Abrocitinib safe, effective in moderate-to-severe atopic dermatitis after dupilumab use

Treatment with abrocitinib is both safe and effective in patients with moderate-to-severe atopic dermatitis (AD), regardless of prior dupilumab response status, a study has shown.

“Abrocitinib represents an effective systemic oral treatment option for patients with moderate-to-severe AD, regardless of prior dupilumab response status,” according to the researchers, led by Vivian Shy from the Department of Medicine, University of Arkansas for Medical Sciences, Arkansas, US.

“Patients with AD that fail to respond to dupilumab, who cannot tolerate or experience AEs with dupilumab, or who prefer an oral therapy may consider abrocitinib treatment,” they added.

This phase III extension study (JADE EXTEND) assessed the efficacy and safety of abrocitinib who received prior dupilumab. Patients with moderate-to-severe AD received either 200- or 100-mg abrocitinib once daily after dupilumab in double-blind, placebo-controlled phase III JADE COMPARE.

Among prior dupilumab responders, 93.5 percent and 90.2 percent of patients who received 12 weeks of abrocitinib 200 and 100 mg, respectively, achieved ≥75-percent improvement in Eczema Area and Severity Index (EASI). In addition, 89.7 percent and 81.6 percent attained ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PPNRS), respectively. [J Am Acad Dermatol 2022;87:351-358]

Among nonresponders, 80.0 percent and 67.7 percent of patients treated with 200- and 100-mg abrocitinib respectively achieved ≥75-percent improvement in EASI, while 77.3 percent and 37.8 percent attained ≥4-point improvement in PPNRS.

Nasopharyngitis, nausea, acne, and headache were the most common adverse events in patients who received abrocitinib. Compared with prior dupilumab, abrocitinib resulted in fewer incidences of conjunctivitis among trial participants.

“In this analysis, patients who responded to prior dupilumab in JADE COMPARE maintained most of these clinical benefits with abrocitinib treatment for 12 weeks in JADE EXTEND,” the researchers said.

“Furthermore, substantial proportions of patients who did not respond to dupilumab in JADE COMPARE were able to achieve clinical benefit with abrocitinib treatment for 12 weeks, both in terms of skin clearance and itch relief,” they added.

One possible reason why prior dupilumab nonresponders were able to achieve response to abrocitinib was that the latter targets more relevant cytokines that are associated with components of AD pathophysiology than dupilumab. [Front Immunol 2019;10:2847; Front Immunol 2019;10:2342; Front Immunol 2019;10:1862]

As to why some prior dupilumab responders did not respond to abrocitinib remains unclear. However, Shi and her colleagues posited that such reaction could be attributed to varying pharmacokinetics or pharmacodynamics of the two agents in this population.

“Some patients may derive enhanced efficacy from abrocitinib, based on the observation that >50 percent of subjects who achieved a ≥75-percent to <90-percent improvement in EASI with prior dupilumab in JADE COMPARE were able to achieve EASI-90 after switching to abrocitinib in JADE EXTEND,” the researchers said.

The current study was limited by its short-term duration and the absence of a placebo arm. In addition, there was a difference in study design between JADE COMPARE and JADE EXTEND regarding concomitant medicated topical therapy.