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Efficacy and safety profile of JAK inhibitor for atopic dermatitis from two replicate trials

Read time: 10 mins
Last updated:29th Jun 2022
Published:29th Jun 2022

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

Guttman-Yassky E, Teixeira HD, Simpson EL, Papp KA, Pangan AL, Blauvelt A, et al. Lancet. 2021;397:2151–2168.

  • Measure Up 1 and Measure Up 2 show upadacitinib as a treatment option for adults and adolescents with moderate-to-severe atopic dermatitis
  • Upadacitinib-mediated blockade of cytokine signalling pathways in atopic dermatitis could lead to patients achieving greater therapeutic response and higher thresholds for skin improvement

Atopic dermatitis causes severe itching, skin pain and sleep disruption. Compared with the general population, people with atopic dermatitis have a higher incidence of many inflammatory conditions, and may have lower self-esteem, substandard performance at school or work, and overall impaired health-related quality of life1.

Long-term topical corticosteroid treatment for atopic dermatitis can be insufficient, and can have adverse effects, but currently approved systemic treatments have shown limited efficacy2

Janus kinase (JAK) signalling, especially JAK1 signalling, is associated with the inflammatory cytokines involved in the pathogenesis of atopic dermatitis. Hence, inhibition of JAK signalling is a rational systemic approach to treat moderate-to-severe atopic dermatitis.

Upadacitinib, an oral JAK inhibitor, especially of JAK1, is approved in the USA, Europe, and elsewhere, to treat moderately or severely active rheumatoid arthritis. A previous phase 2b study found once daily upadacitinib monotherapy was effective in patients with moderate-to-severe atopic dermatitis3.

This paper reports the primary results from Measure Up 1 and Measure Up 2 that evaluated the efficacy and safety of upadacitinib monotherapy to treat moderate-to-severe atopic dermatitis in adolescents and adults.

How did the investigators conduct the trials?

The two replicate trials, Measure Up 1 and Measure Up 2, were multicentre, randomised, double-blind, placebo-controlled phase 3 trials. Participants were randomly assigned to receive upadacitinib (15 or 30 mg) or placebo (1:1:1) once daily for 16 weeks (Figure 1).

Atopic Derm_Pubdigest3_Fig1.pngFigure 1. Design of replicate trials Measure Up 1 and Measure Up 2. EASI-75, Eczema Area and Severity Index-75; vIGA-AD, validated Investigator’s Global Assessment for Atopic Dermatitis.

The co-primary endpoints were:

  • Proportion of patients achieving an Eczema Area and Severity Index-75 (EASI-75) response, defined as ≥75% improvement from baseline in EASI score at 16 weeks
  • Proportion of patients achieving a validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) response, defined as a score of 0 (clear) or 1 (almost clear) on the vIGA-AD, with an improvement of ≥2 points from baseline at 16 weeks

Secondary endpoints included quality of life, and the proportions of patients achieving EASI-90 (≥90% improvement from baseline) and EASI-100 (≥100% improvement from baseline) at Week 16.

What did the investigators find?


In both studies:

  • The co-primary endpoints were met at Week 16 (P<0.001 for all) (Figure 2)
  • All secondary efficacy endpoints were met at all timepoints (P≤0001)
  • The proportion of patients achieving EASI-90 and EASI-100 responses at Week 16 was higher in the 15 mg and 30 mg upadacitinib groups, than in the placebo group (all P<0.0001)
  • EASI-75 and vIGA-AD scores and secondary measures showed clear differences from placebo starting at Weeks 2–4; differences either increased or were maintained until Week 16 (Figure 2)
  • Efficacy measures were consistent in adults and adolescents

Atopic Derm_pubdigest3_Fig2.png

Figure 2. Proportion of patients who achieved an EASI-75 response (A) and a vIGA-AD response (B) over the 16-week treatment period in the intention-to-treat population in the Measure Up 1 trial (Adapted8). EASI-75, at least a 75% improvement in Eczema Area and Severity Index score from baseline; vIGA-AD, validated Investigator’s Global Assessment for Atopic Dermatitis. *P≤0·05; **P≤0·01; ***P≤0·001 (based on nominal P values). Trends and absolute values were similar in the Measure Up 2 trial (data not shown).


  • The overall incidence of serious adverse events and serious infections were similar in the upadacitinib and placebo groups
  • The most frequently reported treatment-emergent adverse event (TEAE) with upadacitinib was acne (7–17% of treated patients); most cases (68%) were mild
  • Other frequently reported TEAEs included upper respiratory tract infection, nasopharyngitis, headache, and elevation in plasma creatine phosphokinase levels
  • No new important safety risks were observed for upadacitinib for this new indication

 Key takeaways

  • Measure Up 1 and Measure Up 2 are the largest studies of upadacitinib monotherapy in atopic dermatitis
  • By Week 16, a higher proportion of patients treated with upadacitinib had achieved at least a 90% and 100% improvement in EASI scores than placebo
  • Upadacitinib was well tolerated, with no new important safety risks compared with the labelled upadacitinib
  • Long-term data are needed to determine the efficacy and safety of upadacitinib treatment for this condition


  1. Drucker AM. Atopic dermatitis: burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017;38:3–8.
  2. Cork MJ, Danby SG, Ogg GS. Atopic dermatitis epidemiology and unmet need in the United Kingdom. J Dermatolog Treat. 2020;31(8):801–809.
  3. Guttman-Yassky E, Thaçi D, Pangan AL, Hong HC ho, Papp KA, Reich K, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;145(3):877–884.
  4. Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. Efficacy and safety of oral janus kinase 1 inhibitor abrocitinib for patients with atopic dermatitis: a phase 2 randomized clinical trial. JAMA Dermatology. 2019;155(12):1371–1379.
  5. Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, et al. efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatology. 2020;156(8):863–873.
  6. Guttman-Yassky E, Silverberg JI, Nemoto O, Forman, Seth B, Wilke A, Prescilla R, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. 2019;80:913–921.
  7. Simpson EL, Lacour JP, Spelman L, Galimberti, R, Eichenfield, L F, Bissonnette, R, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020;183:242–255.
  8. Guttman-Yassky E, Teixeira HD, Simpson EL, Papp KA, Pangan AL, Blauvelt A, et al. Lancet. 2021;397:2151–2168.