Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: 2-Year Interim Results from the Phase 3 Rising Up Study

Abstract

Introduction: Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch.

Methods: Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion). This 2-year interim analysis evaluated safety and efficacy through 112 weeks (data cutoff date: 11 August 2021). Adverse events (AEs), AEs of special interest (AESIs), and laboratory data were assessed. Efficacy assessments included ≥ 75% and ≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), achievement of clear or almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), and ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS).

Results: A total of 272 patients were enrolled and 242 were ongoing at data cutoff (UPA15, n = 120; UPA30, n = 122). After 112 weeks of treatment, serious AEs, AEs leading to discontinuation, and most AESIs were generally infrequent, and rates were similar between the two upadacitinib groups. One event each of rectal cancer and cerebellar hemorrhage was reported in the UPA15 group; no thrombosis events were observed. The most common AEs included acne, nasopharyngitis, and herpes zoster. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were maintained through week 112.

Conclusion: UPA15 and UPA30 were well tolerated through 112 weeks of treatment with similar safety profiles to short-term studies and demonstrated durable long-term efficacy for the treatment of moderate-to-severe AD in adults and adolescents.

Trial registration: ClinicalTrials.gov identifier, NCT03661138.

Keywords: Atopic dermatitis; Clinical trial; Eczema; Janus kinase inhibitors; Safety; Topical corticosteroids; Upadacitinib.

© 2022. The Author(s).

Figures

Fig. 1

Patient disposition. All patients received concomitant topical corticosteroids from baseline to week 16. After week 16, the use of concomitant topical corticosteroids was no longer required and was administered per investigator discretion

Fig. 2

Patients achieving EASI 75 and EASI 90 from baseline to week 112. Data are presented using the observed cases approach. All patients received concomitant topical corticosteroids from baseline to week 16. After week 16, the use of concomitant topical corticosteroids was no longer required and was administered per investigator discretion. EASI 75/90 ≥ 75%/ ≥ 90% improvement in Eczema Area Severity Index, PBO placebo, UPA upadacitinib

Fig. 3

Patients achieving vIGA-AD 0/1a from baseline to week 112. Data are presented using the observed cases approach. All patients received concomitant topical corticosteroids from baseline to week 16. After week 16, the use of concomitant topical corticosteroids was no longer required and was administered per investigator discretion. aPatients achieving vIGA-AD 0/1 with at least two grades of reduction from baseline. PBO placebo, UPA upadacitinib, vIGA-AD 0/1 validated Investigator Global Assessment for AD score of clear or almost clear

Fig. 4

Patients achieving WP-NRS ≥ 4-point improvementa from baseline to week 112. Data are presented using the observed cases approach. All patients received concomitant topical corticosteroids from baseline to week 16. After week 16, the use of concomitant topical corticosteroids was no longer required and was administered per investigator discretion. aAmong patients with WP-NRS scores ≥ 4 at baseline. PBO placebo, UPA upadacitinib, WP-NRS Worst Pruritus Numerical Rating Scale