背景:一种用于关节软骨再生的有前途的新型无细胞生物活性制剂,称为BIOF2,最近已在临床前试验中进行了测试。本研究的目的是评估BIOF2在严重膝关节骨关节炎患者关节内应用的有效性和安全性。
方法:前瞻性,随机化,三臂,进行平行组临床试验.包括24例严重膝关节骨性关节炎患者(WOMAC评分65.9±17)。在他们进入书房之前,所有患者都通过非甾体抗炎药(NSAIDs)的标准治疗在骨关节炎控制下,由家庭医生开处方。患者分为三组,每组8例(关节内BIOF2,全关节置换术,或单独使用NSAIDs保守治疗)。WOMAC的分数,RAPID3评分,在治疗前和第3、6和12个月评估Rasmussen临床评分。BIOF2在0、3和6个月应用。治疗前测定BIOF2组的全血细胞计数和血液化学参数,在72小时,在第1、3、6和12个月。此外,在研究开始时和第12个月时评估关节软骨体积(根据MRI)。
结果:NSAID组在随访时无改善。从第3个月开始,关节成形术和BIOF2治疗在所有评分量表中均显示出显着改善。在第6个月(WOMAC评分:19.3±18vs4.3±5;P=0.24)或第12个月(WOMAC评分:15.6±15vs15.7±17;P=1.0),BIOF2组与关节置换术组之间无统计学差异。在12个月(根据WOMAC评分:≤16),75%的患者关节成形术和BIOF2成功,NSAIDs的每日使用减少,与仅使用NSAIDs治疗组相比(RR=0.33,95%CI0.12-0.87,P=0.02。BIOF2与NSAIDs和关节成形术与NSAIDs的结果相同)。BIOF2使关节软骨显着增加22%(26.1±10vs31.9±10cm2,P<0.001),并显着降低了血清脂质。BIOF2耐受性良好,仅在应用时引起轻微至中度疼痛。
结论:新型生物活性无细胞制剂(BIOF2)的关节内应用具有良好的耐受性,与关节成形术治疗严重膝关节骨关节炎没有显着差异。BIOF2可以再生关节软骨,是治疗骨关节炎的一种易于实施的替代疗法。试验登记古巴临床试验公共登记处(RPCEC)数据库RPCEC00000250。2017年8月15日注册-回顾性注册,http://rpcec。sld.cu/en/试验/RPCEC00000250-En.
BACKGROUND: A promising novel cell-free bioactive formulation for articular cartilage regeneration, called BIOF2, has recently been tested in pre-clinical trials. The aim of the present
study was to evaluate the efficacy and safety of BIOF2 for intra-articular application in patients with severe osteoarthritis of the knee.
METHODS: A prospective, randomized, 3-arm, parallel group clinical
trial was conducted. It included 24 patients with severe osteoarthritis of the knee (WOMAC score 65.9 ± 17). Before they entered the
study, all the patients were under osteoarthritis control through the standard treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed by their family physician. Patients were distributed into three groups of 8 patients each (intra-articular BIOF2, total joint arthroplasty, or conservative treatment with NSAIDs alone). The WOMAC score, RAPID3 score, and Rasmussen clinical score were evaluated before treatment and at months 3, 6, and 12. BIOF2 was applied at months 0, 3, and 6. Complete blood count and blood chemistry parameters were determined in the BIOF2 group before treatment, at 72 h, and at months 1, 3, 6, and 12. In addition, articular cartilage volume was evaluated (according to MRI) at the beginning of the
study and at month 12.
RESULTS: The NSAID group showed no improvement at follow-up. Arthroplasty and BIOF2 treatments showed significant improvement in all the scoring scales starting at month 3. There were no statistically significant differences between the BIOF2 group and the arthroplasty group at month 6 (WOMAC score: 19.3 ± 18 vs 4.3 ± 5; P = 0.24) or month 12 (WOMAC score: 15.6 ± 15 vs 15.7 ± 17; P = 1.0). Arthroplasty and BIOF2 were successful at month 12 (according to a WOMAC score: ≤ 16) in 75% of the patients and the daily use of NSAIDs was reduced, compared with the group treated exclusively with NSAIDs (RR = 0.33, 95% CI 0.12-0.87, P = 0.02. This result was the same for BIOF2 vs NSAIDs and arthroplasty vs NSAIDs). BIOF2 significantly increased the articular cartilage by 22% (26.1 ± 10 vs 31.9 ± 10 cm2, P < 0.001) and produced a significant reduction in serum lipids. BIOF2 was well tolerated, causing slight-to-moderate pain only upon application.
CONCLUSIONS: The intra-articular application of the new bioactive cell-free formulation (BIOF2) was well tolerated and showed no significative differences with arthroplasty for the treatment of severe osteoarthritis of the knee. BIOF2 can regenerate articular cartilage and is an easily implemented alternative therapy for the treatment of osteoarthritis.
Trial registration Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000250. Registered 08/15/2017-Retrospectively registered, http://rpcec.sld.cu/en/trials/RPCEC00000250-En .