Several different currently approved immunomodulatory therapies ameliorated arthritis symptoms in chikungunya-infected mice in two studies that separate teams of researchers published online Feb. 1 in Science Translational Medicine.
The first team, led by Jonathan J. Miner, MD, PhD, of Washington University in St. Louis tested six different approved oral and biologic antirheumatic agents (along with control agents) in chikungunya virus-infected mice with acute arthritis and foot swelling ().(Orencia) and tofacitinib (Xeljanz) improved arthritis symptoms while other medications used in rheumatoid arthritis – including etanercept, methotrexate, naproxen, and methylprednisolone – had no significant effect on symptoms at the doses used in the study. Both abatacept and tofacitinib, injected during the peak of acute infection, reduced foot swelling at day 7 in the mice, compared with untreated controls (P less than .005 for both), but neither agent used alone affected viral RNA levels.
When the researchers paired abatacept with an antiviral therapy (monoclonal anti-CHIKV human antibody) the combination “was highly effective at reducing joint inflammation, periarticular swelling, migration of inflammatory leukocytes, and infection, even when administered several days after virus inoculation,” Dr. Miner and his colleagues wrote.
The researchers concluded that a combination of anti-inflammatory and antibody-based antiviral therapy “may serve as a model for treating humans with arthritis caused by CHIKV or other related viruses.”
In the second study, researchers led by Teck-Hui Teo, PhD, of the Agency for Science, Technology and Research (A*STAR) in Singapore, further elucidated the mechanisms by which CHIKV proteins act on T cells ((Gilenya), a drug that blocks T-cell migration from the lymph nodes to the joints and is approved for the treatment of multiple sclerosis, saw reduced arthritis symptoms even without reduction of viral replication.). They also found that CHIKV-infected mice treated with fingolimod
Infection with the chikungunya virus can produce arthritis that mimics symptoms of rheumatoid arthritis and may in some cases lead to joint damage. Though the mechanisms driving chikungunya-related arthritis are not well understood, preliminary studies have suggested a T-cell–mediated adverse response.
The Singapore team received funding from its own agency, A*STAR, while the Washington University researchers received grants from the National Institutes of Health and the Rheumatology Research Foundation. Two coauthors on the U.S. study reported extensive commercial conflicts, including consulting and advisory relationships with pharmaceutical and vaccine manufacturers, and one patent.