Lohmander L S, McKeith D, Svensson O, Malmenäs M, Bolin L, Kalla A, Genti G, Szechinski J, Ramos-Remus C
Department of Orthopaedics, Lund University, SE-221 85 Lund, Sweden.
Ann Rheum Dis. 2005 Mar;64(3):449-56. doi: 10.1136/ard.2004.023572. Epub 2004 Sep 2.
To evaluate the gastrointestinal safety and efficacy of the COX inhibiting nitric oxide donator AZD3582 in patients with hip or knee osteoarthritis.
970 patients were randomised (7:7:2) to AZD3582 750 mg twice daily, naproxen 500 mg twice daily, or placebo twice daily in a double blind study. The primary end point was the six week incidence of endoscopic gastroduodenal ulcers (diameter > or =3 mm). Overall damage measured on the Lanza scale was a secondary end point. Safety and tolerability assessments included endoscopic upper gastrointestinal erosions and the gastrointestinal symptom rating scale (GSRS). Efficacy was primarily assessed by WOMAC.
The incidence of ulcers with AZD3582 was 9.7% and with naproxen 13.7% (p = 0.07, NS), v 0% on placebo. The incidence of Lanza scores >2 was higher with naproxen (43.7%) than with AZD3582 (32.2%) (p<0.001). Compared with baseline, significantly fewer ulcers and erosions developed in stomach and stomach/duodenum combined, and fewer erosions developed in stomach, duodenum, and both combined on AZD3582 than on naproxen. GSRS reflux and abdominal pain subscale scores were lower for AZD3582 than for naproxen but there was no difference for indigestion, constipation, and diarrhoea. AZD3582 was as effective as naproxen at improving WOMAC scores. Both agents were well tolerated, with no significant effects on blood pressure.
At doses with similar efficacy in relieving osteoarthritis symptoms, the primary end point of six week endoscopic gastroduodenal ulcer incidence was not significantly different between AZD3582 and naproxen. Most secondary endoscopic gastrointestinal end points favoured AZD3582.
评估COX抑制性一氧化氮供体AZD3582在髋或膝骨关节炎患者中的胃肠道安全性和疗效。
在一项双盲研究中，970例患者按7:7:2随机分为每日两次服用750 mg AZD3582组、每日两次服用500 mg萘普生组或每日两次服用安慰剂组。主要终点为内镜下胃十二指肠溃疡（直径≥3 mm）的六周发生率。Lanza量表测量的总体损伤为次要终点。安全性和耐受性评估包括内镜下上消化道糜烂和胃肠道症状评分量表（GSRS）。疗效主要通过WOMAC进行评估。
AZD3582组溃疡发生率为9.7%，萘普生组为13.7%（p = 0.07，无统计学意义），安慰剂组为0%。萘普生组Lanza评分>2的发生率（43.7%）高于AZD3582组（32.2%）（p<0.001）。与基线相比，AZD3582组胃及胃/十二指肠联合部位发生的溃疡和糜烂明显少于萘普生组，胃、十二指肠及两者联合部位发生的糜烂也少于萘普生组。AZD3582组的GSRS反流和腹痛子量表评分低于萘普生组，但消化不良、便秘和腹泻方面无差异。AZD3582在改善WOMAC评分方面与萘普生效果相当。两种药物耐受性均良好，对血压无显著影响。
在缓解骨关节炎症状疗效相似的剂量下，AZD3582和萘普生在六周内镜下胃十二指肠溃疡发生率这一主要终点上无显著差异。大多数次要内镜下胃肠道终点指标更有利于AZD3582。
