Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study

CONTEXT: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown. OBJECTIVE: To determine whether celecoxib, a COX-2-specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs. DESIGN: The Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000. SETTING: Three hundred eighty-six clinical sites in the United States and Canada. PARTICIPANTS: A total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months. INTERVENTIONS: Patients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (相似文献   

尼美舒利和萘普生治疗类风湿关节炎的临床研究

目的 :比较研究尼美舒利和萘普生治疗类风湿关节炎的疗效和安全性。方法 :为随机、双盲、平行的比较研究。共完成病例 6 0例 ,尼美舒利和萘普生各 30例。口服尼美舒利 10 0mg每天两次 ;萘普生 2 5 0mg每天两次 ,疗程 4周 ,连用 2个疗程。结果 :4周、8周时尼美舒利总有效率为 5 6 78% ,6 0 71% ;萘普生为 6 0 71% ,6 4 2 9% ,两药均能显著改善患者的症状和体征 ,降低血沉与C -反应蛋白。安全性评价 :两药耐受性无明显差异 ,但不良反应发生率 :尼美舒利 13 33 % ;萘普生 2 6 6 7% ;不良反应主要为消化道症状及皮疹 ,水肿等。尼美舒利不良反应轻 ,一般不予处理或仅给对症处理 ,不需停药 ;萘普生有 2例因不良反应而停药 (皮疹 ,胃痛各 1例 )。结论 :尼美舒利治疗类风湿关节炎疗效与萘普生相近 ,但不良反应发生率较低且症状较轻     

Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs

CONTEXT: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxic effects, such as upper GI tract perforations, symptomatic gastroduodenal ulcers, and upper GI tract bleeding (PUBs), are thought to be attributable to cyclooxygenase 1 (COX-1) inhibition. Rofecoxib specifically inhibits COX-2 and has demonstrated a low potential for causing upper GI injury. OBJECTIVE: To compare the incidence of PUBs in patients with osteoarthritis treated with rofecoxib vs NSAIDs. DESIGN: Prespecified analysis of all 8 double-blind, randomized phase 2b/3 rofecoxib osteoarthritis trials conducted from December 1996 through March 1998, including one 6-week dose-ranging study, two 6-week efficacy studies vs ibuprofen and placebo, two 1-year efficacy studies vs diclofenac, two 6-month endoscopy studies vs ibuprofen and placebo, and one 6-week efficacy study vs nabumetone and placebo. SETTING: Multinational sites. Participants Osteoarthritis patients (N = 5435; mean age, 63 years [range, 38-94 years]; 72.9% women). INTERVENTIONS: Rofecoxib, 12.5, 25, or 50 mg/d (n = 1209, 1603, and 545, respectively, combined) vs ibuprofen, 800 mg 3 times per day (n = 847), diclofenac, 50 mg 3 times per day (n = 590); or nabumetone, 1500 mg/d (n = 127) (combined). MAIN OUTCOME MEASURE: Cumulative incidence of PUBs for rofecoxib vs NSAIDs, based on survival analysis of time to first PUB diagnosis, using PUBs that met pre-specified criteria judged by a blinded, external adjudication committee. RESULTS: The incidence of PUBs over 12 months was significantly lower with rofecoxib vs NSAIDs (12-month cumulative incidence, 1.3% vs 1.8%; P = .046; rate per 100 patient-years, 1.33 vs 2.60; relative risk, 0.51; 95% confidence interval, 0.26-1.00). The cumulative incidence of dyspeptic GI adverse experiences was also lower with rofecoxib vs NSAIDS over 6 months (23.5% vs 25.5%; P = .02), after which the incidence rates converged. CONCLUSION: In a combined analysis of 8 trials of patients with osteoarthritis, treatment with rofecoxib was associated with a significantly lower incidence of PUBs than treatment with NSAIDs.     

