Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Biomarkers and Research, Nordic Bioscience, Hovedgade 205-207, 2730, Herlev, Denmark.
Arthritis Res Ther. 2019 Feb 22;21(1):68. doi: 10.1186/s13075-019-1819-9.
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.
Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography.
Naproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.
This study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure.
疼痛是类风湿关节炎（RA）的一种使人虚弱的症状，由关节炎症和软骨及骨破坏引起。非甾体抗炎药（NSAIDs）用于治疗 RA 中的疼痛和炎症，但它们不是疾病修饰药物，并且单独使用时不能预防关节破坏。KBPs（Key Bioscience 肽）是基于鲑鱼降钙素的合成肽，预计能抑制骨吸收并具有软骨保护作用。在这项研究中，我们研究了在 RA 的大鼠模型中，将 NSAID（萘普生）与 KBP 联合使用是否能改善疼痛评分，以及疾病活动度和结构损伤。
通过用猪型 II 胶原免疫接种，在 40 只雌性 Lewis 大鼠中诱导胶原诱导性关节炎（CIA）；10 只大鼠给予假注射。CIA 大鼠用 KBP 和/或萘普生治疗。每天评估健康评分和关节评分。使用机械和冷感觉异常测试和挖掘测试来评估疼痛样行为。采集血液样本进行生物标志物检测，并采集爪子进行组织学和微计算机断层扫描。
萘普生单药治疗增加了达到人道终点的时间，并改善了健康评分、疼痛评估和小梁厚度，而 KBP 单药治疗没有改善。联合治疗比萘普生单药治疗更有效；联合治疗改善了健康评分，并重要的是降低了机械和冷感觉异常评估。此外，还观察到关节软骨结构的保护和骨结构及骨量的保存。
这项研究表明，将 KBP 和萘普生联合使用可能是治疗 RA 的一种相关治疗策略，可改善整体健康、疼痛、炎症和关节结构。
