In patients with rheumatoid arthritis (RA) with inadequate response to previous conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), combining hydroxychloroquine (HCQ) with other DMARDs may provide clinical improvement, according to study results published in Arthritis Care & Research.

The systematic review included studies that compared the efficacy of HCQ in patients with RA, whether in monotherapy or combined with csDMARDs. The researchers included studies up to November 2017 from MEDLINE, EMBase, Cochrane Library, and the American College of Rheumatology (ACR) and European League Against Rheumatism annual meetings.

Of 197 potential studies, 11 fulfilled the inclusions criteria, comprising 104,278 participants. In the 2 studies that evaluated HCQ monotherapy compared with methotrexate (MTX), the results indicated that disease activity significantly decreased in both groups after 6 months of treatment. However, the clinical response was significantly better in participants treated with MTX compared with HCQ (P <.001).


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In the 4 studies that evaluated HCQ monotherapy compared with sulfasalazine (SSZ), the results indicated that the efficacy of both treatments were similar for:

  • erythrocyte sedimentation rate
  • morning stiffness
  • swollen joint count
  • joint pain
  • mean change in articular index

The researchers found 3 studies that compared HCQ plus MTX with MTX alone. In one study, the odds of achieving 20% improvement in ACR criteria (ACR20) at 12 months did not differ in either group, but the HCQ plus MTX group had a higher rate of adverse events (11% vs 4%, respectively). The other studies found that the 28-joint Disease Activity Score and remission rates were significantly higher with HCQ plus MTX compared with MTX alone.

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In a study that compared HCQ and MTX plus SSZ with MTX plus SSZ, the results indicated that at 2 years, the ACR20 and ACR50 response rates were higher in the triple therapy group compared with the MTX plus SSZ group. In a sub-group analysis, the results indicated that triple therapy was significantly better than MTX plus SSZ in patients with insufficient response to MTX, but not in patients who were MTX-naïve.

“When used in monotherapy, HCQ clinical and structural efficacy seemed to be similar or lower than that of MTX or SSZ,” the researchers wrote. “However, most studies suggested that HCQ could slightly improve various outcome measures of disease activity when combined with other csDMARDs, at least in patients with established RA and insufficient response to csDMARDs.”

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Reference

Rempenault C, Combe B, Barnetche T, et al. Clinical and structural efficacy of hydroxychloroquine in rheumatoid arthritis: a systematic review. [published online January 10, 2019]. Arthritis Care Res. doi:10.1002/acr.23826