The New England Journal of Medicine, 2014, Vol.371(19), pp.1781-1792
Background We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy. Methods Patients with early active disease who had not previously received methotrexate or biologic therapy received 50 mg of etanercept plus methotrexate weekly for 52 weeks (open-label phase). We then randomly assigned patients who had qualifying responses at weeks 39 and 52 to receive 25 mg of etanercept plus methotrexate (combination-therapy group), methotrexate alone, or placebo for 39 weeks (double-blind phase). Patients who had qualifying responses at week 39 of the double-blind phase had all treatment withdrawn at that time and were followed to week 65 (treatment-withdrawal phase). The primary end point was the proportion of patients with sustained remission in the double-blind phase. Results Of 306 patients enrolled, 193 underwent randomization in the double-blind phase; 131 qualified for the treatment-withdrawal phase. More patients in the combination-therapy group than in the methotrexate-alone group or the placebo group met the criterion for the primary end point (40 of 63 [63%] vs. 26 of 65 [40%] and 15 of 65 [23%], respectively; P=0.009 for combination therapy vs. methotrexate alone; P〈0.001 for combination therapy vs. placebo). At 65 weeks, 28 patients (44%) who had received combination therapy, 19 (29%) who had received methotrexate alone, and 15 (23%) who had received placebo were in remission (P=0.10 for combination therapy vs. methotrexate alone; P=0.02 for combination therapy vs. placebo; P=0.55 for methotrexate alone vs. placebo). No significant between-group differences were observed in radiographic progression of disease. Serious adverse events were reported in 3 patients (5%) in the combination-therapy group, 2 (3%) in the methotrexate-alone group, and 2 (3%) in the placebo group. Conclusions In patients with early rheumatoid arthritis who had a remission while receiving full-dose etanercept-plus-methotrexate therapy, continuing combination therapy at a reduced dose resulted in better disease control than switching to methotrexate alone or placebo, but no significant difference was observed in radiographic progression. (Funded by Pfizer; ClinicalTrials.gov number, NCT00913458 .) In a randomized trial involving patients with early rheumatoid arthritis who had a response to methotrexate plus 50 mg of etanercept weekly for 52 weeks, continued treatment with methotrexate plus 25 mg of etanercept was more effective than methotrexate alone or placebo. The duration of disease activity in persons with rheumatoid arthritis is an important factor influencing joint destruction and functional disability.1,2 Joint damage frequently begins within weeks or months after the onset of symptoms and is detectable on radiographs within 2 years.3,4 Evidence indicates that early aggressive treatment results in greater improvement than therapy initiated later in the disease course.5–8 Clinical remission, or at least low disease activity, is a critical treatment target in early rheumatoid arthritis, since control of inflammatory processes may limit structural damage and functional impairment.9 High rates of clinical remission, as well as significant . . .