Home > Dermatology > EADV 2020 > Late-Breaking News > 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
Phase 3, Measure Up
Monotherapy with the oral Janus kinase (JAK)1 inhibitor upadacitinib showed a remarkable efficacy and speed of response in patients with moderate-to-severe atopic dermatitis (AD) in 2 replicate, multicentre, phase 3 trials [1].

The JAK inhibitor upadacitinib was specifically developed for therapy of AD because key cytokines involved in the pathogenesis of AD signal via the JAK1 pathway [2,3]. 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, randomised, double-blind, phase 3 trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) aimed to evaluate the efficacy and safety of monotherapy with upadacitinib versus placebo in adolescents and adults with moderate-to-severe AD [1].

Prof. Emma Guttman-Yassky (Icahn School of Medicine at Mount Sinai, USA) presented the results of both trials [1]. Participants 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 (NRS) of ≥4. In the double-blind treatment phase, participants were randomised to upadacitinib in 2 doses (i.e. 15 mg or 30 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 (vIGA-AD 0/1; i.e. clear or almost clear skin) with ≥2 grades of reduction.

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; see Figure). 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, a noticeable difference was already seen at week 1, which reached a plateau at week 4.


Figure: Co-primary endpoints EASI 75 and validated IGA-AD 0/1 at week 16 [1]
* P≤0.001 vs placebo (multiplicity controlled).
EASI, Eczema Area and Severity Index; UPA, upadacitinib; PBO, placebo; vlGA-AD, validated Investigator’s Global Assessment for atopic dermatitis.

Really early significant improvement in worst pruritus NRS was already seen at days 2 and 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.

Concerning safety, acne was the most frequently reported treatment-related adverse event, 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 reported 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 2020 Virtual Congress, 29-31 Oct.
    2. Parmentier JM, et al. BMC Rheumatol 2018;2:23.
    3. Nader A, et al. J Clin Pharmacol 2019;60:528-39.


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