酮基布洛芬(Ketoprofen)治疗类风湿性关节炎的疗效观察

酮基布洛芬是一种新的非激素类抗炎镇痛药。作者对66例典型的类风湿性关节炎病人用此药(150mg/日)治疗,疗效满意者36例(54.5%),总有效率为87.9%。其中24例还采用酮基布洛芬和消炎痛作了对照互换试验,两者疗效无显著差异,但酮基布洛芬的副作用明显少而轻。酮基布洛芬是一种较满意的治疗类风湿性关节炎新药。     

COX-2 inhibitors

Cyclooxygenase-2 (COX-2) inhibitors constitute a new group of non-steroidal anti-inflammatory drugs (NSAIDs) which, at recommended doses, block prostaglandin production by cyclooxygenase-2, but not by cyclooxygenase-1. Two COX-2 inhibitors are currently available in Australia--celecoxib, which is taken twice daily, and rofecoxib, which is taken once daily. Both drugs act rapidly in providing pain relief and their anti-inflammatory analgesic effect in osteoarthritis and rheumatoid arthritis is equivalent to standard doses of non-selective NSAIDs. Celecoxib and rofecoxib show significantly lower incidences of gastrotoxicity (as measured by endoscopic studies and gastrointestinal ulcers and bleeds) than non-selective NSAIDs. There is Level 2 evidence that COX-2 inhibitors: reduce pain in classic pain models--third-molar extraction, dysmenorrhoea and after orthopaedic surgery; reduce pain and disability in osteoarthritis of the hip and knee; and reduce pain and disability in rheumatoid arthritis. Other adverse effects, such as interference with antihypertensive agents and the potential to produce renal dysfunction in patients with compromised renal function by COX-2 inhibitors, seem similar to those of non-selective NSAIDs.     

尼美舒利治疗类风湿关节炎的双盲随机对照临床试验

目的：研究尼美舒利（NIM）治疗类风湿关节炎（RA）的疗效和安全性。方法：将试验设计为随机,双盲,平行性和多中心的比较研究。试验组NIM和对照组萘普生（NAP）分别治疗60例RA患者;分别口服NIM100mg/次和NAP250mg/次,一日二次,疗程设计为4周,累计用药为8周。结果：经4周治疗后,NIM总有效率为61．67％,NAP总有效率为39．65％;经8周治疗后,NIM总有效率为68．33％,NAP总有效率为65．52％。两药4周和8周均能改善患者的症状和体征,降低血沉和C－反应蛋白水平,肿胀关节指数以及8周时对肿胀关节数,肿胀关节指数,C－反应蛋白的改善程度明显优于NAP组。经安全性评价,NIM和NAP的耐受性均较好,不良反应以胃肠道系统为主。结论：经4周治疗后,NIM的疗效优于NAP疗效,经8周治疗后,NIM和NAP疗效差异无显著性,两药的耐受性无差异。     

Clinical Study on sustained release tablet of tripterygium Wilfordii in treating rheumatoid arthritis

Adopting prospective, multi-center, random, single-blind and equal rank-control methods, 226 patients with rheumatoid arthritis (RA) were divided into two groups. The 114 patients of the test group were treated with oral sustained release tablets of Tripterygium Wilfordii (TW-SR), 2 tablets twice a day for 4 weeks, 112 patients of the control group received tablets of Tripterygium Wilfordii (TW) orally 2 tablets 3 times per day for 4 weeks. Testing results showed the total effective rates of the two groups were 92.11 % and 90.65 %, respectively (P>0.05). The adverse reaction rate of TW-SR was 20.18%, which was lower than that of TW group of 70.54% (P<0. 01). Results of pre-clinical pharmacologic experimental study demonstrated that TW-SR has obvious anti-inflammatory, analgesic and immunosuppressive actions the same as TW, while the toxicity of TW-SR was less than that of TW significantly.     

紫草素对类风湿关节炎滑膜成纤维细胞COX-2表达的影响

目的观察紫草素对人滑膜成纤维细胞环氧化酶-2(COX-2)mRNA表达的影响,探讨紫草素可能的免疫抗炎作用机制。方法分离并培养人膝关节滑膜成纤维细胞,各加入IL-1β、TNF-α15 ng/mL,体外模拟人类风湿关节炎滑膜细胞。以塞来昔布作阳性对照,进行紫草素(浓度为5～80μg/L)干预,分别作用24、48、72 h后终止培养。用半定量逆转录-聚合酶链反应(RT-PCR)技术检测滑膜成纤维细胞COX-2 mRNA表达情况。结果紫草素对滑膜成纤维细胞COX-2 mRNA的表达,对浓度无明显依赖性(P=0.089),用药时间上有显著统计学意义(P<0.0001)。塞来昔布抑制滑膜成纤维细胞COX-2mRNA水平的表达亦无明显浓度依赖性(P=0.051),而与用药时间显著相关(P<0.0001)。紫草素对滑膜成纤维细胞COX-2 mRNA表达的影响与塞来昔布相比,其抑制作用无明显差异。结论紫草素可通过抑制COX-2 mRNA基因表达,减少炎症性细胞因子的产生而发挥其对类风湿关节炎的免疫抗炎作用,为开发紫草素成为COX-2抑制剂提供一定的实验基础。     

