relief in patients with ulcerative colitis (UC) within 1 to 3 days compared with placebo, according to study results published in Clinical Gastroenterology and Hepatology.
Researchers reported pooled findings from post hoc analyses of the phase 3 U-ACHIEVE Induction and U-ACCOMPLISH induction trials, which were randomized, placebo-controlled, double-blind trials that assessed the safety and efficacy of upadacitinib 45 mg QD in patients with moderately to severely active UC for 8 weeks compared with placebo.
The U-ACHIEVE Induction trial enrolled 474 patients from October 2018 to September 2020, and the U-ACCOMPLISH trial comprised 522 patients from December 2018 to January 2021.
Participants used an electronic diary to record daily symptoms, including stool frequency, rectal bleeding frequency, bowel urgency, and abdominal pain. The endpoints that were assessed in the first 14 days were the percentage of patients who achieved a stool frequency subscore (SFS) of 1 or below, SFS of 0, rectal bleeding subscore (RBS) of 0, 2-item patient-reported outcome (PRO2 [SFS≤1 and RBS=0]), no abdominal pain, and no bowel urgency. High sensitivity C reactive protein (hs CRP) and fecal calprotectin (FCP) levels also were measured at week 2 in all patients.
The percentages of patients who had clinical remission or clinical response based on a partial Mayo score were monitored every other week from 2 to 8 weeks, and those who achieved a clinically meaningful within-patient change at weeks 2 and 8 were assessed for health-related quality-of-life (HRQOL) analyses.
A total of 988 patients were included in the efficacy analysis—328 in the placebo group (median age, 42.0 years; 37.8% women) and 660 in the upadacitinib group (median age, 41.0 years; 37.6% women).
As early as day 1, a significantly higher percentage of patients who received upadacitinib 45 mg QD had an SFS of 1 or below (20.7% vs 12.3%), SFS of 0 (3.6% vs 1.3%), RBS of 0 (21.9% vs 15.2%), and PRO2 (SFS ≤1 and RBS=0; 6.3% vs 2.2%) compared with those who received placebo. These differences increased and were sustained through day 14. A significantly higher percentage of patients who received upadacitinib also had an absence of abdominal pain or bowel urgency vs those who received placebo beginning on day 3 through day 14 (P <.05 or better for all endpoints).
Participants who received upadacitinib had an increased rate of clinical remission beginning at week 2 (upadacitinib, 26.9%; 95% CI, 23.5-30.3 vs placebo, 4.3%; 95% CI, 2.1-6.5; P <.001). For clinical response, a more robust rate was observed at week 2 (upadacitinib, 59.4%; 95% CI, 55.6-63.1 vs placebo, 22.3%; 95% CI, 17.8-26.8). These results were maintained through week 8 for both endpoints, with a 39% difference observed for clinical remission at week 8 and a 46% difference occurring at week 8 for clinical response (P <.001).
The percentage of participants who had an hs-CRP response that was more than a 50% decrease from baseline was significantly increased in those who received upadacitinib (75.7%) compared with those who received placebo (21.9%), which resulted in a treatment difference of 54% (P <.001). Upadacitinib was associated with a decrease in intestinal inflammation, with an increase in the percentage of individuals who had an at least 50% decrease in FCP from baseline vs those who received placebo (48.2% vs 20.2%, P <.001).
Participants who received upadacitinib also had improvement in a number of HRQOL assessments at weeks 2 and 8.
The study authors conclude, “Upadacitinib may provide patients with a rapid-acting therapeutic alternative for the management of important UC symptoms as early as 1 day following the first dose of induction treatment.”
Disclosure: This study was funded by AbbVie. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Loftus EV Jr, Colombel J-F, Takeuchi K, et al. Upadacitinib therapy reduces ulcerative colitis symptoms as early as day 1 of induction treatment. Clin Gastroenterol Hepatol. Published online December 1, 2022. doi:10.1016/j.cgh.2022.11.029