Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence

Abstract

OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =<0.0001). CONCLUSION There was a trend towards higher disease activity with lower hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates.

Retinopathy in the Era of Routine Hydroxychloroquine Monitoring

“…A retrospective study of 2361 patients taking HCQ found that actual body weight correlated with risk of retinopathy 1 . In a similar fashion, a prospective study of 300 patients taking HCQ found that actual body weight strongly correlated with blood levels of HCQ 7 , a finding that is corroborated by the study by Durcan, et al 4 . As stated in the editorial, no study has yet definitively linked high blood concentration of HCQ to retinal toxicity 8 , but higher doses and longer durations of therapy have been linked to risk for HCQ retinopathy 1,9 , suggesting that cumulative dose may be a significant risk factor for HCQ retinopathy.…”

“…Currently, primary prevention consists of controlling the daily dose and/or cumulative dose to prevent overdosage 3 . We therefore read with great interest "Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence" by Durcan, et al 4 in The Journal of Rheumatology. We point out the implications of their findings for the use of weight-based dosing and the evidence base for HCQ retinopathy prevalence.…”

“…In their study, Durcan, et al described how regularly measuring blood levels of HCQ in patients with SLE resulted in a higher proportion of patients having blood levels of HCQ within a therapeutic range of 500-2000 ng/ml of blood, and concluded that measuring routine blood levels of HCQ, coupled with counseling, is an effective means to ensure compliance with HCQ to improve longterm outcomes 4 . In addition, Durcan, et al endorsed an actual weight-based calculation to determine the starting dose of HCQ based on the observation that compliance alone, and not dose adjustment, was sufficient to bring the majority of patients into a therapeutic range 4 .…”

“…In addition, Durcan, et al endorsed an actual weight-based calculation to determine the starting dose of HCQ based on the observation that compliance alone, and not dose adjustment, was sufficient to bring the majority of patients into a therapeutic range 4 .…”

Dr. Durcan, et al reply

“…The results of these analyses are shown in Table 1 of our study 2 and will help to answer many of the issues raised by Weinlander, et al…”