The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

Abstract

Introduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI ≥30kg/m2. Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 ± 548.6 vs. 1208 ± 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients [4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 ± 457.3 vs. 1189 ± 449.4 ng/mL, p < 0.001). Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.

Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis

“…Prior studies on determinants of HCQ blood concentrations in adult SLE had demonstrated that daily dose per kilogram of HCQ was associated with blood level of the drug 23 , as also observed herein. However, an inverse correlation between HCQ levels and BMI was reported in adult population 24 , similarly to a recent retrospective report in cSLE patients showing that high BMI was significantly associated with low blood HCQ concentrations.…”

Advances in the clinical use of hydroxychloroquine levels

“…In a 2021 study of 108 lupus nephritis patients, Pedrosa et al determined that obese patients were prescribed a lower daily dose of hydroxychloroquine based upon real body weight (4.4 vs. 4.9 mg/kg/day) but interestingly, the median hydroxychloroquine blood level was higher in the obese patients (BMI ≥30 kg/m 2 ) ( P = 0.002). Although they did not collect data on toxicity, the authors hypothesize that obese patients are, therefore, at an increased risk and posit that dosing based on ideal body weight should be considered [29].…”

Physiologically-Based Pharmacokinetics Modeling for Hydroxychloroquine as a Treatment for Malaria and Optimized Dosing Regimens for Different Populations

“…The renal impairment populations were taken into consideration because patients accepting HCQ treatment with renal impairment conditions have been reported in several studies to have retinal toxicity [ 36 , 37 ], hypoglycemia [ 38 ], and QT interval prolongation caused by delayed HCQ excretion during the treatment because of reduced renal function [ 39 , 40 ], while the administration of HCQ in patients with renal disease is still not well documented. MO population was included in this research because their body weight will lead to a lower drug plasma level [ 41 ], thus leads to reduced treatment effect. The geriatric and pediatric populations usually have special liver and renal function for drug disposition, indicating their special need for dosing adjustment [ 42 , 43 ].…”