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Clinical Pharmacology and Therapeutics Dec 2022The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics...
The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost-effective (CE) (N = 48) or cost-saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high-quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost-effectiveness of preemptive and multigene testing across disease states.
Topics: Humans; Pharmacogenomic Testing; Pharmacogenetics; Cost-Benefit Analysis; Warfarin; Carbamazepine
PubMed: 36149409
DOI: 10.1002/cpt.2754 -
Clinical Pharmacology and Therapeutics Dec 2022Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenomic Testing; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36111494
DOI: 10.1002/cpt.2748 -
BMC Psychiatry Aug 2022The main goal of this work was to identify, describe, characterize, and classify the scientific evidence regarding the use of pharmacogenomic biomarkers in...
OBJECTIVE
The main goal of this work was to identify, describe, characterize, and classify the scientific evidence regarding the use of pharmacogenomic biomarkers in antidepressant treatment.
METHODS
The work was developed in two phases: i) a search for pharmacogenomic biomarkers in summaries of antidepressant drugs with marketing authorization in Portugal; and ii) a systematic literature review based on the data obtained in the first phase, with the main objective of finding international literature that could describe and characterize previously reported biomarkers and identify other relevant biomarkers. Finally, the levels of evidence and recommendation grades were classified.
RESULTS
Among the 26 drugs with marketing authorization in Portugal, only 16 had pharmacogenomic information. The most widely studied pharmacogenomic biomarker was CYP2D6. These results were mostly supported by the systematic literature review, which yielded 103 papers, 63 of which were ultimately included in the review. The systematic literature review also revealed the existence of other relevant biomarkers. Most of the included studies show a good level of evidence, which guarantees reliability and good recommendation grades. For the database (built during phase i), the results were informative but resulted in no specific recommendations.
CONCLUSIONS
Most pharmacogenomic variants are not studied or acknowledged by genetic tests, and more scientific research is needed to confirm their usefulness. Therefore, only a small number of variants are considered when prescribing antidepressant drugs. In addition, genotyping of patients is not common in clinical practice.
Topics: Antidepressive Agents; Biomarkers; Genetic Testing; Humans; Pharmacogenetics; Reproducibility of Results
PubMed: 36042420
DOI: 10.1186/s12888-022-04225-2 -
Journal of Personalized Medicine Jun 2022Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical...
Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response.
PubMed: 35887565
DOI: 10.3390/jpm12071068 -
The Pharmacogenomics Journal Dec 2022The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This...
The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain's performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.
Topics: Humans; Blockchain; Pharmacogenetics; Computer Security; Information Dissemination; Pharmacogenomic Testing
PubMed: 35869255
DOI: 10.1038/s41397-022-00285-5 -
The Pharmacogenomics Journal Jul 2022Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the... (Meta-Analysis)
Meta-Analysis
Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20-15.80, p = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.
Topics: Agranulocytosis; Alleles; Antipsychotic Agents; Clozapine; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35710824
DOI: 10.1038/s41397-022-00281-9 -
Farmacia Hospitalaria : Organo Oficial... Dec 2021The rise in the development of monoclonal antibodies has brought about a revolution in the pharmacotherapy of inflammatory bowel disease (Crohn's disease and...
OBJECTIVE
The rise in the development of monoclonal antibodies has brought about a revolution in the pharmacotherapy of inflammatory bowel disease (Crohn's disease and ulcerative colitis). Systematic plasma concentrations monitoring of these biological drugs in anticipation of potential clinical failures of treatment is known as proactive therapeutic drug monitoring. New pharmacogenetic analysis techniques have recently been developed that can predict response to these treatments even before they are administered. The goal of this systematic review is to analyze the potential benefits of proactive therapeutic drug monitoring and of the harmacogenetic analysis of biological drugs in inflammatory bowel disease patients in terms of clinical remission.
METHOD
A systematic search was performed in the MEDLINE/Pubmed, Embase and Cochrane Library databases using the escriptors proactive drug monitoring, biological drugs, inflammatory bowel disease and pharmacogenetics. Only randomized clinical trials published between January 2015 and May 2021 were included; all articles whose main topic was not related to the topic were excluded by hand. The quality of the articles was assessed using the Jadad scale and risk of bias was assessed using the Cochrane Collaboration tool.
