alone or MTX alone.
d Major clinical response is achieving an ACR 70 response for a continuous 6-month period.
The time course for ACR 20 response rates for patients receiving placebo or 25 mg etanercept in Studies I and II issummarized in Figure 1. The time course of responses to etanercept in Study III was similar.
Figure 1:
Time Course of ACR 20 Responses
Among patients receiving etanercept, the clinical responses generally appeared within 1 to 2 weeks after initiation oftherapy and nearly always occurred by 3 months. A dose response was seen in Studies I and III: 25 mg etanercept wasmore effective than 10 mg (10 mg was not eva luated in Study II). Etanercept was significantly better than placebo inall components of the ACR criteria as well as other measures of RA disease activity not included in the ACR responsecriteria, such as morning stiffness.
In Study III, ACR response rates and improvement in all the individual ACR response criteria were maintainedthrough 24 months of etanercept therapy. Over the 2-year study, 23% of etanercept patients achieved a major clinicalresponse, 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 8. Similar results were
observed for etanercept-treated patients in Studies II and III.
Table 8. Components of ACR Response in Study I
Placebo Etanercepta
N= 80 N=78
Parameter (median) Baseline 3 Months Baseline 3 Months*
Number of tender jointsb 34.0 29.5 31.2 10.0f
Number of swollen jointsc 24.0 22.0 23.5 12.6f
Physician global assessmentd 7.0 6.5 7.0 3.0f
Patient global assessmentd 7.0 7.0 7.0 3.0f
Paind 6.9 6.6 6.9 2.4f
Disability indexe 1.7 1.8 1.6 1.0f
ESR (mm/hr) 31.0 32.0 28.0 15.5f
CRP (mg/dL) 2.8 3.9 3.5 0.9f
* Results at 6 months showed similar improvement.
a 25 mg etanercept SC twice weekly.
b Scale 0-71.
c Scale 0-68.
d Visual analog scale: 0 = best; 10 = worst.
e Health Assessment Questionnaire: 0 = best; 3 = worst; includes eight categories: dressing and grooming, arising,eating, walking, hygiene, reach, grip, and activities. f p < 0.01, etanercept vs placebo, based on mean percent change from baseline.
After discontinuation of etanercept, symptoms of arthritis generally returned within a month. Reintroduction oftreatment with etanercept after discontinuations of up to 18 months resulted in the same magnitudes of response as inpatients who received etanercept 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 patientsreceived etanercept without interruption. A substantial number of patients who initially received concomitant MTX orcorticosteroids were able to reduce their doses or discontinue these concomitant therapies while maintaining theirclinical responses.
Physical Function Response
In Studies I, II, and III, physical function and disability were assessed using the Health Assessment Questionnaire(HAQ). Additionally, in Study III, patients were administered the SF-36 Health Survey. In Studies I and II, patientstreated with 25 mg etanercept twice weekly showed greater improvement from baseline in the HAQ score beginningin month 1 through month 6 in comparison to placebo (p < 0.001) for the HAQ disability domain (where 0 = none and3 = severe). In Study I, the mean improvement in the HAQ score from baseline to month |
