Abrocitinib Shows Fast Relief in Itch-Dominant AD

While visible skin involvement of atopic dermatitis (AD) often drives severity assessments, itch remains the most burdensome symptom for many patients. A phenotype described as “itch-dominant” AD—marked by severe itch despite mild-to-moderate lesion severity—has been reported in approximately 21% to 29% of patients and is associated with significant quality-of-life (QoL) impairment.¹ However, evidence to guide systemic therapy selection in this subgroup has been limited.

A recent post hoc analysis of the phase 3 JADE DARE and JADE COMPARE trials examined the comparative efficacy of abrocitinib and dupilumab in adults with itch-dominant AD.²

Study Design and Patient Population

The analysis included adults aged 18 years or older who received oral abrocitinib 200 mg once daily or subcutaneous dupilumab 300 mg every 2 weeks, both in combination with topical therapy, for 16 weeks.

Itch-dominant AD was defined using 2 alternative baseline criteria:

• Investigator’s Global Assessment (IGA) score of 3 with Peak Pruritus Numerical Rating Scale (PP-NRS) 7–10
• Eczema Area and Severity Index (EASI) 16–21 with PP-NRS 7–10

Of 1194 patients with available IGA and PP-NRS data, 498 (41.7%) met itch-dominant criteria. Using EASI-based criteria, 279 of 1190 patients (23.4%) qualified. Demographics and baseline characteristics were comparable between treatment arms. Mean baseline PP-NRS scores were approximately 8, indicating severe itch, and mean Dermatology Life Quality Index (DLQI) scores were approximately 15, reflecting substantial QoL impairment.

Rapid Itch Reduction at Week 2

Early response differentiated the therapies. Among patients defined by IGA plus PP-NRS criteria, 55.7% of those treated with abrocitinib achieved a ≥4-point improvement in PP-NRS (PP-NRS4) at week 2, compared with 30.9% of those treated with dupilumab. Similar patterns were observed when itch-dominant AD was defined using EASI criteria.

By week 16, PP-NRS4 response rates were comparable between treatment groups (68.1% with abrocitinib vs 66.5% with dupilumab), suggesting that the primary distinction was speed of onset rather than ultimate response rate.

Higher-Threshold Itch Outcomes

Differences were more pronounced when examining complete or near-complete itch relief. At week 2, 17.3% of abrocitinib-treated patients achieved an itch-free state (PP-NRS 0/1) compared with 2.9% of dupilumab-treated patients. This advantage persisted through week 16, with 35.3% of patients receiving abrocitinib achieving PP-NRS 0/1 versus 20.9% receiving dupilumab.

Comparable trends were observed in the EASI-defined itch-dominant subgroup.

Quality-of-Life Improvements

QoL improvements paralleled itch reduction. At week 2, 21.2% of patients treated with abrocitinib achieved DLQI <2 (indicating no effect of skin disease on life), compared with 6.3% in the dupilumab arm. By week 16, rates increased to 37.9% and 23.8%, respectively. These findings were consistent regardless of the lesion severity definition used.

Statistical Considerations

Treatment differences were estimated using Cochran–Mantel–Haenszel weighting to control for individual study effects across JADE DARE and JADE COMPARE. When analyzed separately, both trials demonstrated directionally consistent findings.

Clinical Implications

In adults with itch-dominant AD, abrocitinib 200 mg in combination with topical therapy was associated with:

• More rapid itch relief
• Greater likelihood of achieving an itch-free state
• Earlier and sustained improvements in QoL

By week 16, overall PP-NRS4 response rates were similar between treatments, but higher-threshold itch and QoL outcomes continued to favor abrocitinib.

Limitations and Future Directions

As a post hoc analysis, these findings should be interpreted cautiously. The itch-dominant phenotype was defined retrospectively, and the trials were not originally powered for this subgroup. Prospective studies specifically designed to evaluate itch-dominant AD are needed to confirm these observations and assess long-term safety and durability.

Further research into the mechanistic differences between JAK1 inhibition and IL-4/IL-13 pathway blockade may help clarify which patients are most likely to benefit from each approach.

References

1. Silverberg JI, Thyssen JP, Lazariciu I, Myers DE, Güler E, Chovatiya R. Abrocitinib may improve itch and quality of life in patients with itch-dominant atopic dermatitis. Skin Health Dis. 2024;4(4):e382. Published 2024 May 5. doi:10.1002/ski2.382
2. Silverberg JI, de Bruin-Weller M, Ortiz de Frutos J, et al. Efficacy of abrocitinib and dupilumab in itch-dominant atopic dermatitis: An analysis of 2 trials. J Eur Acad Dermatol Venereol. Published online February 17, 2026. doi:10.1111/jdv.70362