title: Effects of a HLA-B*15:02 screening policy on antiepileptic drug use and severe skin reactions.
abstract: 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.
authors.affiliation: From the Department of Medicine (Z.C., D.L., P.K.), The University of Melbourne, Parkville; Melbourne Brain Centre (Z.C., D.L.), Melbourne EpiCentre (D.L.), and Department of Neurology (P.K.), Royal Melbourne Hospital, Parkville, Australia; and Department of Medicine and Therapeutics (P.K.), Chinese University of Hong Kong, Prince of Wales Hospital, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the Department of Medicine (Z.C., D.L., P.K.), The University of Melbourne, Parkville; Melbourne Brain Centre (Z.C., D.L.), Melbourne EpiCentre (D.L.), and Department of Neurology (P.K.), Royal Melbourne Hospital, Parkville, Australia; and Department of Medicine and Therapeutics (P.K.), Chinese University of Hong Kong, Prince of Wales Hospital, China.
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.affiliation: From the Department of Medicine (Z.C., D.L., P.K.), The University of Melbourne, Parkville; Melbourne Brain Centre (Z.C., D.L.), Melbourne EpiCentre (D.L.), and Department of Neurology (P.K.), Royal Melbourne Hospital, Parkville, Australia; and Department of Medicine and Therapeutics (P.K.), Chinese University of Hong Kong, Prince of Wales Hospital, China. patrick.kwan@unimelb.edu.au.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kwan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005076:Exanthema / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D059910:HLA-B15 Antigen / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen