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Journal of Drugs in Dermatology : JDD Jul 2023This article describes the clinical trial, safety, and efficacy of ruxolitinib 1.5% cream or repigmentation in patients with vitiligo.
BACKGROUND
This article describes the clinical trial, safety, and efficacy of ruxolitinib 1.5% cream or repigmentation in patients with vitiligo.
DATA SOURCES
A systematic review was done using ruxolitinib or Opzelura in MEDLINE (PubMed) and EMBASE.
CLINICALTRIALS
gov was used to identify ongoing or unpublished studies.
STUDY SELECTION AND DATA EXTRACTION
Studies included were written in English and relevant to pharmacology, clinical trials, safety, and efficacy.
DATA SYNTHESIS
In two 52-week phase 3 trials, 52.0% of subjects had at least 75% improvement in their Facial Vitiligo Area Scoring Index (F-VASI).
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Ruxolitinib is a topical Janus kinase (JAK) inhibitor newly approved by the US Food and Drug Administration for repigmentation in patients with vitiligo.
CONCLUSION
Topical ruxolitinib is the first medication approved for repigmentation in patients with vitiligo. It is a safe and effective treatment; however, cost may be a barrier to some patients when prescribing this medication. Trials to compare the efficacy and side effect profile of topical ruxolitinib with other topical treatments are still needed. Grossmann MC, Haidari W, Feldman SR. A Review on the use of topical ruxolitinib for the treatment of vitiligo. J Drugs Dermatol. 2023;22(7):664-667. doi:10.36849/JDD.7268.
Topics: Humans; Vitiligo; Pyrimidines; Nitriles; Pyrazoles; Treatment Outcome; Janus Kinase Inhibitors
PubMed: 37410047
DOI: 10.36849/JDD.7268 -
Journal of the American Academy of... Aug 2022
Meta-Analysis
Topics: Dermatitis, Atopic; Humans; Janus Kinase 1; Janus Kinase Inhibitors; Pyrroles; Treatment Outcome
PubMed: 35358602
DOI: 10.1016/j.jaad.2022.03.039 -
Journal of the European Academy of... May 2024Alopecia areata (AA) is an autoimmune disorder that affects the hair follicles, resulting in patchy recurrent hair loss. A large body of evidence has demonstrated the... (Comparative Study)
Comparative Study Meta-Analysis
Alopecia areata (AA) is an autoimmune disorder that affects the hair follicles, resulting in patchy recurrent hair loss. A large body of evidence has demonstrated the favourable clinical response of the Janus kinase (JAK) inhibitors and biologics, but a lack of comprehensive comparison among these therapies exists in the current literature. This study aimed to compare their efficacy. A systematic review and meta-analysis were performed including randomized trials that report the outcomes of the Severity of Alopecia Tool (SALT) and/or the mean change in SALT. These articles were pooled and a network meta-analysis (NAM) was conducted. Based on the surface under the cumulative ranking curve estimates obtained for the mean change in SALT score, baricitinib_4 mg (0.7949656) had the best probability of being the most effective therapy, followed by ritlecitinib_200_50 mg (0.7391906) and ivarmacitinib_4 mg (0.7292594). In contrast, dupilumab, secukinumab, tralokinumab and apremilast were less likely to be effective. Targeting the JAK signalling pathway holds great potential for restoring hair regrowth, albeit the contribution of JAK1, JAK2, JAK3 and TYK2 inhibition to the therapeutic effect on AA is apparently different. Baricitinib_4 mg and ritlecitinib 200_50 mg demonstrated notable efficacy, and both molecules displayed a dose-dependent effect, which is not observed with ivarmacitinib. Further investigations into the specific mechanisms of action of these JAK inhibitors are warranted to elucidate the reasons behind these differences.
Topics: Adult; Humans; Administration, Oral; Alopecia Areata; Bayes Theorem; Biological Products; Janus Kinase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38279559
DOI: 10.1111/jdv.19797 -
Rheumatology and Therapy Apr 2022Rheumatoid arthritis (RA) is a chronic debilitating illness, usually associated with mental health ailments. Literature reports contradictory observations about the... (Review)
Review
INTRODUCTION
Rheumatoid arthritis (RA) is a chronic debilitating illness, usually associated with mental health ailments. Literature reports contradictory observations about the association between recent RA pharmacotherapies and mental health. We systematically reviewed RA randomized control trials to synthesize the association between Janus kinases (JAK) inhibitors therapy and mental health.
