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BMC Cancer Feb 2024To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung... (Meta-Analysis)
Meta-Analysis
Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.
OBJECTIVES
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
METHODS
The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed.
RESULTS
A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs.
CONCLUSIONS
Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Crizotinib; Lung Neoplasms; Network Meta-Analysis; Bayes Theorem; Quality of Life; Anaplastic Lymphoma Kinase; Protein Kinase Inhibitors; Carbazoles; Sulfones; Aminopyridines; Lactams; Pyrimidines; Pyrazoles; Organophosphorus Compounds
PubMed: 38331773
DOI: 10.1186/s12885-024-11916-4 -
International Immunopharmacology Jan 2024Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over... (Review)
Review
BACKGROUNDS AND AIMS
Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over the last few years, with the advancement of novel treatment approaches. The current systematic review aims to evaluate the safety and efficacy of Janus kinase (JAK) inhibitors and spleen tyrosine kinase (Syk) inhibitors in treating HS.
METHOD
A thorough systematic search was performed on PubMed/Medline, Web of Science, and Ovid Embase databases up to September 23th, 2023. Clinical studies published in English were included.
RESULTS
Our search yielded ten articles with a total of 165 patients treated with four types of JAK inhibitors (upadacitinib, povorcitinib, tofacitinib, and baricitinib) and one Syk inhibitor (fostamatinib). Upadacitinib, povorcitinib, and tofacitinib improved clinical outcomes, with a significant reduction in hidradenitis suppurativa clinical response (HiSCR) and abscess and inflammatory nodule count (AN count) during the treatment period. Also, these drugs are well tolerated in most HS patients with minimal adverse events (AEs). Moreover, baricitinib depicted an amelioration in signs and symptoms of HS in one case report. Also, fostamatinib exhibited favorable tolerability throughout a 12-week in moderate-to-severe HS patients. The remarkable clinical improvement, as assessed through HiSCR and hidradenitis suppurativa severity (IHS4), corresponded closely with serological indicators of inflammation following fostamatinib administration was achieved.
CONCLUSION
JAK and Syk inhibitors are potentially efficacious in managing moderate-to-severe HS since the proinflammatory cytokines are mediated by JAK and Syk signaling pathways. However, further research with a more rigorous examination is mandatory to evaluate such medication's long-term safety and efficacy.
Topics: Humans; Hidradenitis Suppurativa; Adalimumab; Janus Kinase Inhibitors; Tyrosine Kinase Inhibitors; Spleen; Syk Kinase; Treatment Outcome; Severity of Illness Index; Aminopyridines; Pyrazoles; Sulfonamides; Azetidines; Purines; Pyrimidines; Morpholines
PubMed: 38150881
DOI: 10.1016/j.intimp.2023.111435 -
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 -
Respirology (Carlton, Vic.) May 2018Phosphodiesterase 4 (PDE4) inhibitors are a novel medication approved for airway inflammatory diseases including chronic obstructive pulmonary disease. Their role and... (Meta-Analysis)
Meta-Analysis Review
Phosphodiesterase 4 (PDE4) inhibitors are a novel medication approved for airway inflammatory diseases including chronic obstructive pulmonary disease. Their role and application in asthma are controversial and not defined. A comprehensive search was performed in major databases (1946-2016) using the keywords: 'phosphodiesterase 4 inhibitor' or 'roflumilast' and 'asthma'. Placebo-controlled trials reporting lung function, airway hyperresponsiveness by direct challenge, asthma control and exacerbations, and adverse events were included. Random or fixed-effects models were used to calculate odds ratios (OR) and mean differences between the two treatment groups. Statistical analyses were conducted using Mann-Whitney U-tests and Cochrane systematic review software, Review Manager. Seventeen studies were included in the systematic review, of which 14 studies were included in the meta-analysis. Except for significant statistical heterogeneity in pre- and post-challenge predicted percentage of forced expiratory volume in 1 s (FEV %; I = 72%, χ = 3.35, P = 0.06), there was no heterogeneity in outcome measures. Roflumilast (500 μg) significantly improved FEV (mean difference: 0.05, 95% CI: 0.01-0.09, Z = 2.50, P = 0.01), peak expiratory flow, asthma control and exacerbations, but showed variable effects on airway responsiveness to methacholine and a 20% fall in FEV .Of note, PDE4 inhibitors were accompanied with significantly higher adverse events such as headache (OR: 3.99, 95% CI: 1.65-9.66, Z = 3.07, P = 0.002) and nausea (OR: 5.53, 95% CI: 1.38-22.17, Z = 2.41, P = 0.02). In patients with mild asthma, oral PDE4 inhibitors can be considered as an alternative treatment to regular bronchodilators and inhaled controllers.
