A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysis

JAAD Int. 2021 Dec 20;6:27-36. doi: 10.1016/j.jdin.2021.11.001. eCollection 2022 Mar.

Abstract

Background: Systemic atopic dermatitis treatments that have acceptable safety are needed.

Objective: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis.

Methods: In this phase 3, double-blind study (Rising Up), Japanese patients (12-75 years) with moderate-to-severe atopic dermatitis were randomized in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or a placebo + TCS (rerandomized in a 1:1 ratio to receive either 15 or 30 mg of upadacitinib + TCS at week 16). Adverse events and laboratory data were assessed for safety.

Results: In 272 treated patients, the serious adverse event rates were similar for 15- and 30-mg upadacitinib + TCS at week 24 (15 mg, 56%; 30 mg, 64%) but greater than those for placebo + TCS (42%). Acne (all mild or moderate; none leading to discontinuation) occurred more frequently with upadacitinib + TCS (15 mg, 13.2%; 30 mg, 19.8%) than with placebo + TCS (5.6%). Furthermore, herpes zoster infection (4.4% vs 0%), anemia (1.1% vs 0%), neutropenia (4.4% vs 1.1%), and creatine phosphokinase elevations (2.2% vs 1.1%) occurred more frequently with 30-mg upadacitinib + TCS than with 15-mg upadacitinib + TCS; none of these events were reported with placebo + TCS. No thromboembolic events, malignancies, gastrointestinal perforations, active tuberculosis, or deaths occurred.

Limitations: The limitations included a small sample size and short observation period as well as nongeneralizability of the results beyond Japanese populations.

Conclusions: The results were generally consistent with those of previous reports; no new safety risks were detected.

Keywords: AD, atopic dermatitis; AE, adverse event; AESI, adverse event of special interest; CPK, creatine phosphokinase; EASI 50, ≥50% improvement in eczema area and severity index; EASI 75, ≥75% improvement in Eczema Area and Severity Index; EASI 90, ≥90% improvement in Eczema Area and Severity Index; EASI, Eczema Area and Severity Index; JAK, Janus kinase; Janus kinase inhibitors; SAE, serious adverse event; TCS, topical corticosteroid; TEAE, treatment-emergent adverse event; atopic dermatitis; clinical trial; eczema; safety; topical corticosteroids; upadacitinib; vIGA-AD, validated Investigator's Global Assessment for Atopic Dermatitis.