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.

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 Effectiveness and Safety of Abrocitinib in Patients with Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Hammad Ali Fadlalmola ◽  
Muayad Saud Albadrani ◽  
Amal Mohamed Elhusein ◽  
Wahieba E. Mohamedsalih ◽  
Veerabhadra D. S. Swamy ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Severe Atopic Dermatitis ◽  
Upper Respiratory Tract ◽  
Serious Adverse Events ◽  
Inverse Variance ◽  
Iga Response

Background. Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease characterized by pruritic, intense itching, and eczematous lesions affecting about 25% of children and 2% to 3% of adults worldwide. Abrocitinib is a selective inhibitor of Janus kinase-1 (JAK1) enzyme inhibiting the inflammatory process. Therefore, we aimed to assess the efficacy and safety of abrocitinib for moderate-to-severe AD. Methods. We systematically searched PubMed, Cochrane, Web of Science, Scopus, and EczemATrials till Feb 1, 2021, for reliable trials. The analysis was conducted using an inverse-variance method. The results were pooled as mean difference/event rate and 95% confidence interval. Results. Abrocitinib 100 mg and 200 mg were associated with higher IGA response, EASI-50% responders, EASI-75% responders, EASI-90% responders, number of participants with at least 4-point improvements in NRS, and quality of life measured by DLQI and CDLQI than placebo. Also, 100 mg and 200 mg were associated with lower SCORAD index, %BSA, PSAAD index, and POEM index than placebo. Abrocitinib 100 mg and 200 mg were not associated with adverse events such as upper respiratory tract infection, nasopharyngitis, dermatitis, atopic, any serious adverse events, and death. Conclusion. Abrocitinib in dose 100 mg or 200 mg is an effective, well-tolerated, and promising drug in treating patients with moderate-to-severe atopic dermatitis. However, the analysis favored the efficacy of abrocitinib 200 mg over 100 mg, but side effects such as nausea and headache are likely to occur more with 200 mg.

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 Janus Kinase-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Lucas Walz ◽  
Avi J. Cohen ◽  
Andre P. Rebaza ◽  
James Vanchieri ◽  
Martin D. Slade ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Randomized Clinical Trials ◽  
Type I Interferon ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Type I Interferons ◽  
Type I ◽  
Jak Inhibitor ◽  
Jak Inhibitors

Background Novel coronavirus (SARS-CoV-2) has infected over 17 million. Novel therapies are urgently needed. Janus-kinase (JAK) inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients for their proven efficacy against diseases with excessive cytokine release and by their ability to promote viral clearance in past coronaviruses, respectively. We conducted a systemic review and meta-analysis to evaluate role of these therapies in COVID-19 patients. Methods MEDLINE and MedRxiv were searched until July 30th, 2020, including studies that compared treatment outcomes of humans treated with JAK-inhibitor or Type I interferon against controls. Inclusion necessitated data with clear risk estimates or those that permitted back-calculation. Results We searched 733 studies, ultimately including four randomized and eleven non-randomized clinical trials. JAK-inhibitor recipients had significantly reduced odds of mortality (OR, 0.12; 95%CI, 0.03-0.39, p=0.0005) and ICU admission (OR, 0.05; 95%CI, 0.01-0.26, p=0.0005), and had significantly increased odds of hospital discharge (OR, 22.76; 95%CI, 10.68-48.54, p<0.00001), when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95%CI, 0.04-0.85, p=0.03), and increased odds of discharge bordering significance (OR, 1.89; 95%CI, 1.00-3.59, p=0.05). Conclusions JAK-inhibitor treatment is significantly associated with positive clinical outcomes regarding mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes regarding mortality and discharge. While these data show promise, additional randomized clinical trials are needed to further elucidate the efficacy of JAK-inhibitors and Type I interferons and clinical outcomes in COVID-19.

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.

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