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M. F. Marmor, F. Wolfe; Hydroxychloroquine Toxicity: New Estimates of Risk From a Large National Database. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4324.
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Hydroxychloroquine (HCQ) retinopathy is of concern because of the potential visual loss and the medico-legal consequences of failure to detect toxicity. However, there has been limited demographic data on which to base recommendations for screening. We have studied the largest unselected series of patients to date, to evaluate the risk of toxicity and the relevance of purported risk factors.
The National Data Bank for Rheumatic Disease includes 3,995 patients with rheumatoid arthritis or systemic lupus erythematosus who had used HCQ currently or in the past. We searched for self-reported toxicity, and followed-up on positive cases with detailed interviews and ophthalmologist/optometrist confirmation. We categorized cases as "definite or probable" if there was bull’s eye maculopathy or perifoveal visual field loss.
Of the lifetime users of HCQ, 6.5% discontinued therapy because of an eye problem, including 1.8% who reported HCQ retinal problems. However, definite or probable toxicity was documented in only 0.65% (95% CI 0.31, 0.93). The risk of toxicity was lower (0.2-0.3%) in the initial few years of exposure, and was roughly 5 times higher after 7 years (or 1000 gms) of cumulative usage. The risk neared 3% after 20 years of exposure. Most patients were receiving 400 mg daily regardless of weight. Toxicity was unrelated to age, weight, or daily dose per kilogram. Eye examinations were obtained annually by 50.5% and every 6 months by 40.4% of patients.
Our data, from the largest population of HCQ users yet described, show that HCQ toxicity is uncommon but increases markedly with the duration of therapy (cumulative dosage). The risk of toxicity exceeds 1% after 5-7 years and reaches 3% after 20 years of exposure. Toxicity was unassociated with daily dosage per kg within the dosage range of typical practice. These data may be useful in consideration of the rationale and procedures for the screening of HCQ maculopathy.
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