Topics: Aminopyridines; Asthma; Benzamides; Bronchodilator Agents; Cyclopropanes; Forced Expiratory Volume; Headache; Humans; Nausea; Peak Expiratory Flow Rate; Phosphodiesterase 4 Inhibitors
PubMed: 29502338
DOI: 10.1111/resp.13276 -
European Neurology 2017Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS... (Review)
Review
BACKGROUND
Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS.
SUMMARY
This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long-term studies are needed on related gait and functional parameters.
Topics: 4-Aminopyridine; Adult; Female; Gait; Gait Disorders, Neurologic; Humans; Male; Middle Aged; Multiple Sclerosis; Potassium Channel Blockers
PubMed: 28992626
DOI: 10.1159/000480729 -
Neurological Sciences : Official... Sep 2023Gait imbalance is one of the frequent complications in subjects with multiple sclerosis (MS). Fampridine (4-aminopyridine) is a potassium-channel blocker that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gait imbalance is one of the frequent complications in subjects with multiple sclerosis (MS). Fampridine (4-aminopyridine) is a potassium-channel blocker that is administered for gait imbalance in MS. Different studies showed the effects of fampridine on gait status based on various tests in subjects with MS. Some showed significant improvement after treatment, and others did not. So, we designed this systematic review, and meta-analysis to estimate the pooled effects of fampridine on gait status in patients with MS.
METHODS
The main goal is the evaluation of times of different gait test pre and post fampridine treatment. Two independent expert researchers conducted a systematic and comprehensive search in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar and also gray literature, including references of the references and conference abstracts. The search was done on September 16, 2022. Before-after studies trials reporting scores of the walking tests. We extracted data regarding the total number of participants, first author, publication year, country of origin, mean age, Expanded Disability Status Scale (EDSS), and the results of walking tests.
RESULTS
The literature search revealed 1963 studies; after deleting duplicates, 1098 studies remained. Seventy-seven full texts were evaluated. Finally, 18 studies were included for meta-analysis, while most of them were not placebo-controlled trials. The most frequent country of origin was Germany, and the mean age and EDSS ranged between 44 and 56 years and 4 and 6, respectively. The studies were published between 2013 and 2019. The pooled standardized mean difference (SMD) (after-before) of the MS Walking Scale (MSWS-12) was - 1.97 (95%CI: - 1.7, - 1.03) (I = 93.1%, P < 0.001). The pooled SMD (after-before) of the six-minute walk test (6MWT) was 0.49 (95%CI: 0.22, - 0.76) (I = 0%, P = 0.7). The pooled SMD (after-before) of T Timed 25-Foot Walk (T25FW) was - 0.99(95%CI: - 1.52, - 0.47) (I = 97.5%, P < 0.001).
CONCLUSION
This systematic review and meta-analysis show that fampridine improves gait imbalance in patients with MS.
Topics: Humans; Adult; Middle Aged; Multiple Sclerosis; Treatment Outcome; 4-Aminopyridine; Potassium Channel Blockers; Gait; Walking
PubMed: 37055710
DOI: 10.1007/s10072-023-06795-9 -
The Cochrane Database of Systematic... Dec 2020Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR variant F508del (found in up to 90% of people with CF (pwCF)) is the commonest CF-causing variant. The faulty protein is degraded before reaching the cell membrane, where it needs to be to effect transepithelial salt transport. The F508del variant lacks meaningful CFTR function and corrective therapy could benefit many pwCF. Therapies in this review include single correctors and any combination of correctors and potentiators.
