Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Nonsteroidal Anti-Inflammatory (NSAIDs) Drug-Sparing Effect and Sustained Clinical Improvement of Etanercept in Advanced Ankylosing Spondylitis. Results of an Open Label Extension Following a Randomized Double Blind Placebo-Controlled Study (SPINE).
Dougados2, Maxime, Braun5, Jürgen, Szanto6, Sandor, Combe1, Bernard, Geher4, Pal, Leblanc3, Veronique, Logeart3, Isabelle
Lapeyronie Hospital, Montpellier, France
Paris-Descartes Univ, Cochin Hospital, Paris, France,
Pfizer France, Paris La Défense, France
Polyclinic of the Hospitaller Brothers of St. John of God, Budapest, Hungary
Ruhrgebiet Univ, Herne, Germany
Univ of Debrecen, Debrecen, Hungary
Etanercept (ETN) was showed to significantly improve rheumatic signs, symptoms and pulmonary function in patients with advanced ankylosing spondylitis during the randomized placebo-controlled trial (RCT) phase of SPINE study (1). A pre-planned open label extension (OLE) was aimed at assessing the sustained rheumatic effects of ETN for 3 additionnal months. In contrast to the RCT phase, the NSAID intake was at the discretion of the patients during this OLE phase. The purpose was to evaluate whether ETN therapy could be maintained with a concomitant NSAID treatment reduction.
Patients: Definite AS patients (modified New York criteria) with active (BASDAI >=40), refractory (at least 2 NSAIDs), severe (at least 2, 3 or 2 inter-vertebral radiological consecutive bridges at the lumbar, thoracic or cervical level respectively), anti-TNF naive. Study design: Multi-center, double blind, RCT vs placebo of 12-week duration followed by a 12-week OLE. Patients who completed RCT phase entered the OLE and received etanercept (ETN). Study drugs: ETN 50 mg OW and identical placebo (PBO) during RCT phase and ETN 50 mg OW during the OLE phase. Outcome measures: BASDAI, BASFI, BASMI, and intake of NSAIDs using the ASAS-NSAIDs scoring system (2).
Of the 82 randomized patients, 77 (males: 92%, age: 47.5±10.5 y, disease duration (since AS diagnosis): 16±10.7 y, B27 positive: 83.1%) entered the OLE phase (original ETN group: n=38; original PBO group, n=39). At baseline, patients had an active (BASDAI: 61.5±13.2, CRP: 20.5±26.1 mg/l) and severe (BASMI: 5.7±1.4, mSASSS: 37±20.2) disease and 83.1% of patients were receiving one NSAID at least at baseline. During the 12 weeks of the OLE trial, 3 patients discontinued the treatment (1 in the original PBO arm [due to withdrawal of consent] and 2 in the original ETN arm [due to withdrawal of consent: 1; due to lost to follow-up:1]). The mean change in BASDAI from baseline showed a sustained improvement reaching -15±20 and -27.4±23.8 at Week 12 and -28.6±24.3 and -37.6±22.4 at Week 24 in the original PBO group and ETN group, respectively.
Whatever the original group, the concomitant intake of NSAIDs significantly decreased during OLE phase in comparison to RCT phase: mean absolute change in ASAS-NSAID equivalent score between OLE and RCT was 39.5 (-36%), p=0.005 and -20.9 (-17%), p=0.0005 in the original ETN and placebo group, respectively.
This prospective study conducted in advanced AS patients confirms the sustained symptomatic efficacy of ETN. Despite a relevant decrease in NSAIDs intake, such findings might be beneficial for the patients, not only in terms of long term symptomatic status but also in terms of prevention of long term NSAIDs toxicity.
This study was sponsored by Wyeth Pharmaceuticals France (Wyeth has been acquired by Pfizer in October 2009)
To cite this abstract, please use the following information:
Dougados, Maxime, Braun, Jürgen, Szanto, Sandor, Combe, Bernard, Geher, Pal, Leblanc, Veronique, et al; Nonsteroidal Anti-Inflammatory (NSAIDs) Drug-Sparing Effect and Sustained Clinical Improvement of Etanercept in Advanced Ankylosing Spondylitis. Results of an Open Label Extension Following a Randomized Double Blind Placebo-Controlled Study (SPINE). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1946