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 B 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change C 16 points; 49%-57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score C 170; 26%-39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P B 0.1) versus placebo were also observed. Larger improvements (P B 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

The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate–Severe Crohn’s Disease: A Systematic Review

“…The Peyrin-Biroulet L et al [45] study was conducted during the phase 2b CELEST clinical trial. During the maintenance phase, patients were randomly allocated (1:1:1) to receive upadacitinib at doses of 3 mg/12 h (n = 32), 12 mg/12 h (n = 29) and 24 mg/24 h (n = 19).…”

Health-Related Quality of Life of Patients Treated with Biological Agents and New Small-Molecule Drugs for Moderate to Severe Crohn’s Disease: A Systematic Review

“…The total number of participants in this review was 7463 and ranged between 108 and 1281. Three studies investigated infliximab [31][32][33], three studies investigated certolizumab pegol [34][35][36], three studies investigated ustekinumab [37], two studies investigated natalizumab [38,39] and one study each investigated adalimumab [40], filgotinib [41], upadacitinib [42], tofacitinib [43] and apilimod mesylate [44]. Nine were induction studies, and six were maintenance studies.…”

“…All outcomes were rated as having low risks in domain 4 (Table 1 and Figure 2). IM UNITI [37] Ustekinumab 1281 Intervention All HRQoL outcomes 18 ENCORE [38] Natalizumab 509 Intervention All HRQoL outcomes 3 ENACT 2 [39] Natalizumab 339 Intervention All HRQoL outcomes 24 FITZROY [41] Filgotinib 174 Intervention All HRQoL outcomes 1 CELEST [42] Upadacitinib 220 Intervention All HRQoL outcomes 20 Tofacitinib [43] Tofacitinib 280 Not reported All HRQoL outcomes 8…”

“…All outcomes were rated as having low risks in domain 4 (Table 1 and Figure 2). Intervention All HRQoL outcomes 24 FITZROY [41] Filgotinib 174 Intervention All HRQoL outcomes 1 CELEST [42] Upadacitinib 220 Intervention All HRQoL outcomes 20 Tofacitinib [43] Tofacitinib 280 Not reported All HRQoL outcomes 8…”

“…The CELEST study compared five doses of oral upadacitinib (3 mg, 6 mg, 12 mg or 24 mg twice daily or 24 mg once daily) with a placebo as induction therapy [42,50]. Changes in the mean IBDQ total score at weeks 8 and 16 were only statistically significant in the 6 mg and 24 mg twice-daily groups (p ≤ 0.05, compared to the placebo).…”