Compared to Dupilumab Upadacitinib rapidly improves itching and clears skin in atopic dermatitis: JAMA

Upadacitinib vs Dupilumab in adult atopic dermatitis (AD) : JAMA study

Atopic dermatitis is a severely pruritic relapsing disorder with multiple cytokines like interleukins (IL) like IL- 4, 13, 22,-31, interferon gamma (IFN-γ) and thymic stromal lymphopoietin (TSLP) involved in its pathogenesis. Dupilumab, a monoclonal antibody against α-subunit of IL-4 and IL-13 receptors is approved for the treatment of moderate-to-severe AD. Upadacitinib is an oral, reversible, selective JAK1 inhibitor recently showing evidence of efficacy in AD.²

The present study was a head-to-head, multicenter, randomized, double-blinded, double dummy, active-controlled 24-week clinical trial conducted from February 21, 2019, to December 9, 2020 comparing the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD. Eligible patients diagnosed with moderate to severe AD requiring systemic therapy were recruited.

Criteria for moderate to severe disease was defined as either one or all of the following-≥

• 10% of body surface area affected
• Eczema Area and Severity Index [EASI] ≥16
• validated Investigator's Global Assessment for AD score ≥3
• weekly average Worst Pruritus Numerical Rating Scale [NRS] score ≥4
• Patients were randomized into 2 groups to receive 30 mg of upadacitinib once daily till week 24 or 300mg of dupilumab every 2weeks after a loading dose of 600mg, starting at week 2 and until week 22. The primary end points were fixed at 75% improvement in EASI (EASI75) at week 16. Secondary end points were fixed as:
• percentage change from baseline in Worst Pruritus NRS in total, at week 1 and at week 4
• Worst Pruritus NRS improvement of 4 points or more at week 16
• achievement of EASI100 and EASI90 at week 16
• achievement of EASI75 at week 2
• Efficacy analyses were conducted in the intent-to-treat population.Of 924 patients screened, 692 were enrolled and treated, 348 received upadacitinib and 344 received dupilumab. Most patients completed 16 weeks of treatment. Demographic and baseline characteristics were balanced among the upadacitinib and dupilumab groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All secondary end points demonstrated the superiority of upadacitinib over dupilumab including improvement in Worst Pruritus NRS as early as week 1 (31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 at week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Acne was the most common (55 [15.8%]) AE reported with upadacitinib. Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib. Rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab.

  In conclusion this is the first study directly comparing upadacitinib with dupilumab for AD demonstrating superior efficacy, rapidity of onset of action and higher skin clearance and itch relief of upadacitinib over dupilumab.

  Source-

• Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2021 Aug 4. doi: 10.1001/jamadermatol.2021.3023. Epub ahead of print. PMID: 34347860.
• Guttman-Yassky E, Thaçi D, Pangan AL, 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. doi:10.1016/j.jaci.2019.11.025