Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Arnaldo, 455, 3° andar, sala 3192, Cerqueira César, Sao Paulo, SP, 01246-903, Brazil.
Division of Central Laboratory, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Clin Rheumatol. 2021 Jul;40(7):2745-2751. doi: 10.1007/s10067-021-05600-2. Epub 2021 Jan 24.
The American Academy of Ophthalmology (2016-AAO) recommended hydroxychloroquine (HCQ) dose not to exceed 5 mg/kg/day (real body weight). Recently, it was reported that prescribed 2016-AAO dose provided adequate HCQ levels for most lupus nephritis (LN) patients, with low flare risk. However, the minimum HCQ dose required to keep adequate levels is unknown.
To evaluate if a further reduction in 2016-AAO dose (2-3 mg/kg/day) would sustain 12-month HCQ levels in LN patients with stable inactive disease.
Seventy-three stable LN patients under prescribed full HCQ 2016-AAO dose for ≥6 months and adequate baseline HCQ levels (≥613.5 ng/mL) were divided in two groups: reduced 2016-AAO dose (2-3 mg/kg/day), n = 32, and full 2016-AAO dose (5 mg/kg/day), n = 41. All patients were assessed at baseline, 3, 6, and 12 months. HCQ levels were measured by liquid chromatography-tandem mass spectrometry. Flare was defined as augment ≥ 3 in SLE Disease Activity Index-2000 and/or change in treatment. Rigorous clinical/laboratorial surveillance was performed.
Prospective evaluation revealed for reduced 2016-AAO dose group a decrease of HCQ levels from baseline to 3 months (1,404.9 ± 492.0 vs. 731.6 ± 385.0 ng/mL, p < 0.01), and sustained levels at 6 months (p = 0.273) and 12 months (p = 0.091) compared to 3 months. For the full 2016-AAO dose group, a decrease occurred only from baseline to 12 months (1343.5 ± 521.5 vs. 991.6 ± 576.3 ng/mL, p < 0.001). Frequencies of patients with inadequate levels at 6 months was higher in reduced 2016-AAO group than full 2016-AAO dose (59% vs. 24%, p = 0.005), as well as at 12 months (66% vs. 32%, p = 0.002). Six-month and 12-month flare frequencies were comparable for both groups (p > 0.05).
Prescribed HCQ low-dose regimen (2-3 mg/kg/day) does not sustain, for most patients, 6- and 12-month adequate HCQ levels. Full 2016-AAO dose maintained HCQ levels way above this limit.
ClinicalTrials.gov : NCT03122431, registered on April 20, 2017 Key Points • Reduced American Academy of Ophthalmology (2016-AAO) hydroxychloroquine (HCQ) dose (2-3 mg/kg/day, real body weight) is unable to sustain HCQ blood levels within the safe cut-off defined for flare risk. • Full 2016-AAO dose (5 mg/kg/day) maintains a safe pattern of HCQ levels up to 12 months.
美国眼科学会（2016-AAO）建议羟氯喹（HCQ）剂量不超过 5mg/kg/天（实际体重）。最近有报道称，按照 2016-AAO 推荐剂量，大多数狼疮肾炎（LN）患者可获得充足的 HCQ 水平，且发生 flares 的风险较低。然而，保持充足水平所需的 HCQ 最低剂量尚不清楚。
评估如果进一步降低 2016-AAO 剂量（2-3mg/kg/天）是否能维持病情稳定、不活动的 LN 患者的 12 个月 HCQ 水平。
73 例稳定的 LN 患者接受了至少 6 个月的全剂量 2016-AAO（5mg/kg/天）和足够基线 HCQ 水平（≥613.5ng/mL）的治疗，将他们分为两组：降低剂量 2016-AAO 组（2-3mg/kg/天），n=32；全剂量 2016-AAO 组（5mg/kg/天），n=41。所有患者在基线、3、6 和 12 个月时进行评估。通过液相色谱-串联质谱法测量 HCQ 水平。flare 定义为 SLE 疾病活动指数-2000 增加≥3 或治疗改变。严格进行临床/实验室监测。
前瞻性评估显示，与基线相比，降低剂量 2016-AAO 组在 3 个月时 HCQ 水平下降（1404.9±492.0 与 731.6±385.0ng/mL，p<0.01），并且在 6 个月（p=0.273）和 12 个月（p=0.091）时维持了与 3 个月时相似的水平。对于全剂量 2016-AAO 组，仅从基线到 12 个月时 HCQ 水平下降（1343.5±521.5 与 991.6±576.3ng/mL，p<0.001）。在降低剂量 2016-AAO 组中，6 个月时患者的 HCQ 水平不足发生率高于全剂量 2016-AAO 组（59%比 24%，p=0.005），12 个月时也更高（66%比 32%，p=0.002）。两组的 6 个月和 12 个月 flares 发生率无差异（p>0.05）。
处方 HCQ 低剂量方案（2-3mg/kg/天）不能维持大多数患者 6 个月和 12 个月的 HCQ 充足水平。全剂量 2016-AAO 维持的 HCQ 水平远高于这一限制。
ClinicalTrials.gov：NCT03122431，于 2017 年 4 月 20 日注册。
降低的美国眼科学会（2016-AAO）羟氯喹（HCQ）剂量（2-3mg/kg/天，实际体重）无法维持 flare 风险定义的安全截止值范围内的 HCQ 血药水平。
全剂量 2016-AAO（5mg/kg/天）维持安全的 HCQ 水平模式可达 12 个月。
