The 48-week, double-blind trial was carried out between 2007 and 2010 at 36 sites in the US and Canada and included 353 patients with rheumatoid arthritis who had active disease despite methotrexate therapy. Subjects were randomized to receive either a triple regimen of disease-modifying anti-rheumatic drugs (DMARDs: methotrexate, sulfasalazine and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a pre-specified threshold were switched in a blinded fashion to the other therapy.

The cost of treating rheumatoid arthritis has risen dramatically in recent years, mainly as a result of the use of biological treatments. Therefore, the aim of this study was to see whether there was any difference between the use of DMARDs and biological therapy for the treatment of rheumatoid arthritis where methotrexate therapy alone had not been effective. The DMARDs methotrexate, sulfasalazine and hydroxychloroquine are all available as generics.

The results showed a significant improvement over the course of the first 24 weeks in both groups (p = 0.001 compared to baseline). Of the 27% of participants in each group that required a switch in treatment an improvement was seen (p < 0.001) and the response after switching did not differ significantly between the two groups (p = 0.08).

The authors therefore concluded that ‘with respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was non-inferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy.’

The authors therefore suggest that a strategy of first administering the triple therapy, with a switch to etanercept–methotrexate in patients who do not respond would be much more cost-effective. Lead author James O’Dell estimates that only 35% of patients with rheumatoid arthritis require biologicals, such as Enbrel (etanercept), AbbVie’s Humira (adalimumab) and Johnson & Johnson’s Remicade (infliximab), as opposed to the 40–45% who currently receive them. The average annual cost of the generic triple therapy is about US$1,000 compared to US$25,000 for Enbrel.

Conflict of interest
The study was supported by the Cooperative Studies Program, US Department of Veterans Affairs Office of Research and Development, and the Canadian Institutes for Health Research; and by an inter-agency agreement with the National Institutes of Health–American Recovery and Reinvestment Act.

The authors declared that they had received grant support, consulting, lecture fees and/or reimbursement for travel expenses from Abbott, AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, Janssen, Lilly, Merck, Novartis, Pfizer, Roche and Schering Plough. One author reported holding stock options from Johnson & Johnson, Lexicon, Merck, Pfizer, and Rochester Medical. The authors declared that there were no other conflicts of interest.

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Reference

1.  O’Dell JR, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013 11 Jun. doi: 10.1056/NEJMoa1303006.

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