硫酸羟氯喹在风湿性疾病治疗中的应用及长期安全性的调查  

Clinical application and long-term safety of hydroxychloroquine in rheumatic diseases

作　　者：钟华 徐丽玲[1] 白明欣 张志毅[2] 沈海丽[3] 朱蓉[3] 武丽君[4] 赵金霞[5] 李洋[6] 郭乾育[7] 鲁芙爱 罗增 白玛央金[9] 罗莉[10] 胡永玮[10] 郭倩[11] 顾文[12] 叶华[1] 苏茵[1] Zhong Hua;Xu Liling;Bai Mingxin;Zhang Zhiyi;Shen Haili;Zhu Rong;Wu Lijun;Zhao Jinxia;Li Yang;Guo Qianyu;Lu Fuai;Luo Zeng;Baima Yangjin;Luo Li;Hu Yongwei;Guo Qian;Gu Wen;Ye Hua;Su Yin(Department of Rheumatology and Immunology,Peking University People's Hospital,Beijing 100044,China;Department of Rheumatology and Immunology,the First Affiliated Hospital of Harbin Medical University,Heilongjiang 150001,China;Department of Rheumatology and Immunology,the Second Clinical Medical College of Lanzhou University,Gansu 730030,China;Department of Rheumatology and Immunology,People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China;Department of Rheumatology and Immunology,Peking University Third Hospital,Beijing 100191,China;Department of Rheumatology,the Second Affiliated Hospital of Harbin Medical University,Heilongjiang 150086,China;Department of Rheumatology and Immunology,Shanxi Bethune Hospital,Taiyuan 030032,China;Department of Rheumatology and Immunology,the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014010,China;Department of Rheumatology and Immunology,Tibet Autonomous Region People's Hospital,Lhasa 850000,China;Department of Rheumatology and Immunology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Department of Rheumatology and Immunology,Peking University International Hospital,Beijing 102206,China;Department of Rheumatology,Beijing Traditional Chinese Medicine Hospital,Capital Medical University,Beijing 100029,China)

机构地区：[1]北京大学人民医院风湿免疫科,100044 [2]哈尔滨医科大学附属第一医院风湿免疫科,150001 [3]兰州大学第二医院风湿免疫科,730030 [4]新疆维吾尔自治区人民医院风湿免疫科,乌鲁木齐830001 [5]北京大学第三医院风湿免疫科,100191 [6]哈尔滨医科大学附属第二医院风湿免疫科,150086 [7]山西医科大学第三医院(山西白求恩医院山西医学科学院同济山西医院)风湿免疫科,太原030032 [8]内蒙古科技大学包头医学院第一附属医院风湿免疫科,014010 [9]西藏自治区人民医院风湿免疫科,拉萨850000 [10]新疆医科大学第一附属医院风湿免疫科,乌鲁木齐830054 [11]北京大学国际医院风湿免疫科,102206 [12]首都医科大学附属北京中医医院风湿病科,100029

出　　处：《中华风湿病学杂志》2021年第9期584-589,共6页Chinese Journal of Rheumatology

基　　金：国家自然科学基金(81871290);北京市科技计划项目(Z191100006619109)。

摘　　要：目的探讨临床实践中硫酸羟氯喹在风湿性疾病治疗中的应用及其长期安全性。方法采用多中心横断面的调查方法,设计调查问卷,于2017年8月至2018年8月对风湿免疫科门诊或住院患者进行调查,入选明确诊断并持续服用羟氯喹超过3个月的风湿性疾病患者,详细记录羟氯喹的累积剂量及持续时间,同时记录其相关长期不良反应,并分析比较口服羟氯喹治疗超过3个月的患者用药前后的实验室指标变化。计数资料以频数和百分比(%)表示,组间比较采用χ^(2)检验;计量资料用±s表示,组间比较采用独立样本t检验或Mann-Whitney非参数检验。以P<0.05为差异有统计学意义。结果 886例风湿免疫病患者入选本研究,其中SLE 505例(57.0%)、RA 210例(23.7%)、SS 80例(9.0%),未分化结缔组织病(UCTD)57例(6.4%)、系统性血管炎12例(1.4%)、MCTD 10例(1.1%)、炎性肌病7例(0.8%)及SSc 5例(0.6%)。在886例患者中181例(20.4%)发生过1种或1种以上不良反应,其中以皮肤黏膜(110例,12.4%)和眼部病变(71例,8.0%)最常见,其他不良反应依次涉及消化系统(27例,3.0%)、神经系统(19例,2.1%)、肌肉骨骼系统(10例,1.1%)及心血管系统(8例,0.9%),但仅有54例(6.1%)患者因不良反应停药,其中24例患者因症状缓解再次加用羟氯喹。886例患者中140例(15.8%)在治疗过程中曾停用羟氯喹,除了因不良反应停药外,还有12例(1.4%)因病情缓解停药,74例(8.4%)患者为自行停药;按照服用羟氯喹的累积剂量分为3组,分别为<500 g、500~1 000 g、>1 000 g,3组间不良反应发生率的差异具有统计学意义(χ^(2)=6.382,P=0.041),以>1000 g组不良反应的发生率最高(37.1%)。本研究中未观察到严重不良反应发生。结论临床实践中羟氯喹已经在风湿性疾病的治疗上广泛应用,其不良反应发生率为20.4%,但导致停药的不良反应仅为6.1%,并与累积剂量有关,持续应用过程中应及时根据病情调整剂量。Objective To explore the clinical application and long-term safety of hydroxychloroquine sulfate(HCQ)in the treatment of rheumatic diseases.Methods A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China.Patients who took HCQ for more than 3 months were enrolled into this study.The cumulative dose and long-term side effects of HCQ were recorded.The changes of laboratory indexes before and after treatment with HCQ were analyzed.Categorical variables were presented with counts and proportions,and evaluated by Chi-square test.Continuous parametric data were presented as Mean±standard deviation,and evaluated by Student's t test or Mann-Whitney U test.P-values less than 0.05 were considered statistically significant.Results A total of 886 patients with rheumatic diseases were enrolled into this study,including 505 cases with systemic lupus erythematosus(57.0%),210 cases with rheumatoid arthritis(23.7%),80 cases with Sjögren's syndrome(9.0%),57 cases with undifferentiated connective tissue disease(6.4%),12 cases of systemic vasculitis(1.4%),10 cases of mixed connective tissue disease(1.1%),7 cases of myositis(0.8%)and 5 cases with systemic sclerosis(0.6%).The most common long-term side effects of HCQ was skin or mucous lesions(12.4%)and vision problems(8.0%).Other adverse reactions included problems of digestive system(3.0%),nervous system(2.1%),musculoskeletal system(1.1%)and cardiovascular system(0.9%).140 cases(15.8%)had stopped taking HCQ during the treatment.More than half of them decided to stop taking medicine by themselves.Fifty-four patients(6.1%)stopped using HCQ due to side effects while 24 of them took it again,and another 12 patients(1.4%)stopped the drug due to remission of illness.Patients were divided into three groups according to the cumulative dose of HCQ:less than 500 g,500-1000 g and more than 1000 g respectively.There was significant difference in the incidence of long-term si

关 键 词：风湿性疾病 病人安全 硫酸羟氯喹 临床实践 

分 类 号：R593.2[医药卫生—内科学]