**1. Introduction**

Atopic dermatitis (AD) is the most common inflammatory skin disease affecting approximately 20% of children and 10% of adults worldwide [1,2]. This chronic condition is characterized by intense pruritus and recurrent eczematous lesions and has a considerable negative impact on patients' quality of life [3]. Moreover, AD patients may display different clinical patterns depending on their age, ethnicity, and underlying mechanisms [4]. There are three main types of AD patterns: the persistent form where AD appears in childhood and then persists into adulthood; the relapsing form, in which AD occurs in childhood and recurs in adulthood with a symptom-free interval; and the adult-onset AD, the most difficult type to detect, where the disease is firstly observed in adulthood [5]. Due to its various presentations, the diagnosis and treatment of AD remained a challenge for clinicians [6].

While topical interventions are the mainstay treatment of AD, systemic therapy is recommended for patients with inadequate treatment response [7–9]. Advances have been

**Citation:** Tsai, H.-R.; Lu, J.-W.; Chen, L.-Y.; Chen, T.-L. Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials. *J. Pers. Med.* **2021**, *11*, 279. https://doi.org/10.3390/jpm11040279

Academic Editor: Mircea Tampa

Received: 4 March 2021 Accepted: 4 April 2021 Published: 7 April 2021

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made in systemic AD therapy owing to an improved understanding of the molecular mechanism of AD [10]. Innovative treatment options are available, such as dupilumab (obstructing alpha subunit of the IL-4 receptors), crisaborole (blocking phosphodiesterase 4), and lebrikizumab (preventing IL-13Rα1/IL-4Rα heterodimerization) [11]. Of note, the upregulation of key cytokines (interleukin (IL)-4, IL-5, and IL-13) and subsequent activation of the Janus kinase/signal transducer and transcription (JAK/STAT) pathways play important roles in the complex mechanism of AD [12,13]. In a growing number of preclinical studies, the inhibition of intracellular JAK/STAT signal transmission has demonstrated therapeutic potential [14,15].

Since their first approval, JAK inhibitors have become a promising AD treatment option [16]. In randomized controlled trials (RCTs), several JAK inhibitors (oral/topical) have significantly improved the clinical outcomes of patients with inadequate responses to other therapies [17,18]. An integrated safety analysis indicated similar incidences of adverse events (AEs) between JAK inhibitor application and placebo [19]. An earlier metaanalysis showed that JAK inhibitors lowered the eczema area and severity index (EASI) and pruritus scores [20]. Nevertheless, the sample sizes of the enrolled studies were small, and no phase III RCTs were included [20]. Considering the rapid developments in this field of study, an updated literature review with a meta-analysis is warranted to improve statistical power and provide supporting evidence for current guidelines.

In the present study, we performed a systematic review and meta-analysis of RCTs to compile evidence on the application of JAK inhibitors in the management of AD. We also graded certainty of evidence (CoE) based on the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach and calculated the numbersneeded-to-treat (NNTs) and numbers-needed-to-harm (NNHs) to facilitate decision-making in clinical practice.
