Eczema Review

NEW RANGE OF INVESTIGATIONAL THERAPIES FOR AD

Numerous miscellaneous agents across several additional treatment classes
are being investigated for the treatment of atopic dermatitis (AD). The therapies include targeted topical, oral, systemic, and biologic agents, according to a recent study by Vakharia and Silverberg, published online in Journal of the American Academy of Dermatology.

The researchers performed a nonsystematic review of the literature of the known efficacy and safety to-date for such agents being studied for the treatment of AD. PubMed and ClinicalTrials.gov were searched for studies assessing agents not described in previous chapters for the treatment of AD. Randomized controlled trials were primarily sought, but other study types were also included if they contained pertinent data. Identified agents included omiganan (antimicrobial peptide), tapinarof (nonsteroidal anti-inflammatory agent), PR022 (hypochlorous acid), asimadoline (k-opioid agonist), DS107 (dihomo-gamma-linolenic acid), ZPL-389 (histamine H4 receptor antagonist), secukinumab (Cosentyx; interleukin [IL]-17A inhibitor), and fezakinumab (IL-22 inhibitor).

As recent research has improved the understanding of AD pathogenesis, various agents with unique mechanisms of action have been studied for the treatment of AD.

Many of these hold significant therapeutic promise for AD, and continued research and development is warranted, they concluded. 

Referece: 
Vakharia PP, Silverberg JI. New therapies for atopic dermatitis: additional treatment classes [published online December 14, 2017]. J Am Acad Dermatol. doi:10.1016/j.jaad.2017.12.024

STUDY LOOKS AT 5-YEAR EVIDENCE FOR OFF-LABEL AD SYSTEMIC TREATMENT

Systemic treatment is indicated for moderate to severe atopic dermatitis (AD), refractory to topical treatment.
Gerbens and colleagues investigated the long-term effectiveness, safety, and drug survival of off-label prescribed methotrexate (MTX) and azathioprine (AZA) in a recent study, published online in British Journal of Dermatology.

In the open-label follow-up phase of a clinical trial, patients were seen every 3 months for 5 years. MTX and AZA doses could be increased or decreased concurrent with daily clinical practice. Primary effectiveness outcomes were mean absolute and relative reduction in SCORing Atopic Dermatitis (SCORAD) index and Investigator’s Global Assessment after 5 years compared to baseline. For safety type, frequency, severity, and relatedness to treatment of adverse events were investigated. Drug survival was analyzed by Kaplan-Meier curves.

This study included 35 of the 43 original participants, of which 27 completed follow up. At year 5 mean relative reduction in SCORAD index was similar in the MTX and AZA group: 52.8% and 53.8% by descriptive analysis. Eleven serious adverse events occurred in 5 years, including 3 in which there was a possible causal relationship. Drug survival demonstrated a longer survival for MTX, but survival in both groups was low after 5 years (MTX n=5, AZA n=1).

Based on this relatively small pragmatic study, MTX and AZA seem to be effective and safe as maintenance treatments in moderate to severe AD up to 5 years, the researchers concluded. Few patients in both groups survive on their originally allocated drug although some discontinued due to controlled AD.

Reference
Gerbens LAA, Hamann SAS, Brouwer MWD, et al. Methotrexate and azathioprine in severe atopic dermatitis: a 5-year follow up study of a randomised controlled trial [published online December 13, 2017]. Br J Dermatol. doi:10.1111/ bjd.16240

SERIOUS CUTANEOUS, MULTIORGAN, AND SYSTEMIC INFECTIONS INCREASED IN ADULTS WITH AD

Adults with atopic dermatitis (AD) had increased cutaneous, respiratory, multiorgan, and systemic infections, which were associated with a considerable cost burden, according to a recent study by Narla and Silverberg published in Annals of Allergy, Asthma & Immunology.

AD is associated with barrier disruption, immune dysregulation, and immunosuppressing treatments that can increase the association with an unusual number of infections. In this study, the researchers evaluated whether adults with AD have an un-
usually large number of serious infections and related outcomes. Data from the 2002 to 2012 National Inpatient Sample were analyzed, including an approximately 20% sample of all US hospitalizations (n=72,108,077 adults). Prevalence of serious infections in hospitalized patients with vs without AD, length of stay, cost of care, and inpatient mortality secondary to serious infections were determined.