塞来昔布使实验性结肠炎损伤加重的作用机制

目的:探讨选择性环氧合酶(COX)-2抑制剂塞来昔布使2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠结肠炎损伤加重的作用机制.方法:将大鼠随机分为4组:第1组和第2组为造模组,第3组和第4组为对照组.用0.25 mL TNBS乙醇溶液[含质量浓度为25 g/L的TNBS,50%(体积分数)乙醇]灌肠,诱导大鼠慢性实验性结肠炎模型.在造模前3 h,造模组第1组大鼠以塞来昔布(1.25 mg/kg)灌胃,第2组以蒸馏水(1 mL/0.3 kg)灌胃,此后一天两次灌胃,直到第7天;对照组不造模,其中第4组以塞来昔布(1.25 mg/kg)灌胃,一天两次,直到第7天;第3组大鼠为正常对照组.于第7天实验结束时处死所有存活动物,观察病变处肠组织的炎症程度,同时用免疫组化方法检测肠组织中COX-2的表达.结果:造模组大鼠中,第1组的结肠扩张程度、溃疡面积、肠壁厚度均大于第2组.第1组的结肠炎炎症指数为8.5±2.5,显著低于第2组13.5±1.9(P＜0.05).第1组的结肠组织COX-2的面密度为3.7×10-2±9.5×10-3,显著低于第2组(11.4×10-2±3.8×10-2,P＜0.05).第1组的结肠肠肌间神经丛COX-2表达的阳性率为30%,显著低于第2组(90%,P＜0.05).第3组与第4组比较,炎症指数、结肠组织COX-2面密度、结肠肠肌间神经丛COX-2表达阳性率差异均无统计学意义.结论:选择性COX-2抑制剂塞来昔布使TNBS肠炎大鼠结肠病变处组织学炎症程度减轻,COX-2表达减少,但损伤加重.其机制可能与塞来昔布对大鼠肠肌间神经丛COX-2产生抑制,与肠道收缩力减弱、蠕动减少,与肠麻痹、巨结肠的形成有关.     

特异性COX-2抑制药的临床应用及其前景

特异性环氧化酶-2(COX-2)抑制药为一组新的非甾体类抗炎药(NSAIDs)，此类药能阻止前列腺素合成，但不阻止由COX-1激活的前列腺素类物质的合成。COX-2抑制药能迅速提供镇痛，对骨关节炎和类风湿性关节炎的抗炎镇痛效应相当于非特异性NSAIDs的标准剂量，而其胃肠道副作用较低，其他不良反应与非特异性NSAIDs相似。     

ClinicalStudyonSustainedReleaseTablatotTripterygiumWilfordiiinTreatingRheumatoidArthritis

ＣｌｉｎｉｃａｌＳｔｕｄｙｏｎＳｕｓｔａｉｎｅｄＲｅｌｅａｓｅＴａｂｌａｔｏｔＴｒｉｐｔｅｒｙｇｉｕｍＷｉｌｆｏｒｄｉｉｉｎＴｒｅａｔｉｎｇＲｈｅｕｍａｔｏｉｄＡｒｔｈｒｉｔｉｓＣｌｉｎｉｃａｌＳｔｕｄｙｏｎＳｕｓｔａｉｎｅｄＲｅｌｅａｓｅＴａｂｌａ...     

通心络胶囊治疗类风湿关节炎的临床观察

目的观察通心络胶囊联合西药治疗类风湿性关节炎的疗效。方法88例类风湿性关节炎患者,随机分为治疗组和对照组。对照组予萘普生、泼尼松、甲氨蝶呤、硫酸羟氯喹。以及对症治疗;治疗组在对照组治疗基础上加用通心络胶囊每次4粒,2次／d。疗程半年。结果除治疗组1例未坚持治疗外,治疗半年后,两组其余病人的关节疼痛、肿胀、压痛、关节活动度、晨僵时间。均有明显的改善。治疗组总有效率95．4％,疗效明显优于对照组（88．6％）,且副作用轻微。结论通心络胶囊联合西药治疗类风湿性关节炎,效果显著。安全性较好。     

Effect of superoxide dismutase from bovine erythrocytes on different activity parameters in adjuvant-induced arthritis.

