Background/Purpose: Hydroxychloroquine (HCQ) dose adjustment in patients with impaired renal function has been suggested to prevent toxicity. However, evidence to support this practice is scant.  Recently, focus has shifted to applying principles of therapeutic drug monitoring to HCQ  to assess the potential for toxicity.  We measured HCQ blood levels in connective tissue disease (CTD) patients with normal versus impaired renal function (GFR < 60 ml/min) to assess the impact of renal impairment on HCQ clearance.   We also examined the impact of other patient-specific variables on HCQ levels, including age, concomitant medications, body mass index (BMI), ethnicity, HCQ duration, and disease activity level.

Methods: CTD patients on HCQ at a steady state dose of up to 6.5 mg/kg daily meeting ACR Criteria for Systemic Lupus Erythematosus or Rheumatoid Arthritis were eligible. Patients were excluded if they were i) deemed noncompliant through interview, prescription history review or with a resultant whole blood [HCQ] < 200 ng/ml; ii) on hemodialysis; iii) diagnosed with concomitant underlying liver disease; iv) pregnant; v) morbidly obese (BMI > 40); or vi) hypoalbuminemic (<2 g/dl).  Whole blood random HCQ levels were quantified using high-performance liquid chromatography assay. Univariate analyses were performed on additional variables to evaluate other possible confounders on HCQ levels. SLE disease activity was calculated using SELENA-SLEDAI score at the time of HCQ level.

Results:  There were no statistically significant differences in HCQ levels between the impaired renal function cohort (n = 11, GFR range 21-59 ml/min; mean [HCQ] 1052.7 ng/ml +/- 653.2) and patients with GFR > 60 ml/min (n = 25, range 62-120 ml/min; mean [HCQ] 1010.4 ng/ml +/- 491.5; p = 0.7310).  There was no significant association between age, concomitant use of proton-pump inhibitors or prednisone, ethnicity, body mass index, duration of HCQ therapy or SLEDAI score and HCQ level.         

Conclusion: There is wide inter-patient variability in HCQ blood levels.  The influence of impaired renal function on HCQ metabolism and toxicity has yet to be fully elucidated.  While recent literature indicates a statistically significant difference in HCQ levels for SLE patients with impaired renal function compared with a large cohort with normal renal function, a clinically significant difference in levels between patient populations was not illustrated.  Our smaller study demonstrates the profound variability in levels and associated challenges that must be adjudicated before HCQ level monitoring can have wide clinical applicability. While there is growing interest in utilizing HCQ levels to guide therapy and prevent toxicity, additional studies in larger renal impairment patient populations are required.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/hydroxychloroquine-level-variants-and-predictors-in-a-connective-tissue-disease-population/