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Dermatology (Basel, Switzerland) 2022Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives.
OBJECTIVES
To assess the efficacy and safety of JAK inhibitors for AD treatment.
METHODS
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.
RESULTS
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, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 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, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 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, p = 0.001).
CONCLUSION
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.
Topics: Dermatitis, Atopic; Eczema; Humans; Immunoglobulin A; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34455413
DOI: 10.1159/000518541 -
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 -
Journal of Personalized Medicine Apr 2021Janus 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... (Review)
Review
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; I: 38.9%; NNT = 3.97), Investigator's Global Assessment response (RR: 2.99; 95% CI: 2.26-3.95; I: 0%; NNT = 5.72), and pruritus numerical rating scale response (RR: 2.52; 95% CI: 1.90-3.35; I: 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; I: 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.
PubMed: 33917069
DOI: 10.3390/jpm11040279 -
Auto- Immunity Highlights Apr 2021Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients... (Review)
Review
Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk.
OBJECTIVE
To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone.
METHODS
PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel-Haenszel random-effect method.
RESULTS
659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found.
CONCLUSION
The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.
PubMed: 33910632
DOI: 10.1186/s13317-021-00153-5 -
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 -
RMD Open Dec 2023Synovitis acne pustulosis hyperostosis osteitis (SAPHO) is a rare heterogeneous disease of unknown aetiopathology. Externally validated and internationally agreed... (Review)
Review
BACKGROUND AND OBJECTIVES
Synovitis acne pustulosis hyperostosis osteitis (SAPHO) is a rare heterogeneous disease of unknown aetiopathology. Externally validated and internationally agreed diagnostic criteria or outcomes and, as a result, prospective randomised controlled trials in SAPHO are absent. Consequently, there is no agreed treatment standard. This study aimed to systematically collate and discuss treatment options in SAPHO.
METHODS
Following 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' guidance, a systematic literature search was conducted using PubMed, Scopus and Web of Science databases. Prospective clinical studies and retrospective case collections discussing management and outcomes in SAPHO involving five or more participants were included. Articles not published in English, studies not reporting defined outcomes, and studies solely relying on patient-reported outcomes were excluded.
RESULTS
A total of 28 studies (20 observational, 8 open-label clinical studies) reporting 796 patients of predominantly European ethnicity were included. Reported therapies varied greatly, with many centres using multiple treatments in parallel. Most patients (37.1%) received non-steroidal anti-inflammatory drugs alone or in combination. Bisphosphonates (22.1%), conventional (21.7%) and biological (11.3%) disease-modifying antirheumatic drugs were the next most frequently reported treatments. Reported outcomes varied and delivered mixed results, which complicates comparisons. Bisphosphonates demonstrated the most consistent improvement of osteoarticular symptoms and were associated with transient influenza-like symptoms. Paradoxical skin reactions were reported in patients treated with TNF inhibitors, but no serious adverse events were recorded. Most treatments had limited or mixed effects on cutaneous involvement. A recent study investigating the Janus kinase inhibitor tofacitinib delivered promising results in relation to skin and nail involvement.
CONCLUSIONS
No single currently available treatment option sufficiently addresses all SAPHO-associated symptoms. Variable, sometimes descriptive outcomes and the use of treatment combinations complicate conclusions and treatment recommendations. Randomised clinical trials are necessary to generate reliable evidence.
Topics: Humans; Acquired Hyperostosis Syndrome; Osteitis; Retrospective Studies; Prospective Studies; Synovitis; Hyperostosis; Acne Vulgaris; Diphosphonates
PubMed: 38151265
DOI: 10.1136/rmdopen-2023-003688 -
Frontiers in Medicine 2022Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage...
INTRODUCTION
Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.
METHODS
A systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.
RESULTS
We report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).
CONCLUSION
The results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.
PubMed: 35833101
DOI: 10.3389/fmed.2022.930071 -
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 -
Frontiers in Pharmacology 2022Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in...
Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports. Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger's test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented. We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95% CI, 1,635 to 38,137) but with considerable heterogeneity (I2 = 99.14). As a second-line treatment for csDMARD failed RA, JAK-i is cost-effective than csDMARD/bDMARD with a pooled INB of $23,144 (74.1-46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp $26,157 (-7,284 to 59,598). Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD42021222541.
PubMed: 36582538
DOI: 10.3389/fphar.2022.1090361 -
International Immunopharmacology Oct 2021This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors for COVID-19 patients.
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to July 12, 2021. RCTs comparing the clinical efficacy and safety of JAK inhibitors with a placebo or standard care in treating COVID-19 patients were included. The primary outcome was all-cause mortality rate at day 28.
RESULTS
Three RCTs were included in this meta-analysis. The all-cause mortality rate at day 28 was lower among the patients receiving JAK inhibitors than among the controls (4.1% [28/647] versus 7.0% [48/684], OR, 0.57; 95% CI, 0.36-0.92, I = 0). The clinical recovery rate was higher among the patients receiving JAK inhibitors than among the controls (85.1% (579/680) versus 80.0% [547/684], OR, 1.45; 95% CI, 1.09-1.93, I = 0). Additionally, the use of JAK inhibitors was associated with a shorter time to recovery than among the controls (MD, -2.84; 95% CI, -5.56 to -0.12; I = 50%). The rate of invasive mechanical ventilation (MV) was lower in the patients who used JAK inhibitors than among the controls. Finally, no significant difference was observed between the patients who used JAK inhibitors and the controls in the risk of any adverse events (OR, 0.92; 95% CI, 0.64-1.34; I = 33%) and serious adverse events (OR, 0.80; 95% CI, 0.45-1.44; I = 46%).
CONCLUSIONS
JAK inhibitors can lead to a better clinical outcome of hospitalized COVID-19 patients, and they are a safe agent in the treatment of COVID-19.
Topics: Azetidines; Humans; Janus Kinase Inhibitors; Nitriles; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; SARS-CoV-2; Sulfonamides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34343937
DOI: 10.1016/j.intimp.2021.108027