Mok Chi Chiu, Penn Hannah J, Chan Kar Li, Tse Sau Mei, Langman Loralie J, Jannetto Paul J
Tuen Mun Hospital, Hong Kong, China.
Mayo Clinic, Rochester, Minnesota.
Arthritis Care Res (Hoboken). 2016 Sep;68(9):1295-302. doi: 10.1002/acr.22837. Epub 2016 Jul 27.
To study the relationship between serum hydroxychloroquine (HCQ) concentrations and flares of systemic lupus erythematosus (SLE) in a longitudinal cohort of patients.
Patients who fulfilled ≥4 American College of Rheumatology classification criteria for SLE and had been treated with HCQ for >6 months were studied. Blood was assayed for HCQ levels by tandem mass spectrometry. Patients were serially assessed for disease activity, using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and flares (SELENA flares instrument). Comparison of the mean summated SLEDAI scores over time and rates of flares in groups with different HCQ levels was performed by the Kruskal-Wallis test.
A total of 276 SLE patients were studied (93% women, mean ± SD age 41.0 ± 13.8 years). The proportion of patients with HCQ levels <10 (total noncompliance), 10-500 (subtherapeutic), and >500 ng/ml (therapeutic) was 11%, 77%, and 12%, respectively. HCQ levels correlated significantly with the prescribed dose but not with body weight or renal function. The prescribed HCQ dose also correlated significantly with baseline SLEDAI scores, indicating that higher doses were used for more active manifestations. After a mean ± SD observation period of 32.5 ± 5.5 months, the mean summated SLEDAI score and the incidence of SLE flares was not statistically different among patients with different baseline HCQ levels. In a subgroup of 73 patients with serologic and clinical remission and having therapeutic HCQ levels, a trend of lower disease activity and fewer incidences of flares was observed.
Noncompliance and subtherapeutic serum HCQ levels were seen frequently in these SLE patients, which was partly due to the low prescribed dose. In patients in remission, higher HCQ concentrations were associated with a trend showing fewer flares over time.
在一组纵向队列患者中研究血清羟氯喹（HCQ）浓度与系统性红斑狼疮（SLE）病情复发之间的关系。
对符合≥4条美国风湿病学会SLE分类标准且接受HCQ治疗>6个月的患者进行研究。采用串联质谱法检测血液中的HCQ水平。使用系统性红斑狼疮疾病活动指数（SLEDAI）的狼疮性红斑中雌激素安全性国家评估（SELENA）版本和病情复发情况（SELENA病情复发工具）对患者的疾病活动进行连续评估。通过Kruskal-Wallis检验比较不同HCQ水平组随时间变化的平均累计SLEDAI评分和病情复发率。
共研究了276例SLE患者（93%为女性，平均年龄±标准差为41.0±13.8岁）。HCQ水平<10（完全未依从）、10 - 500（治疗不足）和>500 ng/ml（治疗有效）的患者比例分别为11%、77%和12%。HCQ水平与规定剂量显著相关，但与体重或肾功能无关。规定的HCQ剂量也与基线SLEDAI评分显著相关，表明更高剂量用于更活跃的临床表现。在平均±标准差为32.5±5.5个月的观察期后，不同基线HCQ水平的患者之间，平均累计SLEDAI评分和SLE病情复发率无统计学差异。在73例血清学和临床缓解且HCQ水平处于治疗有效范围的患者亚组中，观察到疾病活动度较低和病情复发率较低的趋势。
这些SLE患者中经常出现未依从和血清HCQ水平治疗不足的情况，部分原因是规定剂量较低。在缓解期患者中，较高的HCQ浓度与随时间病情复发较少的趋势相关。
