In a fourth study, the safety and efficacy of 50 mg etanercept (two 25 mg SC injections) administered once weekly vs. 25 mg etanercept administered twice weekly were evaluated in a double-blind, placebo-controlled study of 356 patients with active ankylosing spondylitis. The safety and efficacy profiles of the 50 mg once-weekly and 25 mg twice-weekly regimens were similar. Adult patients with non-radiographic axial spondyloarthritis Study 1 The efficacy of etanercept in patients with non-radiographic axial spondyloarthritis (nr-AxSpa) was assessed in a randomised, 12-week double-blind, placebo-controlled study.
The study evaluated 215 adult patients (modified intent-to-treat population) with active nr-AxSpa (18 to 49 years of age), defined as those patients meeting the ASAS classification criteria of axial spondyloarthritis but did not meet the modified New York criteria for AS. Patients were also required to have an inadequate response or intolerance to two or more NSAIDs. In the double-blind period, patients received etanercept 50 mg weekly or placebo for 12 weeks. The primary measure of efficacy (ASAS 40) was a 40% improvement in at least three of the four ASAS domains and absence of deterioration in the remaining domain.
The double-blind period was followed by an open-label period during which all patients received etanercept 50 mg weekly for up to an additional 92 weeks. MRIs of the sacroiliac joint and spine were obtained to assess inflammation at baseline and at weeks 12 and 104. Compared to placebo, treatment with etanercept resulted in statistically significant improvement in the ASAS 40, ASAS 20 and ASAS 5/6. Significant improvement was also observed for the ASAS partial remission and BASDAI 50. Week 12 results are shown in the table below. endpoints Efficacy response in placebo-controlled nr-AxSpa study:
percent of patients achieving *Some patients did not provide complete data for each endpoint **ASAS = Assessments in Spondyloarthritis International Society ***Bath Ankylosing Spondylitis Disease Activity Index a: p At week 12, there was a statistically significant improvement in the SPARCC (Spondyloarthritis Research Consortium of Canada) score for the sacroiliac joint (SIJ) as measured by MRI for patients receiving etanercept. Adjusted mean change from baseline was 3.8 for etanercept treated (n = 95) versus 0.8 for placebo treated (n = 105) patients (p the SPARCC score measured on MRI for all etanercept-treated subjects was 4.64 for the SIJ (n = 153) and 1.40 the spine (n = 154).
Etanercept showed statistically significantly greater improvement from baseline to week 12 compared to placebo in most health-related quality of life and physical function assessments, including BASFI (Bath Ankylosing Spondylitis Functional Index), EuroQol 5D Overall Health State Score and SF-36 Physical Component Score. Clinical responses among nr-AxSpa patients who received etanercept were apparent at the time of the first visit (2 weeks) and were maintained through 2 years of therapy. Improvements in health-related quality of life and physical function were also maintained through 2 years of therapy. The 2 year data did not reveal any new safety findings.
At week 104, 8 subjects had progressed to a score of bilateral 23 Double-Blind Clinical Responses at Week 12 Placebo N = 106 to 109* Etanercept N = 103 to 105* ASAS** 40 15.7 32.4b ASAS 20 36.1 52.4c ASAS 5/6 10.4 33.0a ASAS partial remission 11.9 24.8c BASDAI*** 50 23.9 43.8b