scholarly journals Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: Focus on Abrocitinib, Baricitinib, and Upadacitinib

2021 ◽  
pp. e2021145
Author(s):  
Miguel Nogueira ◽  
Tiago Torres
Keyword(s):  
Atopic Dermatitis ◽  
Kinase Inhibitors ◽  
Symptomatic Relief ◽  
Skin Condition ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Janus Kinase Inhibitors ◽  
Th22 Cells ◽  
Th 1

Atopic dermatitis (AD) is a clinically heterogenous, inflammatory skin condition with a high impact on patients’ daily activities that remains difficult to treat. The knowledge acquired over the last decade on AD pathophysiology and disease burden led to the development of new targeted therapeutic options that enable clinicians to better manage AD patients. The JAK/STAT signaling pathway modulates several immune pathways (T helper (Th)1, Th2, Th17, and Th22 cells) that have been found to be involved in AD pathogenesis. For this reason, JAK inhibitors emerged as a possible therapy for AD. Baricitinib, upadacitinib, and abrocitinib are the three oral JAK inhibitors already approved or in advanced clinical development for this purpose. The results showed that this drug class is highly effective achieving symptomatic relief (itch control) in the short term, as well as improving disease severity in the short and medium term. However, their efficacy should be balanced with possible side effects, that have been reported in clinical trials. More data on the long-term efficacy and safety, as well as from head-to-head comparisons and from real-world setting will be crucial to position oral JAK inhibitors in the AD therapeutic armamentarium.

Janus Kinase Inhibitors: A Review of Their Application in the Vitiligo

2021 ◽  
Vol 21 ◽  
Author(s):  
Chao Niu ◽  
Hunjun Xie ◽  
Haji Akber Aisa
Keyword(s):  
Cell Proliferation ◽  
Atopic Dermatitis ◽  
Immune System ◽  
Immune Regulation ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Janus Kinase Inhibitors ◽  
Small Molecular Inhibitors ◽  
Stat Pathway

: The small-molecular inhibitors targeted JAks (JAK inhibitors), could modulate the cytokines-mediated signaling via JAK-STAT pathway, which plays a important role in immune regulation and cell proliferation. The JAK inhibitors are previously designed and synthesized to treat diseases involved with hematologic and immune system. Increasing evidence shows that they are quite effective in atopic dermatitis (AD), alopecia areata (AA), psoriasis, vitiligo, and other autoimmune-induced dermatologic conditions. Currently, many JAK inhibitors possessing anti-vitiligo activity are being investigated in laboratory and clinically. In this view, we would like to summarize so we review the applications of these inhibitors with emphasis on profile of vitiligo, clinical efficacy, dosages, development of new candidates and adverse events through available literatures.

The effectiveness of Janus kinase inhibitors in treating atopic dermatitis: A systematic review and meta‐analysis

2020 ◽  
Vol 33 (4) ◽  
Author(s):  
Charan Jeet Arora ◽  
Fakhre Alam Khattak ◽  
Mohammad Tahir Yousafzai ◽  
Bukola Mary Ibitoye ◽  
Stephen Shumack
Keyword(s):  
Systematic Review ◽  
Atopic Dermatitis ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Janus Kinase Inhibitors

scholarly journals Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Michelle Le ◽  
Melissa Berman-Rosa ◽  
Feras M. Ghazawi ◽  
Marc Bourcier ◽  
Loretta Fiorillo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Atopic Dermatitis ◽  
Safety Profile ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Symptom Control ◽  
Janus Kinase ◽  
Severe Atopic Dermatitis ◽  
Eligibility Criteria ◽  
Janus Kinase Inhibitors

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD).Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD.Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021.Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib.Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time.Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

scholarly journals Activation of Interferon-Stimulated Transcriptomes and ACE2 Isoforms in Human Airway Epithelium Is Curbed by Janus Kinase Inhibitors

2020 ◽  
Author(s):  
Hye Kyung Lee ◽  
Olive Jung ◽  
Lothar Hennighausen
Keyword(s):  
Airway Epithelium ◽  
Kinase Inhibitors ◽  
Regulatory Elements ◽  
Janus Kinase ◽  
Cell Tropism ◽  
Jak Inhibitors ◽  
Janus Kinase Inhibitors ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Airway ◽  
Human Airway Epithelium

Abstract SARS-CoV-2 infection of human airway epithelium activates genetic programs that lead to progressive hyperinflammation in COVID-19 patients. Here we report on genetic programs activated by interferons and the suppression by Janus kinase (JAK) inhibitors. The angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 and deciphering its regulation is paramount for understanding the cell tropism of SARS-CoV-2 infection. We identified candidate regulatory elements in the ACE2 locus in human primary airway cells and lung tissue. Activating histone and promoter marks and Pol II loading characterize the intronic dACE2 and define novel candidate enhancers distal to the genuine ACE2 promoter and within additional introns. dACE2, and to a lesser extent ACE2, RNA levels increased in primary cells treated with interferons and this induction was mitigated by JAK inhibitors that are used therapeutically in COVID-19 patients. Our analyses provide insight into ACE2 regulatory elements and highlight JAK inhibitors as suitable tools to suppress interferon-activated genetic programs in bronchial cells.

scholarly journals Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis

2020 ◽  
Vol Volume 9 ◽  
pp. 255-272
Author(s):  
Rhea Singh ◽  
Courtney E Heron ◽  
Rima I Ghamrawi ◽  
Lindsay C Strowd ◽  
Steven R Feldman
Keyword(s):  
Atopic Dermatitis ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Janus Kinase Inhibitors

scholarly journals Role of Janus Kinase Inhibitors in Therapy of Psoriasis

2021 ◽  
Vol 10 (19) ◽  
pp. 4307
Author(s):  
Sylwia Słuczanowska-Głąbowska ◽  
Anna Ziegler-Krawczyk ◽  
Kamila Szumilas ◽  
Andrzej Pawlik
Keyword(s):  
Side Effects ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Biologic Drugs ◽  
Janus Kinases ◽  
Janus Kinase Inhibitors ◽  
Long Term Treatment

Janus kinases inhibitors are molecules that target Janus kinases—signal transducers and activators of transcription (JAK/STAT). They inhibit this intracellular signal pathway, blocking the gene transcription of crucial proinflammatory cytokines that play a central role in the pathogenesis of many inflammatory and autoimmune diseases, including psoriasis. This process reduces psoriatic inflammation. The JAK inhibitors are divided into two generations. The first generation of JAK inhibitors blocks two or more different Janus kinases. The second generation is more specified and blocks only one type of Janus kinase and has less side effects than the first generation. Tofacitinib, ruxolitinib and baricitinib belong to first generation JAK inhibitors and decernotinib and filgotinib belong to second group. This narrative review summarizes the role of Janus kinase inhibitors in the therapy of psoriasis. Oral JAK inhibitors show promise for efficacy and safety in the treatment of psoriasis. Studies to date do not indicate that JAK inhibitors are superior to recent biologic drugs in terms of efficacy. However, JAK inhibitors, due to their lack of increased incidence of side effects compared to other biologic drugs, can be included in the psoriasis treatment algorithm because they are orally taken. Nevertheless, further studies are needed to evaluate long-term treatment effects with these drugs.

Sign in / Sign up

Export Citation Format

Share Document