OBJECTIVES
To evaluate the effects of CFTR correctors (with or without potentiators) on clinically important benefits and harms in pwCF of any age with class II CFTR mutations (most commonly F508del).
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Cystic Fibrosis Trials Register, reference lists of relevant articles and online trials registries. Most recent search: 14 October 2020.
SELECTION CRITERIA
Randomised controlled trials (RCTs) (parallel design) comparing CFTR correctors to control in pwCF with class II mutations.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias and evidence quality (GRADE); we contacted investigators for additional data.
MAIN RESULTS
We included 19 RCTs (2959 participants), lasting between 1 day and 24 weeks; an extension of two lumacaftor-ivacaftor studies provided additional 96-week safety data (1029 participants). We assessed eight monotherapy RCTs (344 participants) (4PBA, CPX, lumacaftor, cavosonstat and FDL169), six dual-therapy RCTs (1840 participants) (lumacaftor-ivacaftor or tezacaftor-ivacaftor) and five triple-therapy RCTs (775 participants) (elexacaftor-tezacaftor-ivacaftor or VX-659-tezacaftor-ivacaftor); below we report only the data from elexacaftor-tezacaftor-ivacaftor combination which proceeded to Phase 3 trials. In 14 RCTs participants had F508del/F508del genotypes, in three RCTs F508del/minimal function (MF) genotypes and in two RCTs both genotypes. Risk of bias judgements varied across different comparisons. Results from 11 RCTs may not be applicable to all pwCF due to age limits (e.g. adults only) or non-standard design (converting from monotherapy to combination therapy). Monotherapy Investigators reported no deaths or clinically-relevant improvements in quality of life (QoL). There was insufficient evidence to determine any important effects on lung function. No placebo-controlled monotherapy RCT demonstrated differences in mild, moderate or severe adverse effects (AEs); the clinical relevance of these events is difficult to assess with their variety and small number of participants (all F508del/F508del). Dual therapy Investigators reported no deaths (moderate- to high-quality evidence). QoL scores (respiratory domain) favoured both lumacaftor-ivacaftor and tezacaftor-ivacaftor therapy compared to placebo at all time points. At six months lumacaftor 600 mg or 400 mg (both once daily) plus ivacaftor improved Cystic Fibrosis Questionnaire (CFQ) scores slightly compared with placebo (mean difference (MD) 2.62 points (95% confidence interval (CI) 0.64 to 4.59); 1061 participants; high-quality evidence). A similar effect was observed for twice-daily lumacaftor (200 mg) plus ivacaftor (250 mg), but with low-quality evidence (MD 2.50 points (95% CI 0.10 to 5.10)). The mean increase in CFQ scores with twice-daily tezacaftor (100 mg) and ivacaftor (150 mg) was approximately five points (95% CI 3.20 to 7.00; 504 participants; moderate-quality evidence). At six months, the relative change in forced expiratory volume in one second (FEV) % predicted improved with combination therapies compared to placebo by: 5.21% with once-daily lumacaftor-ivacaftor (95% CI 3.61% to 6.80%; 504 participants; high-quality evidence); 2.40% with twice-daily lumacaftor-ivacaftor (95% CI 0.40% to 4.40%; 204 participants; low-quality evidence); and 6.80% with tezacaftor-ivacaftor (95% CI 5.30 to 8.30%; 520 participants; moderate-quality evidence). More pwCF reported early transient breathlessness with lumacaftor-ivacaftor, odds ratio 2.05 (99% CI 1.10 to 3.83; 739 participants; high-quality evidence). Over 120 weeks (initial study period and follow-up) systolic blood pressure rose by 5.1 mmHg and diastolic blood pressure by 4.1 mmHg with twice-daily 400 mg lumacaftor-ivacaftor (80 participants; high-quality evidence). The tezacaftor-ivacaftor RCTs did not report these adverse effects. Pulmonary exacerbation rates decreased in pwCF receiving additional therapies to ivacaftor compared to placebo: lumacaftor 600 mg hazard ratio (HR) 0.70 (95% CI 0.57 to 0.87; 739 participants); lumacaftor 400 mg, HR 0.61 (95% CI 0.49 to 0.76; 740 participants); and tezacaftor, HR 0.64 (95% CI, 0.46 to 0.89; 506 