Delmas P D, Lambert R, Capron M H
Service de Rhumatologie et de Pathologie Osseuse, Hôpital E. Herriot, Lyon.
Rev Rhum Ed Fr. 1994 Feb;61(2):126-31.
A multicenter, double-blind, placebo-controlled study was carried out to determine whether the synthetic prostaglandin E1 analog misoprostol is effective in preventing gastric and duodenal lesions induced by nonsteroidal anti-inflammatory drugs. Two hundred fifty-six patients under nonsteroidal anti-inflammatory drug treatment (diclofenac, naproxen, piroxicam, ibuprofen, indomethacin, ketoprofen, or tiaprofenic acid) for osteoarthritis, rheumatoid arthritis, or other rheumatic diseases were included in the study. None of the patients had patent gastroduodenal damage at entry (0 to 3 mucosal erosions or subepithelial hemorrhages on endoscopy). Patients were randomly assigned to treatment with misoprostol 400 micrograms/d (M 400), misoprostol 800 micrograms/d (M 800) or a placebo. Results of the follow-up endoscopy on day 28 in the 186 evaluable patients showed that gastric erosions were significantly less common (p < or = 0.02) in the two misoprostol groups (5% and 2% in the M 400 and M 800 groups respectively) than in the placebo group (19%). Similar small numbers of patients in the three groups had gastric subepithelial hemorrhages or duodenal lesions. Three patients developed gastric ulcers in the placebo group, versus none in the misoprostol groups. Misoprostol therapy did not modify the efficacy of the nonsteroidal antiinflammatory agent on pain or other rheumatologic manifestations. Diarrhea occurred in 1%, 10%, and 5% of patients in the M 400, M 800, and placebo groups, respectively. In conclusion, misoprostol given in combination with a nonsteroidal anti-inflammatory agent for 28 days significantly reduced the incidence of gastric erosions in a random sample of patients with a variety of rheumatic diseases. The daily dosage associated with the best risk/benefit ratio may be 400 micrograms/day.
开展了一项多中心、双盲、安慰剂对照研究，以确定合成前列腺素E1类似物米索前列醇是否能有效预防非甾体抗炎药所致的胃和十二指肠病变。256例因骨关节炎、类风湿关节炎或其他风湿性疾病接受非甾体抗炎药（双氯芬酸、萘普生、吡罗昔康、布洛芬、吲哚美辛、酮洛芬或噻洛芬酸）治疗的患者纳入该研究。入组时所有患者均无明显的胃十二指肠损害（内镜检查显示0至3处黏膜糜烂或上皮下出血）。患者被随机分配接受400微克/天米索前列醇（M 400）、800微克/天米索前列醇（M 800）或安慰剂治疗。186例可评估患者在第28天的随访内镜检查结果显示，两个米索前列醇组的胃糜烂发生率显著低于安慰剂组（M 400组和M 800组分别为5%和2%，安慰剂组为19%，p≤0.02）。三组中出现胃上皮下出血或十二指肠病变的患者数量相近。安慰剂组有3例发生胃溃疡，米索前列醇组无。米索前列醇治疗未改变非甾体抗炎药对疼痛或其他风湿表现的疗效。M 400组、M 800组和安慰剂组患者腹泻发生率分别为1%、10%和5%。总之，在患有各种风湿性疾病的随机抽样患者中，米索前列醇与非甾体抗炎药联合使用28天可显著降低胃糜烂的发生率。具有最佳风险/效益比的每日剂量可能为400微克/天。
