Laurent Peyrin-Biroulet1,2, Edouard Louis3, Edward V Loftus4, Ana Lacerda5, Qian Zhou5, Yuri Sanchez Gonzalez5, Subrata Ghosh6. 1. Department of Gastroenterology, Nancy University Hospital, Nancy, France. peyrinbiroulet@gmail.com. 2. Université de Lorraine, Nancy, France. peyrinbiroulet@gmail.com. 3. University Hospital CHU of Liège, Liège, Belgium. 4. Mayo Clinic College of Medicine, Rochester, MN, USA. 5. AbbVie Inc., North Chicago, IL, USA. 6. University of Birmingham, Birmingham, UK.
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.
RCT Entities:
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.
Entities:
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
Authors: Mohamad Abbass; Jeremy Cepek; Claire E Parker; Tran M Nguyen; John K MacDonald; Brian G Feagan; Reena Khanna; Vipul Jairath Journal: Cochrane Database Syst Rev Date: 2019-11-14
Authors: Severine Vermeire; Edward V Loftus; Jean-Frédéric Colombel; Brian G Feagan; William J Sandborn; Bruce E Sands; Silvio Danese; Geert R D'Haens; Arthur Kaser; Remo Panaccione; David T Rubin; Ira Shafran; Megan McAuliffe; Arpeat Kaviya; Serap Sankoh; Reema Mody; Brihad Abhyankar; Michael Smyth Journal: J Crohns Colitis Date: 2017-04-01 Impact factor: 9.071