The prevalence of serious infections expressed as a percentage (95% CI) was higher in adults hospitalized with than in those without AD (42.1%; 95% CI, 41.6-42.6 vs 25.4%; CI, 25.2-25.6; P=.0002). In logistic regression models with multiple predictors (multivariable logistic regression models), AD was associated with 32 of 38 infections examined. Associated cutaneous infections included eczema herpeticum (odds ratio [OR] 95% CI adjusted for other predictors: 67.93; 95% CI, 47.93-96.28]), erysipelas (OR, 11.15; 95% CI, 9.47-13.1), and cellulitis (OR, 4.53; 95% CI, 4.42-
4.64). Associated respiratory infections included aspergillosis (OR, 1.51; 95% CI, 1.21-1.88) and tuberculosis (OR, 1.57; 95% CI, 1.41-1.76). AD was associated with extracutaneous, multiorgan, and systemic infections, including infectious arthropathy (OR, 2.01; 95% CI, 1.84-2.20), endocarditis (OR, 1.25; 95% CI, 1.12-1.39), encephalitis (OR, 1.65; 95% CI, 1.40-1.96), and methicillin-resistant Staphylococcus aureus infections (OR, 3.29; 95% CI, 3.17-3.42). Patients with AD hospitalized with vs without any serious infection had an increased geometric mean cost of inpatient care ($8273 [8126-8423] vs $7179 [7052-7307]) and length of stay (5.3 days [5.2-5.3] vs 3.9 [3.9-4.0]; P = .0002), with $11 million to $228 million excess annual costs from hospitalization with serious infections in adults with AD.

Reference
Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Ann Allergy Asthma Immunol. 2018 Jan;120(1):66-72.e11.

PHASE 3 TRIAL BEGINS FOR JAK1 INHIBITOR IN DEVELOPMENT FOR MODERATE TO SEVERE AD

Aphase 3 trial evaluating the efficacy and safety of PF-04965842 (Pfizer), a once-daily Janus kinase 1 (JAK1) inhibitor for the treatment of moderate to severe atopic dermatitis (AD) is under way.This is the first trial in the company’s JAK1 Atopic Dermatitis Efficacy and safety (JADE) global development program.

The JADE trial, a randomized, double-blind, placebo-controlled, parallelgroup study, includes 375 patients aged 12 years and older with moderate to severe AD.The participants will be randomly assigned to receive 200 mg or 100 mg once daily or placebo over 12 weeks, with a 4-week safety follow-up period. Participants also have the option to enter a long-term extension study at week 12.

The study’s primary endpoints are the proportion of patients achieving an Investigator’s Global Assessment score of 0/1 and ≥2-point improvement, as well as the proportion of patients with at least a 75% or greater change from baseline in their Eczema Area and Severity Index score. The secondary endpoints include the pruritus numerical rating scale, the Pruritus and Symptoms Assessment for Atopic Dermatitis electronic diary, and safety measures such as the incidence of treatment emergent adverse events and laboratory abnormalities.

“By initiating this phase 3 program in AD, we hope to provide a new potential treatment option for people suffering with this condition,” said Michael Corbo, chief development officer, inflammation and immunology, Pfizer Global Product Development.

NEA TO LAUNCH THE ECZEMA PROVIDER FINDER

The National Eczema Association (NEA) announced an upcoming free online health care provider directory will soon be available on its website.The Eczema Provider Finder is designed to help the eczema patient community locate providers in their area who are experts in treating eczema. This directory, along with many other initiatives,
is only possible with the support from NEA community.

According to NEA, the important resource was developed after receiving the NEA community’s feedback that they often cycle through several health care providers before finding one who is not only knowledgeable in treating eczema, but with whom they can truly partner.

This search for the right provider can delay relief from symptoms for months, even years, according to NEA. The Eczema Provider Finder will be housed prominently on the association’s website (https://nationaleczema.org) and will be searchable by ZIP code, specialty, and treatments offered.Watch for the launch in early 2018.