Migliore Alberto, Blicharski Tomasz, Plebanski Rafal, Zegota Zbigniew, Gyula Győrfi, Rannou François, Reginster Jean-Yves
Rheumatology Unit, S. Pietro FBF Hospital, Via Cassia 600, 00189, Rome, Italy.
Chair and Department of Rehabilitation and Orthopaedics, Medical University of Lublin, Lublin, Poland.
Rheumatol Ther. 2021 Dec;8(4):1617-1636. doi: 10.1007/s40744-021-00363-3. Epub 2021 Aug 30.
The objective of this study was to compare a single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) versus placebo in treating moderate-to-severe symptomatic knee osteoarthritis.
Subjects with primary osteoarthritis knee pain (Kellgren and Lawrence grade 2-3) were randomly assigned to intra-articular HA-HL or placebo in a prospective, double-blind, 24-week study. The primary outcome variable was change from screening to week 24 of a Visual Analogue Scale (VAS) pain score. Secondary outcomes included Lequesne's algofunctional index, EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) response and rescue medication usage.
In a total of 692 randomized patients, a rapid decrease was observed in mean VAS pain score from baseline to week 1 (26 ± 24 mm in the HA-HL group vs. 23 ± 23 mm in the placebo group); pain intensity continued to decrease during 24 weeks of follow-up, reaching a mean change from baseline of 35 ± 28 mm vs. 32 ± 27 mm at week 24. Mixed model analysis demonstrated statistically significant differences between groups in favor of the HA-HL group at weeks 1, 6, 12, and 24. HA-HL was also more effective than placebo in improving Lequesne's algofunctional index, OMERACT-OARSI response, and health-related quality of life. The use of rescue medication (paracetamol 500 mg tablets; ≤ 6 per day) was lower in the HA-HL group. Both treatments were similarly well tolerated.
A single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) is effective in providing fast, sustained, and clinically relevant reductions in pain, functional limitation, and health-related quality of life that were apparent at 1 week after the intra-articular injection and maintained throughout the 24-week follow-up in subjects with painful knee osteoarthritis, with a good safety profile.
ClinicalTrials.gov identifier: NCT03200288.
本研究的目的是比较单次关节腔内注射创新型高分子量和低分子量透明质酸制剂（HA-HL）与安慰剂治疗中重度症状性膝骨关节炎的效果。
在一项前瞻性、双盲、为期24周的研究中，将原发性膝骨关节炎疼痛（凯尔格伦和劳伦斯分级2-3级）的受试者随机分配接受关节腔内注射HA-HL或安慰剂。主要结局变量是从筛查到第24周视觉模拟量表（VAS）疼痛评分的变化。次要结局包括勒凯斯内疼痛功能指数、欧洲五维健康量表（EQ-5D-5L）、关节炎临床试验-国际骨关节炎研究协会结局测量指标（OMERACT-OARSI）反应以及急救药物使用情况。
在总共692名随机分组的患者中，观察到从基线到第1周平均VAS疼痛评分迅速下降（HA-HL组为26±24mm，安慰剂组为23±23mm）；在24周的随访期间疼痛强度持续下降，到第24周时，与基线相比平均变化分别为35±28mm和32±27mm。混合模型分析显示，在第1、6、12和24周时，两组之间存在统计学上的显著差异，支持HA-HL组。HA-HL在改善勒凯斯内疼痛功能指数、OMERACT-OARSI反应和健康相关生活质量方面也比安慰剂更有效。HA-HL组急救药物（对乙酰氨基酚500mg片剂；每天≤6片）的使用量较低。两种治疗的耐受性相似。
单次关节腔内注射创新型高分子量和低分子量透明质酸制剂（HA-HL）可有效快速、持续且在临床上显著减轻疼痛、功能受限以及健康相关生活质量，在关节腔内注射后1周即明显显现，并在有疼痛的膝骨关节炎受试者的24周随访期间持续存在，且安全性良好。
ClinicalTrials.gov标识符：NCT03200288。