participants) (moderate-quality evidence). Triple therapy Three RCTs of elexacaftor to tezacaftor-ivacaftor in pwCF (aged 12 years and older with either one or two F508del variants) reported no deaths (high-quality evidence). All other evidence was graded as moderate quality. In 403 participants with F508del/minimal function (MF) elexacaftor-tezacaftor-ivacaftor improved QoL respiratory scores (MD 20.2 points (95% CI 16.2 to 24.2)) and absolute change in FEV (MD 14.3% predicted (95% CI 12.7 to 15.8)) compared to placebo at 24 weeks. At four weeks in 107 F508del/F508del participants, elexacaftor-tezacaftor-ivacaftor improved QoL respiratory scores (17.4 points (95% CI 11.9 to 22.9)) and absolute change in FEV (MD 10.0% predicted (95% CI 7.5 to 12.5)) compared to tezacaftor-ivacaftor. There was probably little or no difference in the number or severity of AEs between elexacaftor-tezacaftor-ivacaftor and placebo or control (moderate-quality evidence). In 403 F508del/F508del participants, there was a longer time to protocol-defined pulmonary exacerbation with elexacaftor-tezacaftor-ivacaftor over 24 weeks (moderate-quality evidence).
AUTHORS' CONCLUSIONS
There is insufficient evidence that corrector monotherapy has clinically important effects in pwCF with F508del/F508del. Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar improvements in QoL and respiratory function with lower pulmonary exacerbation rates. Lumacaftor-ivacaftor was associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (not observed for tezacaftor-ivacaftor). Tezacaftor-ivacaftor has a better safety profile, although data are lacking in children under 12 years. In this population, lumacaftor-ivacaftor had an important impact on respiratory function with no apparent immediate safety concerns; but this should be balanced against the blood pressure increase and shortness of breath seen in longer-term adult data when considering lumacaftor-ivacaftor. There is high-quality evidence of clinical efficacy with probably little or no difference in AEs for triple (elexacaftor-tezacaftor-ivacaftor) therapy in pwCF with one or two F508del variants aged 12 years or older. Further RCTs are required in children (under 12 years) and those with more severe respiratory function.
Topics: Adult; Aminophenols; Aminopyridines; Benzodioxoles; Bias; Child; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Combinations; Humans; Indoles; Mutation; Phenylbutyrates; Pyrazoles; Pyridines; Quality of Life; Quinolines; Quinolones; Randomized Controlled Trials as Topic
PubMed: 33331662
DOI: 10.1002/14651858.CD010966.pub3 -
European Journal of Pediatrics Feb 2024To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary... (Meta-Analysis)
Meta-Analysis
UNLABELLED
To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary vasodilatory effects. Search of PubMed, EMBASE, and the Cochrane Library up to August 2023. We included all studies that evaluated milrinone in children under 18 years old in neonatal, pediatric, or cardiac intensive care units. We excluded case reports, studies that did not provide tabular information on milrinone's outcomes, and studies focused on non-intensive care populations. We extracted data on the research design, objectives, study sample, and results of each study, including the impact of milrinone and any associated factors. We screened a total of 9423 abstracts and 41 studies were ultimately included. Milrinone significantly improved left ventricular ejection fraction (WMD 3.41 [95% CI 0.61 - 6.21]), left ventricle shortening fraction (WMD 4.25 [95% CI 3.43 - 5.08]), cardiac index (WMD 0.50 [95% CI 0.32 to 0.68]), left ventricle output (WMD 55.81 [95% CI 4.91 to 106.72]), serum lactate (WMD -0.59 [95% CI -1.15 to -0.02]), and stroke volume index (WMD 2.95 [95% CI 0.09 - 5.82]). However, milrinone was not associated with improvements in ventricular myocardial performance index (WMD -0.01 [95% CI -0.06 to 0.04]) and ventricular longitudinal strain (WMD -2.14 [95% CI -4.56 to 0.28]). Furthermore, milrinone was not associated with isovolumetric relaxation time reduction (WMD -8.87 [95% CI -21.40 to 3.66]).
CONCLUSION
Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice.
