Journal
NEUROLOGY
Volume 83, Issue 22, Pages 2077-2084Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000001034
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Funding
- National Health and Medical Research Council of Australia
- Australian Research Council
- National Heart Foundation of Australia
- Pfizer
- AbbVie
- Sanofi
- AstraZeneca
- GlaxoSmithKline
- Amgen
- US NIH
- Hong Kong Research Grants Council
- Innovation and Technology Fund
- Health and Health Services Research Fund
- Health and Medical Research Fund
- Eisai
- Johnson Johnson
- UCB Pharma
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Objective:To assess the effects of an active pharmacogenetic screening policy for antiepileptic drug (AED) therapy on everyday clinical practice and clinical outcomes.Methods:We extracted data covering all public hospitals and clinics in Hong Kong for patients who were newly commenced on carbamazepine or other AEDs, or were tested for HLA-B*15:02 3 years before policy implementation (prepolicy: September 16, 2005 to September 15, 2008) and 3 years after (postpolicy: September 16, 2008 to September 15, 2011). We compared AED prescriptions and the incidence of SJS/TEN between the 2 periods and analyzed adherence to the policy.Results:A total of 111,242 patients were included and 4,149 were tested for HLA-B*15:02. As a proportion of all new AED prescriptions, carbamazepine declined from 16.2% (10,077/62,056) in the pre-policy period to 2.6% (1,910/74,606) in the post-policy period (p < 0.001) while other AEDs increased. Among patients started on their first-ever AEDs, incidence of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) induced by carbamazepine reduced from 0.24% (20/8,284) to 0% (0/1,076; p = 0.027), but SJS/TEN induced by phenytoin increased (0.15% [18/11,839] vs 0.26% [33/12,618], p = 0.058), and the overall incidence of AED-induced SJS/TEN remained unchanged (0.09% [42/45,832] vs 0.07% [39/55,326], p = 0.238). Test-prescription practice was adherent to the policy in only 26.4% (1,302/4,929) of relevant patients.Conclusions:The screening policy was associated with prevention of carbamazepine-induced SJS/TEN without reducing the overall burden of AED-induced SJS/TEN, likely because of clinicians preferring AEDs that do not require genetic screening but may also induce SJS/TEN.
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