Background/Purpose: Chikungunya virus (CHIKV) is a rapidly emerging arthritogenic mosquito-borne alphavirus that has infected more than 1 million individuals in the Western Hemisphere since 2014.  CHIKV arthritis can persist for months to years, but little is known about potential therapies for this epidemic polyarthritis.  We previously reported that CHIKV arthritis and rheumatoid arthritis (RA) exhibit similar clinical features as well as peripheral T cell phenotypes, suggesting immunological overlap in the pathogenesis of CHIKV arthritis and RA.  However, the effects of immunosuppression during CHIKV arthritis are unknown. Here, we describe the clinical and virological effects of immunosuppressive and antiviral therapies in a mouse model of CHIKV arthritis.

Methods: Two hundred and eighty C57BL6/J mice were infected with the La Reunion strain of CHIKV, followed by treatment on day 3 after infection with either neutralizing anti-CHIKV monoclonal antibodies or with one of seven immunomodulatory therapies: CTLA4-Ig, tofacitinib, anti-CD20, etanercept, methylprednisolone, naproxen, and methotrexate.  Clinical disease was assessed by measuring footpad thickness over time.  Viral titers at day 7 were measured by qRT-PCR.   

Results: Treatment with CTLA4-Ig, tofacitinib, or with anti-CHIKV monoclonal antibodies effectively reduced arthritic swelling at day 7 after infection without major effects on viral titers in the affected joints. Administration of anti-CD20 or etanercept exacerbated CHIKV arthritis, distinguishing CHIKV arthritis from RA.

Conclusion: CHIKV arthritis is clinically ameliorated by tofacitinib, CTLA4-Ig or neutralizing monoclonal antibodies directed against the CHIKV E2 envelope protein. By contrast, blockade of TNF-alpha and depletion of CD20+ B cells had deleterious effects.  Our results demonstrate novel potential therapies for CHIKV arthritis in a preclinical model. Additional studies are required to determine the safety and efficacy of these therapies in human patients with CHIKV arthritis since immunosuppression may still pose serious risks, especially during the acute phase of infection.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunomodulatory-and-antiviral-therapies-in-a-mouse-model-of-chikungunya-viral-arthritis/