Next Steps in Derm, in partnership with ODAC Dermatology, Aesthetic and Surgical Conference, interviewed Dr. Neal Bhatia (a board-certified Dermatologist who serves as Director of Clinical Dermatology at Therapeutics Clinical Research ) about the latest with JAK inhibitors. Watch as he summarizes the most recent trials, approvals, and developments. Plus why doctors shouldn’t be afraid to dive in when considering these prescriptions as new solutions for patients.
If you would like to read more about JAK inhibitors, check out the following 3 articles recently published in the Journal of Drugs in Dermatology.
SUPPLEMENT ARTICLE: A Novel Drug Delivery Method: Retrometabolic Drug Design
Soft drugs, a class of retrometabolic drug design, contain a metabolically sensitive moiety that promotes rapid metabolism to inactive metabolites after exerting activity at its target site. The goal of soft drugs is to reduce systemic toxicity while enhancing local efficacy. Soft drugs have been approved for use in multiple medical specialties, such as the soft corticosteroid loteprednol etabonate for treatment of inflammatory ophthalmic disorders and soft beta-blocker derivatives for treatment of hypertensive emergencies in cardiology. Soft drugs have also found widespread use in the field of dermatology. In the setting of topical drug administration, soft drugs minimize the risk of systemic drug absorption and unwanted side effects. Soft janus kinase caspase 1 (JAK) inhibitors, soft transient receptor potential vanilloid (TRPV1), and soft estrogens among others have been explored as therapeutic options for a variety of inflammatory and autoimmune dermatologic conditions. The soft anticholinergic sofpironium bromide represents the latest expansion of soft drug use in dermatology for the treatment of primary axillary hyperhidrosis (PAH). A derivative of glycopyrronium, sofpironium bromide consists of a chemically modified structure that allows the drug to undergo rapid hydrolytic deactivation, and thus minimize the significant side effects associated with traditional anticholinergic drugs. Sofpironium bromide has demonstrated efficacy and safety for treatment of PAH in Phase II and Phase III clinical trials in Japan and the United States. Given the promising results from these studies, sofpironium bromide, in addition to other soft drugs under investigation, highlights the growing utility of retrometabolic drug design in dermatology. Read the full article here.
The Heterogeneity of Atopic Dermatitis
Background: Recent advances were made in characterizing the clinical heterogeneity of atopic dermatitis (AD).
Objective: To review the clinical domains contributing to AD heterogeneity and describe their importance in clinical practice.
Methods: We conducted a focused review of the published literature, including retrospective, observational, and prospective studies, clinical trials, and consensus guidelines.
Results: AD is associated with heterogeneous skin manifestations, symptoms, lesional severity, lesional extent, longitudinal course, burden of signs and symptoms, and comorbidities. Each of these domains characterizes a different aspect of AD and should be used to guide overall severity assessment and clinical management. Primary focus on any one specific clinical domain of AD is insufficient to describe the full burden of disease.
Conclusion: Heterogeneity should be routinely considered during AD clinical encounters. Read the full article here.
Understanding the Potential Role of Abrocitinib in the Time of SARS-CoV-2
The use of Janus kinase inhibitors (JAKi) in the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a topic of interest for many clinicians and researchers.1,2 In recent studies, JAKi has been shown to have rates of infectious events that are only mildly increased compared to placebo. Similarly, there is no reported risk of pulmonary toxicity in JAKi-treated patients compared to placebo-treated patients.1 Though data regarding the possible use of JAKi in COVID 19 patients is growing, clarification of the risks associated with JAKi therapy is critical. Baricitinib and upadacitinib have promising preclinical safety data, and may be therapeutically beneficial in COVID-19 patients with underlying skin disease, potentially reducing cytokine storm seen in severe cases.1,2 The safety potential of abrocitinib, an investigational JAKi, however, has not been addressed.
Abrocitinib is an oral small molecule that selectively inhibits JAK1 and several important cytokine signaling pathways— interleukin (IL)-4, IL-13, IL-31, and interferon —that are known to have an important role in the pathophysiology of AD.3 Like other JAK inhibitors, abrocitinib blocks the activity of IL-6, a cytokine thought to play a central role in SARS-CoV-2 associated cytokine release syndrome (CRS), in addition to other pathogenic cytokines.2 Disease severity in patients with symptoms of CRS correlates with serum cytokine levels, as mean IL-6 concentrations are 2.9 times higher in patients with severe disease and predictive of respiratory failure.5 One potentially important characteristic of abrocitinib is its EPO sparing effect, as recent evidence has supported the use of human recombinant EPO for ameliorating the course and outcome of seriously ill COVID-19 patients.5,6 Read the full article here.
About Dr. Neal Bhatia
Dr. Neal Bhatia is based in San Diego, CA. He is chief medical editor for Practical Dermatology. He has a background in immunology and has interests in mechanisms of therapy, skin cancer, and medical dermatology. Aside from teaching at medical conferences, he sits on several editorial boards and is an active teacher for dermatologists, industry, and patients. In 2021, Dr. Bhatia is the Secretary/Treasurer of the Noah Worcester Dermatological Society, the President of the Pacific Dermatologic Association, and as of March the Vice President of the American Academy of Dermatology.
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