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Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure

INTRODUCTION: Human leukocyte antigen (HLA)‐B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. C...

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Autores principales: Stainsby, Chris M., Perger, Teodora M., Vannappagari, Vani, Mounzer, Karam C., Hsu, Ricky K., Henegar, Cassidy E., Oyee, James, Urbaityte, Rimgaile, Lane, Charlotte E., Carter, Lindsay M., Pakes, Gary E., Shaefer, Mark S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590466/
https://www.ncbi.nlm.nih.gov/pubmed/30414209
http://dx.doi.org/10.1002/phar.2196
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author Stainsby, Chris M.
Perger, Teodora M.
Vannappagari, Vani
Mounzer, Karam C.
Hsu, Ricky K.
Henegar, Cassidy E.
Oyee, James
Urbaityte, Rimgaile
Lane, Charlotte E.
Carter, Lindsay M.
Pakes, Gary E.
Shaefer, Mark S.
author_facet Stainsby, Chris M.
Perger, Teodora M.
Vannappagari, Vani
Mounzer, Karam C.
Hsu, Ricky K.
Henegar, Cassidy E.
Oyee, James
Urbaityte, Rimgaile
Lane, Charlotte E.
Carter, Lindsay M.
Pakes, Gary E.
Shaefer, Mark S.
author_sort Stainsby, Chris M.
collection PubMed
description INTRODUCTION: Human leukocyte antigen (HLA)‐B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. Company meta‐analyses of trials pre–HLA‐B*5701 screening reported HSR rates of 4–8%. We analyzed the effectiveness of HLA‐B*5701 screening on reducing HSR rates using clinical trial, Observational Pharmaco‐Epidemiology Research & Analysis (OPERA) cohort, and spontaneous reporting data. METHODS: A meta‐analysis examined 12 trials in 3063 HLA‐B*5701–negative patients receiving an ABC‐containing regimen from April 9, 2007, to September 22, 2015. Potential cases were identified using prespecified Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (drug hypersensitivity, hypersensitivity, anaphylactic reaction, anaphylaxis) and adjudicated against a Company ABC HSR case definition. Investigator‐diagnosed cases were identified and rates were calculated. In the OPERA cohort, 9619 patients initiating their first ABC‐containing regimen from January 1, 1999, to January 1, 2016, were identified. Patients were observed from regimen start until the earliest‐following censoring event: ABC discontinuation, loss to follow‐up, death, or study end (July 31, 2016). OPERA physicians evaluated events against OPERA definitions for definite/probable cases of ABC HSR; rates were calculated pre‐ and post‐2008. The Company case definition was used to identify spontaneously reported cases for four marketed ABC‐containing products; reporting rates were calculated using estimated exposure from sales data, through December 31, 2016. RESULTS: Suspected ABC HSR rates were 1.3% or less in the meta‐analysis. In the OPERA cohort, the rate was 0.4% among patients initiating ABC post‐2008 versus 1.3% pre‐2008 (p<0.0001). Spontaneous reporting rates were low post‐2008 (54 to 22 cases per 100,000 patient‐years exposure [PYE]) versus pre‐2008 (618 to 55 cases per 100,000 PYE). CONCLUSIONS: Clinically suspected ABC HSR rates were 1.3% or less in HLA‐B*5701–negative patients. Recognizing their limitations, data from the OPERA cohort and spontaneous reporting indicate that HLA‐B*5701 screening has reduced reporting rates of suspected HSR in clinical practice. Where screening for HLA‐B*5701 is standard care, patients should be confirmed negative for this allele before starting ABC treatment.
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spelling pubmed-65904662019-07-08 Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure Stainsby, Chris M. Perger, Teodora M. Vannappagari, Vani Mounzer, Karam C. Hsu, Ricky K. Henegar, Cassidy E. Oyee, James Urbaityte, Rimgaile Lane, Charlotte E. Carter, Lindsay M. Pakes, Gary E. Shaefer, Mark S. Pharmacotherapy Original Research Articles INTRODUCTION: Human leukocyte antigen (HLA)‐B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. Company meta‐analyses of trials pre–HLA‐B*5701 screening reported HSR rates of 4–8%. We analyzed the effectiveness of HLA‐B*5701 screening on reducing HSR rates using clinical trial, Observational Pharmaco‐Epidemiology Research & Analysis (OPERA) cohort, and spontaneous reporting data. METHODS: A meta‐analysis examined 12 trials in 3063 HLA‐B*5701–negative patients receiving an ABC‐containing regimen from April 9, 2007, to September 22, 2015. Potential cases were identified using prespecified Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (drug hypersensitivity, hypersensitivity, anaphylactic reaction, anaphylaxis) and adjudicated against a Company ABC HSR case definition. Investigator‐diagnosed cases were identified and rates were calculated. In the OPERA cohort, 9619 patients initiating their first ABC‐containing regimen from January 1, 1999, to January 1, 2016, were identified. Patients were observed from regimen start until the earliest‐following censoring event: ABC discontinuation, loss to follow‐up, death, or study end (July 31, 2016). OPERA physicians evaluated events against OPERA definitions for definite/probable cases of ABC HSR; rates were calculated pre‐ and post‐2008. The Company case definition was used to identify spontaneously reported cases for four marketed ABC‐containing products; reporting rates were calculated using estimated exposure from sales data, through December 31, 2016. RESULTS: Suspected ABC HSR rates were 1.3% or less in the meta‐analysis. In the OPERA cohort, the rate was 0.4% among patients initiating ABC post‐2008 versus 1.3% pre‐2008 (p<0.0001). Spontaneous reporting rates were low post‐2008 (54 to 22 cases per 100,000 patient‐years exposure [PYE]) versus pre‐2008 (618 to 55 cases per 100,000 PYE). CONCLUSIONS: Clinically suspected ABC HSR rates were 1.3% or less in HLA‐B*5701–negative patients. Recognizing their limitations, data from the OPERA cohort and spontaneous reporting indicate that HLA‐B*5701 screening has reduced reporting rates of suspected HSR in clinical practice. Where screening for HLA‐B*5701 is standard care, patients should be confirmed negative for this allele before starting ABC treatment. John Wiley and Sons Inc. 2018-12-11 2019-01 /pmc/articles/PMC6590466/ /pubmed/30414209 http://dx.doi.org/10.1002/phar.2196 Text en © 2018 ViiV Healthcare. Pharmacotherapy published by Wiley Periodicals, Inc. on behalf of Pharmacotherapy Publications, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research Articles
Stainsby, Chris M.
Perger, Teodora M.
Vannappagari, Vani
Mounzer, Karam C.
Hsu, Ricky K.
Henegar, Cassidy E.
Oyee, James
Urbaityte, Rimgaile
Lane, Charlotte E.
Carter, Lindsay M.
Pakes, Gary E.
Shaefer, Mark S.
Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure
title Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure
title_full Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure
title_fullStr Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure
title_full_unstemmed Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure
title_short Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure
title_sort abacavir hypersensitivity reaction reporting rates during a decade of hla‐b*5701 screening as a risk‐mitigation measure
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590466/
https://www.ncbi.nlm.nih.gov/pubmed/30414209
http://dx.doi.org/10.1002/phar.2196
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