1256 The Journal of Rheumatology 2009; 36:6; doi:10.3899/jrheum.081033
Personal non-commercial use only. The Journal of Rheumatology Copyright © 2009. All rights reserved.
Etanercept in the Longterm Treatment of Patients With
Ankylosing Spondylitis
BEN DIJKMANS, PAUL EMERY, MARKKU HAKALA, MARJATTA LEIRISALO-REPO, EMILIO MARTIN MOLA,
LAURENCE PAOLOZZI, CARLO SALVARANI, RAIMON SANMARTI, JEAN SIBILIA, JOACHIM SIEPER,
FILIPVan Den BOSCH, DÉSIRÉE van der HEIJDE, SJEF van der LINDEN, and JOSEPHWAJDULA
ABSTRACT. Objective. To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing
spondylitis (AS).
Methods. A 96-week open-label extension study, which followed a 12-week double-blind place-
bo-controlled trial, was designed to provide longterm efficacy and safety data, including radio-
graphic outcomes, for patients treated with etanercept 25 mg twice weekly (NCT00421980). In all,
81 patients were enrolled (96% of the participants from the double-blind study). Key efficacy meas-
ures included improvement using theAssessment inAnkylosing Spondylitis 20% (ASAS20) criteria,
the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis
Disease Activity Index (BASDAI). Radiographic progression was evaluated using the modified
Stoke Ankylosing Spondylitis Spine Score (mSASSS) method. Paired t tests were used to test with-
in-group changes from baseline.
Results. The percentage of responders, by ASAS20 criteria, remained relatively constant in patients
who received etanercept during the 12-week double-blind study (60% at Week 0 and 83% at Week
96 of the open-label extension); more patients from the placebo group became responders after being
switched to etanercept (23% and 74%, respectively). A similar trend was also observed using the
ASAS40 and ASAS5/6 criteria, the BASFI, and the BASDAI. Most patients had no change from
baseline in mSASSS values. Etanercept was well tolerated; the most frequent adverse events were
injection site reactions (n = 30; 37.0%) and headache (n = 18; 22.2%), and the most frequent infec-
tions were upper respiratory tract infections (n = 43; 53.1%) and flu syndrome (n = 22; 27.2%).
Conclusion. For 2 years, etanercept was clinically effective and well tolerated, with no unexpected
safety findings. (First Release May 1 2009; J Rheumatol 2009;36:1256–64; doi:10.3899/
jrheum.081033)
Key IndexingTerms:
ANKYLOSING SPONDYLITIS ASSESSMENT INANKYLOSING SPONDYLITIS 20
MODIFIED STOKE ANKYLOSING SPONDYLITIS SPINE SCORE ETANERCEPT
From Universitair Ziekenhuis Gent, Gent, Belgium; Helsinki University
Central Hospital, Helsinki, Finland; Rheumatism Foundation Hospital,
Heinola, Finland; Hôpital Hautepierre, Strasbourg, France; Hôpital
Lapeyronie, Montpellier, France; University Hospital Benjamin Franklin,
Berlin, Germany; University Hospital Erlangen-Nuremberg, Erlangen,
Germany; Arcispedale S. Maria Nuova, Reggio Emilia, Italy; Academisch
Ziekenhuis, Maastricht,The Netherlands; Department of Rheumatology,
VU University Medical Center,Amsterdam,The Netherlands; Department
of Rheumatology, Leiden University Medical Center, Leiden,The
Netherlands; Hospital Clinic i Provincial, Barcelona, Spain; Hospital La
Paz, Madrid, Spain; Leeds General Infirmary, Leeds, UK; Royal National
Hospital for Rheumatic Diseases, Bath, UK; Medical Research, andWyeth
Pharmaceutical, Collegeville, Pennsylvania, USA.
Supported by a grant fromWyeth Research, Collegeville, Pennsylvania,
USA, and Amgen Inc., Thousand Oaks, California, USA.
B.A.C. Dijkmans, MD, PhD, Department of Rheumatology,VU University
Medical Center, and Jan van Breemen Institute,Amsterdam; P. Emery,
MA, MD, FRCP, LeedsTeaching HospitalTrust and Leeds University;
M. Hakala, MD, Rheumatism Foundation Hospital and Department of
Musculoskeletal Medicine and Rehabilitation, Medical School, University
ofTampere,Tampere, Finland; M. Leirisalo-Repo, MD, PhD, Helsinki
University Central Hospital; E. Martin Mola, MD, PhD, Hospital La Paz,
Madrid, Spain; L. Paolozzi, MD, Research and Development,Wyeth
Research, Paris, France; C. Salvarani, MD,Arcispedale S. Maria Nuova;
R. Sanmarti, MD, Hospital Clinic i Provincial; J. Sibilia, MD, PhD,
Hôpital Hautepierre; J. Sieper, MD, University Hospital Benjamin
Franklin; F.Van Den Bosch, MD, PhD, UZ Gent; D. van der Heijde, MD,
PhD, Leiden University Medical Center; S. van der Linden, MD,
Academisch Ziekenhuis Maastricht; J.Wajdula, PhD, Clinical Research
and Development,Wyeth Research, Collegeville, PA.
Address reprint requests to Dr. J.Wajdula, Medical Research,Wyeth
Pharmaceuticals, 500Arcola Road, Collegeville, PA 19426, USA.
E-mail: wajdulj@wyeth.com
Accepted for publication December 31, 2008.
Ankylosing spondylitis (AS) is a chronic rheumatic disease
characterized by inflammatory back pain due to sacroiliitis
and spondylitis that affects young adults. Joint damage,
including erosions, syndesmophytes, and ankylosis, can
result in severe longterm functional impairment leading to a
compromised quality of life.
Tumor necrosis factor-α (TNF-α) antagonists such as
etanercept are remarkably effective at relieving pain and
stiffness
1-4
and improving mobility and quality of life in
AS
5,6
. In 2 double-blind studies
2,3
significantly more
patients receiving etanercept responded to therapy than did
those receiving placebo. In both studies, the difference
between the etanercept and placebo groups was seen as
early as 2 weeks after the start of therapy and was sustained
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