Abrocitinib In The Treatment Of Moderate to Severe Atopic Dermatitis
Overview
This study examined the efficacy and safety of abrocitinib, a treatment for moderate-to-severe atopic dermatitis (AD), specifically focusing on patients with allergic comorbidities.
Data from phase 2b and phase 3 trials were analyzed, pooling information from patients who received abrocitinib or placebo.
The analysis included patients with allergic asthma, rhinitis, conjunctivitis, or food allergy, assessing various outcomes such as Investigator’s Global Assessment (IGA), Eczema Area and Severity Index (EASI-75), Peak Pruritus Numerical Rating Scale (PP-NRS4), and Dermatology Life Quality Index (DLQI) response.
Results showed that regardless of comorbidity status, patients treated with abrocitinib exhibited higher rates of improvement in IGA, EASI-75, PP-NRS4, and DLQI compared to those on placebo from Week 2 to Week 12.
Additionally, changes in other measures such as Patient-Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), and Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) favored abrocitinib over placebo for both comorbidity groups.
Treatment-emergent adverse events (TEAEs) were mostly mild or moderate. This suggests that abrocitinib is effective in treating AD, regardless of the presence of allergic comorbidities, with a favorable safety profile.
Introduction
Atopic dermatitis (AD), a chronic inflammatory skin condition, often coexists with other allergic diseases such as asthma, allergic rhinitis, and food allergies, especially in severe cases.
Recent research, including a systematic review by the American Academy of Dermatology, has highlighted that adults diagnosed with AD are significantly more likely to develop asthma compared to the general population.
Additionally, there’s evidence suggesting a correlation between AD and allergic rhinitis or food allergies, although the strength of this association may vary across studies.
The underlying mechanisms linking AD with allergic diseases are complex and not fully understood, but they are believed to involve type 2 inflammation and immunoglobulin E (IgE) sensitization.
In children, a phenomenon termed the “atopic march” describes the progression from AD to other allergic conditions like food allergies or airway diseases.
This progression is thought to occur due to allergen sensitization through the inflamed skin, leading to systemic allergic responses.
Central to the understanding of AD pathogenesis is the concept of skin barrier dysfunction, where impaired skin barrier function allows allergens to penetrate the skin more easily, triggering inflammatory responses and exacerbating AD symptoms.
This “outside–inside” hypothesis suggests that increased skin permeability for allergens in patients with compromised skin barriers may not only worsen AD symptoms but also predispose them to developing allergic comorbidities such as asthma and food allergies.
Abrocitinib, a Janus kinase 1 (JAK1)-selective inhibitor, has emerged as a promising treatment for moderate-to-severe AD in adults and, in some regions, adolescents.
Clinical trials have demonstrated its efficacy and safety as a monotherapy in improving AD symptoms. However, the impact of allergic comorbidities on the treatment outcomes of abrocitinib remains unclear.
This study aims to address this gap by evaluating the efficacy and safety of abrocitinib as monotherapy specifically in patients with moderate-to-severe AD who also have allergic comorbidities.
Understanding how abrocitinib performs in this subset of patients could provide valuable insights into optimizing treatment strategies for individuals with AD and allergic comorbidities.
Method
This post hoc analysis utilized combined data from three clinical trials investigating abrocitinib monotherapy: one phase 2b trial and two phase 3 trials (JADE MONO-1 and JADE MONO-2).
The trials enrolled adult patients with moderate-to-severe atopic dermatitis (AD) who had an inadequate response to topical therapies or were unable to use them. Patients were randomized to receive once-daily oral abrocitinib (at various doses) or placebo for 12 weeks.
Patients with self-reported allergic comorbidities, including allergic asthma, allergic conjunctivitis, allergic rhinitis, or food allergies, were identified from their medical history. Efficacy endpoints assessed at Week 12 included improvements in Investigator’s Global Assessment (IGA), Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (PP-NRS), and Dermatology Life Quality Index (DLQI).
Patient-reported outcomes such as Patient-Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), and Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) were also analyzed.
Safety evaluations included monitoring treatment-emergent adverse events (TEAEs), with the most common events categorized according to the Medical Dictionary for Regulatory Affairs.
