These data demonstrate a smaller CD4+CD25high regulatory T-cell population in peripheral blood of individuals with early active RA prior to disease-modifying treatment. This may be a contributory factor in the susceptibility to RA and suggests novel approaches to therapy.

Objective. To compare work disability and job loss in early rheumatoid arthritis (RA) patients receiving adalimumab plus methotrexate (adalimumab ؉ MTX) versus MTX alone. Methods. In this multicenter, randomized, controlled trial, patients with RA for <2 years who had never taken MTX and who self-reported work impairment were randomized to adalimumab ؉ MTX or placebo ؉ MTX for 56 weeks. Primary outcome was job loss of any cause and/or imminent job loss at or after week 16. Secondary outcomes included disease activity, function (Health Assessment Questionnaire [HAQ] score), and RA quality of life (RAQoL) questionnaire score. Work was evaluated with work diaries and the RA Work Instability Scale. Results. Although job loss during the 56-week study was significantly lower with adalimumab ؉ MTX (14 of 75 patients) compared with MTX alone (29 of 73 patients; P ‫؍‬ 0.005), the primary end point was not met (12 of 75 versus 20 of 73 patients; P ‫؍‬ 0.092), likely owing to early drop out in the MTX group. There were significant improvements in American College of Rheumatology 20% response criteria, 28-joint Disease Activity Score, ⌬HAQ, ⌬RAQoL, and working time lost in the adalimumab ؉ MTX group. Twenty-four serious adverse events were reported in 17 participants, with no differences between groups. Conclusion. Adalimumab ؉ MTX reduced job loss and improved productivity in early RA when compared with MTX alone, which supports the early use of anti-tumor necrosis factor therapy and suggests its cost efficacy.

Infliximab NRs comprise subtypes with distinct CRP patterns. Failure to suppress the CRP at week 2 identified the majority of patients who were NRs at week 12. CRP suppression at week 12 in the NRs was associated with a late clinical improvement with infliximab treatment (24 weeks), whereas failure to suppress the CRP at week 12 was associated with a good response on switching to etanercept.

Objective. The role of alternative tumor necrosis factor (TNF) antagonist therapies in the context of failure of initial TNF antagonist therapy in patients with rheumatoid arthritis (RA) has yet to be clearly defined. The goal of this study was to determine the efficacy of etanercept in patients who failed to respond to infliximab. Methods. Ninety-five patients with RA who failed to respond to infliximab and methotrexate were treated with etanercept (with continuation of concomitant methotrexate). Thirty-four patients never achieved a response to infliximab (primary nonresponse), 38 had an initial response to infliximab but relapsed (secondary nonresponse), and 23 demonstrated toxicity. Disease Activity Score in 28 joints (DAS28), European League Against Rheumatism (EULAR) response, and American College of Rheumatology (ACR) response were determined after 12 weeks of etanercept. Results. After 12 weeks of etanercept, 38% of patients achieved an ACR 20% response (ACR20) on etanercept. Of these, 24% and 15% achieved ACR50 and ACR70 responses, respectively. In the primary infliximab nonresponse group, 42%, 30%, and 15% achieved ACR20, ACR50, and ACR70 responses, respectively; the percentages for the secondary nonresponse group were 34%, 21%, and 14%, respectively. Significant DAS28 reductions were observed in the entire cohort and nonresponse subtype groups. Sixty-one percent of the cohort achieved either a moderate or good EULAR score (67% of primary and 56% of secondary infliximab failures). No toxicity was observed in patients who stopped infliximab due to intolerance; 19 of 23 continued etanercept after week 12. Conclusion. This study confirms that etanercept is effective in patients who fail to respond to infliximab and suggests a higher response in patients who have never had a response to infliximab. KEY WORDS. Rheumatoid arthritis; Anti-tumor necrosis factor switching.