Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines
IntroductionCertain HLA variants are associated with an increased risk of hypersensitivity reactions to specific drugs. Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) have issued actionable HLA gene – drug interaction guideline...
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doaj-d0497354c08249898fddcf8118e7ae7c2020-11-25T02:50:30ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-09-011110.3389/fphar.2020.567048567048Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG GuidelinesLisanne E. N. Manson0Lisanne E. N. Manson1Jesse J. Swen2Jesse J. Swen3Henk-Jan Guchelaar4Henk-Jan Guchelaar5Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, NetherlandsLeiden Network for Personalized Therapeutics, Leiden, NetherlandsDepartment of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, NetherlandsLeiden Network for Personalized Therapeutics, Leiden, NetherlandsDepartment of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, NetherlandsLeiden Network for Personalized Therapeutics, Leiden, NetherlandsIntroductionCertain HLA variants are associated with an increased risk of hypersensitivity reactions to specific drugs. Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) have issued actionable HLA gene – drug interaction guidelines but diagnostic test criteria remain largely unknown. We present an overview of the diagnostic test criteria of the actionable HLA – drug pairs.MethodsA systematic literature search was conducted in PubMed, Embase, Web of Science and Cochrane Library. Original case-control and cohort studies were selected and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and number needed to genotype (NNG) were calculated for the actionable HLA-drug pairs.ResultsIn general, the HLA tests show high specificity and NPV for predicting hypersensitivity reactions. The sensitivity of HLA tests shows a wide range, from 0-33% for HLA-B*1502 testing to predict lamotrigine induced SJS/TEN up to 100% for HLA-B*5701 to predict immunologically confirmed abacavir hypersensitivity syndrome (ABC-HSR). PPV is low for all tests except for HLA-B*5701 and ABC-HSR which is approximately 50%. HLA-B*5701 to predict ABC-HSR shows the lowest NNG followed by HLA-B*5801 for allopurinol induced severe cutaneous adverse drug reactions and HLA-B*1502 for carbamazepine induced SJS/TEN.DiscussionThis is the first overview of diagnostic test criteria for actionable HLA-drug pairs. Studies researching HLA genes and hypersensitivity are scarce for some of the HLA-drug pairs in some populations and patient numbers in studies are small. Therefore, more research is necessary to calculate the diagnostic test criteria more accurately.https://www.frontiersin.org/article/10.3389/fphar.2020.567048/fullHLA genespharmacogenomicshypersensitivityantiepileptic drugsabacavirallopurinol |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lisanne E. N. Manson Lisanne E. N. Manson Jesse J. Swen Jesse J. Swen Henk-Jan Guchelaar Henk-Jan Guchelaar |
spellingShingle |
Lisanne E. N. Manson Lisanne E. N. Manson Jesse J. Swen Jesse J. Swen Henk-Jan Guchelaar Henk-Jan Guchelaar Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines Frontiers in Pharmacology HLA genes pharmacogenomics hypersensitivity antiepileptic drugs abacavir allopurinol |
author_facet |
Lisanne E. N. Manson Lisanne E. N. Manson Jesse J. Swen Jesse J. Swen Henk-Jan Guchelaar Henk-Jan Guchelaar |
author_sort |
Lisanne E. N. Manson |
title |
Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines |
title_short |
Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines |
title_full |
Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines |
title_fullStr |
Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines |
title_full_unstemmed |
Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines |
title_sort |
diagnostic test criteria for hla genotyping to prevent drug hypersensitivity reactions: a systematic review of actionable hla recommendations in cpic and dpwg guidelines |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-09-01 |
description |
IntroductionCertain HLA variants are associated with an increased risk of hypersensitivity reactions to specific drugs. Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) have issued actionable HLA gene – drug interaction guidelines but diagnostic test criteria remain largely unknown. We present an overview of the diagnostic test criteria of the actionable HLA – drug pairs.MethodsA systematic literature search was conducted in PubMed, Embase, Web of Science and Cochrane Library. Original case-control and cohort studies were selected and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and number needed to genotype (NNG) were calculated for the actionable HLA-drug pairs.ResultsIn general, the HLA tests show high specificity and NPV for predicting hypersensitivity reactions. The sensitivity of HLA tests shows a wide range, from 0-33% for HLA-B*1502 testing to predict lamotrigine induced SJS/TEN up to 100% for HLA-B*5701 to predict immunologically confirmed abacavir hypersensitivity syndrome (ABC-HSR). PPV is low for all tests except for HLA-B*5701 and ABC-HSR which is approximately 50%. HLA-B*5701 to predict ABC-HSR shows the lowest NNG followed by HLA-B*5801 for allopurinol induced severe cutaneous adverse drug reactions and HLA-B*1502 for carbamazepine induced SJS/TEN.DiscussionThis is the first overview of diagnostic test criteria for actionable HLA-drug pairs. Studies researching HLA genes and hypersensitivity are scarce for some of the HLA-drug pairs in some populations and patient numbers in studies are small. Therefore, more research is necessary to calculate the diagnostic test criteria more accurately. |
topic |
HLA genes pharmacogenomics hypersensitivity antiepileptic drugs abacavir allopurinol |
url |
https://www.frontiersin.org/article/10.3389/fphar.2020.567048/full |
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