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Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: The AMBITION study
  1. Graeme Jones (g.jones{at}
  1. Menzies Centre for Population Health, Australia
    1. Anthony Sebba
    1. Arthritis Research of Florida, United States
      1. Jieruo Gu
      1. Department of Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, China
        1. Mitchell B Lowenstein
        1. The Arthritis Center, United States
          1. Armando Calvo
          1. San Felipe Clinic, Peru
            1. Juan J Gomez-Reino
            1. University of Santiago de Compostela, Spain
              1. Daniel A Siri
              1. CAICI Institute, Argentina
                1. Matija Tomšic
                1. Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia
                  1. Emma Alecock
                  1. Roche Products Ltd, United Kingdom
                    1. Thasia Woodworth
                    1. Roche Products Ltd, United Kingdom
                      1. Mark C Genovese
                      1. Division of Immunology and Rheumatology, Stanford University Medical Center, United States


                        Objectives: The anti-IL-6 receptor antibody tocilizumab inhibits signaling of IL-6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. The AMBITION study evaluated tocilizumab monotherapy efficacy and safety vs. methotrexate in patients with active RA, who had not previously failed methotrexate/biologics treatment.

                        Methods: This 24-week, double-blind, double-dummy, parallel-group study, randomized 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 endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at Week 24.

                        Results: The intent-to-treat analysis demonstrated that tocilizumab was superior to methotrexate treatment with a higher ACR20 response (69.9 vs. 52.5%; P<0.0001), and DAS28<2.6 rate (33.6 vs. 12.1%) at Week 24. Mean high sensitivity C-reactive protein (hsCRP) was within the normal range from Week 12 with tocilizumab, whereas levels remained elevated with methotrexate. The incidence of serious adverse events (AEs) with tocilizumab was 3.8% vs. methotrexate, 2.8% (p=0.50), and of serious infections, 1.4% vs. 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 >3x-<5x upper limit of normal (1.0% vs. 2.5%), respectively.

                        Conclusion: Tocilizumab monotherapy is superior to methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favorable benefit-risk, in patients who have not previously failed methotrexate or biologics treatment.

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