nearly always occurred by 3 months. A dose response was seen; results with 10 mg were intermediate between placebo and 25 mg. Etanercept was significantly better than placebo in all components of the ACR criteria, as well as other measures of rheumatoid arthritis disease activity not included in the ACR response criteria, such as morning stiffness. A Health Assessment Questionnaire (HAQ), which included disability, vitality, mental health, general health status, and arthritis-associated health status subdomains, was administered every 3 months during the trial. All subdomains of the HAQ were improved in patients treated with etanercept compared to controls at 3 and 6 months.
After discontinuation of etanercept, symptoms of arthritis generally returned within a month. Re-introduction of treatment with etanercept after discontinuation of up to 24 months resulted in the same magnitudes of responses as patients who received etanercept without interruption of therapy based on results of open-label studies. Continued durable responses have been seen for up to 10 years in open-label extension treatment trials when patients received etanercept without interruption.
The efficacy of etanercept was compared to methotrexate in a randomised, active-controlled study with blinded radiographic evaluations as a primary endpoint in 632 adult patients with active rheumatoid arthritis ( 25 mg etanercept were administered subcutaneously (SC) twice a week for up to 24 months. Methotrexate doses were escalated from 7.5 mg/week to a maximum of 20 mg/week over the first 8 weeks of the trial and continued for up to 24 months. Clinical improvement, including onset of action within 2 weeks with etanercept 25 mg, was similar to that seen in the previous trials and was maintained for up to 24 months.
At baseline, patients had a moderate degree of disability, with mean HAQ scores of 1.4 to 1.5. Treatment with etanercept 25 mg resulted in substantial improvement at 12 months, with about 44% of patients achieving a normal HAQ score (less than 0.5). This benefit was maintained in Year 2 of this study. In this study, structural joint damage was assessed radiographically and expressed as change in Total Sharp Score (TSS) and its components, the erosion score and Joint Space Narrowing (JSN) score. Radiographs of hands/wrists and feet were read at baseline and 6, 12, and 24 months. The 10 mg etanercept dose had consistently less effect on structural damage than the 25 mg dose.
Etanercept 25 mg was significantly superior to methotrexate for erosion scores at both 12 and 24 months. The differences in TSS and JSN were not statistically significant between methotrexate and etanercept 25 mg. The results are shown in the figure below. Radiographic progression: comparison of etanercept vs. methotrexate in patients with RA of years duration In another active-controlled, double-blind, randomised study, clinical efficacy, safety, and radiographic progression in RA patients treated with etanercept alone (25 mg twice weekly), methotrexate alone (7.5 18