Successful Methotrexate Treatment of Chronic Chikungunya Arthritis

J. Kennedy Amaral, MD; Clifton O. Bingham, III, MD; Robert T. Schoen, MD, MBA


J Clin Rheumatol. 2020;26(3):119-124. 

In This Article



Between January and December 2017, 50 patients with persistent rheumatic symptoms (>12 weeks) after CHIK infection were evaluated. All patients were Portuguese speaking, 18 years or older, and seen in the rheumatology practice of by one of us (J.K.A.). Forty-five (90%) were self-referred. Thirty-six (72%) of the 50 patients were seen at baseline, 4 weeks, and 8 weeks. Twelve patients (24%) were seen at weeks 0 and 4, but did not return for week 8 because their symptoms had resolved. Two patients (4%) did not return for evaluation at 4 weeks.

In total, this group consisted of 46 patients; there were women (92%) and 4 men (8%) (Table 1). The mean age of the patients was 61.9 (SD, 12.5) years. All included patients had CHIK infection confirmed by CHIKV-specific immunoglobulin G serology by enzyme-linked immunosorbent assay. The mean time elapsed between CHIK disease onset and the first visit to our clinic was 14.2 (SD, 4.2) months, and 48 (96%) of 50 patients presented with joints symptoms that persisted more than 12 weeks after the onset of CHIKF.

Previous Musculoskeletal Illnesses and Classification

Preexisting rheumatic diseases were osteoarthritis (24%), osteoporosis (14%), osteopenia (8%), FM (6%), and gout (2%). No patients had known RA or spondyloarthritis before the onset of CHIKF. The preexisting rheumatic conditions that occurred prior to CHIK infection were easily distinguished from CHIK-associated symptoms, except for 1 patient with FM, who reported worsening pain after viral infection. Previous treatment for preexisting rheumatic disease and for CHIKV-related arthritic symptoms CHIK or arthritis was assessed during the first consultation. Twenty-nine patients (58%) had received previous treatment for CHIK arthritis, including common analgesics (36%), corticosteroids (28%), NSAIDs (28%), DMARDs (hydroxychloroquine [HCQ], MTX) (4%), or other therapies (duloxetine, or pregabalin) (4%) alone or in combination (Table 1).

Characteristics of the Disease and Previous Treatment

At the first visit (W0), 30 patients (60%) presented with arthralgia, whereas 20 patients (40%) also had arthritis (Table 1). Arthralgia was most common in the hands (56%), ankles (48%), and knees (44%). Arthralgia was polyarticular (>4 joints) (76%) or oligoarticular (2–4 joints) (24%). Of the patients with arthritis, all 20 had hand involvement. Other joints with arthritis were wrists in 16 (32%), ankles in 12 (24%), and ankles and knees in 9 (18%). Overall, both large and small joints of the upper and lower extremities were affected with arthralgia and/or arthritis (Figure 1). Morning stiffness, low back pain, and cervical pain were reported by 3 (6%), 8 (16%), and 3 (6%), respectively, at the first visit. The ACR criteria for RA were met by 11 (22%) of the patients, and another 7 criteria (14%) for FM (Table 2).

Figure 1.

Joints frequency affectedwith arthralgia and/or arthritis in the first visit. Color online-figure is available at

Treatment and Response

Methotrexate was initiated in 48 patients at 7.5 mg/wk and was given with folic acid, with dose escalations for refractory symptoms at 4 weeks. The final mean MTX dose was 9.2 (SD, 3.2) mg/wk. Methotrexate therapy was combined with prednisone at a mean daily dose of 6.1 (SD, 2.2) mg for 9 patients (18%). Two patients received HCQ (400 mg/d) with MTX, and one of these also received sulfasalazine (SSZ) (1000 mg/d). Duloxetine was used as monotherapy for 2 patients (4%) with FM-type symptoms. There was FM only and no discrete arthralgia or arthritis.

At the first consultation (W0), the mean value for pain by VAS was 7.7 (SD, 2.0). There was a rapid decline in pain scores by 4 weeks that persisted through 8 weeks (Figure 2). The mean reductions from baseline pain at 4 and 8 weeks (W4, W8) were, respectively, 4.3 (3.0) (p < 0.0001) and 4.5 (2.6) (p < 0.0001), respectively. Using last-observation-carried-forward analysis, the results at weeks 4 and 8 are very similar, 4.10 (3.05) and 4.88 (2.83), respectively. In 36 patients (80%), the reduction in pain was 2 units or greater, exceeding the minimally clinically important difference. We also assessed improvement in joint swelling among the 20 patients with frank arthritis. In this group, mean swollen joint count decreased from 7.15 (2.25) at study entry to 2.89 (2.49) and 3.0 (1.24) at weeks 4 and 8, (p < 0.0001), respectively (Table 1).

Figure 2.

Pain scores at W0 and W4 in patients treated with MTX for persistent CHIK arthralgia and arthritis (as observed data). NRS indicates numerical rating scale.

No serious adverse events related to treatment were observed throughout the study.