A randomised, multicentre, double-blind, placebo-controlled trial of etanercept in adults with refractory heel enthesitis in spondyloarthritis: the HEEL trial
- Maxime Dougados1,2,
- Bernard Combe3,
- Jürgen Braun4,
- Robert Landewé5,
- Jean Sibilia6,
- Alain Cantagrel7,
- Antoine Feydy8,
- Désirée van der Heijde9,
- Véronique Leblanc10,
- Isabelle Logeart10
- 1Paris-Descartes University, Paris, France
- 2APHP, Rheumatology B Department, Cochin Hospital, Paris, France
- 3Rheumatology Lapeyronie Hospital, Montpellier, France
- 4Rheumazentrum Ruhrgebiet, Universitätsmedizin, Herne, Germany
- 5Rheumatology, University Medical Center, Maastricht, The Netherlands
- 6Rheumatology, Hautepierre Hospital, Strasbourg, France
- 7Rheumatology, Purpan Hospital, Toulouse, France
- 8APHP, Cochin Hospital, Radiology B Department, Paris, France
- 9Rheumatology, University Medical Center, Leiden, The Netherlands
- 10Wyeth Pharmaceuticals, Paris, France
- Correspondence to Maxime Dougados, Rheumatology B Department, Cochin Hospital, 27 Rue du Faubourg Saint Jacques, 75014 Paris, France; maxime.dougados{at}cch.aphp.fr
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Contributors MD was the principal investigator for the study. Authors and the study investigators gathered the data and interpreted the data. IL was a medical monitor during the trial. MD and IL designed the trial, interpreted the data and wrote the report. VL interpreted the data, wrote the report and served as medical monitor during the trial. Vincent Haudiquet (Wyeth) supervised statistical analysis. All authors reviewed and approved the report before submission. MD had full access to all of the data and had final responsibility for the decision to submit the manuscript for publication.
- Accepted 26 January 2010
- Published Online First 28 May 2010
Abstract
Objective Inflammation at the entheses is a distinguishing feature of spondyloarthritis (SpA). Enthesitis at the heel is the most common location and is often chronic, refractory to standard treatment and may have socioeconomic consequences. The objective of this study was to investigate the efficacy of etanercept in refractory heel enthesitis related to SpA.
Methods The present work was a 12-week, randomised, double-blind, placebo-controlled study compared etanercept with placebo in patients with SpA according to Amor's criteria, and heel enthesitis proven by MRI. The primary efficacy end point was the normalised net incremental area under the curve (AUC) between randomisation and week 12 for the patient's global assessment (PGA) of disease activity. Secondary end points included change from baseline in PGA, heel pain, the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) function subscale and improvement in enthesitis as measured by MRI.
Results A total of 24 patients were randomised. Mean normalised net incremental AUC for PGA of disease activity over 12 weeks was significantly greater in the etanercept versus placebo group: −28.5 versus −11.1, respectively (p=0.029). Significant improvements were also reported in the etanercept versus placebo group for PGA, −37.6 versus −11.6 (p=0.007); heel pain, −36.7 versus −13.1 (p=0.022); and WOMAC function, −23.2 versus −7.8 (p=0.024). No significant changes were observed in the MRI findings between groups. No unexpected adverse events or changes in laboratory values or vital signs.
Conclusions This trial is the first randomised placebo-controlled study of an anti-tumour necrosis factor (TNF) agent in refractory heel enthesitis in patients with SpA. It demonstrates that etanercept has a statistically significant and clinically relevant benefit in such patients.
ClinicalTrials.gov identifier NCT00420303.
Footnotes
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Funding This study was sponsored by Wyeth Pharmaceuticals.
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Competing interests MD, Wyeth Pharmaceuticals, consulting fees or other remuneration. BC, Schering, UCB, Wyeth Pharmaceuticals, research grants; UCB, Schering, Wyeth Pharmaceuticals: consulting fees or other remuneration. JB, Wyeth Pharmaceuticals, consulting fees or other remuneration. RL, Wyeth Pharmaceuticals, consulting fees or other remuneration. JS, Bristol-Myers Squibb, Roche Pharmaceuticals, Schering-Plough, research grants; Abbott Immunology Pharmaceuticals, Actelion, Bristol-Myers Squibb, GlaxoSmithKline, LFB, Merck Sharp Dohme, Pfizer Inc, Roche Pharmaceuticals, Schering-Plough, UCB, Wyeth Pharmaceuticals, consulting fees or other remuneration. AC, Roche Pharmaceuticals, research grants; Abbott Immunology Pharmaceuticals, Bristol-Myers Squibb, Merck Pharmaceuticals, Wyeth Pharmaceuticals, consulting fees or other remuneration. DvdH, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Pfizer, Roche, Schering-Plough, UCB, Wyeth Pharmaceuticals consulting fees or other remuneration. VL, Wyeth Pharmaceuticals, employment. IL, Wyeth Pharmaceuticals, employment.
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Ethics approval This study was conducted with the approval of the ERC Cochin Hospital, Paris, France.
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Provenance and peer review Not commissioned; externally peer reviewed.
