Oral Drug Active in Teens With Atopic Dermatitis

Teenagers with moderate or severe atopic dermatitis (AD) had significant improvement at 12 weeks with the investigational oral Janus kinase (JAK) inhibitor abrocitinib plus topical therapy, a placebo-controlled trial showed.

Almost half of the patients had clear or almost clear skin by clinician assessment (IGA), and about 70% of patients treated with either of two doses of the JAK inhibitor had at least 75% improvement in the Eczema Area and Severity Index (EASI-75). In contrast, a fourth of patients who received placebo in addition to topical therapy met the clinician assessment outcome and about 40% met EASI-75 criteria.

Pruritus also improved significantly more with abrocitinib, and adverse event (AE) rates were similar among treatment groups, reported Lawrence F. Eichenfield, MD, of the University of California San Diego, and colleagues, in JAMA Dermatology.

“More patients who were treated with abrocitinib achieved IGA, EASI-75, and [pruritus] response at week 2 compared with placebo, illustrating early onset of activity,” the authors stated. “Larger mean percentage reductions in [pruritus] scores were observed with abrocitinib versus placebo within 2 days of treatment initiation, indicating fast relief of pruritus with abrocitinib. Improvement in signs and symptoms of AD could explain the improvement in the sleep of adolescents and potentially contribute to reported QoL [quality of life] improvement in patients and caregivers.”

AD affects as many as 20% of children and adolescents and has an adverse impact on QoL, academic performance, and social relationships, as well as the QoL of caregivers, according to the authors. Subcutaneous dupilumab (Dupixent) has demonstrated safety and efficacy in moderate-to-severe AD in adolescents, but an oral medication with a favorable risk/benefit profile remains an unmet need, they said.

Abrocitinib, a JAK-1-selective inhibitor, demonstrated efficacy and tolerability in phase III monotherapy studies involving a mixed patient population of adults and adolescents with moderate-to-severe AD (JADE Mono-1, JADE Mono-2). Eichenfield and colleagues reported findings from the phase III JADE TEEN trial to compare abrocitinib 100 mg and 200 mg versus placebo, in addition to topical medication, in teenagers with moderate-to-severe AD.

The trial included 285 patients, ages 12 to 17, and even distribution of sexes. Patients were enrolled at centers in the U.S., Mexico, Europe, Asia, and Australia. The coprimary endpoints were an IGA score of 0/1 with at least a two-grade improvement from baseline, plus an EASI-75 response, with both outcomes assessed at 12 weeks. Secondary endpoints included a 4+ improvement in the Peak Pruritus Numerical Rating Scale (PP-NRS4).

The primary analysis showed an IGA 0/1 response in 46.2% of patients treated with abrocitinib 200 mg and 41.6% of those assigned to abrocitinib 100 mg, both of which were statistically superior to the 24.5% in the placebo group (P<0.05). The proportion of patients who met EASI-75 response criteria was 72% with abrocitinib 200 mg, 68.5% with abrocitinib 100 mg, and 41.5% with placebo (P<0.05). PP-NRS4 rates were 55.4%, 52.6%, and 29.8% (P<0.05 for abrocitinib 200 mg vs placebo).

The overall rates of reported AEs were 62.8% with the higher dose of abrocitinib, 56.8% with the lower dose, and 52.1% in the placebo group. Nausea occurred more often with abrocitinib 200 mg than with abrocitinib 100 mg (18.1% vs 7.4%). Serious AEs occurred in 1.1% of the abrocitinib 200 mg arm, 0% with abrocitinib 100 mg, and 2.1% of the placebo group.

The results suggest abrocitinib has considerable potential as a systemic therapy in adolescents with AD, said John C. Browning, MD, of Texas Dermatology and Laser Specialists in Dallas. Currently, no JAK inhibitor has an approved indication for AD.

“I am very excited about an oral option for treating atopic dermatitis,” he told MedPage Today via email. “Not everyone responds to current systemic therapies, so there is a definite need for new treatments.”

“I think more teens will be open to trying an oral option, but they will need to be committed to taking it every day. Compliance is always an issue with kids, as we see…with acne patients,” added Browning, a scientific/clinical expert for the American Academy of Dermatology. “Both abrocitinib and dupilumab are effect, so there is not a tradeoff in going from injections to oral therapy.”