Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus
Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus
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DOI：
10.1002/art.22156
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发表时间：
2006-10-01
影响因子：
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通讯作者：
Piette, Jean-Charles
中科院分区：
文献类型：
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作者：
Costedoat-Chalumeau, Nathalie;Amoura, Zahir;Piette, Jean-Charles
Objective.目的探讨系统性红斑狼疮（SLE）患者全血羟氯喹（HCQ）浓度与临床疗效的关系。在盲法条件下，测量了143名未经选择的SLE患者的全血HCQ浓度，这些患者已接受HCQ 400 mg每日至少6个月。研究这些浓度与当前疾病活动性和随后6个月随访期间病情加重的关系。基线时，23例患者有活动性疾病（平均+/- SD SLE疾病活动指数12.4 +/- 7.5）。该组的平均全血HCQ浓度显著低于120例非活动性疾病患者（694 +/- 448 ng/ml vs 1，079 +/- 526 ng/ml; P = 0.001）。在120例基线时疾病无活动性的患者中，14例（12%）在随访期间疾病加重的患者基线时的平均HCQ浓度显著低于疾病保持无活动性的患者。多变量logistic回归显示HCQ浓度是急性加重的唯一预测因子（比值比0.4 [95%置信区间0.18-0.85]，P = 0.01）。受试者工作特征曲线分析显示，全血HCQ浓度截止值为1，000 ng/ml时，随访期间急性加重的阴性预测值为96%。低全血HCQ浓度与SLE疾病活动性相关，是疾病恶化的强预测因子。定期进行药物检测和个体化治疗可能有助于提高HCQ治疗SLE的疗效。
Objective. To study the possible relationship between whole-blood hydroxychloroquine (HCQ) concentrations and clinical efficacy of HCQ in patients with systemic lupus erythematosus (SLE).Methods. Whole-blood HCQ concentrations were measured, under blinded conditions, in 143 unselected patients with SLE who had been receiving HCQ 400 mg daily for at least 6 months. The relationship of these concentrations to current disease activity and to subsequent exacerbations during 6 months of followup was investigated.Results. At baseline, 23 patients had active disease (mean +/- SD SLE Disease Activity Index 12.4 +/- 7.5). The mean whole-blood HCQ concentration in this group was significantly lower than that in the 120 patients with inactive disease (694 +/- 448 ng/ml versus 1,079 +/- 526 ng/ml; P = 0.001). Among the 120 patients who had inactive disease at baseline, the mean HCQ concentration at baseline in the 14 (12%) who had disease exacerbations during followup was significantly lower than that in the patients whose disease remained inactive. Multivariate logistic regression showed that the HCQ concentration was the only predictor of exacerbation (odds ratio 0.4 [95% confidence interval 0.18-0.85], P = 0.01). Receiver operating characteristic curve analysis showed that a whole-blood HCQ concentration cutoff of 1,000 ng/ml had a negative predictive value of 96% for exacerbation during followup.Conclusion. Low whole-blood HCQ concentrations are associated with SLE disease activity and are a strong predictor of disease exacerbation. Regular drug assaying and individual tailoring of treatment might help to improve the efficacy of HCQ treatment in patients with SLE.