New JAK Inhibitor Shows Efficacy, Safety in Phase 3 Trials for Atopic Dermatitis

Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, was found to be safe and efficacious for the treatment of atopic dermatitis (AD) in two phase 3 clinical trials. The results of the trials were published in The Lancet.

The Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) trials were replicate multicenter, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of upadacitinib. Patients aged 12 to 75 years with moderate to severe AD were randomly assigned to receive either upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.

In total, 1683 patients were included in the studies, with 557 patients in the 15-mg groups, 567 patients in the 30-mg groups, and 559 patients in the placebo groups. Primary endpoints were the proportion of patients who achieved at least a 75% improvement in Eczema Area and Severity Index (EASI) and the proportion of patients who achieved clear or almost clear on the validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD).

At the end of 16 weeks, the primary endpoints were met in both studies. In Measure Up 1, 70% of patients in the 15-mg group and 80% in the 30-mg group achieved EASI 75 or greater; similarly, in Measure Up 2, 60% receiving 15-mg upadacitinib and 73% receiving 30-mg upadacitinib achieved at least EASI 75. For vIGA-AD, 48% and 39% of patients who received 15-mg upadacitinib and 62% and 52% receiving 30-mg upadacitinib in Measure Up 1 and 2, respectively, achieved clear or almost clear at 16 weeks.

Treatment-emergent adverse events included

• Acne (54 patients receiving 15mg upadacitinib, 90 receiving 30mg);
• Upper respiratory tract infection (44 patients receiving 15mg upadacitinib, 55 receiving 30mg);
• Nasopharyngitis (38 patients receiving 15mg upadacitinib, 51 receiving 30mg);
• Headache (32 patients receiving 15mg upadacitinib, 39 receiving 30mg);
• Elevation in creatine phosphokinase levels (25 patients receiving 15mg upadacitinib, 28 receiving 30mg); and
• Atopic dermatitis (17 patients receiving 15mg upadacitinib, 8 receiving 30mg).

“Monotherapy with upadacitinib might be an effective treatment option and had a positive benefit–risk profile in adolescents and adults with moderate to severe AD,” concluded the study authors.

Reference
Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. Published online May 20, 2021. doi:10.1016/S0140-6736(21)00588-2