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European Journal of Epidemiology Aug 2021To systematically review available evidence of indirect comparisons from RCTs and direct comparisons from observational studies regarding the comparative effectiveness... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To systematically review available evidence of indirect comparisons from RCTs and direct comparisons from observational studies regarding the comparative effectiveness and safety of DOACs in patients with AF.
METHODS
Electronic databases including EMBASE, MEDLINE, and PUBMED were searched up to June 5th, 2020. Primary endpoints included effectiveness (stroke or systemic embolism [SE]) and safety (major bleeding) outcomes. Bucher methods and random-effects models were conducted for indirect and direct comparisons among DOACs, respectively. Ranking probability analyses and the number needed to treat for net effect (NNTnet) were applied.
RESULTS
A total of 36 studies, involving 7 RCTs (n = 60,292 patients) and 29 observational studies (n = 1,164,821 patients), were included for analyses. Regarding the risk of stroke/SE, no significant differences were found from indirect comparisons of RCTs among the DOACs. For major bleeding, apixaban tended to be safer than rivaroxaban and dabigatran based on both direct and indirect comparisons (all p < 0.05; evidence quality: very low to moderate). Ranking probability analysis showed that apixaban had a high probability of being the best treatment in decreased risk of stroke/SE and major bleeding (80.30% and 91.30%, respectively). Likewise, apixaban was found to have the highest net clinical benefit (0.02, 95% CI: 0.014-0.029) and smallest NNTnet (48, 95% CI: 35-74).
CONCLUSIONS
Apixaban appeared to have a favorable effectiveness-safety profile compared with the other DOACs in AF for stroke prevention, based on evidence from both direct and indirect comparisons. However, additional high-quality evidence is needed to support firm recommendations on clinical decision-making.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Humans; Pyrazoles; Pyridones; Stroke; Treatment Outcome
PubMed: 33993379
DOI: 10.1007/s10654-021-00751-7 -
Clinical and Experimental Pharmacology... Nov 2022Atopic dermatitis (AD) is one of the most prevalent inflammatory skin diseases. Janus kinase (JAK) inhibitor baricitinib is a promising treatment for AD as shown in... (Meta-Analysis)
Meta-Analysis Review
Atopic dermatitis (AD) is one of the most prevalent inflammatory skin diseases. Janus kinase (JAK) inhibitor baricitinib is a promising treatment for AD as shown in recent clinical trials. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting the efficacy and safety of baricitinib. Data analysis was carried out using Cochrane Collaboration Review Manager 5.4 software and performed as risk ratios (RR) with 95% confidence intervals. Six RCTs involving a total of 2595 patients were included in the review. The meta-analysis revealed that patients in the baricitinib group had significantly higher rates achieving EASI75, EASI90, IGA-Response, SCORAD75, and Itch NRS improvement. Pooled analysis also showed no significant differences in treatment of emergent adverse events (TEAEs) between baricitinib and placebo groups. In conclusion, our meta-analysis showed that baricitinib has promising efficacy for moderate-to-severe AD with favourable safety files.
Topics: Azetidines; Dermatitis, Atopic; Humans; Immunoglobulin A; Janus Kinases; Purines; Pyrazoles; Randomized Controlled Trials as Topic; Severity of Illness Index; Sulfonamides; Treatment Outcome
PubMed: 35876397
DOI: 10.1111/1440-1681.13704 -
Mayo Clinic Proceedings Jul 2020To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase inhibitors, in rheumatoid arthritis (RA).
METHODS
Randomized controlled trials of tofacitinib (5 and 10 mg twice daily) baricitinib (2 and 4 mg daily), and upadacitinib (15 and 30 mg daily) in RA were identified from MEDLINE, EMBASE, and Cochrane databases through December 11, 2019. Random-effects models were used to estimate pooled mean differences and relative risks (RRs). American College of Rheumatology 20%, Health Assessment Questionnaire-Disability Index, adverse events, risk for infection, venous thromboembolic events, and malignancy were calculated.
RESULTS
Twenty trials with an overall low risk of bias involving 8982 patients were identified. Tofacitinib, baricitinib, and upadacitinib improved RA control as determined by American College of Rheumatology 20% (RR, 2.03; 95% CI, 1.87 to 2.20) and Health Assessment Questionnaire-Disability Index scores (mean differences, -0.31; 95% CI, -0.34 to -0.28) compared with placebo. Adverse events were more frequent with upadacitinib, 30 mg, daily (RR, 1.15; 95% CI, 1.02 to 1.30); upadacitinib, 15 mg, daily (RR, 1.14; 95% CI, 1.02 to 1.27); and baricitinib, 4 mg, daily (RR, 1.13; 95% CI, 1.02 to 1.24). The risk for infection was highest with tofacitinib, 10 mg, twice daily (RR, 2.75; 95% CI, 1.72 to 4.41), followed by upadacitinib, 15 mg, daily (RR, 1.35; 95% CI, 1.14 to 1.60) and baricitinib, 4 mg, daily (RR, 1.28; 95% CI, 1.12 to 1.45). Data for venous thromboembolic events were not available for tofacitinib or baricitinib, but there was no increase in risk with upadacitinib (15 mg daily: RR, 2.34; 95% CI, 0.34 to 15.92).
