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  Don Lavoie is alcohol programme manager at Public Health England and Gul Root is lead...
Don Lavoie is alcohol programme manager at Public Health England and Gul Root is lead pharmacist, Health and Wellbeing Directorate, Public Health England
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handApril 27 2016

Methotrexate in combination with sulphasalazine and hydroxychloroquine has been found to be superior than oral methotrexate on its own for treating rheumatoid arthritis.

The effect of triple therapy was considered superior both in patients who have not had methotrexate before as well as those who have. In addition, triple therapy was considered equally effective to methotrexate plus any DMARD or tofacitinib for controlling disease activity, either as initial therapy or after an inadequate response to methotrexate.

With guidelines suggesting methotrexate be used in combination with biological disease modifying anti-rheumatic drugs (DMARDs), researchers are suggesting the ‘triple therapy’ combination of methotrexate, suphasalazine and hydroxychloroquine should be another valid option as it could be significantly cheaper than using methotrexate with biological DMARDs.

A meta-analysis looked at 158 trials covering data from more than 37,000 patients where methotrexate had been compared with any other DMARD or combination of DMARDs. There were number of trials where methotrexate in combination with other drugs - sulfasalazine and hydroxychloroquine (‘triple therapy’), biologics (abatacept, adalimumab, etanercept, infliximab, rituximab, tocilizumab), and tofacitinib (awaiting marketing authorisation in the EU) - was statistically superior to methotrexate on its own.

In addition, “triple therapy had statistically fewer withdrawals due to adverse events than methotrexate plus infliximab,” and “methotrexate plus abatacept had a statistically lower rate of withdrawals due to adverse events than several treatments.”

Methotrexate alone is considered as the first DMARD option for patients with rheumatoid arthritis. Guidelines then propose its use in combination with a biologic DMARD if the response to methotrexate is not adequate.

“Combining methotrexate with other conventional synthetic DMARDs, however, is more controversial,” said the authors. There should be “a therapeutic trial of triple therapy as initial treatment or after an inadequate response to methotrexate,” said the researchers in their study, published in the BMJ.

“As triple therapy costs 10-20 times less than biologic therapy and is not currently recommended strongly by international guidelines, this has important policy implications. Specifically, our results suggest that triple therapy should be considered as a low cost, effective treatment option either as initial treatment or after an inadequate response to methotrexate.”

Links:

GS Hazlewood. ‘Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis’. BMJ 2016; 353: i1777 Published online April 212016 

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