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Dermatology (Basel, Switzerland) 2024Psoriasis is a chronic immune-mediated skin disease. Several clinical trials have studied some topical drugs aiming at new therapeutic targets. However, the comparative... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Psoriasis is a chronic immune-mediated skin disease. Several clinical trials have studied some topical drugs aiming at new therapeutic targets. However, the comparative efficacy and safety of different concentrations and frequencies of newer topical drugs for psoriasis remain unclear. The aim of our study is to assess the comparative efficacy and safety of some newer topical treatments in patients with psoriasis.
METHODS
A systematic review and network meta-analysis (NMA) was conducted using eligible randomized controlled trials (RCTs). Treatments included topical therapeutic aryl hydrocarbon receptor (AhR)-modulating agent (TAMA), topical phosphodiesterase type 4 (PDE-4) inhibitors, and topical janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors. The primary efficacy assessment criterion was the proportion of patients' achieving Physician's Global Assessment 0/1 (PGA response). Secondary criterion was ≥75% reductions in the Psoriasis Area and Severity Index (PASI75). Adverse events (AEs) to represent the safety were also summarized.
RESULTS
Among 6 including newer topical drugs, odds of achieving both PGA response and PASI75 were higher with all regimens of TAMA and roflumilast cream versus vehicle. In terms of safety outcomes, odds of AEs were also higher with all regimens of TAMA. There were no statistically significant differences between topical JAK-STAT inhibitors and vehicle for any outcome, except ruxolitinib ointment 1% once daily (QD).
CONCLUSION
TAMA had a good therapeutic effect on plaque psoriasis but a relatively low treatment safety. Roflumilast cream had both promising efficacy and higher safety.
Topics: Humans; Network Meta-Analysis; Aminopyridines; Benzamides; Psoriasis; Chronic Disease; Treatment Outcome; Cyclopropanes
PubMed: 37939679
DOI: 10.1159/000535056 -
JAMA Dermatology Jan 2024Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions.
OBJECTIVE
To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions.
DATA SOURCES
PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023.
STUDY SELECTION
This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded.
DATA EXTRACTION AND SYNTHESIS
This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO.
MAIN OUTCOMES AND MEASURES
Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE.
RESULTS
The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.
Topics: Humans; Male; Adult; Janus Kinase Inhibitors; Venous Thromboembolism; Arthritis, Rheumatoid; Dermatitis, Atopic; Treatment Outcome
PubMed: 37910098
DOI: 10.1001/jamadermatol.2023.4090 -
Skin Appendage Disorders Oct 2023Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring alopecia. A few studies have shown increased odds of AA in Black individuals compared to...
BACKGROUND
Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring alopecia. A few studies have shown increased odds of AA in Black individuals compared to White individuals and increased odds of AA in Latinos compared to non-Latinos. Another study showed that Asians have lower odds of AA compared to Whites. Baricitinib, a Janus kinase inhibitor (JAKi), became the first Federal Drug Administration (FDA)-approved medication for adult patients with severe AA in June 2022.
OBJECTIVES
The aim of this review was to analyze published JAKi AA randomized controlled trials to characterize and assess the racial and ethnic representation of participants. Animal studies, studies unrelated to AA, and studies not investigating JAKis were excluded.
METHODS
PubMed and clinicaltrials.gov were searched for systematic reviews of clinical trials between 1990 and 2022.
RESULTS
Six clinical trials were included with a total of 1,690 subjects. Four trials were industry-sponsored, while two were university-sponsored. The three largest races represented included White (59.9%), Asian (28.0%), and African American/Black (8.1%). Three out of the 10 patients identified as Hispanic. None of the trials included sub-analyses of clinical efficacy based on race and/or ethnicity.
CONCLUSIONS
Our results show that populations with lower odds of AA (Whites and Asians) are overrepresented in JAKi AA clinical trials compared to Black and Hispanic/Latino patients.
PubMed: 37900778
DOI: 10.1159/000531219 -
RMD Open Oct 2023We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).
METHODS
PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI.
RESULTS
A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=-4.62, 95% CI -8.90 to -0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively.
CONCLUSION
ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD.
