Emery Paul, Kong Sheldon X, Ehrich Elliot W, Watson Douglas J, Towheed Tanveer E
Rheumatology and Rehabilitation Research Unit, Research School of Medicine, University of Leeds, United Kingdom.
Clin Ther. 2002 Aug;24(8):1225-91. doi: 10.1016/s0149-2918(02)80033-9.
Many clinicians believe that higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are more effective than lower doses for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA) but are associated with higher rates of adverse events (AEs). However, there is a lack of consensus on dose-effect relationships with the NSAIDs.
The purpose of this review was to investigate evidence for the relationship between NSAID dose, efficacy, and the occurrence of AEs from clinical trials of RA and OA of the hip and knee.
Relevant English-language publications were identified through a search of EMBASE, MEDLINE, and REFLINE using the terms aceclofenac, diclofenac, etodolac, ibuprofen, isoxicam, lornoxicam, meloxicam, nabumetone, naproxen, piroxicam, tenidap, tenoxicam, arthritis, OA (hip and knee), RA, rheumatic disorders, and musculoskeletal disorders for the period January 1970 to December 1997 (this review was conducted in 1998). Bibliographies of retrieved publications were reviewed for other potentially relevant articles. Selected publications were evaluated for quality (likelihood of bias) based on 4 factors (randomization procedure; completeness of patient and treatment information; standardization and completeness of outcome data; and reporting of attrition data).
This review included 99 publications concerning clinical trials conducted in 24 countries and enrolling 28,239 patients. The majority of reports were published in the 1990s, particularly in the latter half of that decade. The average quality of the publications improved over time, with a significant increase in mean quality score from 5.43 in the 1970s to 9.21 during the last half of the 1990s (P < 0.05). Only 8 reports directly compared high and low doses of the same drug in relation to efficacy.
Data on the relationship of NSAID dose to efficacy and the incidence of AEs were limited. There is a need for clinical trials directly addressing dose-effect relationships of NSAIDs, as well as reviews of more current literature and reports in languages other than English.
许多临床医生认为，较高剂量的非甾体抗炎药（NSAIDs）在治疗类风湿关节炎（RA）和骨关节炎（OA）方面比低剂量更有效，但会带来更高的不良事件（AE）发生率。然而，关于NSAIDs的剂量 - 效应关系尚无共识。
本综述的目的是调查来自髋部和膝部RA和OA临床试验中NSAID剂量、疗效与AE发生之间关系的证据。
通过使用术语醋氯芬酸、双氯芬酸、依托度酸、布洛芬、异恶酰胺、氯诺昔康、美洛昔康、萘丁美酮、萘普生、吡罗昔康、替尼达普、替诺昔康、关节炎、OA（髋部和膝部）、RA、风湿性疾病和肌肉骨骼疾病在1970年1月至1997年12月期间检索EMBASE、MEDLINE和REFLINE来识别相关英文出版物（本综述于1998年进行）。对检索到的出版物的参考文献进行审查以查找其他潜在相关文章。根据4个因素（随机化程序；患者和治疗信息的完整性；结局数据的标准化和完整性；以及损耗数据的报告）对选定的出版物进行质量（偏倚可能性）评估。
本综述纳入了99篇关于在24个国家进行的临床试验且纳入28,239名患者的出版物。大多数报告发表于20世纪90年代，特别是该十年的后半期。出版物的平均质量随时间有所提高，平均质量得分从20世纪70年代的5.43显著增加到20世纪90年代后半期的9.21（P < 0.05）。只有8篇报告直接比较了同一药物的高剂量和低剂量在疗效方面的差异。
关于NSAID剂量与疗效及AE发生率之间关系的数据有限。需要进行直接探讨NSAIDs剂量 - 效应关系的临床试验，以及对更新的文献和非英语语言的报告进行综述。
