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Clinical and Pharmacogenetic Influences on Response to Hydroxychloroquine in Discoid Lupus Erythematosus: A Retrospective Cohort Study

Lookup NU author(s): Dr Shyamal Wahie, Professor Ann DalyORCiD, Professor Heather Cordell, Dr Andrew Carmichael, Dr Mary Carr, Dr Sivakumar Natarajan, Professor Nick ReynoldsORCiD, Dr Simon Meggitt

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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 (Cl): 0.08-0.52; P<0.001) and concomitant systemic lupus erythematosus (SLE; OR: 0.06; 95% Cl: 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.

Publication metadata

Author(s): Daly AK; Wahie S; Cordell HJ; Carr MM; Carmichael AJ; Reynolds NJ; Goodfield MJ; Jones SK; Lovell CR; Drummond A; Natarajan S; Smith CH; Meggitt SJ

Publication type: Article

Publication status: Published

Journal: Journal of Investigative Dermatology

Year: 2011

Volume: 131

Issue: 10

Pages: 1981-1986

Print publication date: 01/10/2011

ISSN (print): 0022-202X

ISSN (electronic): 1523-1747

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/jid.2011.167

DOI: 10.1038/jid.2011.167

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