Effectiveness of chloroquine and inflammatory cytokine response in patients with early persistent musculoskeletal pain and arthritis following chikungunya virus infection.

OBJECTIVE

To evaluate whether chloroquine (CQ) is more effective than meloxicam for treating early musculoskeletal pain and arthritis following acute chikungunya (CHIK) virus infection.

METHODS

During the 2006 CHIK epidemic, 509 rural community cases of acute CHIK virus infection were identified in the district of Sholapur in India. Seventy consenting adult patients (seropositive for IgM/IgG anti-CHIK antibody) with early persistent musculoskeletal pain and arthritis were randomized into a 24-week, 2-arm, parallel efficacy trial of CQ (250 mg/day) and meloxicam (7.5 mg/day). Assessors completed a rheumatology evaluation in a blinded manner and collected blood samples in the patients' homes, as per protocol. Laboratory parameters included serum cytokine assay (interleukin-6 [IL-6], interferon-γ [IFNγ], tumor necrosis factor α, CXCL10/IFNγ-inducible protein 10, and IL-13). Twenty-two patients who failed to meet the eligibility criteria (low pain cohort) were also followed up with similar evaluations. An intent-to-treat analysis was completed. At baseline, the 2 groups (38 patients randomized to receive CQ and 32 patients randomized to receive meloxicam) were well matched.

RESULTS

There were no significant efficacy differences between the meloxicam group and the CQ group (mean changes in the visual analog scale score for pain -3.9 and -4.2, respectively). Patients improved significantly. Cytokine levels remained several-fold increased, were disproportionate to the clinical response, and were not different from those in the low pain cohort. Seven patients withdrew. Adverse events were mild and infrequent.

CONCLUSION

This exploratory community intervention trial failed to identify an advantage of CQ over meloxicam to treat early musculoskeletal pain and arthritis following acute CHIK virus infection, but therapeutic efficacy of CQ was not ruled out. The inflammatory cytokine response was intense and was not consistent with clinical status.