Is long-term etanercept monotherapy ever an option in a patient with moderate to severe rheumatoid arthritis (RA)?

Background/Purpose: Methotrexate is recommended as first-line therapy in patients with early RA. An improvement in efficacy has been demonstrated for all currently available tumor necrosis factor (TNF) inhibitors when used in combination with methotrexate. For the TNF inhibitors infliximab and adalimumab, methotrexate not only increases the response rate to the agent, but also appears to play a role in its continued efficacy by suppressing the formation of anti-drug antibodies. There are patients, however, for whom methotrexate is not an option. Since neutralizing anti-drug antibodies have not been seen with etanercept treatment, we examined long-term efficacy data in patients with moderate to severe early RA on the subset of patients who chose to remain on etanercept monotherapy. Methods: We analyzed data from the Early Rheumatoid Arthritis (ERA) clinical trial of etanercept and up to 9 years of its subsequent long-term open-label extension. In the ERA study, patients were randomized to receive etanercept 10 mg or 25 mg twice weekly (BID) or methotrexate; after 1 year, patients continued on treatment unblinded. The current analysis examined patients who received and continued on etanercept 25 mg BID. Outcome measures included rates of remission and low disease activity based on disease activity scores using the 28-jount count with C-reactive protein as the indicator of inflammation (DAS28) and Simple Disease Activity Index (SDAI) scores, and Health Assessment Questionnaire Disability Index (HAQ-DI) scores. Results: Of 114 patients receiving etanercept monotherapy, 61 patients had chosen to continue etanercept monotherapy through year 9. No discernable baseline characteristics (age, sex, race, rheumatoid factor status, disease severity) distinguished the 61 patients for whom 9-year data regarding etanercept monotherapy was available from the 114 patients originally placed on etanercept monotherapy. Low disease activity was achieved by 1 year in 64.9% and 62.5% of patients by DAS28 and SDAI, respectively, with 45.6% and 14.3% in DAS28 and SDAI remission. At year 9, 67.3% and 61.8% had low disease activity by DAS28 and SDAI with 54.5% and 32.7% in remission, respectively. Although SDAI scores varied widely from visit to visit for individual patients, most patients in SDAI remission at year 9 had been in SDAI low disease activity or better at each time point starting from year 1 or 2. HAQ-DI scores improved from mean (standard deviation [SD]) score of 1.41 (0.70) at baseline to 0.65 (0.74) at 6 months. HAQ-DI scores had improved to scores associated with the general population (score <= 0.5) in 54.1% of patients at year 1 and in 55.7% of patients at year 9. Conclusion: Although combination therapy is the treatment of choice, some patients with moderate to severe RA can derive persistent, significant clinical benefit for at least 9 years from etanercept monotherapy.