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

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.