Novel oral agent effective in teens with moderate-to-severe atopic dermatitis

08 Apr 2021

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition with immune dysfunction that affects lesional and nonlesional skin.1 Characterized by pruritus, skin pain, eczematous lesions and dry skin, AD is associated with substantial comorbidity and impairment in a patient’s quality-of-life.2,3 Current treatments for moderate-to-severe AD have unmet needs such as lower efficacy and tolerability.2 Hence, more efficacious and tolerable treatment options are necessary.2 In the recent phase 3 JADE TEEN trial, abrocitinib, an oral, once-daily Janus kinase (JAK) 1 selective inhibitor, was shown to significantly improve the signs and symptoms of AD in adolescent patients with moderate-to-severe AD.4

AD is the most common inflammatory skin disease worldwide with a globally increasing incidence.1 Current treatment options include immunosuppressive agents and dupilumab, a subcutaneous interleukin 4 (IL-4) receptor-α subunit antagonist that blocks IL-4 and IL-13 signaling to treat patients with moderate-to-severe AD.2 Despite having modest efficacy in patients with moderate-to-severe AD, immunosuppressive agents are associated with adverse events that often limit long-term use.5 On the other hand, not all patients respond to dupilumab and some also lose response to treatment over time.6 Treatment with dupilumab is also associated with injection site reactions, conjunctivitis and/or face and neck erythema.2 To address these adverse effects, additional treatment options are thereby needed for patients with moderate-to-severe AD.2

Abrocitinib is an oral, once-daily JAK1 selective inhibitor under investigation for the treatment of AD.4 Selective inhibition of JAK1 with abrocitinib modulates signaling by IL-4, IL-13 and other cytokines involved in the pathogenesis of AD and pruritus.7 Previous studies have demonstrated that abrocitinib improved the signs and symptoms of AD in adolescent and adult patients with moderate-to-severe AD.4 In the recent JADE TEEN study, Dr. Eichenfield, Professor of Dermatology and Pediatrics at the University of California, San Diego School of Medicine, and colleagues sought to further investigate the efficacy and safety of abrocitinib versus placebo among adolescent patients.4

285 adolescent patients (mean age of 14.9 years; 50.9% male; 56.1% white) with moderate to severe AD were assigned to receive one of the following treatments for 12 weeks: Abrocitinib 200mg plus topical therapy (n=95), abrocitinib 100mg plus topical therapy (n=95) or placebo with topical therapy alone (n=95).4 The coprimary endpoints were an Investigator’s Global Assessment (IGA) response of clear or almost clear (scores of 0 and 1, respectively) with an improvement of at least 2 points, and an improvement in Eczema Area and Severity Index score of at least 75% (EASI-75) at week 12.4 Secondary endpoints included an improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) response of at least 4 points at week 12.4

Results from the study demonstrated that more adolescents treated with abrocitinib at both doses achieved IGA (46.2% and 41.6% for 200mg and 100mg abrocitinib, respectively, vs. 24.5% for placebo; p<0.05), EASI-75 (72.0% and 68.5% for 200mg and 100mg abrocitinib respectively vs. 41.5% for placebo; p<0.01) and PP-NRS (55.4% and 52.6% for 200mg and 100mg abrocitinib respectively vs. 29.8% for placebo; p<0.01 for 200mg vs. placebo) responses as compared to placebo at week 12.4 Larger mean percentage reductions in PP-NRS scores were further observed with abrocitinib versus placebo within 2 days of treatment initiation.4

In summary, adolescents who received abrocitinib combined with medicated topical therapy had significant improvement in the severity of their AD as compared to those in the placebo group.4 The JADE TEEN study thereby provides another option to address the unmet need for AD patients who cannot tolerate or are refractory to current treatment therapies such as immunosuppressive agents and dupilumab.4

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