Clinical Experience

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The early RA trial:

• Multicenter, double-blind, double-dummy, phase 3 trial.
• 632 MTX-naive patients with early active RA (≤ 3 years' duration) were randomized to receive twice-weekly ENBREL 25 mg (n = 207), twice-weekly ENBREL 10 mg (n = 208), or MTX (n = 217). The mean duration of disease for these patients was 11 months.
• The trial became open-label and unblinded after all patients had completed 1 year of evaluation. Patients continued through 1 year of follow-up on the treatment to which they had been randomized. At end of year 2, patients switched to or continued twice-weekly ENBREL 25 mg subcutaneously.
• Subjects could re-enroll in the continuing open-label portion of the study upon meeting specific predefined re-enrollment inclusion criteria.

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The long-standing RA trial:

• Open-label extension trial.
• 714 adult patients with active RA (mean duration of disease: 12 years) who had a previous inadequate response to one or more DMARDs and had received ENBREL either as monotherapy or in combination with MTX in various clinical trials.
• Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted during the study.
• Most patients received ENBREL 25 mg twice weekly. Because all patients did not enter clinical trials at the same time, length of follow-up varies.
• All 714 adult patients who received at least one dose of ENBREL were evaluated for safety. There was no active control or placebo arm in this open-label extension.

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The early RA trial:

• Multicenter, double-blind, double-dummy, phase 3 trial.
• 632 MTX-naive patients with early active RA (≤ 3 years' duration) were randomized to receive twice-weekly ENBREL 25 mg (n = 207), twice-weekly ENBREL 10 mg (n = 208), or MTX (n = 217). The mean duration of disease for these patients was 11 months.
• The trial became open-label and unblinded after all patients had completed 1 year of evaluation. Patients continued through 1 year of follow-up on the treatment to which they had been randomized. At end of year 2, patients switched to or continued twice-weekly ENBREL 25 mg subcutaneously.
• Subjects could re-enroll in the continuing open-label portion of the study upon meeting specific predefined re-enrollment inclusion criteria.

Hide

The long-standing RA trial:

• Open-label extension trial.
• 714 adult patients with active RA (mean duration of disease: 12 years) who had a previous inadequate response to one or more DMARDs and had received ENBREL either as monotherapy or in combination with MTX in various clinical trials.
• Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted during the study.
• Most patients received ENBREL 25 mg twice weekly. Because all patients did not enter clinical trials at the same time, length of follow-up varies.
• All 714 adult patients who received at least one dose of ENBREL were evaluated for safety. There was no active control or placebo arm in this open-label extension.

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The JIA trial:

• A two-part, multicenter study of 69 patients ages 4 to 17 with active polyarticular-course JIA who did not tolerate or had an inadequate response to MTX.
• In part 1, which was open-label, all patients received ENBREL 0.4 mg/kg subcutaneously twice weekly for 90 days.
• Responders (n = 51), defined by JIA definition of improvement using the JIA core set criteria, continued into part 2, the double-blind portion, to receive either ENBREL (n = 25) or placebo (n = 26) for 4 months or until disease flare occurred.
• 58 of the original 69 patients (from the nonresponder, ENBREL, and placebo groups) were enrolled in a new unblinded, open-label follow-up using ENBREL 0.4 mg/kg twice weekly.
• Concurrent use of NSAIDs, corticosteroids, and/or MTX was permitted during the open-label extension phase.
• Definition: JIA 30 response is defined as a = 30% improvement in at least 3 of the 6 criteria of a modified JIA core set with no more than 1 of 6 criteria worsening more than 30%. The JIA core set criteria included physician and patient/parent global assessments, active joint count, number of joints with limitation of motion (LOM), functional assessment (CHAQ), and erythrocyte sedimentation rate. Number of joints with LOM was counted only if LOM was accompanied by pain and/or tenderness. JIA 50 and 70 responses are defined as a 50% or 70% improvement, respectively, in at least 3 of 6 response criteria with no more than one criterion worsening by more than 30%.

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The psoriatic arthritis trial:

• Multicenter, double-blind, phase 3 trial of 205 patients with active psoriatic arthritis.
• Mean duration of arthritic disease was about 9.1 years and mean duration of plaque psoriasis was about 19.0 years (with a qualifying target skin lesion).
• Patients were randomized to receive subcutaneous injections of ENBREL 25 mg (n = 101) or placebo (n = 104) administered twice weekly over the 24-week blinded treatment period.
• After the 24-week period, patients continued therapy in a maintenance period until all patients completed double-blind therapy. After the maintenance period, all patients received ENBREL 25 mg twice weekly in an open-label period of 48 weeks.
• The data were stratified by absence or presence of concurrent MTX (either ENBREL alone [n = 59] vs placebo [n = 61] or ENBREL + MTX [n = 42] vs placebo + MTX [n = 43]).
• Stable use of corticosteroids and/or NSAIDs was allowed. Of the 205 patients in the blinded study, 169 patients (81 originally receiving placebo, 88 originally receiving ENBREL) entered the open-label extension. Linear extrapolation was utilized for the radiographic data.
• Nonresponder imputation analysis was conducted during the double-blind portion for ACR response and skin lesion clearing while parameters assessed during the open-label period were analyzed based on the observed population at each time point.
• The primary radiographic endpoint was the annualized rate of change in Total Sharp Score over 1 year of treatment.
• Secondary radiographic endpoints included annualized rate of change in Total Sharp Score, erosion score, and joint space narrowing score at 6, 12, and 24 months.
• Radiographs of hands and wrists were taken at baseline and 6 months in the controlled portion of the trial, at initiation of open-label treatment, at 1 year and 2 years from original baseline, and at early termination from the study during either part of the study.
• All patients who received at least one dose of study drug and who had at least one radiograph were to be included in the radiographic analysis. Scores were adjusted to 6- or 12-month basis using linear interpolation/extrapolation of the observed change.
• The mean duration of ENBREL exposure during the 12-month radiographic period was 331.6 days in the ENBREL group and 27.6 days in the placebo group.
• Definition:Total Sharp Score is based on combined scores of joint erosions in the hands and wrists on a scale of 0 to 5 (0 = no damage) and joint space narrowing in the hands and wrists on a scale of 0 to 4 (0 = no narrowing) and was modified to include an assessment of the distal interphalangeal joints. Data are shown for all patients having a 2-year radiograph (n = 141).