Long-term outcome of patients with active ankylosing spondylitis with etanercept-sustained efficacy and safety after seven years

Abstract

Introduction: Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-α therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNFα fusion protein etanercept over seven years (y).

Methods: Overall, 26 patients with active AS were initially treated with etanercept 2 × 25 mg s.c./week with no concomitant disease modifying anti-rheumatic drugs (DMARDs) or steroids. The clinical response was assessed by standardized parameters. The primary outcome was the proportion of patients in the Spondyloarthritis International Society (ASAS) partial remission at seven years. AS disease activity scores (ASDAS) for status and improvement were compared to conventional outcome measures.

Results: Overall, 21/26 patients (81%) completed two years of treatment and 16/26 patients (62%) completed seven years. In the completer analysis, 31% patients were in ASAS partial remission at seven years, while 44% patients showed an ASDAS inactive disease status. Mean Bath AS activity index (BASDAI) scores, which were elevated at baseline (6.3 ± 0.9), showed constant improvement and remained low: 3.1 ± 2.5 at two years and 2.5 ± 2.2 at seven years, while ASDAS also improved (3.9 ± 0.7 at baseline, 1.8 ± 0.9 at two years, 1.6 ± 0.8 at seven years), all P <0.001. From the 10 dropouts, only 5 patients discontinued treatment due to adverse events. Patients who completed the study had lower baseline Bath AS function index (BASFI) scores vs. patients who discontinued. No other clinical parameter at baseline could predict any long-term outcome.

Conclusions: This study confirms the clinical efficacy and safety of etanercept in patients with active AS over seven years of continuous treatment. After seven years, more than half of the initially treated patients remained on anti-TNF therapy, and one-third were in partial remission.

Trial registration: ClinicalTrials.gov: NCT01289743

Figures

Figure 1

Treatment outcome for each study year. Response data for the 16 patients reaching Year 7. Treatment outcome according to established clinical parameters for each year of the study. ASAS20, ASAS 20% response, ASAS40, ASAS 40% response, ASAS 5/6, ASAS 5/6 response, BASDAI50, BASDAI 50% response, ASAS PR, ASAS partial remission. Shown are the response data for the 16 patients reaching Year 7 at different time points. ASAS, SpondyloArthritis international Society; BASDAI, Bath Ankylosing Spondylitis Activity Index

Figure 2

Completer analysis for ASDAS status over seven years. Completer analysis (n = 16) for the disease activity status as defined by the ASDAS over the entire study period of seven years. Numbers in the columns indicate the number of patients achieving the outcome. ASDAS, Ankylosing Spondylitis Disease Activity Score

Figure 3

Course of disease related clinical parameters: ASDAS, BASDAI, BASFI, BASMI. Completer analysis. Course of disease related clinical parameters: ASDAS, Ankylosing spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index, BASFI, Bath Ankylosing Spondylitis Function Index; BASMI, Bath Ankylosing Spondylitis Metrology Index. Completer analysis of the 16 patients who reached Year 7 of the study.

Figure 4

ASDAS Change status for completers over seven years. Change status of the ASDAS for the 16 completers over the entire study period of seven years. Numbers within the columns indicate the number of patients achieving the outcome. ASDAS, Ankylosing spondylitis Disease Activity Score.