igure 1. The time course of responses to ENBREL® in Study III was similar.
Figure 1: Time Course of ACR 20 Responses
Among patients receiving ENBREL®, the clinical responses generally appeared within 1 to 2 weeks after initiation of therapy and nearly always occurred by 3 months. A dose response was seen in Studies I and III: 25 mg ENBREL® was more effective than 10 mg (10 mg was not eva luated in Study II). ENBREL® was significantly better than placebo in all components of the ACR criteria as well as other measures of RA disease activity not included in the ACR response criteria, such as morning stiffness.
In Study III, ACR response rates and improvement in all the individual ACR response criteria were maintained through 24 months of ENBREL® therapy. Over the 2-year study, 23% of ENBREL® patients achieved a major clinical response, defined as maintenance of an ACR 70 response over a 6-month period.
The results of the components of the ACR response criteria for Study I are shown in Table 3. Similar results were observed for ENBREL®-treated patients in Studies II and III.
Table 3: Components of ACR Response in Study I *
25 mg ENBREL ® SC twice weekly.
†
Results at 6 months showed similar improvement.
‡
Scale 0 – 71.
§
p < 0.01, ENBREL ® vs. placebo, based on mean percent change from baseline.
¶
Scale 0 – 68.
#
Visual analog scale; 0 = best, 10 = worst.
Þ
Health Assessment Questionnaire 1; 0 = best, 3 = worst; includes eight categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities.
Placebo
N = 80
ENBREL®*
N = 78
Parameter (median) Baseline 3 Months Baseline 3 Months†
Number of tender joints‡ 34.0 29.5 31.2 10.0§
Number of swollen joints¶ 24.0 22.0 23.5 12.6§
Physician global assessment# 7.0 6.5 7.0 3.0§
Patient global assessment# 7.0 7.0 7.0 3.0§
Pain# 6.9 6.6 6.9 2.4§
Disability indexÞ 1.7 1.8 1.6 1.0§
ESR (mm/hr) 31.0 32.0 28.0 15.5§
CRP (mg/dL) 2.8 3.9 3.5 0.9§
After discontinuation of ENBREL®, symptoms of arthritis generally returned within a month. Reintroduction of treatment with ENBREL® after discontinuations of up to 18 months resulted in the same magnitudes of response as patients who received ENBREL® without interruption of therapy based on results of open-label studies.
Continued durable responses were seen for over 60 months in open-label extension treatment trials when patients received ENBREL® without interruption. A substantial number of patients who initially received concomitant MTX or corticosteroids were able to reduce their doses or discontinue these concomitant therapies while maintaining their clinical responses.
A 24-week study was conducted in 242 patients with active RA on background methotrexate who were randomized to receive either ENBREL® alone or the combination of ENBREL® and anakinra. The ACR 50 response rate was 31% for patients treated with the combination of ENBREL® and anakinra and 41% for patients treated with ENBREL® alone, indicating no added clinical benefit of the combination over ENBREL® alone. Serious infections were increased with the combination compared to ENBREL® alone (see WARNINGS).
l Function Response
In Studies I, II, and III, physical function and disability were assessed using the Health Assessme |