PROSPERO REGISTRATION NUMBER
CRD42022356816.
Topics: Humans; Rituximab; Antirheumatic Agents; Arthritis, Rheumatoid; Lung Diseases, Interstitial; Abatacept
PubMed: 37899093
DOI: 10.1136/rmdopen-2023-003487 -
JAMA Dermatology Dec 2023Janus kinase (JAK) inhibitors are increasingly used across a range of dermatologic conditions. Adverse events of acne have been noted in some studies in clinical... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Janus kinase (JAK) inhibitors are increasingly used across a range of dermatologic conditions. Adverse events of acne have been noted in some studies in clinical practice, but the scope of this outcome across JAK inhibitors has not been established.
OBJECTIVE
To systematically analyze all published phase 2 and 3 placebo-controlled randomized clinical trials (RCTs) of JAK inhibitors for the risk of acne as an adverse effect of these medications.
DATA SOURCES
Comprehensive search of Ovid MEDLINE and PubMed databases through January 31, 2023.
STUDY SELECTION
Inclusion criteria were phase 2 and 3 placebo-controlled RCTs of JAK inhibitors published in English with reported adverse events of acne.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently reviewed and extracted information from all included studies.
MAIN OUTCOMES AND MEASURES
The primary outcome of interest was the incidence of acne following JAK inhibitor use. A meta-analysis was conducted using random-effects models.
RESULTS
A total of 25 unique studies (10 839 unique participants; 54% male and 46% female) were included in the final analysis. The pooled odds ratio (OR) was calculated to be 3.83 (95% CI, 2.76-5.32) with increased ORs for abrocitinib (13.47 [95% CI, 3.25-55.91]), baricitinib (4.96 [95% CI, 2.52-9.78]), upadacitinib (4.79 [95% CI, 3.61-6.37]), deucravacitinib (2.64 [95% CI, 1.44-4.86]), and deuruxolitinib (3.30 [95% CI, 1.22-8.93]). Estimated ORs were higher across studies investigating the use of JAK inhibitors for the management of dermatologic compared with nondermatologic conditions (4.67 [95% CI, 3.10-7.05]) as well as for JAK1-specific inhibitors (4.69 [95% CI, 3.56-6.18]), combined JAK1 and JAK2 inhibitors (3.43 [95% CI, 2.14-5.49]), and tyrosine kinase 2 inhibitors (2.64 [95% CI, 1.44-4.86]).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, JAK inhibitor use was associated with an elevated odds of acne. Patients should be properly counseled on this potential adverse effect of these medications before treatment initiation. Future studies are needed to further elucidate the pathophysiology of this association.
Topics: Male; Female; Humans; Janus Kinase Inhibitors; Acne Vulgaris
PubMed: 37851459
DOI: 10.1001/jamadermatol.2023.3830 -
Hematology (Amsterdam, Netherlands) Dec 2023Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in...
OBJECTIVES
Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in diagnosing polycythemia.
METHODS
We conducted a systematic literature review of the Medline data through Pubmed and Google Scholar. We included the articles which described confirmed PV associated with elevated EPO level. Our search strategy included the following terms in Pubmed (((polycythemia vera[MeSH Terms]) OR (jak2 protein tyrosine kinase[MeSH Terms])) OR (Myeloproliferative Disorders[MeSH Terms])) AND (Erythropoietin[MeSH Terms]), and 'polycythemia vera with erythropoietin' in Google Scholar.
RESULTS
Our research yielded four cases of PV with elevated EPO levels. The most common symptom was a headache. Thrombotic phenomena happened in a single case in the form of Budd-Chiari syndrome. The mean Hb level was 20.2 gm/dl, and the EPO level was 213 mlU/mL.
DISCUSSION
Although PV is usually associated with low EPO levels, high levels do not exclude this diagnosis. Workup should include testing for JAK2 mutation and bone marrow biopsy in the presence of suggestive signs and symptoms. Novel biomarkers are also being proposed to aid in the diagnosis.
CONCLUSION
Although elevated EPO levels suggest secondary causes of polycythemia, cases where elevated EPO levels were associated with an underlying PV are reported in the literature, and we have summarized a review of them. Workup for polycythemia should include JAK2 mutation testing if signs and symptoms suggest PV even if EPO is elevated.
