scholarly journals Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials

2021 ◽  
Vol 11 (4) ◽  
pp. 279
Author(s):  
Hou-Ren Tsai ◽  
Jing-Wun Lu ◽  
Li-Yu Chen ◽  
Tai-Li Chen
Keyword(s):  
Atopic Dermatitis ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Meta Analysis ◽  
Severity Index ◽  
Janus Kinase ◽  
Drug Discontinuation ◽  
Jak Inhibitors

Janus kinase (JAK) inhibitors are promising treatments for atopic dermatitis (AD). The aim of this study was to assess the efficacy and safety of JAK inhibitors for AD treatment via the “Grading of Recommendations Assessment, Development, and Evaluation” approach. We identified 15 randomized controlled trials comparing oral or topical JAK inhibitors against placebo to treat AD. A random-effects meta-analysis was performed, and the numbers-needed-to-treat (NNTs)/numbers-needed-to-harm (NNHs) were calculated. Patients treated with JAK inhibitors were associated with higher rates of achieving eczema area and severity index-75 (rate ratio (RR): 2.84; 95% confidence interval (CI): 2.20–3.67; I2: 38.9%; NNT = 3.97), Investigator’s Global Assessment response (RR: 2.99; 95% CI: 2.26–3.95; I2: 0%; NNT = 5.72), and pruritus numerical rating scale response (RR: 2.52; 95% CI: 1.90–3.35; I2: 39.4%; NNT = 4.91) than those treated with placebo. Moreover, patients treated with JAK inhibitors had a higher risk of treatment-emergent adverse events (RR: 1.14; 95% CI: 1.02–1.28; I2: 52%; NNH = 14.80) but not adverse events leading to drug discontinuation. According to the evidence-based results, JAK inhibitors are potentially effective strategies (certainty of evidence: “moderate”) for treating AD with tolerable side effects (certainty of evidence: “low”). Nevertheless, long-term follow-up is required.

scholarly journals Efficacy and Safety of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis

Dermatology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Chenyang Li ◽  
Xun Sun ◽  
Kun Zhao ◽  
Fanxiang Meng ◽  
Lin Li ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Primary Study ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Iga Response

<b><i>Background:</i></b> Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. <b><i>Objectives:</i></b> To assess the efficacy and safety of JAK inhibitors for AD treatment. <b><i>Methods:</i></b> We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator’s Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI. <b><i>Results:</i></b> We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25–3.56, <i>p</i> &#x3c; 0.001) and EASI score (WMD –28.82, 95% CI –34.48 to −23.16, <i>p</i> &#x3c; 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66–4.84, <i>p</i> &#x3c; 0.001) and EASI score (WMD –42.00, 95% CI –48.64 to −35.36, <i>p</i> &#x3c; 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD –53.92, 95% CI –69.26 to −38.58, <i>p</i> &#x3c; 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74–10.93, <i>p</i> &#x3c; 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10–1.42, <i>p</i> = 0.001). <b><i>Conclusion:</i></b> Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.

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.

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.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section II: Tools for Assessing the Severity of Atopic Dermatitis

2018 ◽  
Vol 22 (1_suppl) ◽  
pp. 10S-16S ◽  
Author(s):  
Melinda J. Gooderham ◽  
Robert Bissonnette ◽  
Parbeer Grewal ◽  
Perla Lansang ◽  
Kim A. Papp ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Life Quality ◽  
Severity Index ◽  
Adult Patients ◽  
Physician Global Assessment ◽  
Atopic Dermatitis Severity ◽  
Patient Reported

Clinicians rely on clinical measures to define the severity of atopic dermatitis and assess outcomes of therapy. These measures can be objective (ie, physician assessments of disease severity) or subjective (ie, patient-reported symptoms and quality of life outcomes). In this review, the most commonly used tools for assessing atopic dermatitis severity in adult patients are presented and compared. These include Eczema Area and Severity Index (EASI); SCORing Atopic Dermatitis (SCORAD); Physician Global Assessment (PGA); body surface area (BSA); Atopic Dermatitis Severity Index (ADSI); Six Area, Six Sign Atopic Dermatitis (SASSAD); Patient Oriented Eczema Measure (POEM); Dermatology Life Quality Index (DLQI); and pruritus Numerical Rating Scale (NRS). Available severity strata for the tools are summarized, although the use of severity strata in clinical practice is not recommended. Since both objective and subjective assessments of disease severity are important to assess, consideration of clinical characteristics such as disease recurrence or persistence, as well as location of the affected areas, should be considered in the overall judgement of disease severity and consideration of therapy choice.

