Symptomatic Efficacy of Etanercept and Its Effects on Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Authors

  • Maxime Dougados,

    Corresponding author
    1. Université Pierre et Marie Curie Paris 6, Hôpital Cochin, AP-HP, INSERM U1153, and PRES Sorbonne Paris Cité, Paris, France
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    • Dr. Dougados has received consulting fees from Pfizer, AbbVie, Celgene, Eli Lilly, Novartis, Roche, and Sanofi-Aventis (less than $10,000 each).

  • Désirée van der Heijde,

    1. Leiden University Medical Center, Leiden, The Netherlands
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    • Dr. van der Heijde has received consulting fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex (less than $10,000 each) and is the director of Imaging Rheumatology BV.

  • Joachim Sieper,

    1. Charité–Universitätsmedizin Berlin, Berlin, Germany
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    • Dr. Sieper has received consulting fees from Novartis and UCB (less than $10,000 each) and from AbbVie, Merck, and Pfizer (more than $10,000 each).

  • Jürgen Braun,

    1. Rheumazentrum Ruhrgebiet, Herne, Germany
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    • Dr. Braun has received consulting fees from AbbVie, Celltrion, MSD, Novartis, Pfizer, and UCB (less than $10,000 each).

  • Walter P. Maksymowych,

    1. University of Alberta, Edmonton, Alberta, Canada
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    • Dr. Maksymowych has received consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Pfizer, Synarc, and UCB (less than $10,000 each), and is the chief medical officer of CaRE Arthritis Ltd.

  • Gustavo Citera,

    1. Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina
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    • Dr. Citera has received consulting fees from AbbVie, Bristol-Myers Squibb, Pfizer, and Roche (less than $10,000 each) and research grants from Pfizer.

  • Corinne Miceli-Richard,

    1. Hôpital de Bicêtre, AP-HP, and Université Paris-Sud 11, Le Kremlin-Bicêtre, Paris, France
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    • Dr. Miceli-Richard has received consulting fees from AbbVie, Bristol-Myers Squibb, Janssen, and Pfizer (less than $10,000 each).

  • James Cheng-Chung Wei,

    1. Chung Shan Medical University Hospital, Taichung, Taiwan
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    • Dr. Wei has received research grants or consulting fees from Abbott, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB.

  • Ron Pedersen,

    1. Pfizer Inc., Collegeville, Pennsylvania
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Randi Bonin,

    1. Pfizer Inc., Collegeville, Pennsylvania
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Mahboob U. Rahman,

    1. Pfizer Inc., Collegeville, Pennsylvania
    Current affiliation:
    1. University of Pennsylvania Perelman School of Medicine, Philadelphia
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Isabelle Logeart,

    1. Pfizer International Operations, Paris, France
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Joseph Wajdula,

    1. Pfizer Inc., Collegeville, Pennsylvania
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Andrew S. Koenig,

    1. Pfizer Inc., Collegeville, Pennsylvania
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Bonnie Vlahos,

    1. Pfizer Inc., Collegeville, Pennsylvania
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Daniel Alvarez,

    1. Pfizer Inc., Collegeville, Pennsylvania
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.

  • Jack F. Bukowski

    1. Pfizer Inc., Collegeville, Pennsylvania
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    • Mr. Pedersen, Ms Bonin, Dr. Rahman, Dr. Logeart, Dr. Wajdula, Dr. Koenig, Ms Vlahos, Dr. Alvarez, and Dr. Bukowski own stock or stock options in Pfizer.


Abstract

Objective

To assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)–refractory nonradiographic axial spondyloarthritis (SpA).

Methods

The study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double-blind study); during the subsequent open-label period, all patients received etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the sacroiliac joints and spine was performed at baseline and week 12.

Results

One hundred six patients were randomized to the etanercept group and 109 to the placebo group. Of the 215 patients, the mean ± SD age at baseline was 32.0 ± 7.8 years, 154 (72%) were HLA–B27 positive, and 174 (81%) had MRI-confirmed sacroiliitis. At 12 weeks, the proportion of patients with improvement according to the ASAS40 was significantly higher in the etanercept group than in the placebo group (34 of 105 [32%] versus 17 of 108 [16%]; P = 0.006). Patients who received etanercept exhibited a greater reduction in MRI-based scores for sacroiliac joint inflammation (−46.9% versus −10.9%; P < 0.001) and spinal inflammation (−45.4% versus −33.4%; P = 0.04) compared with placebo-treated patients at week 12. Post hoc analyses suggested a possible association between higher baseline C-reactive protein levels or MRI sacroiliac joint inflammation scores and higher rates of ASAS40 response to etanercept. At week 24, patients in the placebo group who had switched to etanercept at 12 weeks exhibited improvement similar to that observed in patients who had received etanercept for 24 weeks.

Conclusion

In patients with nonradiographic axial SpA, etanercept treatment was associated with rapid, significant improvement in symptomatic disease activity, function, and systemic and skeletal inflammation over 12 weeks; clinical/functional improvement was sustained over 24 weeks.

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