CONCLUSION
Tofacitinib, baricitinib, and upadacitinib significantly improve RA control. Head-to-head Janus activated kinase inhibitor clinical trials are needed to further inform decision making.
Topics: Arthritis, Rheumatoid; Azetidines; Dose-Response Relationship, Drug; Drug Administration Schedule; Heterocyclic Compounds, 3-Ring; Humans; Janus Kinase Inhibitors; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Sulfonamides
PubMed: 32499126
DOI: 10.1016/j.mayocp.2020.01.039 -
Clinical Drug Investigation Apr 2021Rivaroxaban and apixaban are direct oral anticoagulants increasing in popularity as convenient alternatives to warfarin. However, current guidelines recommend against...
BACKGROUND AND OBJECTIVE
Rivaroxaban and apixaban are direct oral anticoagulants increasing in popularity as convenient alternatives to warfarin. However, current guidelines recommend against use in patients with a BMI > 40 kg/m or bodyweight > 120 kg unless drug-specific levels are measured, which may not be feasible across all clinical practices. Accordingly, the objective of this study was to broadly examine literature evaluating the clinical outcomes of rivaroxaban and/or apixaban in patients with increased body mass.
METHODS
A systematic literature review (guided by PRISMA) was performed through January 27, 2021 using PubMed, Embase, and Scopus. Key search term clusters included drug and weight-related concepts (overweight/obese, body mass index [BMI], waist circumference). DistillerSR was utilized to review and process search results. Studies met inclusion if they analyzed the risk of bleeding and/or thrombosis in patients with increased body mass (i.e., via BMI or other criteria) receiving rivaroxaban or apixaban. Clinical guidelines, case reports/series, pharmacokinetic/dynamic analyses, and commentaries were excluded. Bias was examined qualitatively across studies.
RESULTS
After duplicates were removed, the original search rendered 1822 abstracts and 200 full-texts for screening, ultimately providing a final set of 24 studies for qualitative review. Of these studies, 13 (54.2%) enabled comparisons between patients of increased versus normal body mass, while 11 (45.8%) reported outcomes only for patients of increased body mass. The working definition of 'increased body mass' varied amongst the studies, including 11 (45.8%) studies that utilized BMI, seven (29.2%) with a combination of BMI and body measurement, two (8.3%) that relied on body weight alone, and four (16.7%) that identified obesity-related ICD codes. All 13 comparative studies found similar or reduced rates of safety and efficacy outcomes with rivaroxaban and apixaban.
CONCLUSION
The literature reports similar or lower bleeding and thrombotic risk for rivaroxaban and apixaban in patients of increased body mass compared to patients of normal body mass. Future prospective controlled studies are needed to further define guidelines for use in this population.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Body Mass Index; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Warfarin
PubMed: 33677803
DOI: 10.1007/s40261-021-01019-4 -
Journal of Thrombosis and Thrombolysis Mar 2024Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE.
METHODS
We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively.
RESULTS
Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04, I = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61-0.76, I = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61-0.92, I = 50%; RR 0.58, 95% CI 0.50-0.67, I = 7%; RR 0.64, 95% CI 0.59-0.70, I = 0%, respectively).
CONCLUSIONS
Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.
Topics: Humans; Rivaroxaban; Venous Thromboembolism; Anticoagulants; Hemorrhage; Administration, Oral; Observational Studies as Topic; Pyrazoles; Pyridones
PubMed: 38127261
DOI: 10.1007/s11239-023-02926-3 -
PloS One 2022Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD.
OBJECTIVES
To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects.
STUDY DESIGN
Meta-analysis.
SEARCH METHODS
Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias.
RESULTS
In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications.
CONCLUSIONS
Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Nitriles; Pyrazoles; Pyrimidines; Steroids
PubMed: 35905125
DOI: 10.1371/journal.pone.0271979 -
Respiratory Medicine Oct 2022There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim of the current systematic review and meta-analysis was to evaluate the efficacy of baricitinib in COVID-19 patients.
METHODS
Databases like ScienceDirect, PubMed/Medline, Publons, Google Scholar and other sources like ClinicalTrials.gov, Cochrane, medRxiv, Research Square and reference lists were thoroughly searched.
RESULTS
Fifteen (15) articles which met the inclusion criteria were qualitatively and quantitatively analysed. Based on Cochrane and Newcastle-Ottawa Scale (NOS) risk of bias (RoB) analyses, 14/15 articles are grouped as high-quality. Meta-analyses revealed that randomised control trials (RCTs) and non-randomised control trials (nRCTs) statistically significantly reduced the mortality rate in COVID-19 patients, with a risk ratio (RR) in the fixed-effect model was RR = 0.64 [95% CI: 0.51 to 0.79; p < 0.0001] and RR = 0.58 [95% CI: 0.45 to 0.73; p < 0.00001], respectively, with insignificant heterogeneity and no publication bias found. For block/reduce disease progression (BDP), baricitinib did not statistically significantly reduce disease progression for RCTs. The RR in the random effect model was RR = 0.80 [95% CI: 0.58 to 1.10: p = 0.17], with significant heterogeneity, where I was 60%. On the other hand, baricitinib statistically significantly reduced disease progression in nRCTs, as the RR of the fixed effect model was RR = 0.54 [95% CI: 0.37 to 0.78; p = 0.001] with insignificant heterogeneity.
