Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenerative joint disease of the knee
Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenerative joint disease of the knee
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DOI：
10.1016/j.joca.2015.06.019
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发表时间：
2015-12-01
影响因子：
7
通讯作者：
Mont, M. A.
中科院分区：
文献类型：
--
作者：
Cherian, J. J.;Parvizi, J.;Mont, M. A.
目的：本研究的目的是初步评估注射基因工程软骨细胞病毒转导与TGF-β 1（GEC-TGF-β 1）的疗效和结果相比，安慰剂。设计：一个多中心，双盲，安慰剂对照，随机研究成人膝关节骨关节炎。共102例患者以2：1的比例随机分配至GEC-TGF-b1组或安慰剂组。评估的主要结局为（1）膝关节功能，采用国际膝关节文献委员会（IKDC）评分;和（2）疼痛，采用视觉模拟量表（VAS）测量。次要终点评估疼痛和止痛剂的使用，生活质量（QOL），和不良事件（AE），包括需要全膝关节置换术后treatment.Results：IKDC显示显着改善GEC-TGF-b1组比安慰剂在第12周（最小均方差（LSMD）：10.3; P = 0.0342）、第52周（LSMD：13.6; P = 0.0082）和总体（LSMD：8.6; P = 0.0453）。VAS分析显示，与安慰剂组相比，GEC-TGF-β 1组在第12周（LSMD：-13.8; P = 0.0162）、第52周（LSMD：-13.1; P = 0.0332）和总体（LSMD：-10.1; P = 0.0350）时显著改善。在第12周和第52周，在24小时和第52周的频率，在GEC-TGF-β 1组接受镇痛药在第4周（27对40%）和第12周（27对37%）的患者的百分比疼痛严重程度的降低被observed.Conclusions：GEC-TGF-β 1患者有更多的积极响应IKDC，VAS，并不太可能需要镇痛药。(C)2015国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: The aim of this study was to preliminarily evaluate the efficacy and outcomes of injectable genetically engineered chondrocytes virally transduced with TGF-beta 1 (GEC-TGF-beta 1) compared to placebo.Design: A multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 2: 1 randomized to GEC-TGF-b1 or placebo. Primary outcomes assessed were (1) function of the knee joint, scored using the International Knee Documentation Committee (IKDC); and (2) pain, measured by Visual Analog Scale (VAS). Secondary endpoints assessed were pain and analgesic use, quality of life (QOL), and adverse events (AEs) including need for total knee arthroplasty after treatment.Results: IKDC showed significant improvement in the GEC-TGF-b1 group over the placebo at week 12 (least mean square difference (LSMD): 10.3; P = 0.0342), week 52 (LSMD: 13.6; P = 0.0082), and overall (LSMD: 8.6; P = 0.0453). VAS Analysis showed a significant improvement in GEC-TGF-beta 1 group compared to placebo at weeks 12 (LSMD: - 13.8; P = 0.0162), 52 (LSMD: - 13.1; P = 0.0332), and overall (LSMD: - 10.1; P = 0.0350). Reduction in pain severity at week 12 and 52, frequency at 24 h and week 52, and the percentage of patients in the GEC-TGF-beta 1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed.Conclusions: GEC-TGF-beta 1 patients had more positive responses on the IKDC, VAS, and were less likely to require analgesics. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.