Abrocitinib Demonstrates High Efficacy In Itch-Dominant Atopic Dermatitis

Itch is regularly reported by patients with atopic dermatitis (AD) as the single most bothersome symptom, as more severe itch is associated with lowered quality of life, mental health concerns such as anxiety and depression, and worsened sleep quality. It contributes significantly to the overall burden of disease in AD.¹

While there is a great deal of AD research, despite the inclusion of patients with itch-dominant AD in clinical trial settings, there is a lack of independent assessment of this patient subset, according to authors of a new study.

With this in mind, researchers Silverberg et al. conducted a study titled, "Abrocitinib may improve itch and quality of life in patients with itch-dominant atopic dermatitis," which was recently published in Skin Health and Disease.²

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Background and Methods

Researchers conducted the post hoc study by analyzing data from patients involved in trials for abrocitinib, including analysis from arms of the phase 2b (NCT02780167) and phase 3 JADE MONO-1 (NCT03349060) trials, as well as the and JADE MONO-2 trials (NCT03575871). Data from the JADE COMPARE (NCT03720470) trials and ongoing JADE EXTEND study (NCT03422822) was also evaluated.

Patients aged 12 years and older with moderate-to-severe AD were included. Short-term efficacy was assessed over 12 weeks, and long-term efficacy was evaluated up to week 48. Short-term assessments included improvements in itch, lesions, and quality of life. Long-term assessments focused on changes from baseline in itch and lesional severity.

Findings

The study analyzed data from 937 patients involved in monotherapy trials, focusing on individuals with AD characterized by itch dominance, which accounted for 37.5% and 21.1% of patients, according to baseline Peak Pruritus Numerical Rating Scale (PP-NRS) and Investigator's Global Assessment (IGA) scores, and PP-NRS and Eczema Area and Severity Index (EASI) scores, respectively.

When comparing the overall population to patients with itch-dominant AD, researchers noted similar baseline characteristics. A higher proportion of patients with itch-dominant AD reported severe AD, according to Patient Global Assessment (PtGA) scores, compared to the overall pooled monotherapy population.

Further analysis revealed that in the subset of patients with itch-dominant AD, defined either by PP-NRS and IGA or PP-NRS and EASI scores, all patients had an IGA score of 3. Treatment arms varied in average EASI scores, with slight differences observed among groups. Furthermore, a considerable proportion of patients in the itch-dominant AD subset experienced severe itch at baseline.

Short-term efficacy assessments over 12 weeks showed significant improvements in itch response and patient-reported outcomes (PROs) among patients with itch-dominant AD. Both abrocitinib doses demonstrated substantial efficacy, with higher proportions of patients achieving improvement in PP-NRS scores compared to patients in the placebo group. This improvement was maintained through the 12-week period.

Similar patterns were observed in PROs, including the Patient-Oriented Eczema Measure and DLQI, indicating improved disease severity and quality of life.

Long-term analysis over 48 weeks in the JADE EXTEND study, involving 1116 patients, demonstrated sustained improvements in itch and lesional severity among those with itch-dominant AD. A significant decrease in the proportion of patients with itch-dominant AD was observed at week 24, with further reductions at week 48, indicating a durable response to abrocitinib treatment.

Most patients experienced improvements in itch severity, with a substantial proportion reporting no or almost complete itch relief and clear or almost clear lesions by week 24, which were sustained or further improved by week 48.

Conclusions

These findings are in line with previous reports of a similar nature, wherein researchers have reported disparities between patient and physician- reported evaluations of AD severity, according to the study's authors.

Limitations of the study include the exclusion of patients with mild skin lesions who might have itch-dominant AD, the inability to determine whether all patients had completed the 48-week mark at the time of analysis (given the JADE EXTEND study is ongoing), and the small sample sizes of the subgroup analyses.

"In this post hoc analysis, abrocitinib has shown rapid improvement in itch, including at stringent thresholds of improvement, in patients with itch-dominant AD, for whom effective options are few," according to Silverberg et al. "Improvements in AD symptoms translated to better QoL outcomes, and majority of patients with itch-dominant AD at baseline experienced itch improvement without worsening of lesional severity by 48 weeks of abrocitinib treatment."

Moving forward, they note that longer-term outcomes with later data cutoffs are necessary to further explore the role of abrocitinib as a treatment for itch-dominant AD.

References

1. Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018; 121(3): 340–347. https://doi.org/10.1016/j.anai.2018.07.006
2. 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. May 5, 2024. https://doi.org/10.1002/ski2.382