scholarly journals JAK INHIBITORS AS A NEW MODALITY FOR TREATING ATOPIC DERMATITIS: A BETTER UNDERSTANDING OF ITS EFFICACY AND SAFETY

2021 ◽  
Vol 9 (10) ◽  
pp. 1177-1198
Author(s):  
Abdullah Alnama ◽  
Hassan Mahmood
Keyword(s):  
Atopic Dermatitis ◽  
Randomized Clinical Trials ◽  
Inflammatory Diseases ◽  
Lymphocyte Activation ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Administration Routes ◽  
Feedback Cycle ◽  
Causal Pathway ◽  
New Treatment

AD is a chronic relapsing disease characterized by pruritis and chronic inflammatory skin changes, (1) which affects approximately 10–30% of children and as much as 10% of adults worldwide.(2) This condition has a great significant impact on morbidity and presents an outstanding social economic burden.(3) AD is a multifactorial disease that develop by interaction between these factors in a positive feedback cycle. Treatment of AD interrupts the causal pathway. Management with conventional therapies has been a challenge, but a novel biological treatment called dupilumab was recently approved for the treatment of moderate-to-severe AD, but this drug only achieved 40% clear skin in combination with TCs.(4). JAK inhibitors are another new drug family that inhibit JAK-signaling pathways, which involve JAK1, JAK2, JAK3 and TYK2. JAK inhibitors have been approved to treat inflammatory diseases like rheumatoid arthritis, and high attention is currently being focused on the clinical development of JAK inhibitors for the treatment of AD. Which are a possible treatment for certain disease that are related to lymphocyte activation, such as psoriasis, alopecia areata, vitiligo and AD. JAK inhibitors are available in topical and oral forms, thereby allowing more administration routes depending on the severity of AD, which ranges from mild to severe. Since JAK inhibitors are a new treatment modality in dermatology, the efficacy of this new medicine and the safety thereof are still being debated. A systematic review and meta‐analysis were done for all randomized clinical trials that evaluated JAK inhibitors for Atopic dermatitis to investigate their pooled efficacy and safety compared to placebo. Results might be useful as a milestone to develop a more accurate view of this medication and provide direction for further research.

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 JAK-inhibitors: pharmacological properties and comparative clinical efficacy and safety

2021 ◽  
Vol 30 (1) ◽  
pp. 51-60
Author(s):  
P. Novikov ◽  
T. Shevtsova ◽  
E. Shchegoleva ◽  
S. Moiseev
Keyword(s):  
Clinical Trials ◽  
Inflammatory Diseases ◽  
Controlled Trials ◽  
Similar Response ◽  
Pharmacological Properties ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Randomized Controlled ◽  
Immune Mediated ◽  
Direct Head

JAK-inhibitors interrupt the intracellular JAK-STAT signalling pathway that mediates action of various cytokines which are involved in the pathogenesis of rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. The objective of literature review was to compare the results of clinical trials of three JAK-inhibitors, that is, tofacitinib, baricitinib and upadacitinib, that differ in selectivity against JAK, in patients with RA. We have found no direct head-to-head clinical trials of JAK-inhibitoris. However, in the randomized controlled trials both non-selective (tofacitinib and baricitinib) and selective (upadacitinib) JAK-inhibitors were proved to be more effective than placebo and were associated with the similar response rates. Safety profiles of JAK-inhibitors were also comparable.

scholarly journals Biological Therapies for Atopic Dermatitis: A Systematic Review

Dermatology ◽  
2021 ◽  
pp. 1-11 ◽  
Author(s):  
Shuying Zhou ◽  
Fei Qi ◽  
Yue Gong ◽  
Jinping Zhang ◽  
Binghua Zhu
Keyword(s):  
Clinical Trial ◽  
Atopic Dermatitis ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Phase Iii ◽  
Therapeutic Effects ◽  
Phase 2 ◽  
Biological Therapies ◽  
Jak Inhibitors

Background: Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory skin disease. Biologics are now widely used in patients with moderate-to-severe AD. Objective: This work aims to summarize both label and off-label biologics on AD treatment in phase II and phase III stages, and compile evidence on the efficacy of the most-studied biologics. Methods: We conducted a comprehensive literature search through PubMed, EMBASE, and ClinicalTrials.gov to identify all documented biological therapies for AD. The criteria were further refined to focus on those treatments with the highest evidence level for AD with at least one randomized clinical trial supporting their use. Only studies or articles published in English were enrolled in this study. Findings: Primary searches identified 525 relevant articles and 27 trials. Duplicated articles and papers without a full text were excluded. Only completed trials were enrolled. We included 28 randomized controlled trials, 4 unpublished trials, 2 observational studies, and 1 meta-analysis. Eight kinds of biologics, including IL-4/IL-13 inhibitors, JAK inhibitors, anti-IL-13 antibodies, anti-IL-22 antibodies, anti-IL-33 antibodies, thymic stromal lymphopoietin inhibitor (TSLP), OX40 antibodies, and H4R-antagonists were included in this work. Dupliumab, as the most widely used and investigated biologic, was reported in 1 meta-analysis and 4 trials exploring its long-term use and application in both adults and pediatric patients. Besides dupilumab, four other IL-4/IL-13 inhibitors recruited were all randomized, clinical trials at phase 2–3 stage. Six different kinds of JAK inhibitors were summarized with strong evidence revealing their significant therapeutic effects on AD. There were 3 trials for nemolizumab, an anti-IL-13 antibody, all of which were in the phase 2 clinical trial stage. Results showed nemolizumab could be another alternative therapy for moderate-to-severe AD with long-term efficiency and safety. Conclusion: The biological therapies with the most robust evidence on efficacy and long-term safety for AD treatment include dupilumab, barcitinib, abrocitinib, and delgocitinib. Most of the biologics mentioned in this review were still at the exploratory stage. This review will help practitioners advise patients seeking suitable biological therapies and offer experimental study directions for treatment.

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