title: Clinical and pharmacogenetic influences on response to hydroxychloroquine in discoid lupus erythematosus: a retrospective cohort study.
abstract: The recommended systemic therapy of choice for discoid lupus erythematosus (DLE) is the 4-aminoquinolone antimalarial hydroxychloroquine. There is limited published information on the likelihood of clinical response and, in particular, what factors influence outcome. We conducted a multicenter observational and pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine. The primary outcome was clinical response to hydroxychloroquine. We investigated the effects of disease attributes and metabolizing cytochrome P450 (CYP) polymorphisms on clinical outcome. Although the majority of patients responded to hydroxychloroquine, a significant proportion (39%) either failed to respond or was intolerant of the drug. Cigarette smoking and CYP genotype did not have any significant influence on response to hydroxychloroquine. Moreover, multivariate analysis indicated that disseminated disease (odds ratio (OR): 0.21; 95% confidence interval (CI): 0.08-0.52; P<0.001) and concomitant systemic lupus erythematosus (SLE; OR: 0.06; 95% CI: 0.01-0.49; P = 0.009) were significantly associated with lack of response to hydroxychloroquine. These findings suggest that baseline lupus severity and SLE are predictors of response to hydroxychloroquine. A prospective study is now required to further investigate the relationship between disease activity and response to hydroxychloroquine. This will have the potential to further inform the clinical management of this disfiguring photosensitive disease.
authors: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. shyamal.wahie@ncl.ac.uk
authors: Shyamal
authors: S
authors: Wahie
authors: Ann K
authors: AK
authors: Daly
authors: Heather J
authors: HJ
authors: Cordell
authors: Mark J
authors: MJ
authors: Goodfield
authors: Stephen K
authors: SK
authors: Jones
authors: Christopher R
authors: CR
authors: Lovell
authors: Andrew J
authors: AJ
authors: Carmichael
authors: Mary M
authors: MM
authors: Carr
authors: Angela
authors: A
authors: Drummond
authors: Sivakumar
authors: S
authors: Natarajan
authors: Catherine H
authors: CH
authors: Smith
authors: Nick J
authors: NJ
authors: Reynolds
authors: Simon J
authors: SJ
authors: Meggitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D008179:Lupus Erythematosus, Discoid / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012907:Smoking; D016896:Treatment Outcome
chemical_list: D006886:Hydroxychloroquine; D003577:Cytochrome P-450 Enzyme System