RESULTS
After applying inclusion and exclusion criteria, seven of the 228 retrieved articles were selected for review. Almost all the studies measured the same clinical variables (Harvey-Bradshaw index for Crohn's disease and Mayo score for ulcerative colitis). Only in two of the included studies was proactive therapeutic drug monitoring superior to reactive monitoring- or no level-guided dose adjustments. No pharmacogenetic analyses were found that met the criteria defined. Conclusions: This review shows that the data supporting the use of proactive therapeutic drug monitoring in inflammatory bowel disease is limited and of low quality. Although pharmacogenetic analysis can be a useful tool for personalizing treatment, further and better designed randomized clinical trials are needed to determine the role of proactive drug monitoring strategies in clinical practice.
Topics: Colitis, Ulcerative; Crohn Disease; Drug Monitoring; Humans; Inflammatory Bowel Diseases; Pharmacogenomic Testing
PubMed: 35379111
DOI: No ID Found -
The Pharmacogenomics Journal May 2022The major challenges that delay the implementation of pharmacogenomics based clinical practice in the developing countries, primarily the low- and middle-income... (Review)
Review
The major challenges that delay the implementation of pharmacogenomics based clinical practice in the developing countries, primarily the low- and middle-income countries need to be recognized. This review was conducted to systematically review evidence of the cost-effectiveness for the conduct of pharmacogenomics testing in the developing countries. Studies that evaluated the cost-effectiveness of pharmacogenomics testing in the developing countries as defined by the United Nations were included in this study. Twenty-seven articles met the criteria. Pharmacogenomics effectiveness were evaluated for drugs used in the treatment of cancers, cardiovascular diseases and severe cutaneous adverse reactions in gout and epilepsy. Most studies had reported pharmacogenomics testing to be cost-effective (cancers, cardiovascular diseases, and tuberculosis) and economic models were evaluated from multiple perspectives, different cost categories and time horizons. Additionally, most studies used a single gene, rather than a gene panel for the pharmacogenomics testing. Genotyping cost and frequency of risk alleles in the populations influence the cost-effectiveness outcome. Further studies are warranted to examine the clinical and economic validity of pharmacogenomics testing in the developing countries.
Topics: Cardiovascular Diseases; Cost-Benefit Analysis; Developing Countries; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35319010
DOI: 10.1038/s41397-022-00272-w -
Psychiatry Research May 2022Bipolar Disorder (BD) and Major Depressive Disorder (MDD) have a huge impact on functioning and quality of life; moreover, they are linked to extensive direct and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bipolar Disorder (BD) and Major Depressive Disorder (MDD) have a huge impact on functioning and quality of life; moreover, they are linked to extensive direct and indirect costs. This systematic review with meta-analysis aims to evaluate the utility of pharmacogenetic tests (PGT) in terms of efficacy and tolerability into the routine clinical treatment of mood disorders.
MATERIALS AND METHODS
The first part of the review is a qualitative overview of the PGTs used in the included studies. The second part aims to compare, in terms of efficacy and tolerability, patients affected by BD and MDD treated as usual (TAU), according to the clinicians' prescribing attitude, versus patients whose psychopharmacological treatments were set up following the PGT suggestions.
RESULTS
6 studies on MDD and 2 studies on BD were included. Regarding MDD, the meta-analysis shows a significantly higher number of patients achieving better outcome in terms of efficacy, through the evaluation of response rate and remission rate at the HDRS (Hamilton Depression Rating Scale) in the group of patients treated under the PGT suggestions; regarding BD the meta-analysis does not show any significant difference in terms of efficacy. In terms of adverse events, the available data suggest promising results about the utility of PGT to set more tolerated therapies.
CONCLUSIONS
Although the limited number of studies, results confirm the importance of PGT in setting up psychopharmacological therapies as a support to clinicians' choices.
Topics: Bipolar Disorder; Depressive Disorder, Major; Humans; Mood Disorders; Pharmacogenomic Testing; Quality of Life
PubMed: 35247747
DOI: 10.1016/j.psychres.2022.114482 -
The Pharmacogenomics Journal Mar 2022Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to... (Meta-Analysis)
Meta-Analysis Review
Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.
Topics: Humans; Multimorbidity; Pharmacists; Pharmacogenetics; Pharmacogenomic Testing; Polypharmacy
PubMed: 35194175
DOI: 10.1038/s41397-021-00260-6