Introduction: JADE REGIMEN (NCT03627767) was conducted to evaluate the feasibility of continual, reduced dose or withdrawal of abrocitinib after induction of response in patients with ...moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated patient factors associated with a higher probability of persistent clinical response with abrocitinib, without flare, during a 40-week maintenance period.Methods: Data were analyzed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo in the maintenance period (40 weeks). A multivariable logistic regression model with fixed and random effects was fit to determine factors associated with not experiencing flare by week 52. Fixed effects (factors) considered were randomly allocated treatment, age (<18 vs ≥18 years), race, weight, prior use of systemic agents, AD duration, onset of response in induction (early vs late), Investigator’s Global Assessment score at randomization, body surface area (BSA, ≤50% vs >50%) at baseline, and percentage change in Eczema Area and Severity Index (EASI) at randomization. Backward elimination and stepwise model selection procedures were applied with entry and exit criteria based on a P value threshold of 5%.Results:1233 patients received abrocitinib 200 mg in the induction period. By week 12, 798 (64.7%) achieved a response and were randomly assigned to receive maintenance treatment for 40 weeks. In total, 356 patients (44.6%) experienced a protocol-defined flare: 16.5% (200 mg), 39.6% (100 mg), and 77.5% (placebo). After model selection, the analysis identified continuation of treatment with abrocitinib 200 mg (odds ratio OR, 19.51; 95% CI, 11.28-33.75) or reduced-dose abrocitinib 100 mg (5.27; 3.29-8.46) as the greatest predictors of not experiencing flare during maintenance. Not having previously used systemic agents (OR, 1.53; 95% CI, 1.09-2.14), lower baseline BSA (1.55; 1.10-2.17), and greater percentage reduction of EASI during induction (1.35; 1.15-1.59) were also associated with not experiencing flare.Conclusions: Multivariable analysis of JADE REGIMEN indicated that maintenance treatment with abrocitinib in patients with AD reduced the risk for flare in a dose-dependent manner. Other factors associated with maintaining response to treatment without flare included no previous exposure to systemic agents, lower extent of BSA involvement at baseline, and greater percent change in EASI during induction. These findings may assist clinicians with abrocitinib dosing decisions in the future.
Abstract Objectives Natural rubber latex (NRL) contains over 200 proteins of which 13 have been identified as allergens and the cause of type I latex allergy. Health care workers share a high ...occupational risk for developing latex allergy. Filaggrin null mutations increase the risk of type I sensitizations to aeroallergens and it is possible that filaggrin null mutations also increase the risk of latex allergy. The aim of this paper was to examine the association between filaggrin null mutations and type I latex allergy. Methods Twenty latex allergic and 24 non-latex allergic dentists and dental assistants, occupationally exposed to latex, were genotyped for filaggrin null mutations R501X and 2282del4. Latex allergy was determined by a positive reaction or a historical positive reaction to a skin prick test with NRL. Results 41 individuals were successfully genotyped. Three individuals were filaggrin mutation carriers. One (2.4%) was a 2282del4 heterozygote and two (4.9%) were R501X heterozygote. No homozygote or compound heterozygote carriers were detected. No association between filaggrin null mutations and type I latex allergy was found ( p = 0.24). Patients with type I latex allergy more often reported contact dermatitis. Conclusions This is the first study to examine a highly plausible association between filaggrin null mutations and type I latex allergy. The study subjects were occupationally exposed to latex but no association between latex allergy and filaggrin mutations were detected. Sensitization to latex in the cases in this study may not have occurred through direct skin contact but through the respiratory organs via latex proteins that are absorbed in glove powder and aerosolized.
Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD ...GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.
Purpose of Review
It is still debated whether the risk of allergic contact dermatitis (ACD) is altered in patients with atopic dermatitis (AD). In this article, the recent literature on the risk of ...ACD in AD patients is reviewed and put into a clinical context.
Recent Findings
ACD is common in AD patients, but a literature review showed conflicting results on the exact risk compared to non-AD individuals. The development of ACD in AD patients is affected by the dysfunctional skin barrier in particular due to filaggrin deficiency, the Th2 inflammatory immune dysregulation, and microbial dysbiosis. While the increased exposure to topical allergens in AD patients increases the risk of ACD in AD, the Th2-skewed immune response observed in AD reduces the risk of ACD in a severity-dependent manner.
Summary
ACD should be considered in AD patients with eczema worsening, or atypical morphology and generalization despite relevant treatment. Special attention should be paid to the increased risk of ACD to allergens found in topical products.
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