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

Xenofon Baraliakos,Frank Heldmann,Joachim Sieper,Joachim Listing,Claudia Fritz,Juergen Braun,Hildrun Haibel

doi:10.1186/ar4244

Abstract

IntroductionData 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).MethodsOverall, 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.ResultsOverall, 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.ConclusionsThis 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 RegistrationClinicalTrials.gov: NCT01289743

Highlights

Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-a therapy in patients with ankylosing spondylitis (AS) are scarce
There is no evidence that disease modifying anti-rheumatic drugs (DMARDs) work in axial manifestations of AS with the exception of sulfasalazine, which has some efficacy in AS patients with peripheral symptoms [5,6]
After our first report from a placebo-controlled study of over three months with successful etanercept treatment in patients with initially active AS [8], and successful and safe re-administration after treatment discontinuation, we reported the clinical experience of the efficacy and safety of continuous therapy with etanercept over two years [15]

Summary

Introduction

Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-a therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNFa fusion protein etanercept over seven years (y). The efficacy of the recombinant 75 kD-TNF receptor IgG1 fusion protein etanercept has been demonstrated in clinical studies with patients with active AS [8,9,10,11,12], showing a significant decrease of disease activity already after the first two weeks [8,9,10] of treatment. A significant decrease of inflammatory lesions in the sacroiliac joints and the spine as detected by magnetic resonance imaging (MRI) was detected as early as six weeks after the start of treatment [13,14]

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Conclusion