Hydroxychloroquine–DMARD combination therapy supported for RA
medwireNews: Findings from a systematic review suggest that adding hydroxychloroquine to conventional DMARDs may improve clinical outcomes among patients with rheumatoid arthritis (RA).
Claire Rempenault (Montpellier University, France) and colleagues analysed data from 11 studies – including journal publications and conference reports – investigating the efficacy of hydroxychloroquine in RA patients, both as a monotherapy and in combination with other agents.
As reported in Arthritis Care & Research, the addition of hydroxychloroquine to methotrexate improved efficacy in two of three studies investigating the combination. One randomised controlled trial demonstrated that patients treated with hydroxychloroquine plus methotrexate experienced significantly greater improvements in disease activity after 3 and 12 months of treatment than those given methotrexate alone, while another showed that patients treated with the combination had significantly higher rates of remission at 1 year than patients in the methotrexate monotherapy group.
Similarly, patients treated with a triple combination of hydroxychloroquine, methotrexate and sulphasalazine in one randomised trial were significantly more likely to achieve an at least a 20% or 50% improvement in ACR criteria at 2 years than those given dual therapy with methotrexate plus sulphasalazine.
Other combinations were less successful, say the researchers. For instance, hydroxychloroquine plus sulphasalazine was not superior to sulphasalazine monotherapy for a number of outcomes including erythrocyte sedimentation rate (ESR), morning stiffness and structural progression in one randomised trial, and treatment with hydroxychloroquine–leflunomide combination therapy resulted in comparable outcomes to leflunomide alone in another.
Despite the potential benefits of hydroxychloroquine combination therapy, Rempenault and team found no evidence to suggest that hydroxychloroquine monotherapy is beneficial for RA patients. For example, one open-label clinical trial demonstrated similar decreases in disease activity among patients receiving hydroxychloroquine versus methotrexate, and three studies demonstrated comparable improvements in ESR, morning stiffness, patient or physician global assessment, swollen joint count and pain among patients treated with hydroxychloroquine and those given sulphasalazine. The majority of studies investigating hydroxychloroquine monotherapy involved patients with disease duration of less than 5 years.
Therefore, hydroxychloroquine “should not be considered as monotherapy for the majority of patients with early RA but might provide moderate clinical benefit to RA patients in terms of disease activity control when used in combination with other [conventional] DMARDs”, write the study authors.
“The known metabolic and protective cardiovascular effects of [hydroxychloroquine] as well as its low cost and good safety profile are arguments strengthening this hypothesis”, they add.
Rempenault et al caution, however, that their systematic review had “several limitations”, including varying treatment doses, a limited number of studies investigating structural efficacy and publication dates prior to the year 2000.
They conclude that “recent and well-conducted studies are warranted” to verify their findings.
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