Home > Oral JAK 1 inhibitor leads to fast itch relieve and remarkable skin clearance in AD

Oral JAK 1 inhibitor leads to fast itch relieve and remarkable skin clearance in AD

Presented by
Prof. Emma Guttman-Yassky, Icahn School of Medicine at Mount Sinai, USA
EADV 2020
Oral administration of the JAK1 inhibitor upadacitinib given as monotherapy showed a remarkable efficacy and speed of response in patients with moderate-to-severe atopic dermatitis (AD) in 2 replicate, multicentre, phase 3 trials.

The Janus kinase (JAK) inhibitor upadacitinib was specifically developed for therapy of AD as key cytokines involved in the pathogenesis of AD signal via the JAK1 pathway. A previous phase 2b trial demonstrated that upadacitinib monotherapy was efficacious with a favourable benefit-risk profile compared with placebo in adults with moderate-to-severe AD. The 2 replicate, randomized, double-blind, phase 3 trials Measure Up 1 and Measure Up 2 aimed to evaluate the efficacy and safety of monotherapy with upadacitinib versus placebo in adolescents and adults with moderate-to-severe AD.

Prof. Emma Guttman-Yassky (Icahn School of Medicine at Mount Sinai, USA) presented the results of both trials [1]. Both trials included patients who were 12-75 years old and had AD symptoms for at least 3 years. Their Eczema Area and Severity Index (EASI) was ≥16 and they had a worst pruritus score on a numerical rating scale of ≥4. In the double-blinded treatment phase, participants were randomised to upadacitinib in 2 doses (i.e. 30 mg or 15 mg once daily) or placebo. Co-primary endpoints of the trials were a ≥75% reduction in EASI and a validated Investigator´s Global Assessment of 0 or 1 (i.e. clear or almost clear skin) with ≥2 grades of reduction (vIGA-AD 0/1).

Data from 847 participants in Measure Up 1 and 836 participants in Measure Up 2 were analysed at the end of the double-blind phase. At week 16, significantly more patients treated with upadacitinib in the Measure Up 1 and 2 studies achieved the co-primary endpoints EASI 75 and vIGA-AD 0/1 (P<0.001 for all doses and endpoints). In addition, both studies met all ranked secondary endpoints. The higher dose of upadacitinib achieved numerically better results, but both doses were significantly superior to placebo. “An EASI 100 response was achieved in 27% of patients treated with the high dose,” said Prof. Guttman-Yassky. Regarding the co-primary endpoints, there was a noticeable difference already at week 1 that reached a plateau at week 4.
Relieve of pruritus after the first dose

Very early significant improvement in worst pruritus NRS was already seen at day 2 and day 3. The proportion of patients achieving a clinically meaningful itch reduction was significantly higher than placebo from day 2 on, the effect reached a plateau at week 4 and was maintained through week 16.

With regard to safety, acne was the most frequently reported treatment-related adverse event, which was reported in 19 patients treated with the low dose and 49 patients with the high dose, but only 2 patients discontinued treatment due to acne. “We saw some eczema herpeticum in the higher dose group, but no patient discontinued,” added Prof. Guttman. No new safety signals and no death were observed in the treatment arms. “The speed and the magnitude of response are really characteristic features of upadacitinib,” Prof. Gutmann-Yassky concluded.


    1. Guttman-Yassky E, et al. Safety and efficacy of upadacitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis: Results from 2 pivotal, phase 3, randomized, double-blinded, monotherapy, placebo-controlled studies (Measure Up 1 and Measure Up 2). Late-Breaker D3T03.3B, EADV Virtual, 29-31 October 2020.


Posted on