Topics: Humans; Polycythemia; Polycythemia Vera; Janus Kinase 2; Bone Marrow; Erythropoietin
PubMed: 37843428
DOI: 10.1080/16078454.2023.2269510 -
Dermatology and Therapy Dec 2023Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition.... (Review)
Review
Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. As a better understanding of the evidence supporting the management of AA in clinical practice is needed, we conducted a systematic literature review and subsequent narrative review to describe available evidence pertaining to the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA. From 2557 identified records, a total of 53 records were retained for data extraction: 9 reported data from 7 randomized controlled trials (RCTs) versus placebo, and 44 reported data from unique RCTs with no placebo arm, non-randomized trials, or observational studies. Across drug classes, data were reported heterogeneously, with little consistency of data collection or clinical endpoints used. The most robust evidence was for the JAK inhibitor class, in particular the JAK1/JAK2 inhibitor baricitinib. Five RCTs (three for baricitinib) demonstrated a consistent benefit of JAK inhibitor therapy over placebo across various clinical outcomes in adult patients with at least 50% scalp hair loss. Overall, hair regrowth varied widely for the other drug classes and was generally low for patients with moderate-to-severe AA. Relapses were commonly observed during treatment and upon discontinuation. Adverse effects were generally consistent with the known safety profile of each intervention. The heterogeneity observed prevented the conduct of a network meta-analysis or an indirect comparison of different treatments. We found that the current management of patients with moderate-to-severe AA often relies on the use of treatments that have not been well evaluated in clinical trials. The most robust evidence identified supported the use of baricitinib, and other oral JAK inhibitors, in patients with severe AA.
PubMed: 37833617
DOI: 10.1007/s13555-023-01044-5 -
Clinical Gastroenterology and... May 2024Recent studies raise concern for increased risk of major adverse cardiovascular events (MACE) with Janus kinase (JAK) inhibitors used to treat immune-mediated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Recent studies raise concern for increased risk of major adverse cardiovascular events (MACE) with Janus kinase (JAK) inhibitors used to treat immune-mediated inflammatory disorders (IMIDs). We aimed to examine MACE risk with licensed biologics and small molecules used commonly between IMIDs: inflammatory bowel disease, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis.
METHODS
Data were obtained from systematic searches (from inception to May 31, 2022) in PubMed, Embase, Ovid Medline, Scopus, Cochrane Central, and ClinicalTrials.gov. Studies that assessed a predefined MACE (myocardial infarction, cerebrovascular accident, unstable angina, cardiovascular death, or heart failure) risk in those ≥18 years of age with IMIDs treated with anti-interleukin (IL)-23 antibodies, anti-IL-12/23, anti-tumor necrosis factor α antibodies (anti-TNF-α), or JAK inhibitors were included in a network meta-analysis using a random-effects model with pooled odds ratios (ORs) reported with 95% credible intervals (CrIs) by drug class and disease state.
RESULTS
Among 3528 studies identified, 40 (36 randomized controlled trials and 4 cohort studies) were included in the systematic review, comprising 126,961 patients with IMIDs. Based on network meta-analysis of randomized controlled trials, regardless of disease state, anti-TNF-α (OR, 2.49; 95% CrI, 1.14-5.62), JAK inhibitors (OR, 2.64; 95% CrI, 1.26-5.99), and anti-IL-12/23 (OR, 3.15; 95% CrI, 1.01-13.35) were associated with increased MACE risk compared with placebo. There was no significant difference in the magnitude of the MACE risk between classes or based on IMID type.
CONCLUSIONS
Anti-IL-12/23, JAK inhibitors, and anti-TNF-α were associated with higher risk of MACE compared with placebo. The magnitude of the increased MACE risk was not different by IMID type. These results require confirmation in larger prospective studies.