METHODS
We systematically searched clinical trials of JAK inhibitor intervention reporting mental health outcomes using short form-36 (SF-36) in PubMed, Embase, and Scopus databases from inception to February 2021. We have selected the studies and extracted the data, adhering to Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We have pooled the mean change of SF-36 mental component score (MCS) between JAK inhibitors and comparator therapy with a 95% confidence interval.
RESULTS
Of the 2915 searched studies for systematic review, 19 studies involving 14,323 individuals were included for the meta-analysis. The pooled mean reduction in SF-36 MCS scores (after minus before) with JAK inhibitors was 4.95 (4.41-5.48). The pooled mean difference of incremental mean change in SF-36 MCS score between JAK monotherapy and comparator was 1.53 (0.88-2.18). The improvement in SF-36 MCS scores with JAK inhibitor therapy is greater than the minimum clinically important difference (MCID) value of 2.5. However, on separate analysis with comparator drugs like methotrexate and standard treatment, the MCS scores did not exceeded the MCID value and were also not statistically significant.
CONCLUSIONS
JAK inhibitors results in clinically meaningful improvement in the mental health scores of the RA patients.
PROSPERO REGISTRATION ID
2021 CRD42021234466.
PubMed: 34902113
DOI: 10.1007/s40744-021-00409-6 -
European Journal of Internal Medicine Aug 2022To assess the efficacy and safety of janus kinase (JAK) inhibitors in the treatment of ankylosing spondylitis (AS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the efficacy and safety of janus kinase (JAK) inhibitors in the treatment of ankylosing spondylitis (AS).
METHODS
We searched the PubMed and Cochrane Central Register of Controlled Trials to Nov 1, 2021. We included all randomized controlled trials (RCTs) evaluating JAK inhibitors in the treatment of AS. Two reviewers independently selected studies, extracted data and assessed the risk of bias.
RESULTS
Four RCT studies with 779 participants were included in the meta-analysis. Compared with placebo group, percentages of participants achieving responses of Assessment of spondyloarthritis international society(ASAS) 20, ASAS 40, ASAS 5/6, Bath AS disease activity index (BASDAI) 50 were significantly higher in JAK inhibitor group respectively; changes from baseline in AS disease activity score using C-reactive protein(ASDAS-CRP), Maastricht AS enthesitis score (MASES), AS Quality of Life (ASQoL) score, short-form-36 health survey physical component summary (SF-36 PCS) score, BASDAI, Bath AS functional index (BASFI), Bath AS metrology index (BASMI), Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) score, SPARCC joint score and Work Productivity and Activity Impairment (WPAI) Overall Work Impairment score showed significant improvements in JAK inhibitor group. The incidence of adverse events (AEs) and severe adverse events (SAEs) showed no significant differences between the JAK inhibitor and placebo groups.
CONCLUSIONS
JAK inhibitors showed a satisfactory and promising efficacy in the treatment of active AS not only in mitigating disease activity, but also substantially improving patient's physical function, emotional well-being and social participation. The results of this meta-analysis provide solid evidence for JAK inhibitor as a novel therapeutic strategy for patients with active AS.
Topics: C-Reactive Protein; Fatigue; Humans; Janus Kinase Inhibitors; Quality of Life; Severity of Illness Index; Spondylitis, Ankylosing
PubMed: 35461744
DOI: 10.1016/j.ejim.2022.04.007 -
Clinical Epidemiology and Global Health 2021The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of...
BACKGROUND
The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of Janus Kinase (JAK) Inhibitors in reducing risk of mortality among hospitalized patients with COVID-19.
METHODS
Several electronic databases, including PubMed, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords "COVID-19″ AND ("JAK inhibitor" OR "Ruxolitinib" OR "Tofacitinib" OR "Fedratinib" OR "Baricitinib") AND ("Severe" OR "Mortality"), were used to perform a systematic literature search up to December 11, 2020. All studies pertinent to the predetermined eligibility criteria were included in the analysis. Our outcome of interest was all types of mortality, clinical improvement, and clinical deterioration. Dichotomous variables of our outcomes of interest were analyzed using Maentel-Haenszel formula to obtain odds ratios (ORs) and 95% confidence intervals (CI) with random-effects modeling regardless of heterogeneity.
