CR500® 治疗可改善膝骨关节炎患者的algofunctional 评分：一项上市后确证性、单臂临床研究。

Treatment with CR500® improves algofunctional scores in patients with knee osteoarthritis: a post-market confirmatory interventional, single arm clinical investigation.

机构信息

Laboratorio di Biotecnologie Applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, Milan, 20161, Italy.

Orthopedics and Traumatology Department, Humanitas Mater Domini, Varese, Italy.

出版信息

BMC Musculoskelet Disord. 2023 Aug 12;24(1):647. doi: 10.1186/s12891-023-06754-7.

DOI:10.1186/s12891-023-06754-7

PMID:37573322

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10422714/

Abstract

BACKGROUND

Knee osteoarthritis (OA) is a progressive and degenerative condition. Several pharmacological and non-pharmacological treatments are able to improve the OA symptoms and the structural characteristics of the affected joints. Among these, infiltrative therapy with hyaluronic acid (HA) is the most used and consolidated procedure for the pain management. The addition of skin conditioning peptides to HA promotes the cartilage remodeling processes and a better permeation of the HA-based gel containing a peptide mixture, CR500®. Furthermore, the topic route of administration is convenient over the routinely used intra-articular injective procedures. In this study, the effectiveness of CR500® was evaluated in terms of improvement of the algo-functional symptoms related to unilateral knee OA.

METHODS

38 mild and moderate OA patients were enrolled at a screening visit (V-1), treated at baseline visit (V1), and then continued the topical application of CR500® twice a week for 4 weeks, and followed-up for 3 visits (V2-V4) from week 2 to 4. Lequesne Knee Index (LKI) and Knee injury and Osteoarthritis Outcome Score (KOOS) were collected. Synovial fluid was collected and used for the quantification of neoepitope of type II collagen (C2C), C-terminal telopeptide of type II collagen (CTX-II), type II collagen propeptide (CPII), tumor necrosis factor alpha (TNFα) and HA. The expression of CD11c and CD206 was evaluated on cell pellets.

RESULTS

Three patients were excluded, thus 35 patients were included in the analysis. The treatment with CR500® was safe and well tolerated, with 7.9% patients had mild adverse events, not related to the device. The LKI total score showed a significant decrease from V1 to V4. KOOS score also showed a significant improvement of patient condition at V2, V3 and V4 in comparison with V1 for all subscales, except for KOOS sport subscale which improved only from V3. At V1 a negative correlation among KOOS pain subscale values and C2C, CPII and TNFα levels was observed, as well as a positive correlation between KOOS pain subscale and CD11c/CD206 ratio.

CONCLUSION

CR500® is safe and appear to be effective in improving pain and function in OA patients during the 4 weeks of treatment.

TRIAL REGISTRATION

ClinicalTrials.gov ID: NCT05661162. This trial was registered on 22/12/2022.

摘要

背景

膝骨关节炎（OA）是一种进行性和退行性疾病。有几种药理学和非药理学的治疗方法能够改善 OA 症状和受影响关节的结构特征。在这些方法中，透明质酸（HA）的渗透治疗是最常用和最成熟的用于疼痛管理的方法。将皮肤调理肽添加到 HA 中可促进软骨重塑过程，并使含有肽混合物 CR500®的 HA 基凝胶更好地渗透。此外，该主题给药途径比常规关节内注射程序更方便。在这项研究中，评估了 CR500®在改善单侧膝骨关节炎相关algofunctional 症状方面的有效性。

方法

在筛选访问（V-1）时纳入 38 名轻度和中度 OA 患者，在基线访问（V1）时进行治疗，然后继续每周两次局部应用 CR500®，持续 4 周，并在第 2 周到第 4 周进行 3 次随访（V2-V4）。收集 Lequesne 膝关节指数（LKI）和膝关节损伤和骨关节炎结果评分（KOOS）。收集滑液用于定量 II 型胶原的新表位（C2C）、II 型胶原 C 端肽（CTX-II）、II 型胶原前肽（CPII）、肿瘤坏死因子-α（TNFα）和 HA。评估细胞沉淀上的 CD11c 和 CD206 的表达。

结果

有 3 名患者被排除在外，因此有 35 名患者纳入分析。CR500®治疗安全且耐受性良好，7.9%的患者出现轻度不良事件，与设备无关。LKI 总分从 V1 到 V4 显示出显著下降。KOOS 评分也显示，在 V2、V3 和 V4 时，与 V1 相比，所有子量表的患者病情均有显著改善，除了 KOOS 运动子量表仅从 V3 改善。在 V1 时，观察到 KOOS 疼痛子量表值与 C2C、CPII 和 TNFα水平之间存在负相关，以及 KOOS 疼痛子量表与 CD11c/CD206 比值之间存在正相关。