Objective To assess early effects on joint structures of VX-509 in combination with stable disease-modifying antirheumatic drug (DMARD) therapy using MRI in adults with rheumatoid arthritis (RA).
Methods This phase II, placebo-controlled, double-blind, dose-ranging study randomised patients with RA and inadequate DMARD response to VX-509 100 mg (n=11), 200 mg (n=10) or 300 mg (n=10) or placebo (n=12) once daily for 12 weeks. Outcome measures included American College of Rheumatology score (ACR20; improvement of ≥20%) and disease activity score (DAS28) using C reactive protein (CRP), and the RA MRI scoring (RAMRIS) system.
Results ACR20 response at week 12 was 63.6%, 60.0% and 60.0% in the VX-509 100-mg, 200-mg and 300-mg groups, respectively, compared with 25.0% in the placebo group. DAS28-CRP scores decreased in a dose-dependent manner with increasing VX-509 doses. Decreases in RAMRIS synovitis scores were significantly different from placebo for all VX-509 doses (p<0.01) and for RAMRIS osteitis scores (p<0.01) for VX-509 300 mg. Treatment was generally well tolerated.
Conclusions VX-509 plus a DMARD reduced the signs and symptoms of RA in patients with an inadequate response to a DMARD alone. MRI responses were detected at week 12. Treatment was generally well tolerated.
Trial registration number NCT01754935; results.
- Rheumatoid Arthritis
- Magnetic Resonance Imaging
- DMARDs (biologic)
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Handling editor Tore K Kvien
Contributors MO and MG participated in designing the study. MG was a study investigator and collected/assembled data. FY and NK prepared the manuscript. All authors participated in data analysis and interpretation, and all provided critical review and revisions to the manuscript. All authors granted final approval of the manuscript.
Funding This study was sponsored by Vertex Pharmaceuticals Incorporated.
Competing interests MG has received consultancy fees from Eli Lilly, Pfizer and Vertex Pharmaceuticals Incorporated, and study grants from Sanofi and Regeneron Pharmaceuticals. FY and NK are employees of Vertex Pharmaceuticals Incorporated. MO has received consultancy/speaker fees and/or research support form Abbott/Abbvie, BMS, Boehringer-Ingelheim, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth.
Patient consent Obtained
Ethics approval University of the Witwatersrand, Johannesburg, Human Research Ethics Committee, South Africa: 121002. Pharma-ethics, South Africa: 20121127. Administrative Panel on Human Subjects in Medical Research, Stanford University, California, USA: 350 (Panel: 3). Human Subjects Committee, The University of Kansas Medical Center, Kansas, USA: 13571. New England Institutional Review Board, Massachusetts, USA: 12-322. Lithuanian Bioethics Committee, Lithuania: P-12-84. The Committee on Biomedical Research Ethics for the Region North Jutland, Denmark: N-2012-003439-41. Western Institutional Review Board, Washington, USA: 1138506. Medische Ethische Toetsingscommissie University Medical Center, The Netherlands: NL42286.041.12. Tallinn Medical Research Ethics Committee, Estonia: 2956. University of California San Diego, California, USA: 130843.
Provenance and peer review Not commissioned; externally peer reviewed.