CONCLUSION
The current meta-analyses revealed that baricitinib statistically significantly reduced mortality rate and disease progression in COVID-19 patients.
PROSPERO REGISTRATION NUMBER
CRD42021281556.
Topics: Azetidines; Disease Progression; Humans; Purines; Pyrazoles; SARS-CoV-2; Sulfonamides; COVID-19 Drug Treatment
PubMed: 36150282
DOI: 10.1016/j.rmed.2022.106986 -
Journal of Cosmetic Dermatology Jan 2024
Meta-Analysis
Topics: Humans; Nitriles; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Vitiligo; Pyrazoles
PubMed: 38161317
DOI: 10.1111/jocd.15921 -
BMJ Open Sep 2022To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with brain metastases, and update the overall survival (OS) outcomes of the second-generation and third-generation ALK (ALK-2G/3G) inhibitors versus first-generation (ALK-1G) inhibitors.
DESIGN
The study is in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Randomised controlled trials (RCTs) published up to 3 November 2021 were retrieved from PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov.
SETTING
RCTs from any country and healthcare setting.
PARTICIPANTS
Patients with advanced ALK-positive NSCLC with or without brain metastases.
INTERVENTIONS AND COMPARISONS
The interventions were ALK-2G/3G; the control arm was ALK-1G or crizotinib.
PRIMARY AND SECONDARY OUTCOME MEASURES
Primary outcomes included median progression-free survival and median OS. Secondary outcomes included systemic objective response rate, intracranial response rate and rate of grade ≥3 adverse events (AEs).
RESULTS
A total of 12 RCTs involving 3156 patients were analysed. Compared with ALK-1G (crizotinib), ALK-2G (alectinib, brigatinib, ceritinib and ensartinib) significantly improved the OS (HR: 0.72, 95% CI: 0.57 to 0.90, p=0.004) and intracranial response of patients with any brain metastases, especially with measurable (diameter ≥10 mm) brain metastases. Network meta-analysis demonstrated that ALK-3G (lorlatinib) had superior efficacy for patients with brain lesions, but performed a distinct side-effect profile. Moreover, alectinib showed superior efficacy and lower toxicity in ALK-positive NSCLC.
CONCLUSION
Treatment with ALK-2G inhibitors significantly improved OS compared with crizotinib, and alectinib has less severe AEs than any other ALK inhibitors with moderate-high efficacy. The limited OS follow-up and inadequate sample sizes might contribute to having no statistically significant difference in OS of lorlatinib versus crizotinib. More high-quality and longer follow-up RCTs are warranted to prove our findings.
PROSPERO REGISTRATION NUMBER
CRD42021292245.
Topics: Aminopyridines; Anaplastic Lymphoma Kinase; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Lactams; Lactams, Macrocyclic; Lung Neoplasms; Network Meta-Analysis; Protein Kinase Inhibitors; Pyrazoles
PubMed: 36123063
DOI: 10.1136/bmjopen-2022-060782 -
Journal of the American Pharmacists... 2021Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer after disease progression. Thus, timely initiation of anticoagulation after... (Review)
Review
BACKGROUND
Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer after disease progression. Thus, timely initiation of anticoagulation after diagnosis of a VTE is required to prevent significant sequelae. Direct oral anticoagulants (DOACs) are newer anticoagulant options for cancer associated VTE (CA-VTE), which historically has been treated with low molecular weight heparin.
OBJECTIVE
The objective of this study was to review the available literature evaluating the use of apixaban for CA-VTE.
METHODS
A systematic review (following PRISMA Guidelines) of MEDLINE and EMBASE using the search terms "apixaban" AND "cancer" AND "VTE" was performed from database inception through May 20, 2020. Articles were eligible for inclusion if they were full articles fulfilling the following criteria: (1) randomized controlled trial (RCT) or prospective cohort study, or (2) subgroup analysis of an RCT, and (3) reported clinical outcomes associated with apixaban for prevention or treatment of VTE in patients with cancer.
RESULTS
A total of 532 articles were identified. After duplicates were removed, 423 articles were screened, and 12 articles were eligible for full-text review. Of the 12 articles, 2 were excluded for having no comparator group, and 2 were excluded for being abstracts only. Ultimately, 8 articles met the inclusion criteria.
CONCLUSIONS
The available literature supports the safety and efficacy of apixaban for the treatment and prevention of CA-VTE. With the recent publication of the CARAVAGGIO trial, we anticipate that apixaban will be uniformly recommended in national guidelines as a treatment option for CA-VTE.
Topics: Administration, Oral; Anticoagulants; Humans; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34229946
DOI: 10.1016/j.japh.2021.06.005