S854 Upadacitinib Is Effective at Inducing Clinical Remission and Response in Ulcerative Colitis Patients Regardless of Baseline Corticosteroid Use: Results From Two Phase 3 Studies

Introduction: Corticosteroid (CS) therapy is often used to treat ulcerative colitis (UC) relapses. It is efficient at reducing inflammation and clinical symptoms but is not effective nor is it recommended in the management of maintenance phases due to associated adverse events. The need for an effective, targeted induction therapy in the absence of CS is of key interest. Upadacitinib (UPA) is an oral selective and reversible JAK inhibitor that demonstrated significantly greater efficacy as an induction therapy compared with placebo (PBO) in patients with moderately to severely active UC during two phase 3 trials (U-ACHIEVE [NCT02819635] and U-ACCOMPLISH [NCT03653026]). This subgroup analysis evaluated the impact of baseline CS use on UPA efficacy in UC patients from these trials. Methods: U-ACHIEVE and U-ACCOMPLISH were multicentre, double-blind, PBO-controlled trials that enrolled patients who have had moderately to severely UC with an Adapted Mayo Score of 5 to 9 points and a baseline endoscopy subscore of 2 to 3. Patients (n=988 in both studies) were randomized to receive UPA 45mg once daily (QD) or PBO for 8 weeks (wks). Endpoints presented here are the percentage of patients in clinical remission at wk 8, per Adapted Mayo score, and the percentage of patients with a clinical response at wk 2, per partial Adapted Mayo score (both defined in Table footnotes), respectively, in patients who were on concomitant CS at baseline, at a dose maintained to the end of induction and in those treated with UPA without concomitant CS. Results: UPA was superior to PBO, with a higher percentage of UPA-treated patients achieving clinical remission at wk 8 and clinical response at wk 2 regardless of baseline CS use. No significant differences were observed in the wk 8 clinical remission rate between UPA-treated patients receiving baseline CS (U-ACHIEVE: 24.3%; U-ACCOMPLISH: 28.8%) and those who received UPA without CS (U-ACHIEVE: 27.3%; U-ACCOMPLISH: 35.9%). Similar results were found with the clinical response rate at wk 2, with no difference between UPA-treated patients who received baseline CS (U-ACHIEVE: 58.1%; U-ACCOMPLISH: 55.1%) and those that received UPA without CS (U-ACHIEVE: 61.4%; U-ACCOMPLISH: 67.7%). Conclusion: In patients with moderately to severely active UC, UPA is superior to PBO in conferring clinical remission and response, with similar rates in patients on CS at baseline and those without CS use.Table 1.: Efficacy Endpoints in Ulcerative Colitis Patients Based on Baseline Corticosteroid Use. Adapted Mayo score = stool frequency subscore + rectal bleeding subscore (RBS) + endoscopic subscore. week, wk Clinical remission per adapted Mayo score: defined as Adapted Mayo score ≤ 2, stool frequency subscore [SFS] ≤ 1 and not greater than baseline, RBS of 0, and endoscopic subscore ≤ 1. Clinical response per partial adapted Mayo score: decrease in partial adapted Mayo score ≥ 1 point and ≥ 30% from Baseline, PLUS a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. Non-responder imputation incorporating multiple imputation was used to handle missing data due to COVID-19. Subjects were considered "non-responder" for binary endpoints at and after the UC-related corticosteroids censoring time point through the end of the Induction Study. † Dosing for main corticosteroids were as follows: prednisone. 10-40 mg QD, budesonide, 9 mg QD; or beclomethasone, 5 mg QD. § 95% CI for response rate is the synthetic result based on Student's t-distribution from PROC MIANALYZE procedure if there were missing data due to COVID-19 or is based on the normal approximation to the binomial distribution if there are no missing data due to COVID-19. ‡ 95% CI for response rate difference was calculated based on normal approximation to the binomial distribution. The calculations are based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or non-responder imputation if there were no missing data due to COVID-19. Number of patients missing at week 8 due to COVID-19 in the U-ACHIEVE trial: 1, 2 (PBO, UPA; with corticosteroid use). Number of patients missing at week 8 due to COVID-19 in the U-ACHIEVE trial: 0, 4 (PBO, UPA; without corticosteroid use). Number of patients missing at week 8 due to COVID-19 in the U-ACCOMPLISH trial: 0, 0 (PBO, UPA; with corticosteroid use). Number of patients missing at week 8 due to COVID-19 in the U-ACCOMPLISH trial: 3, 1 (PBO, UPA; without corticosteroid use). At week 2, 1 patient is missing due to COVID-19 in U-ACHIEVE trial (UPA; without corticosteroid use).

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