Baricitinib for the treatment of atopic dermatitis

Abstract

Introduction: Atopic dermatitis is a common, chronic and recurrent inflammatory skin disease, with a prevalence of 15 to 20% in developed countries. It often appears in childhood but can last into adulthood. It negatively impacts patients, their families and society in general. Treatments are meant to reduce symptoms and prevent worsening of the disease, in association with a favorable safety profile. There is an unmet need in this area, with patients requiring new pharmacologic agents that are safe and effective. New developments on the pathophysiology of atopic dermatitis and its relationship with the JAK/STAT pathways has led to the development of agents that block this intracellular signaling pathway, the JAK inhibitors. Baricitinib shows high selectivity for JAK1 and JAK2, making it appealing for the treatment of this condition. Objectives:The purpose of this review is to make an assessment of the safety and clinical effectiveness of baricitinib for the treatment of atopic dermatitis.Methods: A search on the pathophysiology and the role of JAK/STAT pathway in atopic dermatitis was made, along with a review of the data on clinical evidence of the efficacy and safety of baricitinib. The research for this review was performed using PubMed and GoogleScholar. The publication of the articles used covers the period from 1995 to 2021. The articles were selected by the relevance of the abstract and established objectives. Bibliographic references present in the selected articles were also included.Discussion: Atopic dermatitis is a condition with intricate environmental and genetic susceptibility elements. There are many factors involved in its pathogenesis, including a Th2skewed immune response. The JAK/STAT pathway is used for signal transduction by various cytokines and growth factors, being involved in many processes that are critical in the pathogenesis of this disease, such as Th2 cell response augmentation. Phase II and phase III trials have been carried out to assess the efficacy and safety of baricitinib, a selective oral JAK1/2 inhibitor. The results are encouraging concerning its efficacy, in addition to a favorable safety profile. Conclusion:JAK inhibitors act in a broad way, inhibiting multiple steps that are associated with the pathogenesis of atopic dermatitis, which can potentially translate into greater therapeutic advantages. Baricitinib, being a selective JAK1 and JAK2 inhibitor, may have an advantage from a therapeutic standpoint over the other oral JAK inhibitors being studied for this condition due to the additional inhibition of JAK2. This drug represents one more treatment option for atopic dermatitis patients who have no history of serious renal impairment or severe hepatic impairment and who favor oral therapy over injections. Nevertheless, more studies will be necessary to assess the long-term safety of this drug in atopic dermatitis, including the clinical setting.

Efficacy and safety of baricitinib for the treatment of moderate‐to‐severe atopic dermatitis: A systematic review and meta‐analysis of randomized clinical trials

“…IL-4 and IL-13 are known to play an important role in the pathogenesis of this condition and AD has been proven to be genetically related to IL-4 and IL-13 polymorphisms. 3 It was also reported that the keratinocytes show an appreciable decrease in filaggrin gene expression in the presence of IL-4 and IL-13. 17 STAT pathway is critical to mediating the effect of several key cytokines that bind to immune cells, keratinocytes and peripheral sensory neurons to propagate inflammation and itch.…”

“…19 Baricitinib is a small-molecule, competitive inhibitor of the JAK family, with the chemical formula of C 16 H 17 N 7 O 2 S and a molecular weight of 371.42 g/mol. 3 Baricitinib selectively and reversibly inhibits JAK1 and JAK2, targeting the ATPase of JAK, which blocks the intracellular transmission of cytokines through the JAK-STAT pathway. 20 Baricitinib was approved by Food and Drugs Administration (FDA) for adult moderate-to-severe rheumatoid arthritis.…”

“…AD negatively impacts the quality of life of patients, imposing psychological and social burdens, and it also brings increased overall healthcare costs to patients. 3 The aetiologies of AD are multifactorial, including environmental factors, genetic disposition, immune dysregulation and impaired skin barrier function. 4 The management of AD is meant to improve symptoms and establish long-term disease control.…”

Current views on the pathogenesis and treatment of atopic dermatitis in adults. Experience with the JAK inhibitor baricitinib in patients with moderate to severe atopic dermatitis

“…Большинство симптомов АтД появляется в течение первого года жизни, это занимает примерно 60% случаев. В 30% случаев первые симптомы АтД появятся в период между первым и пятым годами жизни и в 10% случаев после шестого года жизни [1]. Однако заболевание может проявиться уже и у взрослого.…”

“…Благодаря своей химический структуре и размеру барицитиниб может вводиться перорально, метаболизируясь в печени, быстро достигает максимальной концентрации в плазме (C max = ~94-112 нМ (4 мг 1 р/сут) в течение 1,5 ч после приема, выведение происходит в основном за счет почечной экскреции (в среднем 64,1% препарата выводится в неизмененном виде с мочой) 1 .…”