The Changing Landscape of Atopic Dermatitis - Focusing on JAK Inhibitors

Rodrigues, Maria do Céu; Torres, Tiago

doi:10.23822/eurannaci.1764-1489.120

Cited by 5 publications

(7 citation statements)

References 22 publications

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“…and IL-31 that undertake pathophysiologic roles in AD, including triggering Th2, activating eosinophils, maturing B-cells, up-regulating epidermal chemokines and down-regulating anti-microbial peptides. 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.…”

Section: Discussionmentioning

confidence: 99%

“…The JAK–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 18 . In general, the JAK–STAT pathway is used by several cytokines such as IL‐4, IL‐5, IL‐13 and IL‐31 that undertake pathophysiologic roles in AD, including triggering Th2, activating eosinophils, maturing B‐cells, up‐regulating epidermal chemokines and down‐regulating anti‐microbial peptides 19 …”

Section: Discussionmentioning

confidence: 99%

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

Wang

Pan

Yao

et al. 2022

Clin Exp Pharma Physio

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Atopic dermatitis (AD) is one of the most prevalent inflammatory skin diseases. Janus kinase (JAK) inhibitor baricitinib is a promising treatment for AD as shown in recent clinical trials. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting the efficacy and safety of baricitinib. Data analysis was carried out using Cochrane Collaboration Review Manager 5.4 software and performed as risk ratios (RR) with 95% confidence intervals. Six RCTs involving a total of 2595 patients were included in the review. The meta-analysis revealed that patients in the baricitinib group had significantly higher rates achieving EASI75, EASI90, IGA-Response, SCORAD75, and Itch NRS improvement. Pooled analysis also showed no significant differences in treatment of emergent adverse events (TEAEs) between baricitinib and placebo groups. In conclusion, our meta-analysis showed that baricitinib has promising efficacy for moderate-to-severe AD with favourable safety files.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Wang

Pan

Yao

et al. 2022

Clin Exp Pharma Physio

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“…(64) Also, TSLP binds to a heterodimeric receptor consisting of the TSLP receptor and the IL-7 receptor to activate JAK1 and JAK2, resulting in STAT5 activation. (73) In addition, IL-4 and IL-13 bind to the IL-4 receptor or the IL-13 receptor, activating JAK1 and JAK3, which in turn activates STAT6. (73) The JAK-STAT pathway is, therefore, used by several cytokines that are critical in the pathogenesis of AD, such as IL-4, IL-5, IL-13, that undertake pathophysiologic roles, such as triggering Th2, activating eosinophils, maturing B-cells, up-regulating epidermal chemokines and down-regulating anti-microbial peptides.…”

Section: Transducer and Activator Of Transcription (Stat) Pathwaymentioning

confidence: 99%

“…(73) In addition, IL-4 and IL-13 bind to the IL-4 receptor or the IL-13 receptor, activating JAK1 and JAK3, which in turn activates STAT6. (73) The JAK-STAT pathway is, therefore, used by several cytokines that are critical in the pathogenesis of AD, such as IL-4, IL-5, IL-13, that undertake pathophysiologic roles, such as triggering Th2, activating eosinophils, maturing B-cells, up-regulating epidermal chemokines and down-regulating anti-microbial peptides. (73) Baricitinib:…”

Section: Transducer and Activator Of Transcription (Stat) Pathwaymentioning

confidence: 99%

Baricitinib for the treatment of atopic dermatitis

Melo

Carrascosa

Torres

2021

Journal of Dermatological Treatment

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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.

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“…Дефекты кожного барьера происходят за счет нарушения процессов ороговения, повышенной активности протеолитических ферментов, нарушения липидного состава кожного сала, мутаций в генах филаггрина, лорикрина, корнулина, репетина. Многообразие нарушений барьерных свой ств кожи влечет за собой такие изменения, как увеличение проницаемости кожного барьера, повышение трансэпидермальной потери воды, снижение в роговом слое количества церамидов, и способствует более легкому проникновению аллергенов, что приводит к сенсибилизации и, в свою очередь, провоцирует ряд иммунологических реакций воспаления [6].…”

Section: Introductionunclassified

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

Svechnikova

Zhufina²,

Evdokimov

2022

Medicinskij sovet

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Atopic dermatitis is a common, chronic, immunoinflammatory disease, the study of the pathogenesis of which has recently stepped forward and served as the impetus for the development of new drugs. For the last 10–15 years, in clinical practice, the choice of therapy for patients with moderate and severe atopic dermatitis, which would provide a stable positive effect and possess a favorable safety profile for patients, including those with comorbidities, has become a rather pressing problem. The main links in the pathogenesis of atopic dermatitis and an approach to the management of adult patients with moderate to severe atopic dermatitis are considered. The role of JAK and the JAK-STAT signaling pathway in the mechanisms of inflammation in atopic dermatitis is discussed. The article presents two clinical cases of successful treatment of patients with moderate to severe atopic dermatitis with the JAK inhibitor baricitinib, who had an insufficient response to standard baseline anti-inflammatory therapy. The first case involved the treatment of a 32-year-old patient, who had been ill since early childhood, followed by a long remission and exacerbation in 2016 when the disease began to have a frequent relapsing character. In the second case, a 45-year-old patient had had frequent relapses since the age of 16. Fast and stable results in both cases were achieved with treatment with baricitinib. The drug showed a favorable safety profile and satisfactory tolerability.

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The Changing Landscape of Atopic Dermatitis - Focusing on JAK Inhibitors

Cited by 5 publications

References 22 publications

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

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

Baricitinib for the treatment of atopic dermatitis

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

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