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Addition of a TNF antagonist better option for patients with early rheumatoid arthritis who have poor response to methotrexate


Treating all patients with early rheumatoid arthritis (RA) with methotrexate monotherapy for a short period, followed by the addition of a tumour necrosis factor (TNF) antagonist such as infliximab in patients with inadequate response to methotrexate, is the best treatment option and could prevent overtreatment, as well as reducing the side-effects and costs associated with aggressive combination therapy. The findings are in an Article published in this week's edition of the Lancet.

Given in combination with methotrexate, both TNF 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 20-40% 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, Ronald van Vollenhoven from the Karolinska University Hospital and the Karolinska Institute, Sweden, and colleagues undertook the Swedish Pharmacotherapy (Swefot) trial and recruited 487 patients with early RA (less than 1 year's duration) from 15 rheumatology units in Sweden between October 2002 and December 2005. All patients were initially treated with methotrexate. After 3𔃂 months patients with an inadequate response were randomised to receive addition of either infliximab (128) or sulfasalazine and hydroxychloroquine (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 had previously been reported with 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."

In an accompanying Comment, Tuulikki Sokka from Jyväskylä Central Hospital, Finland and Theodore Pincus from New York University Hospital for Joint Diseases, USA, say that the results highlight that the treatment strategy is more important than the agent in treating RA: "The Swefot trialists ask (properly) whether a 3-month delay of optimum therapy is ethical to offset the risks and costs of biological agents versus methotrexate and DMARD therapy. The data suggest that this delay is acceptable, because most patients with rheumatoid arthritis have an adequate response without biological agents, and 3 months of methotrexate followed by 3 months of triple therapy might be a reasonable standard."


Dr Ronald F van Vollenhoven, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. T) +46 739 789 158 E)

Dr Tuulikki Sokka, Jyväskylä Central Hospital,Jyväskylä ,Finland.T) +358 40 735 2087 E)

For full Article and Comment, see:

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