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Triple DMARDs backed by North American study

By News team

Prescribers should consider triple therapy with disease modifying antirheumatic drugs (DMARDs) for patients with rheumatoid arthritis who have active disease despite treatment with methotrexate, say the authors of a new study (New England Journal of Medicine online 11 June 2013).

The study shows that a regimen of sulfasalazine, hydroxychloroquine and methotrexate is non-inferior to treatment with the tumour necrosis factor inhibitor etanercept plus methotrexate.

Ian Scott, pharmacist at Queen Elizabeth hospital, King’s Lynn, who has a specialist interest in rheumatology, said that the paper raises interesting points but that in the UK it is now common to initiate combination treatment with two DMARDs shortly after diagnosis rather than methotrexate monotherapy, which will restrict the paper’s impact on current practice.

The US and Canadian study was a double-blind, non-inferiority trial. Patients who did not have an improvement at 24 weeks were switched to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28) at week 48; 309 patients completed a week 48 assessment.

The change in DAS28 was similar in the two groups (P=0.26). There was a trend to more rapid response in the etanercept-methotrexate group, but results did not differ significantly at 48 weeks.

There were no significant between-group differences in secondary outcomes, including radiographic progression (measured by modified Sharp score) and health-related quality of life. Overall frequency of serious adverse events was similar in the two groups.

The researchers say that in their countries most clinicians add a TNF inhibitor to methotrexate after methotrexate failure. “Our findings suggest that a strategy of first administering triple therapy, with a switch to etanercept-methotrexate in patients who do not have an adequate response, will allow a substantial percentage of patients to be treated in a more cost-effective way without adversely affecting the clinical outcomes.”

Mr Scott commented that the DAS28, which measures symptoms, does not always reflect the Sharp score, which measures joint damage and hence long-term outcome. Longer-term data from the study will be helpful, he said.  

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2013.11122600

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