BACKGROUND: The purpose of this work was to evaluate the effect of superoxide dismutase (SOD) on primary swelling, lipoperoxidation, body thymus, and spleen weight in the adjuvant-induced arthritis (AIA) model in rats. METHODS: Orally and intraperitoneally administered SOD (100 U/kg) from bovine erythrocytes, as well as naproxen (40 mg/kg) and dexamethasone (25 mg/kg), were evaluated against placebo. RESULTS: Primary edema was not decreased by SOD; in contrast, naproxen and dexamethasone showed good anti-inflammatory activity. Lipoperoxidation increased 1.8, 2.5, and 2.8 times with intraperitoneal SOD, naproxen, and dexamethasone administration, respectively, while oral SOD decreased lipoperoxidation levels to approximately one-half of that found in the control group. Body weight increased with SOD but decreased with dexamethasone. Naproxen did not change the animal weight. Thymus weight remained unchanged with SOD and naproxen, while it decreased with dexamethasone. Spleen weight remained the same with SOD, but increased with naproxen and decreased with dexamethasone. No side effects were observed in the SOD group, whereas 20% of the rats in the naproxen group died of gastrointestinal hemorrhage, and 50% of the rats in the dexamethasone group, of pulmonary infection. CONCLUSIONS: In conclusion, SOD showed no anti-inflammatory activity but decreased lipoperoxidation when administered orally. No deleterious effects in primary and secondary immunologic organs were observed with this agent.     

萘丁美酮治疗类风湿关节炎的临床研究

萘丁美酮（ＮＡＢ）是一种新型非甾体抗炎药。为研究该药与阳性对照药萘普生（ＮＡＰ）对类风湿关节炎（ＲＡ）的疗效与安全性，我们对ＮＡＢ和ＮＡＰ治疗ＲＡ进行了随机、双盲、多中心和平行性的Ⅱ期临床试验。结果表明：ＮＡＢ１０００ｍｇ睡前顿服，连续４ｗｋ治疗１８８例ＲＡ的总有效率为６５．９６％，ＮＡＰ２５０ｍｇＢｉｄ连续４ｗｋ治疗１４６例ＲＡ的总有效率为６０．２７％。ＮＡＢ的不良反应发生率为１６．４１％，ＮＡＰ的不良反应发生率为３６．００％。提示ＮＡＢ治疗ＲＡ的疗效与ＮＡＰ相近，但不良反应发生率明显低于ＮＡＰ。     

卡培他滨节拍化疗联合塞来昔布治疗晚期结直肠癌的临床疗效观察

目的:评价卡培他滨节拍化疗联合塞来昔布治疗晚期结直肠癌的临床疗效和不良反应.方法:对51例晚期结直肠癌患者应用卡培他滨节拍化疗联合塞来昔布治疗.卡培他滨500 mg,2次·d(-1),塞来昔布胶囊400 mg,2次·d(-1),4周为1个周期.患者至少完成2个周期,中位治疗周期数为4.8个.结果:51例患者无一例完全缓...     

Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial

Background A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis （RA）. To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients. Methods In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo （n=95） or T-614 at 50 mg （n=93） or 25 mg （n=92） daily. Active disease was defined by 4 of the following 5 criteria： 〉5 tender joints, 〉3 swollen joints, morning stiffness lasting for 〉60 minutes, and Westergren erythrocyte sedimentation rate （ESR） 〉28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology （ACR） response rate using the intent-to-treat population. Results The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo （P〈0.0001）, and the 50 mg/d dose compared to the 25 mg/d dose （P〈0.05） when using the ACR response analyses after 24 weeks. ESR and c-reactive protein （CRP） were significantly different in the treatment groups after 24 weeks. The incidence of adverse events （AEs） was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase （sALT）, skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups. Conclusion     

