Pusan National University Researchers Dive Deep Into the Safety of JAK Inhibitors for Atopic Dermatitis

BUSAN, South Korea, Dec. 15, 2023 /PRNewswire/ -- Atopic dermatitis (or AD) is a heterogenous, inflammatory condition of the skin and is usually accompanied by itch, redness, and swelling. AD can have a significant impact on the patient's quality of life. While several biologic treatment approaches have been proposed in the recent years for the treatment of AD, they often fall short of providing the required care in relieving symptoms of moderate-to-severe AD.

In this context, Janus kinase (or JAK) inhibitors are small molecules that have emerged as a promising treatment option for managing AD. They act by blocking the JAK family kinases and inhibiting the inflammatory pathways involved in AD and other inflammatory diseases. Recently, ten JAK inhibitors have been approved by the US Food and Drug Administration (FDA) to treat diseases like rheumatoid arthritis, ankylosing spondylarthritis, COVID-19, and AD, among others. However, the FDA has also issued a boxed warning for JAK inhibitors to include the risk of major adverse events. Since then, many meta-analyses focusing on the safety of JAK inhibitors have been published, but these analyses are fraught with several limitations. Further research is therefore needed to understand the safety profile of JAK inhibitors. This can help in tailoring the therapeutic strategies of AD as per patient's needs, while also minimizing adverse effects and enhancing the effectiveness of JAK inhibitors.

To this end, a group of researchers from Pusan National University led by Associate Professor Yun Hak Kim, affiliated with the university's Department of Anatomy and Department of Biomedical Informatics, conducted an extensive analysis of randomized controlled trials (RCTs) involving JAK inhibitors in patients with AD. The systematic review and meta-analysis, published in the Journal of the European Academy of Dermatology & Venereology on 19 August 2023, examined whether the use of JAK inhibitors increased the occurrence of adverse events in patients with AD. They identified studies reporting the adverse events associated with JAK inhibitor use from Medline, Embase, Clinicaltrials.gov, among others for this study. They reviewed the available safety data and analyzed the risk of 11 adverse events from 14 RCTs published between 2019 and 2022.

Their analysis revealed that the relative risk of developing herpes zoster, headache, acne, elevated blood creatinine phosphokinase, and nausea increased among those patients with AD who received treatment with JAK inhibitors. However, the incidence of serious conditions did not increase significantly in JAK inhibitors-exposed patients with AD. "The comprehensive safety analysis revealed that, contrary to concerns regarding malignancy, venous thromboembolism, and major adverse cardiac events, use of JAK inhibitors was not associated with a significant increase in the overall risk in patients with AD. Therefore, we believe that understanding and managing common adverse events is the need of the hour, particularly those like headache, acne, and nausea, among others," explains Prof. Kim.

This analysis revealed a higher risk of acne in patients receiving upadacitinib and abrocitinib, and this increased in risk was dose-dependent. Moreover, higher dose of JAK inhibitors was correlated with an increased risk of acne and elevated blood pressure.  

Overall, these findings underscore the importance of comprehending the safety of JAK inhibitors for informed decision-making and managing AD, with a particular emphasis on long-term observations of major cardiovascular events with typically prolonged courses.

Reference
Title of original paper: The safety of systemic Janus kinase inhibitors in atopic dermatitis:
A systematic review and meta-analysis of randomized controlled trials
Journal: Journal of the European Academy of Dermatology & Venereology
DOI: https://doi.org/10.1111/jdv.19426 

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SOURCE Pusan National University (PNU)