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

Abstract
Background: There is a need for systemic treatments for atopic dermatitis that offer an acceptable safety profile.

Objective: This study aimed to assess the safety of the oral Janus kinase inhibitor upadacitinib, when used alongside topical corticosteroids (TCSs), in treating atopic dermatitis.

Methods: In the phase 3, double-blind “Rising Up” trial, Japanese patients aged 12 to 75 years with moderate-to-severe atopic dermatitis were randomly assigned in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or placebo + TCS. At week 16, placebo recipients were rerandomized in a 1:1 ratio to receive either 15 mg or 30 mg of upadacitinib + TCS. Safety was evaluated based on adverse events and laboratory findings.

Results: Among 272 patients treated, serious adverse event rates at week 24 were comparable between the 15 mg and 30 mg upadacitinib + TCS groups (56% and 64%, respectively), but higher than those observed in the placebo + TCS group (42%). Acne, all mild or moderate and not leading to treatment discontinuation, occurred more frequently with upadacitinib (15 mg, 13.2%; 30 mg, 19.8%) compared to placebo (5.6%). The 30 mg dose was also associated with higher rates of herpes zoster infection (4.4% vs. 0%), anemia (1.1% vs. 0%), neutropenia (4.4% vs. 1.1%), and elevated creatine phosphokinase levels (2.2% vs. 1.1%) compared to the 15 mg dose. None of these events were reported in the placebo group. No thromboembolic events, malignancies, gastrointestinal perforations, active tuberculosis, or deaths occurred.

Limitations: Study limitations included a small sample size, short follow-up duration, and restricted generalizability to populations outside of Japan.

Conclusions: The safety profile observed was consistent with previous findings, and no new safety concerns were identified.