三联疗法根除幽门螺杆菌36例疗效观察

目的：应用阿莫西林-克拉维酸钾、克拉霉素、奥美拉唑三联疗法治疗幽门螺杆菌（Hp）感染效果。方法：治疗组予克拉霉素10～15mg/（kg·d）;分为2次,餐后口服;阿莫西林-克拉维酸钾颗粒3～7岁228.5mg/次;7～14岁457mg/次,2次/d餐后口服;奥美拉唑镁片10mg/次,3～7岁1次/d;7～14岁2次/d,餐前口服。对照组予克拉霉素10～15mg/（kg·d）,分为2次,餐后口服;阿莫西林-克拉维酸钾颗粒3～7岁228.5mg/次;7～14岁457mg/次,2次/d餐后口服,胶体次枸橼铋9mgkg/（kg·d）,分3次餐前给药。治疗期间不加用其他药物。治疗14d再次行胃镜检查并行Hp检测。结果：治疗组：Hp根除30例,根除率为83.33%,3d疼痛缓解29例,疼痛缓解率为80.56%。对照组：Hp根除24例,根除率为60.00%,3d疼痛缓解22例,疼痛缓解率为55.00%。两组Hp根除率、3d疼痛缓解率比较差异均有统计学意义（P〈0.05）。结论：克拉霉素、阿莫西林-克拉维酸钾、奥美拉唑三联疗法不仅是良好的初治方案,也是较好的复治方案。     

国产美洛西康治疗类风湿关节炎的随机对照试验

①目的观察国产美洛西康治疗类风湿关节炎的有效性和安全性。②方法采用随机、单盲、对照、多中心研究。本中心类风湿关节炎病人40例，国产美洛西康试验组20例，莫比可对照组20例，试验药与对照药用法均为15mg早餐后顿服，疗程8周，根据标准疗效判定方法进行评估。③结果国产美洛西康在改善类风湿关节炎症状体征方面有明显效果，治疗类风湿关节炎4周有效率65％，8周有效率75％，和同等剂量莫比可疗效相近，国产美洛西康和莫比可每日早餐后顿服15mg，病人均有良好的耐受性。④结论国产美洛西康是治疗类风湿关节炎的有效药物，疗效与等剂量莫比可相当。     

The effect of folic acid on the development of stomach and other gast rointestinal cancers

Objective To evaluate the roles of folic acid and β-carotene in the chemoprevention of gastric and other gastrointestinal(GI)cancers.Methods In a randomized,double-blind,placebo-controlled trial,a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups:①folate(FA),20 mg per day plus vitamin B12 1 mg,intramuscularty,per month for one year,then 20 mg two times a week plus 1 mg per three months for the next year);②naural β-carotene(N-βC,30mg per day for first year,then 30mg two times a week for the next);③synthetic β-carotene(S-βC,administered as in N-βC);and ④placebo.Follow-ups continued from 1994 to 2001.Results A total of 7new cases of gastrointestinal cancers were diagnosed with 3 stomach,1 colon and 1 esophageal cancers occurring in the placebo group;1 stomach cancer in both of the N-βC and S-βC groups,and no cancer occurring if FA group.In terms of GI cancers,there was a significant reduction in the FA group,compared with the placebo group(P=0.04).A similar trend was observed in both N-βC and S-βC groups(P=0.07-0.08),Taken together,the three intervention groups displayed a highly significant decrease in occurrence(P=0.04,vs placebo),and a lower risk for GI cancers(OR=0.12;95?confidence interval,0.03-0.51).For development of gastric cancer,any one of the three active-treated groups did not reach statistically significant reduction.The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation(P=0.04).reversed intestinal metaplasia(P=0.06)at the end of follow-up,and reversed displasia(P=0.017)at 12 months.Two cases of false jaundice were found in β-carotene groups with no influence on administration,and no side-effects were reported in FA group. Conclusions This trial revealed the interventional effect of folic acid on the development of GI cancers,a similar effect of β-carotene was also detected.Also,folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.     

Treatment of rheumatoid arthritis with low doses of multi-glycosides of Tripterygium wilfordii

Thirty two cases of rheumatoid arthritis were treated with multi-glycosides of Tripterygium wilfordii (T2) in a dosage of 30 mg daily for 12 weeks. Significant improvements in clinical and laboratory variables were observed. In comparison with the results of routine dose of T2 (60 mg per day) treatment, there was no significant difference to be seen between the two treatment plans. Meanwhile, symptom of rash and slightly alimentary canal lower incidences and milder manifestations of side effects of T2 were found in the patients of low dose group than in that of routine dose group. It is suggested that it is reasonable to choose the dose of 30 mg daily as the routine treatment for rheumatoid arthritis patients.