ArticlesAddition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial
Introduction
New treatment options have resulted in remarkable changes in the therapeutic approach to newly diagnosed rheumatoid arthritis. Specifically, findings of randomised clinical trials show that the tumour necrosis factor antagonists adalimumab,1 etanercept,2 and infliximab,3 given in combination with methotrexate, provide superior results compared with methotrexate alone. However, data of these three trials also indicate that a sizeable subset of patients (20–40%) have a good clinical response to methotrexate monotherapy. Some researchers have suggested that this subgroup could be identified prospectively with specific baseline characteristics.4 However, in practice, doctors could opt to treat patients with methotrexate monotherapy for a short period, thus enabling them to identify individuals who do not need an intensive therapeutic strategy while not losing too much ground with those who do.
For patients who have an incomplete or no response to methotrexate, will addition of an antagonist to tumour necrosis factor, which is more effective than placebo,5, 6, 7 be superior to addition of conventional disease-modifying antirheumatic drugs? Data show combinations of methotrexate with sulfasalazine and hydroxychloroquine8, 9 and with ciclosporin A10 are better than methotrexate alone. We designed the Swedish Pharmacotherapy (Swefot) study—an investigator-initiated, multicentre, randomised, active-controlled, clinical trial—with the aim to assess two aggressive treatment options in patients with early rheumatoid arthritis who did not respond well to methotrexate monotherapy after 3–4 months. We compared addition of sulfasalazine and hydroxychloroquine with addition of the tumour necrosis factor antagonist infliximab. Here, we report 1-year clinical results.
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Patients
15 rheumatology units in Sweden collaborated in this trial. We invited adults (age ≥18 years) diagnosed with rheumatoid arthritis and with symptom duration of less than 1 year to participate in the trial. Key inclusion criteria were: rheumatoid arthritis diagnosed according to revised American College of Rheumatology (ACR) criteria; no previous treatment with disease-modifying antirheumatic drugs; either no oral glucocorticoid or stable glucocorticoid therapy for at least 4 weeks of, at most,
Results
Between October, 2002, and December, 2005, a total of 493 patients were screened for inclusion in the Swefot trial. Figure 2 shows how participants progressed through the trial. Six patients failed screening mostly because of abnormal liver function tests. Of the 487 people who received methotrexate monotherapy, 229 did not undergo random allocation after 3–4 months. Of these, 145 had responded well to methotrexate monotherapy, 27 were intolerant to methotrexate, nine developed another illness
Discussion
1-year findings of the Swefot study show that for patients who do not respond sufficiently to methotrexate monotherapy, addition of a tumour necrosis factor antagonist (eg, infliximab) is superior to addition of conventional disease-modifying antirheumatic drugs (eg, sulfasalazine and hydroxychloroquine), with respect to achievement of a good response according to EULAR criteria. This finding was robust statistically and because the primary outcome was supported by most secondary clinical
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