Abrocitinib Promising for Treatment of Atopic Dermatitis

The Janus kinase (JAK) inhibitor abrocitinib is an effective, safe systemic oral treatment option for patients with moderate to severe atopic dermatitis (AD), regardless of previous dupilumab response status. The phase 3 JADE EXTEND trial (ClinicalTrials.gov identifier: NCT03422822) was conducted to evaluate the long-term efficacy and safety of orally administered abrocitinib 200 mg or 100 mg once daily in patients with moderate to severe AD. Results of the analysis were published in the Journal of the American Academy of Dermatology. 

Patients enrolled in JADE EXTEND had received treatment with dupilumab — an anti–interkeukin (IL)-4 receptor α monoclonal antibody that is administered by injection — in the double-blind, placebo-controlled, phase 3 JADE COMPARE study (ClinicalTrials.gov identifier: NCT03720470). Some of the participants in JADE COMPARE, however, had AD that did not respond to dupilumab (ie, dupilumab nonresponders) or experience side effects associated with the agent.

Abrocitinib and dupilumab have different mechanisms of action in AD. Dupilumab binds to the shared α-chain of IL-4 and IL-13 receptors, inhibiting helper T-cell 2-driven inflammation, whereas abrocitinib inhibits JAK1-mediated signaling and therefore targets multiple cytokines that are key to the pathogenesis of AD.

In JADE COMPARE, participants were randomly assigned in a 2:2:2:1 ratio to 16 weeks of treatment with 1 of the following 4 regimens: oral abrocitinib 200 mg once daily; oral abrocitinib 100 mg once daily; subcutaneous dupilumab 300 mg every other week (following a 600-mg loading dose); or placebo.

Among a total of 223 individuals who completed treatment in the dupilumab arm in JADE COMPARE, 91.0% were enrolled in JADE EXTEND. In fact, in JADE EXTEND, 95.9% of the patients randomly assigned to abrocitinib 200 mg and 93.8% of those randomly assigned to abrocitinib 100 mg completed 12 weeks of treatment.

Results of the JADE EXTEND study showed that among previous dupilumab responders, a 75% or greater improvement in Eczema Area and Severity Index (EASI) was attained in 93.5% (95% CI, 86.3% to 100.0%) and 90.2% (95% CI, 84.1% to 96.3%) of participants who were treated with 12 weeks of abrocitinib 200 mg and abrocitinib 100 mg, respectively. Further, a 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) was attained in 89.7% (95% CI, 80.2% to 99.3%) and 81.6% (95% CI, 72.9% to 90.3%) of participants, respectively.

In addition, among dupilumab nonresponders, a 75% or greater improvement in EASI was attained with abrocitinib 200 mg and abrocitinib 100 mg in 80.0% (95% CI, 62.5% to 97.5%) and 67.7% (95% CI, 51.3% to 84.2%) of participants, respectively. Further, a 4-point or greater improvement in PP-NRS was attained in 77.3% (95% CI, 59.8% to 94.8%) and 37.8% (95% CI, 23.6% to 51.9%) of participants, respectively.

Among abrocitinib-treated patients, the most common treatment-emergent adverse events reported included nasopharyngitis, nausea, acne, and headache. Conjunctivitis was observed less often with abrocitinib compared with those who received previous dupilumab therapy.

Limitations of the study include that it was a short-term, 12-week post hoc analysis that had no placebo control arm.

Investigators concluded that the current analysis supports the role of abrocitinib as a treatment for patients with moderate to severe AD, regardless of their previous response to dupilumab.

Disclosure: Several of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Shi VY, Bhutani T, Fonacier L, et al. Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND). J Am Acad Dermatol. 2022;87(2):351-358. doi:10.1016/j.jaad.2022.04.009