ORIGINAL ARTICLE Efficacy of combination DMARD therapy vs. hydroxychloroquine monotherapy in chronic persistent chikungunya arthritis: a 24-week randomized controlled open label study Vinod Ravindran 1,2 & George Alias 1 Received: 12 September 2016 /Revised: 18 September 2016 /Accepted: 20 September 2016 # International League of Associations for Rheumatology (ILAR) 2016 Abstract 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 arthri- tis 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 ran- domized 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 opti- mized) 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 com- bination therapy, 35 monotherapy). Both groups were well matched in all respects. At 24 weeks, the combination therapy group showed significant improvement in both disease activ- ity (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 with- drew from the combination group (inefficacy; 2, adverse event; 1) and seven from monotherapy (inefficacy; 7). This study provide evidence that for chronic persistent CA combi- nation DMARD therapy with methotrexate, sulfasalazine and HCQ is superior to monotherapy with HCQ. Keywords Arbovirus . Epidemic . Methotrexate . Musculoskeletal . Viral arthritis Introduction Chikungunya (CHIK) infection is mainly endemic to tropics [1]. Since late 2000, several countries have experienced epi- demics of CHIK infection which is predominantly a self-lim- iting, severely painful, febrile, arboviral musculoskeletal ill- ness, though many infected will remain asymptomatic [1–4]. Due to international travel, many non-endemic countries have also come across patients suffering from chikungunya arthritis (CA) [5]. Outbreaks have been reported in Italy [6] and in 2014 in the Caribbean where over 10,000 confirmed/ suspected cases were reported [7]. In the acute phase, the arthralgias are predominantly peripheral involving ankles, wrists, and phalanges and can be disabling [2, 8]. In about 10–20 %, CA might run into a persistent polyarticular phase which may even resemble rheumatoid arthritis (RA) [8, 9]. The acute phase of CA is generally managed with non- steroidal anti-inflammatory agents and/or hydroxychloroquine (HCQ) [2, 5, 10]. However, the therapy of the chronic persistent CA is not very clear and many pa- tients continue to receive HCQ without any evidence of same benefit as in the acute phase. Given the fact that chronic per- sistent CA is very disabling and has the potential to damage the joints in a similar way as RA, it appears logical to consider aggressive therapy with Disease-Modifying Anti-Rheumatic Drugs (DMARDs) [9, 11]. Though attractive, such approach in the management of chronic persistent CA has not been * Vinod Ravindran drvinod12@gmail.com 1 Department of Rheumatology, PVS Hospital, Calicut, India 2 Centre for Rheumatology, Calicut, Kerala 673009, India Clin Rheumatol DOI 10.1007/s10067-016-3429-0