Costedoat-Chalumeau Nathalie, Amoura Zahir, Hulot Jean-Sébastien, Hammoud Hala Abou, Aymard Guy, Cacoub Patrice, Francès Camille, Wechsler Bertrand, Huong Du Le Thi, Ghillani Pascale, Musset Lucile, Lechat Philippe, Piette Jean-Charles
Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire Pitié-Salpêtrière, Université Paris VI Pierre et Marie Curie, Paris, France.
Arthritis Rheum. 2006 Oct;54(10):3284-90. doi: 10.1002/art.22156.
To study the possible relationship between whole-blood hydroxychloroquine (HCQ) concentrations and clinical efficacy of HCQ in patients with systemic lupus erythematosus (SLE).
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.
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.
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.
研究系统性红斑狼疮（SLE）患者全血羟氯喹（HCQ）浓度与HCQ临床疗效之间的可能关系。
在盲法条件下，对143例未经过筛选、每日接受400 mg HCQ治疗至少6个月的SLE患者测量全血HCQ浓度。研究这些浓度与当前疾病活动度以及随访6个月期间后续病情加重情况的关系。
基线时，23例患者疾病活动（平均±标准差SLE疾病活动指数为12.4±7.5）。该组患者的平均全血HCQ浓度显著低于120例疾病非活动患者（694±448 ng/ml对1,079±526 ng/ml；P = 0.001）。在基线时疾病非活动的120例患者中，随访期间病情加重的14例（12%）患者的基线平均HCQ浓度显著低于疾病仍保持非活动状态的患者。多因素逻辑回归显示，HCQ浓度是病情加重的唯一预测因素（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浓度截断值为1,000 ng/ml对随访期间病情加重的阴性预测值为96%。
全血HCQ浓度低与SLE疾病活动相关，是疾病加重的有力预测因素。定期进行药物检测和个体化调整治疗可能有助于提高SLE患者HCQ治疗的疗效。
