Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn's Disease

Abstract

Introduction: In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn's disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST.

Methods: CELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52.

Results: At Week 16, a significant percentage (P ≤ 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change ≥ 16 points; 49%-57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score ≥ 170; 26%-39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P ≤ 0.1) versus placebo were also observed. Larger improvements (P ≤ 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group.

Conclusion: Improvements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in patients with moderate to severe Crohn's disease.

Trial registration: ClinicalTrials.gov identifier, NCT02365649.

Keywords: CELEST; European Quality of Life-5 Dimensions Visual Analog Scale; Inflammatory Bowel Disease Questionnaire; Janus kinase 1; Quality of life; Upadacitinib; Work Productivity and Activity Impairment Questionnaire.

Figures

Fig. 1

Study design. *Clinical responders defined as ≥ 30% decrease from baseline in average daily very soft/liquid stool frequency OR ≥ 30% decrease from baseline in average daily abdominal pain score, and neither worse than baseline. †Upadacitinib 6-mg BID dosage initiated and randomization for upadacitinib 24-mg QD dosage stopped with those currently enrolled at 24 mg QD continuing treatment per protocol amendment. BID twice daily; HRQOL health-related quality of life; QD once daily

Fig. 2

IBDQ improvements with upadacitinib. a IBDQ response. b IBDQ remission. c Change in IBDQ total score. *P ≤ 0.1 vs. placebo. **P ≤ 0.05 vs. placebo. ***P ≤ 0.01 vs placebo. †P ≤ 0.1 vs UPA 3 mg BID. ††P ≤ 0.05 vs. UPA 3 mg BID. IBDQ response and remission for induction period used the mITT population and LOCF, with P values calculated based on Cochran-Mantel–Haenszel test stratified by baseline SES-CD. IBDQ response and remission for maintenance period used the ITT population and OC, with period P values calculated based on Chi-square test (or Fischer’s exact test if ≥ 20% of the cells had expected cell count < 5). Change in IBDQ score for induction period used the mITT population and LOCF, and was analyzed using ANCOVA, adjusting for treatment, baseline disease severity, and baseline value. Change in IBDQ score for maintenance period used the ITT population and OC, and was analyzed using ANCOVA, adjusting for treatment and baseline value. ANCOVA analysis of covariance; BID twice daily; BL baseline; IBDQ Inflammatory Bowel Disease Questionnaire; ITT intent-to-treat; LOCF last observation carried forward; mITT modified intent-to-treat; OC observed cases; QD once daily; SES-CD Simplified Endoscopic Score for Crohn's Disease; UPA upadacitinib

Fig. 3

Change in EQ-5D VAS score with upadacitinib. *P ≤ 0.1 vs. placebo. **P ≤ 0.05 vs. placebo. †P ≤ 0.1 vs. UPA 3 mg BID. ††P ≤ 0.05 vs. UPA 3 mg BID. Change in EQ-5D VAS score for induction period used the mITT population and LOCF, and was analyzed using ANCOVA, adjusting for treatment, baseline disease severity, and baseline value. Change in EQ-5D VAS score for maintenance period used the ITT population and OC, and was analyzed using ANCOVA, adjusting for treatment and baseline value. ANCOVA analysis of covariance, BID twice daily, EQ-5D VAS European Quality of Life-5 Dimensions visual analog scale, ITT intent-to-treat, LOCF last observation carried forward, mITT modified intent-to-treat, OC observed cases, QD once daily, UPA upadacitinib

Fig. 4

Mean change in WPAI score with upadacitinib. a Activity impairment. b Presenteeism. c Overall work impairment. d Absenteeism. *P ≤ 0.1 vs. placebo. **P ≤ 0.05 vs. placebo. ***P ≤ 0.01 vs. placebo. †P ≤ 0.1 vs. UPA 3 mg BID. Change in WPAI score for induction period used the mITT population and LOCF, and was analyzed using ANCOVA, adjusting for treatment, baseline disease severity, and baseline value. Change in WPAI score for maintenance period used the ITT population and OC, and was analyzed using ANCOVA, adjusting for treatment and baseline value. ANCOVA analysis of covariance; BID twice daily; ITT intent-to-treat; LOCF last observation carried forward; MCID minimum clinically important difference; mITT modified intent-to-treat; OC observed cases; QD once daily; UPA upadacitinib; WPAI Work Productivity and Activity Impairment questionnaire