海兰G-F20治疗症状性膝关节骨关节炎有效性与安全性的前瞻性单臂多中心临床研究

Evaluation on the efficacy and safety of Hylan G-F20（ Synvisc） for the treatment of knee osteoarthritis inChinese patients： a prospective, single arm, multicenter study

目的本研究采用前瞻性干涉性开放单臂多中心试验设计评价海兰G-F20(欣维可&#174;)注射治疗症状性膝关节骨关节炎的有效性和安全性。方法入选患膝关节骨关节炎的合格受试者237例,接受连续3次隔周关节腔内注射2 ml海兰G-F20。在给药后第8周、第12周、第26周,对受试者进行膝关节检查并对Western Ontario and Mc Master Universities(WOMAC),患者对目标膝关节的整体评价(patient global assessment,PTGA)、研究者对患者疾病的整体评价(clinical observer global assessment,COGA)问卷调查进行评估。结果注射海兰G-F20后,232例受试者在第8周、12周、第26周时目标膝关节行走痛评分均值较基线期都显著降低。其中给药后第26周时,主要观察指标目标膝关节行走痛(WOMAC A1)评分均值较基线期显著降低33.0±17.71(x-±s),(P<0.0001)。与基线期比较,降低幅度达59%。此外,第26周时受试者目标膝关节的疼痛程度(WOMAC A)、僵硬程度(WOMAC B)和关节功能(WOMAC C)评分均值较基线期显著降低121.5±77.2、36.6±39.8、358.4±270.5(P<0.0001)。受试者PTGA和COGA在第8周、第12周和第26周时的分布相对于其在基线期时的分布变化差异有统计意义,说明受试者自评或研究者评价受试者的总体状况随试验进行不断改善。共66例(27.8%)受试者发生不良事件(AE),其中9例(3.8%)受试者发生了与治疗相关的AE。整个试验期间,无治疗相关的严重不良事件(SAE),无死亡病例。结论使用海兰G-F20,患者关节疼痛、关节僵硬、关节功能都得到了有统计学意义的改善,其中关节行走痛的改善程度具有临床意义。在整个研究过程中,海兰G-F20治疗的临床副作用少,严重程度低,患者耐受性好。

Objective To assess the efficacy and safety of Hylan G-F20（ Synvisc） in a study on the treatment of knee steoarthritis in Chinese patients conducted as a prospective interventional single arm clinical trial. Methods Totally 237 patients with symptomatic knee osteoarthritis were enrolled. After signing the informed consent form, patients meeting the inclusion and exclusion criteria received three intra-articular injections of 2 ml Hylan G-F20 at weekly intervals and were followed up for evaluating the changes in Western Ontario and Mc Master Universities Osteoarthritis Index（ WOMAC）, Patient Global Assessment（ PTGA） score and Clinical Observer Global Assessment（ COGA） between baseline and weeks 8, 12 and 26. Results The score of walk associated pain（ WOMAC A1） was changed significantly over 8, 12 and 26 weeks from baseline in 232 patients injected with Hylan G-F20. Particularly the primary outcome of WOMAC A1 score at week of 26 was reduced significantly by 33.0 ± 17.71（ x- ± s）（ P 0.0001） with reduction rate of 59%. At week 26, the scores of WOMAC A, WOMAC B and WOMAC C were respectivelyreduced by 121.5 ± 77.2, 36.6 ± 39.8 and 358.4 ± 270.5（ P 0.0001）. The pattern of PIGA and COGA assessments significantly changed at 8, 12 and 26 weeks, which indicate the greater improvement of knee osteoarthritis of subjects along with the proceeding of the trial. In the study, adverse effects were reported in 66 patients（ 27.8%）, including 9 of whom（ 3.8%） were related to the treatment. Neither serious adverse effect due to the treatment nor death were reported. Conclusions This study demonstrated that in patients with knee osteoarthritis, an intra-articular injection of Hylan G-F20 is safe and effective in providing statistically significant, clinically relevant pain relief over 26 weeks.