Distinct trajectories of symptomatic response in ulcerative colitis during filgotinib therapy: A post hoc analysis from the SELECTION study

United European Gastroenterol J. 2024 Nov;12(9):1243-1255. doi: 10.1002/ueg2.12686. Epub 2024 Oct 25.

Abstract

Background: Filgotinib is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for treatment of ulcerative colitis (UC) following the phase 2b/3 SELECTION trial. Identification of patient populations and factors associated with long-term treatment response trajectories may improve UC management.

Objective: We aimed to identify and describe distinct patient subgroups of response to filgotinib based on partial Mayo Clinic Score (pMCS) trajectories over time.

Methods: In these post hoc analyses of SELECTION, group-based trajectory modeling (GBTM) was applied to pMCS to describe groups of distinct, symptom-based patient trajectories using data from patients who responded to filgotinib 200 or 100 mg and continued receiving filgotinib up to week 58. Patient demographics, disease characteristics, and week 10 response were compared between the groups. Achievement of a patient-level multi-component endpoint of comprehensive disease control (CDC) was assessed in each group.

Results: GBTM identified five distinct patient populations with different response trajectories; 67.5% of patients had beneficial trajectories. The beneficial trajectory groups generally had higher proportions of patients who were recently diagnosed (<1 year), were receiving filgotinib 200 mg and were biologic-naive versus the relapsing trajectory groups (4%-9% vs. 4%-5%; 43%-65% vs. 36%-46%; 54%-70% vs. 35%-58%, respectively). Furthermore, 55.4% of patients had sustained beneficial trajectories, with low baseline endoscopic subscores (≥43% of patients had a subscore of 2) and strong week 10 FCP responses (≥61% of patients with >50% decrease in FCP from baseline). Sustained beneficial trajectory groups had a higher probability of achieving CDC at week 58 than other groups (31%-32% vs. 0%-7%).

Conclusions: Beneficial long-term response trajectories and achievement of CDC with filgotinib were associated with being biologic-naive and having less severe disease at baseline. Early estimation of sustained and CDC may facilitate patient identification and development of personalized management strategies in UC.

Gov identifier: NCT02914522.

Keywords: Janus kinase 1 inhibitor; clinical trials; comprehensive disease control; filgotinib; inflammatory bowel disease; symptom trajectories; ulcerative colitis.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Colitis, Ulcerative* / diagnosis
  • Colitis, Ulcerative* / drug therapy
  • Double-Blind Method
  • Female
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / therapeutic use

Substances

  • GLPG0634
  • Janus Kinase 1
  • Triazoles

Associated data

  • ClinicalTrials.gov/NCT02914522

Grants and funding