New therapeutic strategies have substantially altered the outcomes in RA. On particular strategy, the addition of biologics to methotrexate has demonstrated substantial efficacy in patients with an inadequate response to methotrexate. As well, early studies with conventional DMARDs have also shown improvement when added to methotrexate in a similar population.. To date, however, there has been no published data to suggest which strategy is more effective. Thus, no randomized trial has been published comparing the addition of conventional DMARDs versus biologics to MTX in patients with an inadequate response to MTX. The authors undertook an unblinded trial of 487 patients with early RA (symptom duration <1 year) treated with up to 20mg of methotrexate, patients who had not achieved low disease activity (DAS) after 3-4 months were randomized to addition of either sulfasalazine and hydroxychloroquine or infliximab. The primary outcome was achievement of a good EULAR response at 12 months. The results showed that a greater proportion of patients receiving infliximab (39%) achieved a good EULAR response compared to 25% of patients receiving sulfasalazine and hydroxychloroquine. Of significance, adverse events were balanced fairly well between the groups. The data suggest that in patients with early RA failing MTX, addition of a TNF inhibitor to MTX is clinically superior to the addition of sulfasalazine and hydroxychloroquine. However, the open label design may have contributed to the results. The authors addressed this by hypothesizing that patients receiving infliximab would continue therapy knowing that no obvious superior alternative was availabl,e while patients on combination DMARDs would more readily discontinue for lack of effectiveness. While they adequately addressed the issue, the concept of expectation bias was not considered. Thus, expectation bias on the part of physicians and patients that infliximab was an IV therapy - a new, potent and potentially superior agent could also account for the differences observed. Surprisingly statistical differences between the groups was not achieved until 12 months. This might be accounted for by the continuing improvement with MTX after 3-4 months even in partial responders not achieving a LDAS at that time. There is clear evidence MTX may require as long as 6-9 months to achieve a peak response. Despite the limitations of the study, the results showed that a significant proportion of patients randomized to conventional DMARD therapy achieved low disease activity. This suggests that from a cost perspective, consideration may be given to the addition of conventional DMARDs prior to the use of a biologics in the MTX inadequate responders. Whether the delay in using a biologic will have long term effects such as irreversible joint damage and disability remains unclear. Data regarding radiographic outcomes as well as the ability to withdraw infliximab in the responder populations are pending. Edward Keystone, MD