Pusan National University Researchers Dive Deep Into the Safety of JAK Inhibitors for Atopic Dermatitis
The comprehensive safety analysis establishes evidence regarding the safety of systematic Janus kinase inhibitors in patients with atopic dermatitis
Janus kinase (JAK) inhibitors are widely used for the treatment of atopic dermatitis (AD). However, the safety of these drugs for AD treatment has not been well examined. Now, however, researchers have comprehensively assessed the safety profile of JAK inhibitors by analyzing the results of 14 randomized controlled trials. Their study revealed that JAK inhibitor use is not associated with a greater risk of serious adverse events like malignancy, thromboembolism, or major adverse cardiac events.
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.
Recent reports suggested that the adverse effects of JAK inhibitors may be dose-dependent, and so, the researchers also conducted a subgroup analysis according safety profile of these inhibitors according to the JAK inhibitor type and dose, making this study unique. They looked at three types of JAK inhibitors — abrocitinib, upadacitinib, and baricitinib. Although baricitinib is yet to receive FDA approval, the drug is clinically approved for the treatment of AD in European countries, Japan, and Korea.
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.
Explaining how these findings could have potential long-term implications, Prof. Kim says, “Insights gained from this research could lead to refined treatment guidelines and personalized therapeutic strategies, enhance the confidence in prescribed treatments in terms of safety and efficacy, and enhance the quality of life for patients with AD.”
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
About the institute
Pusan National University, located in Busan, South Korea, was founded in 1946 and is now the №1 national university of South Korea in research and educational competency. The multi-campus university also has other smaller campuses in Yangsan, Miryang, and Ami. The university prides itself on the principles of truth, freedom, and service, and has approximately 30,000 students, 1200 professors, and 750 faculty members. The university is composed of 14 colleges (schools) and one independent division, with 103 departments in all.
Website: https://www.pusan.ac.kr/eng/Main.do