WHAT IS KNOWN
• Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. • Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation.
WHAT IS NEW
• Milrinone may not have a significant inotropic effect. • Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect.
Topics: Adolescent; Child; Humans; Infant, Newborn; Cardiotonic Agents; Heart Failure; Hypertension, Pulmonary; Milrinone; Stroke Volume; Ventricular Function, Left; Infant; Child, Preschool
PubMed: 37999764
DOI: 10.1007/s00431-023-05342-0 -
Cellular and Molecular Biology... Mar 2023Cardiovascular failure is the main cause of death in industrialized societies. The results of recent studies have shown that some mutations in the MEFV gene are common... (Meta-Analysis)
Meta-Analysis
Cardiovascular failure is the main cause of death in industrialized societies. The results of recent studies have shown that some mutations in the MEFV gene are common in heart failure patients. For this reason, the study of mutations and genetic factors has been of great help in the treatment of this disease, but despite this, due to the heterogeneity of clinical symptoms, multiple pathophysiological processes, and environmental genetic factors, the complete understanding of the genetic causes of this disease is very complicated. As the new generation of phosphodiesterase (PDE) III inhibitor, olprinone, the inhibition of human heart PDE III by olprinone is highly selective. It is suitable for the treatment of acute heart failure (HF) and acute cardiac insufficiency after cardiac surgery. In this study Olprinone, milrinone, PDE inhibitors, cardiac failure, and HF were selected as the search terms to retrieve articles published between January 1999 and March 2022. RevMan5.3 and Stata were employed to analyze and evaluate the risk bias of the included articles. Besides, the Q test and heterogeneity were utilized to evaluate the heterogeneity between articles. The results of this research showed No heterogeneity was found between each research group. The sensitivity (Sen) and specificity (Spe) of the two methods were compared. Olprinone showed more significant therapeutic effects than other PDE inhibitors. Besides, the therapeutic effect on the patients with HF in the two groups was obvious. The incidence of postoperative adverse reactions among the patients without relieving HF was low. The influences on urine flow of the two group's demonstrated heterogeneity, and its effect revealed no statistical meaning. The meta-analysis confirmed that the Spe and Sen of olprinone treatment were higher than those of other PDE inhibitors. In terms of hemodynamics, there was little difference between various treatment methods.
Topics: Humans; Heart Failure; Imidazoles; Milrinone; Phosphodiesterase Inhibitors; Pyridones
PubMed: 37300686
DOI: 10.14715/cmb/2023.69.3.11 -
Expert Opinion on Drug Safety 2023Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and thrombosis.
RESEARCH DESIGN AND METHODS
A retrospective pharmacovigilance analysis based on real-world data combined with a systematic review was used to explore the thrombotic risk profiles of CDK4/6i. The study has been registered with Prospero (CRD42021284218).
RESULT
In the pharmacovigilance analysis, CDK4/6i showed a higher rate of reported venous thromboembolism (VTE) (ROR = 2.78, 95% CI = 2.64-2.92), with the highest signal for trilaciclib (ROR = 27.55, 95% CI = 13.43-56.52) but only 9 cases, followed by abemaciclib (ROR = 3.73, 95% CI = 3.19-4.37). For arterial thromboembolism (ATE), only ribociclib increased the reporting rate (ROR = 2.14, 95% CI = 1.91-2.41). In the meta-analysis, palbociclib, abemaciclib, and trilaciclib all increased the risk of VTE (OR = 2.23, 3.17, and 3.90). In the subgroup analysis, only abemaciclib increased the risk of ATE (OR = 2.11, 95% CI = 1.12-3.99) .
CONCLUSIONS
CDK4/6i had different profiles of thromboembolism. Palbociclib, abemaciclib, or trilaciclib increased the risk of VTE. Ribociclib and abemaciclib showed a weak association with the risk of ATE.
Topics: Humans; Female; Cyclin-Dependent Kinase 4; Venous Thromboembolism; Pharmacovigilance; Retrospective Studies; Aminopyridines; Thrombosis; Protein Kinase Inhibitors; Breast Neoplasms
PubMed: 36794339
DOI: 10.1080/14740338.2023.2181338