Impact of Baseline Corticosteroid Use on the Efficacy and Safety of Upadacitinib in Patients with Ulcerative Colitis: A Post Hoc Analysis of the Phase 3 Clinical Trial Programme

J Crohns Colitis. 2024 May 31;18(5):695-707. doi: 10.1093/ecco-jcc/jjad190.

Abstract

Background and aims: This post hoc analysis assessed the efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis stratified by corticosteroid use from the ulcerative colitis Phase 3 clinical trial programme.

Methods: Patients were randomised [1:2] to 8 weeks' placebo or upadacitinib 45 mg once daily; Week 8 responders were re-randomised [1:1:1] to 52 weeks' placebo or upadacitinib 15 or 30 mg daily. Corticosteroid dose was kept stable during induction but tapered according to a protocol-defined schedule [or investigator discretion] during maintenance Weeks 0-8. Efficacy outcomes and exposure-adjusted, treatment-emergent adverse event [TEAE] rates were assessed for induction and maintenance stratified by corticosteroid use at induction baseline.

Results: Overall, 377/988 [38%] patients were receiving corticosteroids at induction baseline [placebo, n = 133; upadacitinib 45 mg, n = 244] and 252 [37%] of the 681 clinical responders who entered maintenance were on corticosteroids at induction baseline [n = 84 for each treatment]. Similar proportions of patients receiving upadacitinib achieved clinical remission per Adapted Mayo Score with and without baseline corticosteroids at Weeks 8 and 52. The total proportion of patients re-initiating corticosteroids was higher with placebo [24/84;29%] vs upadacitinib 15 mg [16/81; 20%)] and 30 mg [11/81; 14%]. During induction, patients receiving corticosteroids at baseline had higher rates of TEAEs, serious TEAEs, and serious infections vs those not receiving corticosteroids; however, TEAE rates were similar during maintenance after corticosteroid withdrawal.

Conclusions: Upadacitinib is an effective steroid-sparing treatment in patients with moderately to severely active ulcerative colitis. Clinicaltrials.gov identifiers: NCT02819635; NCT03653026.

Keywords: Clinical trials.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Colitis, Ulcerative* / drug therapy
  • Double-Blind Method
  • Female
  • Heterocyclic Compounds, 3-Ring* / administration & dosage
  • Heterocyclic Compounds, 3-Ring* / adverse effects
  • Heterocyclic Compounds, 3-Ring* / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • upadacitinib
  • Heterocyclic Compounds, 3-Ring
  • Adrenal Cortex Hormones

Associated data

  • ClinicalTrials.gov/NCT02819635
  • ClinicalTrials.gov/NCT03653026

Grants and funding