Methotrexate treatment of Arthritis caused by Chikungunya virus (MARCH): A randomized controlled trial of methotrexate versus placebo in the treatment of chronic arthritis after chikungunya infection

摘要 基孔肯雅病毒(CHIKV)是一种由蚊子传播的甲型病毒，可导致持续性关节炎 大约25%的人在初次感染两年后。目前还没有标准的基于证据的 CHIKV慢性关节炎的治疗。法国指南建议使用甲氨蝶呤治疗 然而，慢性CHIKV关节炎没有甲氨蝶呤的随机安慰剂对照试验来支持 这是一项建议。我们的长期目标是指导CHIKV关节炎的循证治疗。主 这项建议的目的是确定6个月的治疗滑膜炎的疗效和病理影响。 哥伦比亚慢性CHIKV关节炎的甲氨蝶呤(n=100)与安慰剂(n=100)治疗的随机对照研究 对照试验。我们的中心假设是甲氨蝶呤将显著降低慢性CHIKV 关节炎疾病严重程度与安慰剂的比较及通过抑制白细胞对CHIKV诱导的滑膜炎的影响 在滑膜组织中堆积。这一假设将在两个具体目标中进行评估。在目标1中，我们将确定 口服甲氨蝶呤与安慰剂治疗慢性CHIKV关节炎6个月的疗效比较。在目标2中，我们 将通过获取滑膜活检样本来确定甲氨蝶呤对滑膜炎症的影响 并在治疗后。理论基础：这项工作将确定甲氨蝶呤在慢性CHIKV治疗中的作用 关节炎，目标是将该领域推向循证标准治疗。潜力 这项工作的更广泛的影响是可能确定慢性病毒性关节炎的病理机制。 以及一种可能的治疗选择。

ABSTRACT Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes persistent arthritis in approximately 25% of people two years after initial infection. There is currently no standard evidence-based treatment for CHIKV chronic arthritis. The French guidelines suggest the use of methotrexate in the treatment of chronic CHIKV arthritis however there are no randomized placebo-controlled trials of methotrexate to support this recommendation. Our long-term goal is to guide the evidence-based treatment of CHIKV arthritis. The main goal of this proposal is to determine the efficacy and pathologic effects on synovitis of 6 months of methotrexate (n=100) versus placebo (n=100) therapy for chronic CHIKV arthritis in Colombia in a randomized controlled trial. Our central hypothesis is that methotrexate will significantly decrease the chronic CHIKV arthritis disease severity compared to placebo and effect CHIKV-induced synovitis via suppression of leukocyte accumulation in synovial tissue. This hypothesis will be evaluated in 2 specific aims. In Aim 1, we will determine the efficacy of oral methotrexate treatment versus placebo for 6 months in chronic CHIKV arthritis. In Aim 2, we will determine the effect of methotrexate on synovial inflammation by obtaining synovial biopsy samples before and after treatment. Rationale: This work will define the role of methotrexate in the treatment of chronic CHIKV arthritis with the goal of advancing the field towards an evidence-based standard treatment. The potential broader impact of this work is the potential identification of the pathologic mechanism of chronic viral arthritis and a possible therapeutic option.