Eosinophil levels were measured at various time points to assess eosinophilia and hypereosinophilia. The analysis aimed to assess the efficacy and safety of abrocitinib monotherapy specifically in patients with moderate-to-severe AD and allergic comorbidities.
Statistical Analysis
The analysis involved evaluating the efficacy of abrocitinib in patients with or without allergic comorbidities, pooling data from the full analysis set across three abrocitinib monotherapy trials.
Patients included in the analysis were those who received at least one dose of the study medication. Efficacy endpoints, including response rates and changes from baseline in disease severity scores, were compared across treatment arms (abrocitinib 200 mg, abrocitinib 100 mg, and placebo) for both patient groups.
Baseline disease severity differences between patients with and without allergic comorbidities were examined using appropriate statistical tests, such as Fisher’s exact test or the Satterthwaite approximation.
Treatment differences in binary outcomes were estimated using the Cochran–Mantel–Haenszel weighted-average difference method, with confidence intervals calculated based on binomial proportions.
To assess the significance of differences between abrocitinib and placebo, the Cochran–Mantel–Haenszel test was utilized. Patients who discontinued the study were considered nonresponders for subsequent visits, ensuring a comprehensive assessment of treatment efficacy over time.
Continuous outcomes were analyzed using a mixed-effects model with repeated measures, incorporating various fixed factors and covariance matrices to account for potential confounding variables.
No adjustments were made for baseline disease severity differences between patients with and without allergic comorbidities.
Given the post hoc nature of the analysis and the absence of control for multiple hypothesis testing, all p-values were considered nominal, with a significance level set at 0.05.
This rigorous statistical approach ensured a thorough evaluation of abrocitinib’s efficacy and safety profile in patients with moderate-to-severe atopic dermatitis and allergic comorbidities.
Result
In a pooled analysis of data from three clinical trials, comprising one phase 2b and two phase 3 studies, involving patients with moderate-to-severe atopic dermatitis (AD), the impact of allergic comorbidities on the efficacy and safety of abrocitinib monotherapy was assessed.
Among the 942 patients analyzed, more than half reported at least one allergic comorbidity, with various combinations observed, including allergic asthma, allergic conjunctivitis, allergic rhinitis, and food allergies.
The baseline characteristics revealed that patients with allergic comorbidities tended to be younger and had a longer duration of AD compared to those without comorbidities.
Additionally, they exhibited more severe disease at baseline, as indicated by higher Investigator’s Global Assessment (IGA) scores and Eczema Area and Severity Index (EASI) scores.
Efficacy outcomes demonstrated that both doses of abrocitinib (200 mg and 100 mg) were effective in improving AD symptoms, with higher response rates observed compared to placebo, regardless of comorbidity status.
These improvements were sustained throughout the 12-week treatment period. The 200-mg dose consistently showed higher response rates than the 100-mg dose, although the differences were not statistically significant between patients with and without comorbidities.
Regarding safety, treatment-emergent adverse events (TEAEs) were predominantly mild-to-moderate in severity and were similar between patients with and without comorbidities.
The most common TEAEs included nausea, nasopharyngitis, upper respiratory tract infection, headache, and atopic dermatitis. Serious and severe TEAEs were more frequent in patients with comorbidities, particularly in the higher dose (200 mg) abrocitinib group and the placebo group.
Furthermore, eosinophilia and hypereosinophilia were more prevalent at baseline in patients with allergic comorbidities, but these levels declined following treatment with abrocitinib.
This reduction was observed as early as Week 2 and was sustained through Week 12, indicating the efficacy of abrocitinib in managing allergic comorbidities associated with AD.
Conclusion
In conclusion, the findings from this post hoc analysis indicate that abrocitinib demonstrates effectiveness and favorable tolerability profiles in patients diagnosed with moderate-to-severe atopic dermatitis (AD), regardless of the presence of allergic comorbidities.
This suggests that abrocitinib can be a viable treatment choice for AD, irrespective of the concurrent existence of allergic comorbidities. These results underscore the potential of abrocitinib as a therapeutic option offering benefits across a spectrum of AD patients, thereby expanding its applicability in clinical practice.
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