Addition if TNF Antagonist best option for RA patients with poor response to Methotrexate

The addition of a tumour necrosis factor (TNF) antagonist is the best treatment strategy for patients with rheumatoid arthritis (RA), who have an inadequate response to Methotrexate monotherapy. The findings from the Swedish Swefot trial are considered unique, and are presented in this weeks edition of The Lancet.

Given in combination with Methotrexate both tumour necrosis factor antagonists such as infliximab and conventional disease-modifying antirheumatic drugs (DMARDs) such as Sulfasalazine and Hydroxychloroquine are better than Methotrexate alone at reducing the signs and symptoms of RA. However, previous trials have shown that between 2040% of patients have a good response to Methotrexate monotherapy and do not need a more intensive combination treatment. But it is not known which of these aggressive combination treatment options is more effective in patients who do not respond well to Methotrexate.

To resolve this uncertainty, Associated Professor Ronald van Vollenhoven at Karolinska Institutet and colleagues undertook the Swedish Pharmacotherapy (Swefot) trial and recruited 487 patients with early RA for less than 1 year from 15 rheumatology units in Sweden between 2002 and 2008. All patients were initially treated with methotrexate. After 3-4 months patients with an inadequate response were randomised to receive addition of either Infliximab (128) or Sulfasalazine and Hdroxychloroquine (130). Clinical response was assessed by criteria of the European League Against Rheumatism (EULAR).

After 12 months, patients given infliximab achieved better outcomes than those given sulfasalazine and hydroxychloroquine. 32 of 130 (25%) of patients given Sulfasalazine and Hydroxychloroquine and 50 of 128 (39%) of patients given Infliximab achieved a good response according to EULAR scores. Similar numbers of adverse events were recorded in both groups and all were previously known to the drugs used.

The authors conclude: "We believe that by treating all patients with methotrexate for 3-4 months, we screened out a sizeable proportion (30% in this trial),who would have been overtreated if aggressive combination therapy was used for all, an approach that could have increased the risk of side-effects and potentially entailed high costs."

Publication:

• Read previous press release on the study

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