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Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study

Citation

Jones, G and Sebba, A and Gu, J and Lowenstein, MB and Calvo, A and Gomez-Reino, JJ and Siri, DA and Tomsic, M and Alecock, E and Woodworth, T and Genovese, MC, Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study , Annals of The Rheumatic Diseases: The Eular Journal, 69, (1) pp. 88-96. ISSN 0003-4967 (2010) [Refereed Article]


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Copyright Statement

Copyright © 2010 BMJ Publishing Group Ltd.

DOI: doi:10.1136/ard.2008.105197

Abstract

Background: The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. Objective: To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed. Methods: This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24. Results: The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p,0.001), and 28-joint Disease Activity Score (DAS28) ,2.6 rate (33.6 vs 12.1%) at week 24. Mean high-sensitivity Creactive protein was within the normal range from week 12 with tocilizumab, whereas levels remained elevated with methotrexate. The incidence of serious adverse events with tocilizumab was 3.8% versus 2.8% with methotrexate (p=0.50), and of serious infections, 1.4% versus 0.7%, respectively. There was a higher incidence of reversible grade 3 neutropenia (3.1% vs 0.4%) and increased total cholesterol >240 mg/dl (13.2% vs 0.4%), and a lower incidence of alanine aminotransferase elevations .36–,56upper limit of normal (1.0% vs 2.5%), respectively. Conclusion: Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit–risk, in patients for whom treatment with methotrexate or biological agents has not previously failed.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Rheumatology and Arthritis
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Skeletal System and Disorders (incl. Arthritis)
Author:Jones, G (Professor Graeme Jones)
ID Code:64030
Year Published:2010
Web of Science® Times Cited:367
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-06-17
Last Modified:2011-06-10
Downloads:3 View Download Statistics

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