PMID- 29298994
OWN - NLM
STAT- MEDLINE
DCOM- 20190802
LR  - 20200225
IS  - 1473-1150 (Electronic)
IS  - 1470-269X (Print)
IS  - 1470-269X (Linking)
VI  - 19
IP  - 2
DP  - 2019 Apr
TI  - Cost-effectiveness of HLA-DQB1/HLA-B pharmacogenetic-guided treatment and blood 
      monitoring in US patients taking clozapine.
PG  - 211-218
LID - 10.1038/s41397-017-0004-2 [doi]
AB  - Less than 1% of adult patients with schizophrenia taking clozapine develop 
      agranulocytosis, and most of these cases occur within the first weeks of 
      treatment. The human leukocyte antigen (HLA) region has been associated with 
      genetic susceptibility to clozapine-induced agranulocytosis (single amino acid 
      changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate 
      the cost-effectiveness, from a healthcare provider's perspective, of an HLA 
      genotype-guided approach in patients with treatment-resistant schizophrenia who 
      were taking clozapine and to compare the results with the current absolute 
      neutrophil count monitoring (ANCM) schemes used in the USA. A semi-Markovian 
      model was developed to simulate the progress of a cohort of adult men and women 
      who received clozapine as a third-line antipsychotic medication. We compared 
      current practices using two genotype-guided strategies: (1) HLA genotyping 
      followed by clozapine, with ANCM only for patients who tested positive for one or 
      both alleles (genotype-guided blood sampling); (2) HLA genotyping followed by 
      clozapine for low-risk patients and alternative antipsychotics for patients who 
      tested positive (clozapine substitution scheme). Up to a decision threshold of 
      $3.9 million per quality-adjusted life-year (90-fold the US gross domestic 
      product per capita), the base-case results indicate that compared with current 
      ANCM, genotype-guided blood sampling prior to clozapine initiation appeared 
      cost-effective for targeted blood monitoring only in patients with HLA 
      susceptibility alleles. Sensitivity analysis demonstrated that at a cost of 
      genotype testing of up to USD700, HLA genotype-guided blood monitoring remained a 
      cost-effective strategy compared with either current ANCM or clozapine 
      substitution.
FAU - Girardin, Francois R
AU  - Girardin FR
AUID- ORCID: 0000-0002-0842-927X
AD  - Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, 
      Intensive Care, and Clinical Pharmacology, University Hospitals of Geneva and 
      University of Geneva, Geneva, Switzerland. francois.girardin@hcuge.ch.
AD  - Medical Direction, University Hospitals of Geneva and University of Geneva, 
      Geneva, Switzerland. francois.girardin@hcuge.ch.
FAU - Poncet, Antoine
AU  - Poncet A
AD  - The Clinical Research Centre, Division of Clinical Epidemiology, Department of 
      Health and Community Medicine, University of Geneva and University Hospitals of 
      Geneva, Geneva, Switzerland.
FAU - Perrier, Arnaud
AU  - Perrier A
AD  - Medical Direction, University Hospitals of Geneva and University of Geneva, 
      Geneva, Switzerland.
AD  - Department of Internal Medicine, Rehabilitation and Geriatrics, Geneva University 
      Hospitals and Geneva Faculty of Medicine, Geneva, Switzerland.
FAU - Vernaz, Nathalie
AU  - Vernaz N
AD  - Medical Direction, University Hospitals of Geneva and University of Geneva, 
      Geneva, Switzerland.
AD  - Finance Direction, University Hospitals and University of Geneva, 1205, Geneva, 
      Switzerland.
FAU - Pletscher, Mark
AU  - Pletscher M
AD  - Winterthur Institute of Health Economics, Zurich University of Applied Sciences, 
      Winterthur, Switzerland.
FAU - F Samer, Caroline
AU  - F Samer C
AD  - Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, 
      Intensive Care, and Clinical Pharmacology, University Hospitals of Geneva and 
      University of Geneva, Geneva, Switzerland.
FAU - Lieberman, Jeffrey A
AU  - Lieberman JA
AD  - Department of Psychiatry, Columbia University and New York State Psychiatric 
      Institute, New York, NY, 10032, USA.
FAU - Villard, Jean
AU  - Villard J
AD  - Division of Nephrology, University Hospitals of Geneva and University of Geneva, 
      Geneva, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180103
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - J60AR2IKIC (Clozapine)
MH  - Adult
MH  - Agranulocytosis/chemically induced/*epidemiology/*genetics/pathology
MH  - Alleles
MH  - Clozapine/administration & dosage/*adverse effects
MH  - Cohort Studies
MH  - Cost-Benefit Analysis
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-B Antigens/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pharmacogenomic Testing
MH  - Schizophrenia/complications/drug therapy/*epidemiology/genetics
PMC - PMC6462824
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/01/05 06:00
MHDA- 2019/08/03 06:00
PMCR- 2018/01/03
CRDT- 2018/01/05 06:00
PHST- 2017/04/30 00:00 [received]
PHST- 2017/09/18 00:00 [accepted]
PHST- 2017/08/18 00:00 [revised]
PHST- 2018/01/05 06:00 [pubmed]
PHST- 2019/08/03 06:00 [medline]
PHST- 2018/01/05 06:00 [entrez]
PHST- 2018/01/03 00:00 [pmc-release]
AID - 10.1038/s41397-017-0004-2 [pii]
AID - 4 [pii]
AID - 10.1038/s41397-017-0004-2 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2019 Apr;19(2):211-218. doi: 10.1038/s41397-017-0004-2. Epub 
      2018 Jan 3.