Bocanegra T S, Weaver A L, Tindall E A, Sikes D H, Ball J A, Wallemark C B, Geis G S, Fort J G
Arthritis Center of Nebraska, Lincoln, USA.
J Rheumatol. 1998 Aug;25(8):1602-11.
Gastric (GU) and duodenal ulcers (DU) are common adverse effects of nonsteroidal anti-inflammatory drugs (NSAID). Endoscopically diagnosed upper gastrointestinal (GI) ulceration occurs in about 24% of longterm NSAID users. Coadministration of misoprostol with the NSAID reduces the incidence of NSAID induced GU and DU and their complications. However, compliance is limited by the different dosing regimens of misoprostol and NSAID and GI symptoms associated with misoprostol at its recommended q.i.d. dose. We compared the efficacy, safety, and incidence of endoscopic upper GI ulceration associated with the administration of 2 combinations of diclofenac (50 or 75 mg) and misoprostol 200 microg (D50/M200 t.i.d., D75/M200 b.i.d.), diclofenac 75 mg b.i.d., and placebo in a 6 week, randomized, double blind study in patients with osteoarthritis (OA) of the knee or hip.
A total of 572 patients with symptomatic OA of the knee or hip and history of GU, DU. or 10 or more erosions were randomized to receive D50/M200 t.i.d., D75/M200 b.i.d., diclofenac 75 mg b.i.d., or placebo for 6 weeks. Arthritis assessments were performed at baseline, 2, and 6 weeks, and upper GI endoscopies at baseline and end of treatment.
All active treatment groups were significantly better than placebo, at all visits, in improving OA symptoms. There were no significant differences in arthritis efficacy between the diclofenac/ misoprostol combinations and diclofenac. However, endoscopically diagnosed GU and/or DU were significantly less frequent in patients receiving D50/M200 t.i.d. (8%), D75/M200 b.i.d. (7%), and placebo (4%) compared to diclofenac 75 mg b.i.d. (17%). Adverse events were not different between the active treatment groups, except for higher incidences of flatulence with D75/M200 and diarrhea with D50/M200.
Diclofenac 50 mg/misoprostol 200 microg t.i.d. and diclofenac 75 mg/misoprostol 200 microg b.i.d. are as efficacious as diclofenac 75 mg b.i.d. in the treatment of OA, but are associated with a significantly lower incidence of gastric and/or duodenal ulcers.
胃溃疡（GU）和十二指肠溃疡（DU）是非甾体抗炎药（NSAID）常见的不良反应。内镜诊断的上消化道（GI）溃疡在长期服用NSAID的患者中发生率约为24%。米索前列醇与NSAID联合使用可降低NSAID诱发的GU和DU及其并发症的发生率。然而，米索前列醇和NSAID不同的给药方案以及米索前列醇推荐每日四次给药时出现的胃肠道症状限制了患者的依从性。在一项为期6周的随机双盲研究中，我们比较了双氯芬酸（50或75毫克）与米索前列醇200微克的两种联合用药方案（双氯芬酸50毫克/米索前列醇200微克每日三次、双氯芬酸75毫克/米索前列醇200微克每日两次）、双氯芬酸75毫克每日两次以及安慰剂在膝或髋骨关节炎（OA）患者中的疗效、安全性和内镜诊断的上消化道溃疡发生率。
共有572例有症状的膝或髋OA患者，且有GU、DU病史或10处及以上糜烂，被随机分为接受双氯芬酸50毫克/米索前列醇200微克每日三次、双氯芬酸75毫克/米索前列醇200微克每日两次、双氯芬酸75毫克每日两次或安慰剂治疗6周。在基线、第2周和第6周进行关节炎评估，并在基线和治疗结束时进行上消化道内镜检查。
在所有访视中，所有活性治疗组在改善OA症状方面均显著优于安慰剂。双氯芬酸/米索前列醇联合用药组与双氯芬酸组在关节炎疗效方面无显著差异。然而，与双氯芬酸75毫克每日两次组（17%）相比，接受双氯芬酸50毫克/米索前列醇200微克每日三次组（8%）、双氯芬酸75毫克/米索前列醇200微克每日两次组（7%）和安慰剂组（4%）内镜诊断的GU和/或DU发生率显著更低。活性治疗组之间不良事件无差异，只是双氯芬酸75毫克/米索前列醇200微克组腹胀发生率较高，双氯芬酸50毫克/米索前列醇200微克组腹泻发生率较高。
双氯芬酸50毫克/米索前列醇200微克每日三次和双氯芬酸75毫克/米索前列醇200微克每日两次在治疗OA方面与双氯芬酸75毫克每日两次疗效相当，但胃和/或十二指肠溃疡发生率显著更低。