Topics: Humans; Cardiovascular Diseases; Biological Products; Network Meta-Analysis; Janus Kinase Inhibitors
PubMed: 37821035
DOI: 10.1016/j.cgh.2023.09.033 -
Cureus Sep 2023The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions... (Review)
Review
Recent Clinical Studies on the Effects of Tumor Necrosis Factor-Alpha (TNF-α) and Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Antibody Therapies in Refractory Cutaneous Sarcoidosis: A Systematic Review.
The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions must be considered. In this review, we report the current progress of clinical studies on various monoclonal antibody therapies and their future potential as primary interventions for refractory cutaneous sarcoidosis. In this systematic review, clinical studies on the management of refractory cutaneous sarcoidosis were retrieved from PubMed and ScienceDirect databases. Studies were screened based on article type, publication within the last 10 years, and access to free full text. The articles selected consisted of case studies, clinical trials, and observational studies. The studies needed to focus on cases of diagnosed cutaneous sarcoidosis at the time of the study and involve adult patients resistant to corticosteroid regimens, with or without additional immunomodulators. Only interventions that included tumor necrosis factor-alpha (TNF-α) (e.g., infliximab and adalimumab) or Janus kinase/signal transducers and activators of transcription (JAK/STAT) (e.g., ruxolitinib and tofacitinib) antibody therapy were considered. Two authors independently conducted quality assessments using the Joanna Briggs Institute Critical Appraisal and NIH Study Quality Assessment tools. A total of 16 clinical studies were included in this systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Of the 16 cases included, 15 studies demonstrated partial to complete resolution of cutaneous lesions within a range of two weeks to 18 months from initiation of antibody therapy. Studies on anti-TNF-α intervention demonstrated the most adverse events, including two deaths and one case associated with cutaneous exacerbation. Studies on anti-JAK-STAT interventions demonstrate no adverse events after treatment; however, patient study size was limiting. Recent studies have shown promising potential for anti-TNF-α and anti-JAK-STAT inhibitors to become the mainstay interventions in refractory cutaneous sarcoidosis. Due to limited population studies, the current data on the efficacy and safety of antibody therapies have not yielded a standardized FDA-approved steroid-sparing treatment. Therefore, a need for more population studies on the effectiveness of third-line intervention in refractory cutaneous sarcoidosis is necessary.
PubMed: 37818515
DOI: 10.7759/cureus.44901 -
International Journal of Dermatology Dec 2023Necrobiosis lipoidica (NL) is a rare, idiopathic, and recalcitrant disease of collagen degeneration for which treatment options have been poorly studied. Due to its...
BACKGROUND
Necrobiosis lipoidica (NL) is a rare, idiopathic, and recalcitrant disease of collagen degeneration for which treatment options have been poorly studied. Due to its recurring nature, risk for ulceration, and high morbidity, there is a need to understand existing treatment modalities to better inform clinical care.
OBJECTIVE
This review aims to describe the therapeutic modalities reported in the literature for the treatment of NL.
METHODS
A literature search of treatments was performed by searching for publications between January 2016 and May 2022 on PubMed and Scopus. Given the limited high-quality evidence, case reports and series were included. Only publications presenting information on both attempted treatments and outcomes were included.
RESULTS
A total of 60 novel articles were identified (54 case reports, two case series, and four retrospective cohort studies). These studies cumulatively reported on 274 patients and covered treatments including phototherapy, topical corticosteroids, topical calcineurin inhibitors, biologics, immunosuppressants, JAK inhibitors, combination therapies, and several others. The greatest amount of evidence was found for photodynamic therapy (improvement in 72 of 80 patients), UVA-based phototherapy (12 of 33), topical corticosteroids (21 of 46), compression therapy (15 of 20), and topical calcineurin inhibitors (11 of 17). Several newer treatments were also described, including ustekinumab and JAK inhibitors.
CONCLUSIONS
This systematic review provides a comprehensive summary of recently published treatments for NL. As the existing data comes predominantly from case reports and series, statistical conclusions are not assessed. A greater number of randomized controlled trials with standardized endpoints are necessary to compare treatment efficacy.
Topics: Humans; Necrobiosis Lipoidica; Calcineurin Inhibitors; Retrospective Studies; Janus Kinase Inhibitors; Glucocorticoids
PubMed: 37772666
DOI: 10.1111/ijd.16856