Immunomodulatory therapy of chikungunya arthritis: systematic review and meta-analysis

Abstract Background Chikungunya virus (CHIKV) infection can lead to chronic musculoskeletal complications, including persistent arthritis that resembles autoimmune inflammatory conditions. These symptoms have been reported both in endemic populations and in international travellers, with substantial functional and economic consequences. Objective This systematic review and meta-analysis aimed to assess the efficacy and safety of immunomodulatory therapies in chikungunya-related arthritis. Methods A systematic search was conducted in PubMed, Scopus, Cochrane, Web of Science, SciELO, and LILACS. Risk of bias was assessed using RoB 2.0 for randomized trials, the Newcastle-Ottawa Scale for observational studies, and the JBI Checklist for case series. A random-effects meta-analysis was performed due to significant heterogeneity (I2 > 97%). Results Eleven studies comprising 742 patients met the inclusion criteria. Methotrexate (MTX) was the most studied immunomodulator. The meta-analysis showed a mean reduction in DAS28 (disease Activity score) of 2.67 (95% CI, 1.84 - 3.49, p < 0.001, I2 = 97.0%) and a decrease in VAS (visual analogue scale) pain scores of 4.31 (95% CI, 2.56 - 6.06, p < 0.001, I2 = 99.1%). Subgroup analysis suggested greater pain reduction in short-term studies. No severe adverse events were reported, but long-term safety data are limited. Conclusions Immunomodulatory therapy, particularly methotrexate, may provide symptom relief in chikungunya arthritis. These findings are relevant not only for endemic settings but also for travel medicine, as chikungunya-related arthritis has been increasingly reported in travellers. However, high study heterogeneity and the lack of randomized trials limit definitive conclusions. Future research should focus on standardizing outcome measures, biomarker-driven patient selection, and long-term safety assessments. Clinicians treating returning travellers with chronic joint symptoms should consider post-CHIKV arthritis as part of the differential diagnosis and be aware of potential treatment options