尼美舒利治疗类风湿关节炎和骨关节炎上市后安全性再评价

Safety re-evaluation on nimesulide in treatment of rheumatoid arthritis and osteoarthritis after postmarketing

目的评价尼美舒利片治疗类风湿关节炎(RA)和骨关节炎(OA)的有效性和安全性。方法符合入组标准且不符合排除标准的RA和OA病人共140例(其中男性56人,女性84人),口服尼美舒利片0.1g,每日2次,疗程为30d。对RA病人,观察指标包括休息痛、晨僵、28个关节肿胀关节数及指数、28个关节压痛关节数及指数、健康状况问卷、病人及医师对目前疾病状况的评估;对OA病人膝关节活动痛、膝关节压痛指数、日常活动能力、病人及医师对目前疾病状况的评估。观察药物使用期间出现的临床和实验室不良反应。结果意向性(ITT)分析、符合方案(PP)分析的综合疗效评价总有效率分别为80.0%和86.2%。脱落10例,脱落率为7.1%。主要临床不良反应为消化道不良反应(15/140,10.7%),表现为恶心、腹胀和上腹痛。肝功能异常发生率为3.6%(5/140),4例转氨酶治疗前正常、治疗后异常,1例转氨酶治疗前异常、治疗后异常加重。其中原肝功能正常者中有2例病人用药后转氨酶异常超过正常的3倍以上,最高ALT达593U·L-1。结论尼美舒利治疗RA和OA有效,但在使用过程中应密切关注其所致肝损害可能性。

AIM To evaluate the efficacy and safety study on nimesulide in treatment of rheumatoid arthritis （RA） and osteoarthritis （OA） after postmarketing. METHODS Coincided and non-exluded with the enrolled standard RA and OA patients, altogether 140 patients （including 56 males and 84 females） were admihistered orally nimesulide table 0.1 g, bid, individually for 30 d as a course. Assessments for RA patient included pain visual analogue scale （VAS）, morning stiffness, numbers of 28 joint swellings and tendernesses with their coefficients, health assessment questionary （HAQ）, patient＇ s and physician＇ s global assessment of disease.activity VAS and for OA patients included knee pain VAS, knee tenderness, HAQ, patient＇s and physician＇ s global assessment of disease activity VAS, with furthermore clinical and laboratory advert reactions of the studied drug were closely observed and investigated. RESULTS 10 （7.1%） out of 70 RA and 70 OA patients were discontinued early from the study; and the rest completed the clinical trial. The intention-to-treat （ITT） analysis and per-protocol population （PP） analysis showed the total effective c.ompre-hensive therapeutic effective rates were 80.0% and 86.2%, respectively for RA and OA patients. The most frequent adverse reactions involved gastrointestinal tract （15/140, 10.7%） manifesting as nausea, abdominal distension and upper abdominal pain. The incidence of liver dysfunction was 3.6% （5/140）. The liver function in 8 of the 5 normal liver function patients before the treatment became abnormal after the treatment, and 4 of them with alanine aminotransferase or aspartate aminotransferase exceeded 3 times the upper normal limit of was the liver function and furthermore in 2 of 10 the normal ones was aggravated after the treatment. COCLUSION Nimesulide is an effective non-steroid anti-inflammation drugs （NSAID） in the treatment of RA and OA, however close attention should always be aware for the possible hepatic damage.