![Page 1: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/1.jpg)
A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE
UK AND IRELAND
Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton,
William Newman
![Page 2: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/2.jpg)
Background
Imatinib (Glivec/Gleevec)
• Gastrointestinal stromal tumor (GIST) a is a rare tumor of the gastrointestinal tract resistant to chemotherapy.
• Due to somatic activating mutations in c-KIT exons 9, 11 13, 17 or PDGFRA exons 12, 14 and 18
![Page 3: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/3.jpg)
Current Scope of the UKGTN
•
![Page 4: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/4.jpg)
Molecular testing for acquired changes
Published in May 2008
50 labs surveyed 33 responded22 using molecular tests.
• FISH (haematology)• IHC (CRC, BrCa, haematology)• DNA (somatic mutations/MSI/ LOH/arrays)
![Page 5: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/5.jpg)
cKIT and PDGFR in GISTS - Imatinib (Glivec)
KRAS in colorectal cancer - Cetuximab (Erbitux)
EGF receptor in non-small cell lung cancer Erlotinib (Tarceva)
None reported characterising tumours for drug response
![Page 6: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/6.jpg)
Pharmacogenetics in Australia and NZ
•
2005
Questionnaires sent to 629 labs (Aus & NZ) – 510 (81%) responses
Genotyping – 10 Phenotyping – 18
![Page 7: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/7.jpg)
Pharmacogenetics in Australia and NZ
•
Phenotyping:
• TPMT (Azathioprine/6 mercaptopurine)• Pseudocholinesterase suxamethonium/mivacurium)• CYP2D6 (Codeine/Perhexiline)
Genotyping:
• TPMT • Pseudocholinesterase
PGx tests performed rarely in clinical
practice.
![Page 8: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/8.jpg)
Irinotecan (Camptosar)
Chemotherapy agent used is in treatment of colon cancer
Extreme suppression of the immune system
Particular caution should be exercised ……in patients known
to be homozygous for UGT1A1*28 allele.
![Page 9: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/9.jpg)
Current prescribing advice
“Between 2000 and 2005 43 new drug labels were approved [by the FDA] that contained pharmacogenomic information reflecting 37% of all new approved labels.”
![Page 10: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/10.jpg)
Scope of Questionnaire
• Multidisciplinary:- CMGS HoLs- H&I National Network- RCPath Bulletin
• UK and Ireland
• Inherited changes
![Page 11: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/11.jpg)
Participants by specialty
• 10 Genetics
• 16 Histocompatibility & Immunogenetics
• 5 Biochemistry
• 1 Haematology
Total 32
![Page 12: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/12.jpg)
Accreditation
30/32 labs CPA accredited
100% of all UK NHS labs were
![Page 13: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/13.jpg)
Does your laboratory offer any pharmacogenetic test services?
• 3/10 Genetics
• 14/16 Histocompatibility & Immunogenetics
• 4/5 Biochemistry
• 0/1 Haematology
![Page 14: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/14.jpg)
Current pharmacogenetic services
Genetics Biochem H & I
Cytochrome P450 2D6 (CYP2D6) (codeine)
1 2 1
Cytochrome P450 3A4 (CYP3A4)(Cyclosporin/Sirolimus)
1
HLA-B*1502 (Carbamazepine) 6
HLA-B*5701 (Abacavir) 14
Thiopurine methyltransferase (TPMT) (Azathioprine/6-MP)
1 1 3
UDP-glucuronosyltransferase 1A1 (UGT1A1) (Irinotecan)
1
![Page 15: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/15.jpg)
Current pharmacogenetic services
Genetics Biochem H & I
Cytochrome P450 2D6 (CYP2D6) (codeine)
1 2 1
Cytochrome P450 3A4 (CYP3A4)(Cyclosporin/Sirolimus)
1
HLA-B*1502 (Carbamazepine) 6
HLA-B*5701 (Abacavir) 14
Thiopurine methyltransferase (TPMT) (Azathioprine/6-MP)
1 2 labs >55,000 samples pa 3
UDP-glucuronosyltransferase 1A1 (UGT1A1) (Irinotecan)
1
![Page 16: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/16.jpg)
Current pharmacogenetic services
Genetics Biochem H & I
Cytochrome P450 2D6 (CYP2D6) (codeine)
1 2 1
Cytochrome P450 3A4 (CYP3A4)(Cyclosporin/Sirolimus)
1
HLA-B*1502 (Carbamazepine) Immune mediated toxic effects
6
HLA-B*5701 (Abacavir) 14
Thiopurine methyltransferase (TPMT) (Azathioprine/6-MP)
1 1 3
UDP-glucuronosyltransferase 1A1 (UGT1A1) (Irinotecan)
1
![Page 17: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/17.jpg)
Carbamazepine - Brand names Carbatrol, Equetro, Tegretol, Tegretol XR, Epitol
• Anticonvulsant/mood stabilizing drug - epilepsy and bipolar disorder
• Dangerous/fatal skin reactions esp. in patients with HLA-B*1502
• HLA-B*1502 almost exclusively in patients South Asian ancestry.
• Widely prescribed
• PGx only offered selectively
![Page 18: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/18.jpg)
Abacavir - Brand name Ziagen
• Antiviral reverse transcriptase inhibitor - HIV-1 infection.
• Hypersensitivity reactions occur in approximately 5% - strongly associated with HLA-B*5701 and can be fatal
• Prevalence of HLA-B*5701. Highest in India lowest in SE Asia.
• Widely prescribed
• PGx widely offered
![Page 19: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/19.jpg)
For what reasons does your laboratory not offer pharmacogenetic test services?
H & I• No Demand
Genetics• No demand• Not previously cost effective• No proven clinical validity or utility• Lack of guidelines or evidence for clinical
benefit or effectiveness
![Page 20: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/20.jpg)
Co-ordination of PGx tests
• Do you believe there is a need for an implementing body whose main function will be to co-ordinate pharmacogenetic laboratory services in the UK (similar to the UK Genetic Testing Network)?
• Genetics – 10/10 labs voted yes (prevent monopoly)
• H & I: 8/15 – yes (no: restrictive/protectivist)
• Biochem: 0/5 – yes• Haem: 1/1 - yes
![Page 21: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/21.jpg)
Conclusions – The Present
• Compared to previous surveys - big increase in PGx
• Many labs across different disciplines
• Lab offering tests depends on nature of test (ie not to a generic PGx lab)
![Page 22: A SURVEY OF CURRENT PHARMACOGENETIC TESTING IN THE UK AND IRELAND Simon Ramsden, Nikki Gambhir, Jennifer Higgs, Kay Poulton, William Newman](https://reader036.vdocuments.us/reader036/viewer/2022062712/56649c955503460f949522f1/html5/thumbnails/22.jpg)
Conclusions – The Future
• More tests being developed:– Poor response to tamoxifen in
BRCA predicted by CYP2D6– Antibiotic (aminoglycoside)
ototoxicity associated with m.1555A>G
• Setting standards – – American Association of
Biochemists practice guidelines– EQA
• Is there a role for the UKGTN.