Etanercept versus methotrexate in patients with early rheumatoid arthritis: Two‐year radiographic and clinical outcomes

Abstract

Objective. To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy.Methods. In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner. Radiograph readers remained blinded to treatment group assignment and the chronologic order of images.Results. At 24 months, more 25-mg etanercept patients than MTX patients met American College of Rheumatology 20% improvement criteria (72% and 59%, respectively; P ‫؍‬ 0.005), and more had no increase in total score and erosion scores on the Sharp scale (P ‫؍‬ 0.017 and P ‫؍‬ 0.012, respectively). The mean changes in total Sharp score and erosion score in the 25-mg etanercept group (1.3 and 0.66 units, respectively) were significantly lower than those in the MTX group (3.2 and 1.86 units, respectively; P ‫؍‬ 0.001). Significantly more patients in the 25-mg etanercept group (55%) than in the MTX group (37%) had at least 0.5 units of improvement in the Health Assessment Questionnaire disability index (P < 0.001). Fewer patients in the etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events.Conclusion. Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.

TNFα blockade in human diseases: An overview of efficacy and safety

“…Subsequent clinical trials evaluated whether the combination of a DMARD and an anti-TNFα agent was superior to either agent alone [11,12] or compared an anti-TNF agent with placebo [13,14]. Emboldened by the positive results of these trials, investigators probed a window of opportunity by asking whether treating patients with an anti-TNF agent in early stages (less than 3 years) of disease could 'wipe out' the disease and provide long-lasting remissions [12,[15][16][17].…”

Understanding the window of opportunity concept in early rheumatoid arthritis

“…In that trial, a dose-related response in terms of both disease activity and radiographic damage was observed during the 2 followup years. The recently presented followup results of the Enbrel ERA (early rheumatoid arthritis) trial (in which etanercept was compared with high-dose MTX) (7,8) and those of the Fin-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial (comparing step-down combination-DMARD therapy and single-DMARD therapy) (9,10) showed advantages of aggressive therapy in terms of progression of radiographic damage at 2 years. Finally, results of a recent cohort study also provided support for use of aggressive initial therapy (11).…”

Limits of add-on trials: antirheumatic drugs

“…Indication for treatment (in combination with MTX) of early RA patients not previously treated with MTX followed in 2004, with two phase III studies [11,12] comparing ETN and MTX and with the combination of the new agent and MTX. An add-on study supported approval of the 50-mg strength (2005) [13].…”