-
CNS Drugs Dec 2022Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced... (Meta-Analysis)
Meta-Analysis
Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.
INTRODUCTION
Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD.
METHODS
A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness.
RESULTS
A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL.
CONCLUSIONS
This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
Topics: Humans; Middle Aged; Aged; Carbidopa; Levodopa; Quality of Life; Network Meta-Analysis; Parkinson Disease; Apomorphine
PubMed: 36414908
DOI: 10.1007/s40263-022-00963-9 -
Cancer Metastasis Reviews Mar 2022Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine... (Review)
Review
BACKGROUND
Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis.
METHODS
Statistical correlations for all RTK family members' expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates.
RESULTS
Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets.
CONCLUSIONS
Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.
Topics: Carcinogenesis; Cell Line, Tumor; Child; Humans; Neuroblastoma; Receptor Protein-Tyrosine Kinases; Signal Transduction
PubMed: 34716856
DOI: 10.1007/s10555-021-10001-7 -
Cancer Medicine Sep 2023Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-mutated who progressed on EGFR tyrosine-kinase inhibitor (EGFR-TKI) therapy... (Review)
Review
The efficacy and safety of immune checkpoint inhibitors for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy: A systematic review and network meta-analysis.
BACKGROUND
Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-mutated who progressed on EGFR tyrosine-kinase inhibitor (EGFR-TKI) therapy have limited therapeutic options. There is still no consensus on the role of immune checkpoint inhibitors (ICIs) in NSCLC with EGFR mutations.
METHODS
We did a network meta-analysis (NMA) with a systematic literature search on PubMed, Embase, Web of Science, and The Cochrane Library. We included all phase II and III randomized controlled trials (RCTs), non-randomized controlled trials (Non-RCTs), and retrospective studies. Progression-free survival (PFS) and overall survival (OS) were assessed through hazard ratios (HR). Objective response rate (ORR) and adverse events (AEs) were assessed through odds ratio (OR) and relative risk (RR), respectively. R software was used to compare the outcomes of different treatments by Bayesian NMA.
FINDINGS
We identified 1835 published results and 17 studies were included ultimately. A total of 2085 patients were included and accepted the following six treatments: ICIs plus chemotherapy (ICIs+Chemo), chemotherapy (Chemo), ICIs monotherapy (ICIs), ICIs plus chemotherapy and antiangiogenic therapy (ICIs+Chemo+Antiangio), antiangiogenic therapy plus chemotherapy (Antiangio+Chemo), ICIs plus antiangiogenic therapy (ICIs+Antiangio). ICIs+Chemo+Antiangio was associated with longer PFS and OS, as well as higher ORR (surface under the cumulative ranking curve [SUCRA], 96%, 90%, 91%). ICIs conferred the safety profile in terms of any-grade AEs, grade greater than or equal to 3 AEs and any grade leading to treatment discontinuation occurred AEs (SUCRA, 99%, 68%, 94%).
INTERPRETATION
ICIs+Chemo+Antiangio brings the greatest survival benefit in NSCLC patients with EGFR mutations who progressed on EGFR-TKI therapy, even for whom with baseline brain metastases. Compared with chemotherapy, ICIs has a low incidence of AEs and a benefit in OS.
PubMed: 37584242
DOI: 10.1002/cam4.6453 -
Cureus Sep 2022Regorafenib, a multi-kinase inhibitor, has been widely used to treat patients with gastrointestinal stromal tumors (GIST) who failed the initial treatment with imatinib... (Review)
Review
Regorafenib, a multi-kinase inhibitor, has been widely used to treat patients with gastrointestinal stromal tumors (GIST) who failed the initial treatment with imatinib and sunitinib. This systematic review aims to demonstrate the efficacy and safety of regorafenib for patients with metastatic and/or unresectable GIST. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform this systematic review. We searched PubMed, Science Direct, and Cochrane databases to identify relevant articles based on predefined selection criteria. The implication of the search strategy results in 776 records from all databases. We excluded conference abstracts, discussion articles, case reports, case series, systematic reviews, and other observational non-intervention studies from the study, along with the articles published in languages other than English. After the screening and quality assessment, 10 studies were selected for final review - two randomized controlled trials and eight non-randomized prospective and retrospective review articles of intervention. Regorafenib improved the survival rates of patients after the failure of imatinib and sunitinib treatment, with an acceptable safety profile. Close monitoring of the patients may be needed to detect and manage the grade 4 or higher adverse events.
PubMed: 36199644
DOI: 10.7759/cureus.28665 -
Medicine Jul 2023EGFR-TKI (tyrosine kinase inhibitor) monotherapy has become the first-line treatment option for patients with EGFR-mutated non-small cell lung cancer (NSCLC). Prolonging... (Meta-Analysis)
Meta-Analysis
Comparation of EGFR-TKI (EGFR tyrosine kinase inhibitors) combination therapy and osimertinib for untreated EGFR-mutated advanced non-small cell lung cancers: A systematic review and network meta-analysis.
BACKGROUND
EGFR-TKI (tyrosine kinase inhibitor) monotherapy has become the first-line treatment option for patients with EGFR-mutated non-small cell lung cancer (NSCLC). Prolonging the survival time, improving the progression-free survival of front-line treatment, and delaying the occurrence of drug resistance. At present, combination therapy is being widely used. Evaluate the therapeutic effect of TKI joint and Osimertinib drug therapy for positive patients with gene positive.
MATERIAL AND METHODS
Articles that met the inclusion criteria were searched through electronic databases. treatment emergent adverse events were summarized, and progression-free survival (PFS) and overall survival (OS) were calculated. Appropriate networks for different outcomes were created to incorporate all the evidence. Bayesian network-based multitreatment was used to compare the efficacy and specific toxicity of all treatment regimens.
RESULTS
Fourteen eligible studies involving 2325 patients were included. Of these, 7 studies compared EGFR-TKI plus chemotherapy with EGFR-TKI alone, and 6 studies compared EGFR-TKI plus antiangiogenic therapy with EGFR-TKI alone. One study compared Osimertinib and GP, ER, EB, and GCP were more effective than SOC in PFS analysis; however, there was no significant difference between osimertinib and the other 4 combination regimens. The cumulative probabilities of being the most efficacious treatments were (PFS, OS, treatment emergent adverse events): O (73%, 16%, 0%, 0%), GCP (14%, 64%, 10%, 16%), GP (2%, 17%,8%), and EB (3%, 3%, 8%), ER (5%, NA, 4%);GA(1%, NA, 69%).
CONCLUSION
Osimertinib has the lowest side effects and provides better PFS first-line treatment in advanced EGFR-mutated NSCLC.GCP is the best regimen for OS, but its toxicity limits its application, and it may be the first choice for patients with higher survival requirements.
Topics: Humans; Bayes Theorem; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Lung Neoplasms; Mutation; Network Meta-Analysis; Tyrosine Kinase Inhibitors
PubMed: 37505120
DOI: 10.1097/MD.0000000000034483 -
Frontiers in Medicine 2023Orally effective therapeutics for plaque psoriasis with improved response rates, lower toxicity and costs are needed in clinical practices. This study aims to assess the...
The efficacy and safety of tyrosine kinase 2 inhibitor deucravacitinib in the treatment of plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Orally effective therapeutics for plaque psoriasis with improved response rates, lower toxicity and costs are needed in clinical practices. This study aims to assess the efficacy and safety of the recently approved TYK2 inhibitor deucravacitinib in adults with moderate to severe plaque psoriasis through meta-analysis.
METHODS
A systematic search was performed for eligible studies using electronic databases, including PubMed, Embase, Cochrane Library, Clinical Trials, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform (ICTRP). Randomized controlled trials (RCTs) comparing the efficacy and safety of deucravacitinib vs. placebo or active comparators in adult patients with plaque psoriasis were included. The effectiveness of deucravacitinib was evaluated using a 75% improvement in Psoriasis Area and Severity Index (PASI 75) from baseline and the proportion of patients achieving the static Physician's Global Assessment (sPGA) response. The secondary endpoint was the proportion of patients achieving PASI 90, PASI 100, ssPGA 0/1, and Dermatology Life Quality Index 0/1 (DLQI). The incidence of adverse events (AEs), serious AEs (SAEs), and AE-related treatment discontinuation were statistically analyzed to determine the safety of deucravacitinib.
RESULTS
The systematic review and meta-analysis included five RCTs involving 2,198 patients with moderate to severe plaque psoriasis. Results showed that deucravacitinib was superior to placebo as well as active comparator apremilast in multiple key endpoints, including PASI 75, sPGA 0/1, PASI 90, PASI 100, DLQI 0/1 at week 16. Moreover, a durable response was seen in the two 52-week studies. Safety assessment showed that deucravacitinib was generally well tolerated, and the incidence of AEs, SAEs, and AE-related treatment discontinuation was low and balanced across groups.
