Rheumatology Division, Universidade de Sao Paulo, Sao Paulo, Brazil.
Division of Central Laboratory, Universidade de Sao Paulo, Sao Paulo, Brazil.
Lupus. 2021 Apr;30(4):554-559. doi: 10.1177/0961203320985214. Epub 2021 Jan 5.
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.
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.
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/m.
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) 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 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).
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.
2016 年，美国眼科学会（2016-AAO）建议根据最低化眼毒性的原则，将每日最大羟氯喹使用量限制在 5.0mg/kg 实际体重（RBW）以内。最近，系统性红斑狼疮（SLE）患者的视网膜病变与肥胖有关，而这种情况在这些患者中越来越普遍。然而，肥胖对羟氯喹血药浓度的影响仍存在争议。
确定 2016-AAO 基于 RBW 并限制最大日剂量的建议是否会导致肥胖狼疮肾炎（LN）患者达到足够和安全的血药浓度。
对 108 例接受至少 3 个月 2016-AAO 规定剂量治疗的 LN 患者进行了一项横断面研究。对患者的人口统计学特征、体重指数（BMI）、疾病参数、羟氯喹剂量、伴随治疗以及通过液相色谱-串联质谱法测量的羟氯喹血药浓度进行评估。肥胖定义为 BMI≥30kg/m。
108 例 LN 患者中有 35 例（32%）被确定为肥胖。根据实际体重（RBW）计算羟氯喹的日剂量表明，由于使用了最大限制，肥胖患者的日规定剂量较低[4.4（2.9-5.4）vs. 4.9（4-5.5）mg/kg/天，p<0.001]。尽管如此，与非肥胖患者相比，肥胖患者的羟氯喹血药浓度中位数显著更高（1562±548.6 vs. 1208±448.9ng/ml，p=0.002）。进一步分析根据 RBW 且不限制最大日剂量的 2016-AAO 建议的患者，尽管肥胖的 14 例患者和非肥胖的 61 例患者的每日剂量相当[4.8（4.5-5.4）vs. 5.0（4.5-5.5）mg/kg，p=0.312]，但肥胖患者的羟氯喹血药浓度中位数仍显著高于非肥胖患者（1734±457.3 vs. 1189±449.4ng/ml，p<0.001）。
根据 RBW 并限制最大日剂量，接受 2016-AAO 规定剂量羟氯喹治疗的肥胖患者与非肥胖患者相比，羟氯喹血药浓度非常高，有潜在的眼毒性增加风险。对于这组患者，应考虑根据理想体重使用 2016-AAO 剂量的羟氯喹。临床试验.gov #NCT0312243。
