Department of Rheumatology and UR 4490, University Hospital of Lille, Lille, France.
SLC Biostatistics Consulting, Chamesey, France.
Adv Ther. 2021 May;38(5):2271-2283. doi: 10.1007/s12325-021-01648-3. Epub 2021 Mar 16.
Several viscosupplement treatments are available for patients suffering from painful osteoarthritis (OA) of the knee, but few comparative clinical trials have been conducted. The primary objective of the trial was to demonstrate the non-inferiority of Synolis VA (80 mg hyaluronic acid and 160 mg sorbitol) (Group HA1) to Synvisc-One (48 mg hylan GF-20) (Group HA2) at Day 168 in terms of pain relief efficacy in patients with knee OA (Kellgren and Lawrence radiological stage II or III) in whom oral treatment with analgesics, NSAIDs or weak opioids provided insufficient clinical responses or were poorly tolerated.
This was a prospective, multicentre, comparative, randomized, double-blinded trial comparing the two previously indicated viscosupplements, HA1 and HA2. The average VAS pain score (1-100) was 62.5 at baseline (Day 0). The patients were randomized into two parallel groups at Day 0 and followed until Day 168. They received one injection of either HA1 or HA2. The primary end point was the evolution of the Western Ontario and McMaster University (WOMAC) pain index at D168 in the groups. One of the secondary end points was the daily assessment of this index by the patient for 7 days following the injection and thereafter at Day 14. The other secondary end points were the WOMAC pain, stiffness, function and total scores assessed at Day 28, Day 84 and Day 168. At Day 168, efficacy and satisfaction were assessed by the evaluator and by the patient using a Likert scale (7 points). Moreover, the number of strict responders in each group was evaluated according to the The Osteoarthritis Research Society International (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology (OMERACT) criteria (OMERACT-OARSI). The per protocol (PP) population was used for the primary analysis.
A total of 202 patients were randomized. The patients were predominantly female (66%). The median age of the whole population was 65 years, and the median body mass index was 27.4 kg/m. No statistically significant differences between the two treatment groups were observed for any of the demographic criteria. At Day 168, 197 had had no protocol violations (94 in the HA1 group and 103 in the HA2 group). The WOMAC pain score decreased in the two groups: - 29.2 ± 24.1 (SD) in the HA1 group and - 31.6 ± 25.5 (SD) in the HA2 group, confirming the non-inferiority of Synolis VA (P = 0.57 for the difference between groups). Regarding the secondary end points, no significant difference was observed at Day 14, Day 28, Day 84 or Day 168 for all the outcomes except stiffness at Day 28 (P = in favour of treatment received in HA2). The rate of responders was comparable between the two groups: 79% for HA1 and 77% for HA2. Both products were well tolerated. Serious adverse events were reported by four patients in the HA1 group and 3 in the HA2 group.
In this trial, we confirmed the non-inferiority of Synolis VA compared to Synvisc-One at Day 168 according to the WOMAC pain score. Safety was satisfying and comparable in the two groups.
2017-A00034-49.
有几种黏弹性补充治疗可供患有疼痛性骨关节炎（OA）的膝关节患者使用，但很少有比较性临床试验。该试验的主要目的是证明 Synolis VA（80mg 透明质酸和 160mg 山梨醇）（HA1 组）在第 168 天在疼痛缓解疗效方面不劣于 Synvisc-One（48mg 透明质酸钠-20）（HA2 组）在口服镇痛药、非甾体抗炎药或弱阿片类药物治疗反应不足或耐受性差的膝关节 OA（Kellgren 和 Lawrence 放射学 II 或 III 期）患者中。
这是一项前瞻性、多中心、比较、随机、双盲试验，比较了两种先前指出的黏弹性补充剂，HA1 和 HA2。平均 VAS 疼痛评分（1-100）在基线（第 0 天）为 62.5。患者在第 0 天随机分为两组，并随访至第 168 天。他们接受了一次 HA1 或 HA2 的注射。主要终点是在第 168 天时两组的西部安大略省和麦克马斯特大学（WOMAC）疼痛指数的演变。次要终点之一是患者在注射后 7 天内和此后第 14 天每天评估该指数。其他次要终点是在第 28、84 和 168 天评估 WOMAC 疼痛、僵硬、功能和总评分。在第 168 天，由评估者和患者使用李克特量表（7 分）评估疗效和满意度。此外，根据骨关节炎研究协会国际（OARSI）临床试验反应标准倡议和风湿病终点措施（OMERACT）标准（OMERACT-OARSI）评估了每组中严格应答者的数量。主要分析使用符合方案（PP）人群。
共有 202 名患者被随机分组。患者主要为女性（66%）。整个人群的中位年龄为 65 岁，中位体重指数为 27.4kg/m。两组之间没有观察到任何人口统计学标准的统计学显著差异。在第 168 天，197 名患者没有违反方案（HA1 组 94 名，HA2 组 103 名）。两组的 WOMAC 疼痛评分均下降：HA1 组下降了 29.2±24.1（SD），HA2 组下降了 31.6±25.5（SD），证实了 Synolis VA 的非劣效性（组间差异 P=0.57）。关于次要终点，除了第 28 天的僵硬外（有利于 HA2 治疗），在第 14、28、84 或 168 天，所有结果均未观察到显著差异。应答率在两组之间相似：HA1 组为 79%，HA2 组为 77%。两种产品均具有良好的耐受性。HA1 组有 4 名患者和 HA2 组有 3 名患者报告了严重不良事件。
在这项试验中，我们根据 WOMAC 疼痛评分证实了 Synolis VA 在第 168 天与 Synvisc-One 的非劣效性。安全性令人满意，两组之间相似。
2017-A00034-49。