CONCLUSION
Deucravacitinib demonstrated superior efficacy to apremilast in adult patients with moderate to severe plaque psoriasis with an acceptable safety profile and has the potential to be used as the first-line oral therapy for plaque psoriasis.
PubMed: 37841017
DOI: 10.3389/fmed.2023.1264667 -
Frontiers in Immunology 2023Orally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy in plaque psoriasis. However, no previous articles evaluated the benefit and risk profile of TYK2 and PDE4 inhibitors in psoriasis.
OBJECTIVES
The objective of this study was to compare the efficacy and safety of oral small-molecule drugs, including TYK2 and PDE4 inhibitors, in treating moderate-to-severe plaque psoriasis.
METHODS
PubMed, Embase, and Cochrane library were searched for eligible randomized clinical trials (RCTs). Response rates for a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment score of 0 or 1 (PGA 0/1) were used for efficacy assessment. Safety was evaluated with the incidence of adverse events (AEs). A Bayesian multiple treatment network meta-analysis (NMA) was performed.
RESULTS
In total, 13 RCTs (five for TYK2 inhibitors and eight for PDE4 inhibitors) involving 5274 patients were included. The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. In addition, deucravacitinib (3 mg BID, 6 mg QD, 6 mg BID, and 12 mg QD), and ropsacitinib (400 mg QD) showed superior efficacy than apremilast (30 mg BID). In terms of safety, deucravacitinib or ropsacitinib at any dose did not lead to a higher incidence of AEs than apremilast (30 mg BID). The ranking analysis of efficacy revealed that deucravacitinib 12 mg QD and deucravacitinib 3 mg BID had the highest chance of being the most effective oral treatment, followed by deucravacitinib 6 mg BID and ropsacitinib 400 mg QD.
CONCLUSIONS
Oral TYK2 inhibitors demonstrated satisfactory performance in treating psoriasis, surpassing apremilast at certain doses. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859.
Topics: Humans; Network Meta-Analysis; Phosphodiesterase 4 Inhibitors; Psoriasis; Severity of Illness Index; TYK2 Kinase
PubMed: 37334353
DOI: 10.3389/fimmu.2023.1180170 -
Medicine Oct 2023The use of tirofiban as an adjunct to endovascular therapy (EVT) for acute ischemic stroke has been controversial. We aimed to assess the differences in safety and... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis of the efficacy and safety of adjunctive use of tirofiban in patients treated with endovascular therapy for acute ischemic stroke at different embolic sites.
BACKGROUND
The use of tirofiban as an adjunct to endovascular therapy (EVT) for acute ischemic stroke has been controversial. We aimed to assess the differences in safety and efficacy of EVT adjuvant to tirofiban in patients with anterior circulation stroke (ACS) and posterior circulation stroke (PCS).
METHODS
We systematically searched Pubmed, Embase, Cochrane Library, and Web of Science. Cohort studies and randomized controlled trials that compared treatment with tirofiban combined with EVT and EVT alone were included in our meta-analysis. The safety outcomes were symptomatic intracranial hemorrhage, and 3-month mortality. The efficacy outcomes were good functional outcome, excellent functional outcome, and successful recanalization (mTICI ≥ 2b). We performed subgroup analyses of anterior and posterior circulation strokes.
RESULTS
We included 15 studies with 4608 patients. For safety outcomes, tirofiban significantly reduced 3-month mortality in the ACS subgroup (odd ratio [OR] = 0.80, 95% confidence interval [CI] = 0.65-0.98, P = .03) without increasing the rate of symptomatic intracranial hemorrhage (OR = 1.12, 95% CI = 0.88-1.44, P = .35). In the PCS subgroup, tirofiban significantly reduced 3-month mortality (OR = 0.63, 95% CI = 0.50-0.80, P = .0001) and symptomatic intracranial hemorrhage (OR = 0.60, 95% CI = 0.37-0.95, P = .03). For efficacy outcomes, in the ACS subgroup, tirofiban significantly improved good functional outcome (OR = 1.24, 95% CI = 1.06-1.45, P = .008) but did not improve recanalization (OR = 1.17, 95% CI = 0.93-1.47, P = .17) and excellent functional outcome (OR = 1.19, 95% CI = 0.97-1.46, P = .10). In the PCS subgroup, tirofiban significantly improved recanalization rate (OR = 1.94, 95% CI = 1.43-2.65, P < .0001) and did not improve good functional outcome (OR = 1.03, 95% CI = 0.81-1.30, P = .81) and excellent functional outcome (OR = 0.84, 95% CI = 0.58-1.20, P = .34).
