In a proportion of patients, chikungunya arthritis (CA) might run into a chronic persistent phase. The treatment for this phase is not very clear. In this randomized parallel group open label study of 24 weeks duration, we evaluated the efficacy of DMARD combination in persistent CA. Consecutive 139 patients with persistent CA (persistent arthritis for >1 year after the chikungunya fever either in 2008 or 2009 fulfilling epidemiological criteria for CA) were screened. Of these patients who were already taking hydroxychloroquine (HCQ) and had active arthritis were randomized to receive either fixed-dose combination therapy (methotrexate 15 mg/day, sulfasalazine 1 g/day, and HCQ 400 mg/day) or continue with HCQ 400 mg/day (dose optimized) monotherapy. Both groups received oral prednisolone up to 6 weeks. Assessments at every 4 weeks were carried out for primary efficacy (disease activity score; DAS ESR 28) and secondary efficacies, HAQ-Indian version and pain VAS100mm. Seventy-two patients were randomized (37 combination therapy, 35 monotherapy). Both groups were well matched in all respects. At 24 weeks, the combination therapy group showed significant improvement in both disease activity (mean ± SD DAS28; 3.39 ± 0.87 vs. 4.74 ± 0.65, p < 0.0001) and disability (mean ± SD HAQ; 1.4 ± 0.31 vs. 1.88 ± 0.47, p < 0.0001). At the study end, pain VAS was significantly less in the combination therapy group (46 ± 6.13 vs. 60.8 ± 11.6, p < 0.0001). Three patients withdrew from the combination group (inefficacy; 2, adverse event; 1) and seven from monotherapy (inefficacy; 7). This study provide evidence that for chronic persistent CA combination DMARD therapy with methotrexate, sulfasalazine and HCQ is superior to monotherapy with HCQ.

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