Altman R D, Moskowitz R
Department of Rheumatology and Immunology, University of Miami, Florida, USA.
J Rheumatol. 1998 Nov;25(11):2203-12.
To determine efficacy and safety of intraarticular (IA) hyaluronic acid (HA; Hyalgan) versus placebo and a nonsteroidal antiinflammatory drug for osteoarthritis (OA) of the knee.
A series of 5 weekly IA injections of HA (20 mg each) was compared to placebo or oral naproxen in a 26 week, double blind, masked observer, multicenter trial of 495 patients with idiopathic OA. Acetaminophen was permitted for escape analgesia. The primary measurement was pain experienced on a 50 foot walk test for those completing the study (completers) as measured on a 10 cm visual analog scale (VAS). Also measured were the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (pain, stiffness, function) and categorical assessments of pain.
Patients receiving HA improved more with respect to pain on the 50 foot walk compared to placebo at Week 26 (HA vs placebo difference 8.8 mm; p < 0.005); 56% of HA treated patients compared to 41 % of placebo treated patients had > or = 20 mm reduction in the VAS from Week 5 continuously through Week 26 (p=0.031). At 26 weeks, more HA treated patients (47.6%) had slight pain or were pain-free in contrast to placebo treated (33.1%; p=0.039) or naproxen treated (36.9%; p=0.22) [corrected] patients. Improvement in secondary outcome variables was generally superior in the HA group compared to those receiving placebo and was significantly better at Week 26 with respect to the WOMAC pain (p=0.041) and WOMAC physical function (p=0.047) subscales. The HA group also tended to have better results relative to the naproxen group in both primary and secondary assessments. For all randomized patients, there was a > or = 20 mm improvement in pain experienced on the 50 foot walk in 28% [corrected] of placebo treated patients vs 36% [corrected] of the HA treated patients (p=0.127; 67% of patients completed the trial). Injection site pain, more commonly reported in the HA group (38/164=23%) than in the placebo group (22/168=13%; p < 0.001), resulted in withdrawal in 6 patients (4%). One withdrawal was associated with the HA injection (< 1%). Gastrointestinal adverse events were significantly more common in the naproxen group than the HA or the placebo groups and 14 naproxen treated patients (8.3%) discontinued prematurely due to these events.
This large, controlled randomized clinical trial confirms that 5 weekly IA injections of HA (Hyalgan) in patients with OA of the knee are generally well tolerated, provide sustained relief of pain and improved patient function, and were at least as effective with fewer adverse reactions as continuous treatment with naproxen for 26 weeks.
确定关节内注射透明质酸（HA；施沛特）与安慰剂及一种非甾体抗炎药相比，治疗膝关节骨关节炎（OA）的疗效和安全性。
在一项为期26周的双盲、观察者设盲、多中心试验中，将495例特发性OA患者分为三组，一组接受每周1次、连续5周的关节内注射HA（每次20 mg），另两组分别接受安慰剂或口服萘普生治疗。允许使用对乙酰氨基酚进行解救镇痛。主要测量指标是完成研究的患者（完成者）在50英尺步行试验中经历的疼痛，采用10厘米视觉模拟量表（VAS）进行测量。还测量了西安大略和麦克马斯特大学（WOMAC）骨关节炎指数（疼痛、僵硬、功能）以及疼痛的分类评估。
在第26周时，与安慰剂相比，接受HA治疗的患者在50英尺步行试验中的疼痛改善更明显（HA与安慰剂的差异为8.8 mm；p < 0.005）；从第5周持续到第26周，接受HA治疗的患者中有56%的VAS降低≥20 mm，而接受安慰剂治疗的患者中这一比例为41%（p = 0.031）。在26周时，与接受安慰剂治疗（33.1%；p = 0.039）或萘普生治疗（36.9%；p = 0.22）[校正后]的患者相比，接受HA治疗的患者中有更多（47.6%）有轻微疼痛或无痛。与接受安慰剂的患者相比，HA组次要结局变量的改善总体上更优，并且在第26周时，在WOMAC疼痛（p = 0.041）和WOMAC身体功能（p = 0.047）子量表方面明显更好。在主要和次要评估中，HA组相对于萘普生组也往往有更好的结果。对于所有随机分组的患者，接受安慰剂治疗的患者中有28%[校正后]在50英尺步行试验中经历的疼痛改善≥20 mm，而接受HA治疗的患者中这一比例为36%[校正后]（p = 0.127；67%的患者完成了试验）。注射部位疼痛在HA组（38/164 = 23%）比安慰剂组（22/168 = 13%；p < 0.001）更常报告，导致6例患者（4%）退出。1例退出与HA注射有关（<1%）。胃肠道不良事件在萘普生组比HA组或安慰剂组明显更常见，14例接受萘普生治疗（8.3%）的患者因这些事件提前停药。
这项大型、对照随机临床试验证实，对于膝关节OA患者，每周1次、连续5周的关节内注射HA（施沛特）通常耐受性良好，能持续缓解疼痛并改善患者功能，且至少与连续26周服用萘普生一样有效，不良反应更少。
