The race to treat Atopic dermatitis (AD) is crowded so this has led to a lot of experience in Longboat on AD studies. The second installment in our therapeutic area series therefore centers on AD. Also known as atopic eczema - AD is a common chronic skin disease, and evidence suggests its lifetime prevalence is, for the most part, increasing worldwide. It most often develops in childhood; however, it can persist to, or even begin to develop in, adulthood.
It is an inflammatory disease characterized by recurrent, intensely itchy, eczematous lesions (i.e. red patches/blisters with oozing in early stages and dry, thickened skin in later stages), which can affect any part of the body, and typically shows an age-related morphology and distribution. It is linked not only with other atopic diseases, such as asthma and allergic rhinitis, but also food allergies.
A recent report has estimated the annual cost of AD in the United States alone to be in excess of $5.297 billion.
Current Diagnosis and Treatment
Currently, there are no specific diagnostic tests for AD, and therefore diagnosis is based on criteria that take in to account the patient’s history and clinical features. There are several proposed sets of diagnostic criteria, and the ‘Hanifin and Rajka criteria’ - one of the earliest and most recognized criteria - is still widely used. Guidelines for diagnosis can be found here.
Disease severity is established following diagnosis. Both objective signs and subjective symptoms are evaluated and graded. As with diagnosis, there are a variety of scoring systems for this, and two of the most commonly used in clinical trials are the ‘Eczema Area Severity Index’, or EASI, and the ‘Scoring of Atopic Dermatitis’, or SCORAD index.
AD is not currently curable, and so therapy centers around alleviating symptoms and establishing disease control through a multistep approach. This can include: restoring the skin barrier, trigger avoidance, anti-inflammatory therapy, and treatment of skin infections - therapy selection largely depends on the extent and severity of the disease.
However, current treatments demonstrate limited efficacy in cases of severe AD.
Treatments on the Horizon?
Recently, the understanding of AD has made major advances, particularly with respect to pathogenesis. While this pathogenesis is not yet fully understood, it is known to be complex and multifactorial - involving skin barrier disruption, immunologic factors, and environmental factors.
Driven by this new understanding, therapies that act on specific molecular targets are emerging with many at advanced stages of development.
Challenges in Developing Drugs for AD
AD is a heterogenous disease - shown both clinically and by the absence of distinct, reliable biomarkers that apply to all patients. However, it is still largely considered to be a single disease and treated as such, and while this is effective for some, other patients remain refractory to this treatment model.
Research to identify and characterise subtypes is therefore required, and would allow stratification of the disease in to more homogenous subgroups. This stratification would help to build on current targeted therapies already in the pipeline, potentially allowing a more personalized approach – delivering therapies that are more effective, with fewer side effects than those currently available.
The Future Clinical Landscape
The understanding of AD has made major advances, particularly with respect to its complex pathogenesis. Novel insights have led to thriving drug development; the pipeline is crowded with many biologics and small molecules that target different pathways all in the hope of improving the lives of AD patients. If approved, they will provide new and exciting options for AD management.