Artikel
Secukinumab Efficacy in Anti-TNF-Naive Patients and Patients Previously Exposed to Anti-TNF Therapy: Results of A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study (MEASURE 2) in Active Ankylosing Spondylitis
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Autoren
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Joachim Sieper
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektologie, Rheumatologie, Berlin
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Jürgen Braun
- Rheumazentrum Ruhrgebiet, Herne
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Xenofon Baraliakos
- Rheumazentrum Ruhrgebiet, Herne
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Dominique Baeten
- Academic Medical Center/University of Amsterdam, Clinical Immunology and Rheumatology, Amsterdam, The Netherlands
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Maxime Dougados
- Hôpital Cochin, Department of Rheumatology, Paris, France
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Paul Emery
- Johns Hopkins University, Baltimore, United States
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Atul Deodhar
- Oregon Health & Science University, Arthritis & Rheumatic Diseases, Portland, United States of America
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Brian Porter
- Novartis Pharmaceuticals Corporation, NJ, USA, New Jersey, USA
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Mats Andersson
- Novartis Pharma AG, Basel, Switzerland
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Hanno B. Richards
- Novartis Pharma AG, Basel, Switzerland
| Veröffentlicht: | 1. September 2015 |
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Gliederung
Text
Introduction: Current treatment options for ankylosing spondylitis (AS) patients with intolerance or an inadequate response to tumor necrosis factor alpha inhibitors (anti-TNF) are limited. Secukinumab, a human anti-interleukin (IL)-17A monoclonal antibody, significantly improved the signs and symptoms of AS in the phase 3 MEASURE 2 study (NCT01649375) [1].
The objective of this analysis is to evaluate the efficacy and safety of secukinumab by anti-TNF history in the MEASURE 2 study.
Methods: 219 adults with active AS were randomised to receive subcutaneous (s.c.) secukinumab (150 or 75 mg) or PBO at baseline, Wk 1, 2 and 3, and every 4 wks starting at Wk 4. Randomization was stratified according to prior anti-TNF experience: anti-TNF-naïve, or inadequate response or intolerance to not more than one anti-TNF biologic agent (anti-TNF-IR). At Wk 16 PBO-treated subjects were re-randomized to secukinumab 150 or 75 mg. Pre-planned subgroup analyses of the primary and secondary endpoints were conducted among anti-TNF-naïve and anti-TNF-IR subjects and included: the proportion of subjects achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 response (primary endpoint), ASAS40, high sensitivity C-reactive protein (hsCRP), ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Short Form-36 (SF-36), Ankylosing Spondylitis Quality of Life (ASQoL), and ASAS partial remission. Analyses at Wk 16 used non-responder imputation (for binary variables) and mixed-effects repeated measures model (for continuous variables). Wk 52 data are as observed.
Results: 62% of subjects enrolled were anti-TNF-naïve and 38% were anti-TNF-IR. At Wk 16, secukinumab 150 mg (but not 75 mg) improved ASAS20 response rates compared with PBO in both anti-TNF-naïve (68.2% vs 31.1%, respectively; P< 0.001) and anti-TNF-IR (50.0% vs 24.1%; P < 0.05) subjects. Improvements with secukinumab 150 mg were observed for all secondary endpoints in anti-TNF-naïve subjects, except ASAS partial remission, and for most secondary endpoints in anti-TNF-IR subjects. Clinical responses to secukinumab were sustained or continued to improve in both anti-TNF-naïve and anti-TNF-IR subjects through 52 wks.
Conclusion: Secukinumab 150 mg s.c. provided sustained improvement in the signs and symptoms of AS, with associated reduction in inflammation and improvement in physical function and health-related QoL in both anti-TNF-naïve and anti-TNF-IR subjects.