CONCLUSION
In acute ischemic stroke patients undergoing EVT, tirofiban improves good functional outcomes in ACS patients and increases recanalization rates in PCS patients on the 1 hand, reduces mortality, and does not increase the risk of symptomatic intracranial hemorrhage on the other. Tirofiban is safe and effective in both anterior circulation stroke and posterior circulation stroke patients undergoing EVT. More large multicentre randomized controlled studies are needed in the future.
Topics: Humans; Tirofiban; Ischemic Stroke; Brain Ischemia; Treatment Outcome; Stroke; Intracranial Hemorrhages; Endovascular Procedures; Thrombectomy
PubMed: 37800797
DOI: 10.1097/MD.0000000000035091 -
The Cochrane Database of Systematic... Jun 2013Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap. However, the diet is very restrictive and unpalatable and can be difficult to follow. A deficiency of the amino acid tyrosine has been suggested as a cause of some of the neuropsychological problems exhibited in phenylketonuria. Therefore, this review aims to assess the efficacy of tyrosine supplementation for phenylketonuria.
OBJECTIVES
To assess the effects of tyrosine supplementation alongside or instead of a phenylalanine-restricted diet for people with phenylketonuria, who commenced on diet at diagnosis and either continued on the diet or relaxed the diet later in life. To assess the evidence that tyrosine supplementation alongside, or instead of a phenylalanine-restricted diet improves intelligence, neuropsychological performance, growth and nutritional status, mortality rate and quality of life.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register which is comprised of references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional studies were identified from handsearches of the Journal of Inherited Metabolic Disease (from inception in 1978 to 1998). The manufacturers of prescribable dietary products used in the treatment of phenylketonuria were also contacted for further references.Date of the most recent search of the Group's Inborn Errors of Metabolism Trials Register: 28 June 2012.
SELECTION CRITERIA
All randomised or quasi-randomised trials investigating the use of tyrosine supplementation versus placebo in people with phenylketonuria in addition to, or instead of, a phenylalanine-restricted diet. People treated for maternal phenylketonuria were excluded.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the trial eligibility, methodological quality and extracted the data.
MAIN RESULTS
Six trials were found, of which three trials reporting the results of a total of 56 participants, were suitable for inclusion in the review. The blood tyrosine concentrations were significantly higher in the participants receiving tyrosine supplements than those in the placebo group, mean difference 23.46 (95% confidence interval 12.87 to 34.05). No significant differences were found between any of the other outcomes measured.
AUTHORS' CONCLUSIONS
From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice. Further randomised controlled studies are required to provide more evidence.
Topics: Dietary Supplements; Humans; Intelligence; Neuropsychological Tests; Phenylalanine; Phenylketonurias; Randomized Controlled Trials as Topic; Tyrosine
PubMed: 23737086
DOI: 10.1002/14651858.CD001507.pub3 -
Cancers Jul 2022HER2-positive breast cancer brain metastasis (BCBM) is an important clinical problem. A systematic review and network meta-analysis were conducted to compare the... (Review)
Review
Comparative Efficacy of Tyrosine Kinase Inhibitors and Antibody-Drug Conjugates in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A Systematic Review and Network Meta-Analysis.
HER2-positive breast cancer brain metastasis (BCBM) is an important clinical problem. A systematic review and network meta-analysis were conducted to compare the efficacy of tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), two categories of emerging agents in this field. We implemented a comprehensive literature search of PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and abstracts of oncology conferences. A network meta-analysis following Bayesian approaches was performed. Pooled hazard ratios (HRs) and odds ratios (ORs) with credible intervals (CrIs) were calculated to estimate progression-free survival (PFS), overall survival (OS), and the incidence of central nervous system (CNS) disease progression. Sixteen studies were included. Pairwise comparisons of PFS showed salient divergency between T-DXd and the physician's choice of treatment (HR 0.17; 95% CrI 0.03-0.82) or afatinib (HR 0.14; 95% CrI 0.02-1.00). T-DXd and T-DM1 ranked first regarding PFS and OS, respectively, followed by TKI-containing regimens. The incidence of CNS disease progression was analyzed separately according to baseline BCBM status, among which neratinib-containing regimens were most likely to rank the best. In conclusion, ADCs including T-DXd and T-DM1 showed better efficacy than TKIs in the survival outcomes for HER2-positive BCBM patients. Treatments based on neratinib or T-DM1 revealed favorable results in reducing the recurrent rate of CNS.
PubMed: 35884431
DOI: 10.3390/cancers14143372