RESULTS
Five studies with a total of 1190 patients and were included in this systematic review and meta-analysis. The use of JAK inhibitors was associated with a reduced risk of mortality (OR 0.51, 95% CI 0.28-0.93, P = 0.02; I: 7.8%, P = 0.354) and clinical improvement (OR 1.76, 95% CI 1.05-2.95, P = 0.032; I: 26.4%, P = 0.253). The use of JAK inhibitors was not associated with a reduced risk of clinical deterioration (OR 0.58, 95% CI 0.28-1.19, P = 0.136; I: 24.1%, P = 0.267).
CONCLUSION
The use of JAK inhibitors was significantly associated with a reduced risk of mortality, and clinical improvement in hospitalized patients with COVID-19.
PubMed: 33969237
DOI: 10.1016/j.cegh.2021.100755 -
Frontiers in Medicine 2021Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs)...
BACKGROUND
Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19.
METHODS
Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR).
RESULTS
Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis ( = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51-0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41-0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42-0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49-0.78) with no increase in the risk of adverse events.
CONCLUSION
Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.
PubMed: 35155477
DOI: 10.3389/fmed.2021.800492 -
Rheumatology (Oxford, England) Oct 2023Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs).
METHODS
Randomized controlled trials (RCTs) on JAKi in patients with IMIDs were identified by the MEDLINE and EMBASE databases until October 2021. Risk of bias was assessed according to Cochrane criteria. The beta-binomial model was applied to calculate pooled odds ratio (OR) and corresponding 95% CI. The PROSPERO registration number is CRD42022324143.
RESULTS
We have included one phase I, 21 phase II, three phase II-III and 36 phase III RCTs for a total of 19 443 patients in the JAKi group and 6354 in the control group. Thirty-one (unweighted rate 0.16%; 95% CI: 0.10, 0.21) events were reported in the JAKi group and 20 (unweighted rate 0.22%; 95% CI: 0.12, 0.32) in the control group in a mean follow-up of 16.8 weeks. IMID patients treated with JAKi did not have an increased thromboembolic risk compared with those treated with placebo (OR 0.82; 95% CI: 0.43, 1.56). No statistically different results were seen in subanalyses for each investigated IMID, drug and dosage.
CONCLUSION
JAKi do not increase thromboembolic risk compared with placebo in IMID patients enrolled in selected RCTs.
Topics: Humans; Janus Kinase Inhibitors; Immunomodulating Agents; Thromboembolism; Thrombosis
PubMed: 37202344
DOI: 10.1093/rheumatology/kead211 -
Journal of Clinical Medicine Apr 2023Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset...
INTRODUCTION
Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity.
METHODS
We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment.
RESULTS
Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis.
CONCLUSIONS
JAKi represent a promising option in the treatment of lung disease associated with sJIA.
PubMed: 37048785
DOI: 10.3390/jcm12072702 -
Expert Review of Anti-infective Therapy Mar 2022Currently, JAK-inhibitors are repurposed for therapy of Covid-19 because of their ability in restraining immune response, yet the corroboration regarding their advantage... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, JAK-inhibitors are repurposed for therapy of Covid-19 because of their ability in restraining immune response, yet the corroboration regarding their advantage is still unclear. This study sought to analyze the efficacy of JAK-inhibitors to ameliorate the outcomes of Covid-19 sufferer. Using specific keywords, we comprehensively go through the potential articles on ClinicalTrials.gov, Europe PMC, and PubMed sources until June 2, 2021. All published studies on JAK-inhibitors and Covid-19 were collected.
RESULTS
There were 14 studies with 4,363 Covid-19 patients contained in the meta-analysis. Based on our data, we suggested that JAK-inhibitors corresponded with increased recovery rate (RR 1.17; 95%CI: 1.01-1.36, = 0.040, = 91%, random-effect modeling); shortened time to recovery (mean difference -0.96; 95%CI: -1.15, -0.77, < 0.00001, = 28%, random-effect modeling); reduction of clinical deterioration risk (RR 0.66; 95%CI: 0.48-0.89, = 0.008, = 57%, random-effect modeling); and reduction of Covid-19 mortality (RR 0.52; 95%CI: 0.36-0.76, = 0.0006, = 33%, random-effect modeling).
CONCLUSIONS
This study propose that JAK-inhibitors perhaps provide advantageous effects on Covid-19 outcomes. JAK-inhibitors may be given during 1-2 weeks of disease to optimize its beneficial effects in halting the exaggerated immune response.
Topics: Europe; Humans; Janus Kinase Inhibitors; Janus Kinases; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34538216
DOI: 10.1080/14787210.2021.1982695