scholarly journals Efficacy of Dupilumab on Different Phenotypes of Atopic Dermatitis: One-Year Experience of 221 Patients

2020 ◽  
Vol 9 (9) ◽  
pp. 2684
Author(s):  
Simona Tavecchio ◽  
Luisa Angileri ◽  
Francesco Pozzo Giuffrida ◽  
Francesca Germiniasi ◽  
Angelo Valerio Marzano ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Atopic Dermatitis ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Clinical Manifestations ◽  
Life Quality ◽  
Daily Practice ◽  
Severity Index ◽  
Efficacy And Safety

Background: The clinical features of adult-onset atopic dermatitis (AD) are heterogeneous and the diagnosis can be a challenge. A new biologic drug (dupilumab) has been approved for moderate to severe AD in adult patients. The efficacy and safety have been demonstrated in clinical trials, but these studies do not reflect conditions in daily practice and do not consider the different clinical manifestations of AD. Objectives: Analyzing the dupilumab activity in a real-world setting and comparing its efficacy on different AD phenotypes. Methods: We retrospectively evaluated 221 AD patients treated with dupilumab, stratified into six clinical phenotypes: classic, generalized eczema inflammatory and lichenoid patterns, prurigo, nummular eczema, and erythroderma. At baseline and at weeks 4, 16, and 52, the disease severity was assessed through the Eczema Area and Severity Index (EASI) and the quality of life was assessed through the Dermatology Life Quality Index (DLQI) questionnaire, Peak Pruritus Numerical Rating Scale (itch NRS), and Peak Sleep NRS. Results: We found a significant improvement after 16 weeks of treatment (p < 0.0001) in all six phenotypes for all the assessed scores mentioned above, persisting up to week 52. The best improvement was seen in the more severe phenotypes, particularly the erythrodermic one. Conclusions: The present study confirmed the efficacy and safety of dupilumab in the treatment of severe AD. Its strength was in the stratification of AD patients in six different phenotypes based on their clinical presentation, all of whom markedly improved in terms of both clinically evident and reported symptoms, as well as their quality of life.

scholarly journals Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis -The ANSWER cohort study-

2020 ◽  
Author(s):  
Kosuke Ebina ◽  
Toru Hirano ◽  
Yuichi Maeda ◽  
Wataru Yamamoto ◽  
Motomu Hashimoto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Disease Duration ◽  
Kinase Inhibitors ◽  
Certolizumab Pegol ◽  
Janus Kinase ◽  
Retention Rates ◽  
Drug Discontinuation ◽  
Naive Group ◽  
Drug Retention

Abstract Background: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA). Methods: This study assessed 3,897 patients and 4,415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2,737 bDMARDs-naïve patients and 1,678 bDMARDs-switched patients [59.5% switched to their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [42.4%], and methotrexate [MTX] dose 8.5 mg/week [60.9%]). Treatment courses included abatacept (ABT; n=663), adalimumab (ADA; n=536), certolizumab pegol (CZP; n=226), etanercept (ETN; n=856), golimumab (GLM; n=458), infliximab (IFX; n=724), tocilizumab (TCZ; n=851), and TOF (n=101/only bDMARDs-switched cases). Drug discontinuation reasons (categorized into lack of effectiveness, toxic adverse events, non-toxic reasons, or remission) and rates were estimated at 36 months using the Gray’s test, and statistically evaluated after adjusted by potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX usage, starting date, and number of switched bDMARDs) using the Fine-Gray model. Results: Cumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; P<0.001 between agents) and the bDMARDs-switched group (from 18.9% [TCZ] to 46.1% [CZP]; P<0.001 between agents). Toxic adverse events in the bDMARDs-naïve group (from 4.6% [ABT] to 11.2% [ETN]; P<0.001 between agents) and the bDMARDs-switched group (from 5.0% [ETN] to 15.7% [TOF]; P=0.004 between agents). Remission in the bDMARDs-naïve group (from 2.9% [ETN] to 10.0% [IFX]; P<0.001 between agents) and the bDMARDs-switched group (from 1.1% [CZP] to 3.3% [GLM]; P=0.9 between agents). Conclusions: Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.

scholarly journals Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews

2022 ◽  
Vol 12 ◽  
Author(s):  
Yun-Kyoung Song ◽  
Junu Song ◽  
Kyungim Kim ◽  
Jin-Won Kwon
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Proportional Reporting Ratio ◽  
Gastrointestinal Disorder ◽  
Interstitial Lung Diseases ◽  
Janus Kinase ◽  
Reporting Odds Ratio ◽  
Jak Inhibitors ◽  
Spontaneous Reports

The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.

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.

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