The multicentre, randomised JADE-COMPARE trial (NCT03720470), published on March 25, 2021 in the New England Journal of Medicine, showed that the higher dose of experimental oral Janus kinase 1 (JAK1) inhibitor, abrocitinib, showed greater itch reduction after 2 weeks of treatment than dupilumab in patients with moderate to severe atopic dermatitis (AD) . Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Abrocitinib is associated with a different set of adverse reactions than dupilumab, according to investigators.
In 2017, dupilumab became the first systemic drug approved specifically for AD, monoclonal antibody delivered by subcutaneous injection which binds to interleukin (IL)-4 receptors to block signaling pathways involved in AD. In contrast, abrocitinib is an oral small molecule inhibitor of JAK1, which modulates interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
In JADE-COMPARE, 838 people with moderate to severe AD used emollients twice a day for at least 7 days before being randomly assigned to one of 4 systemic treatments: abrocitinib 200 mg once daily (n=226), 100 mg of abrocitinib once daily (n=238), 300-mg dupilumab injection every other week (n=243), or placebo versions of both medications (n=131), for 16 weeks.
To assess efficacy, the investigators measured 3 outcomes (Table): the 2-week Itch Response, the Investigator’s Global Assessment (IGA) response at 12 weeks (defined as clear or almost clear), and the Eczema Area and Severity Index (EASI-75) response (defined as an improvement of at least 75%) at 12 weeks. After 2 weeks, the 2-week Itch Response showed that 49% of the patients taking 200 mg abrocitinib and 32% of taking 100mg dose had at least a 4-point improvement from baseline in the 0-10 Peak Pruritus Numerical Rating Scale. This was compared with 26.4% of those taking dupilumab and 13.8% of those on placebo. At 12 weeks after randomisation, both the IGA and EASI-75 responses, which were the primary endpoints, favoured 200mg abrocitinib over lower dose abrocitinib, dupilumab, or placebo.
Thus, the 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16.
- Bieber T, Simpson EL, Silverberg JI, Thaçi D, Paul C, Pink AE, Kataoka Y, Chu CY, DiBonaventura M, Rojo R, Antinew J, Ionita I, Sinclair R, Forman S, Zdybski J, Biswas P, Malhotra B, Zhang F, Valdez H; JADE COMPARE Investigators. Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis. N Engl J Med. 2021 Mar 25;384(12):1101-1112.
Treatment Groups and Endpoints
|2-Week Itch Response (%)||12-Week IgA Response (%)||12-Week EASI-75 Response (%)|
|Abrocitinib, 200 mg (n = 226)||49.1||48.4||70.3|
|Abrocitinib, 100 mg (n = 238)||31.8||36.6||58.7|
|Dupilumab (n = 243)||26.4||36.5||58.1|
|Placebo (n = 131)||13.8||14.0||27.1|