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Tocilizumab versus methotrexate monotherapy in RA

Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: The AMBITION study Jones G et al. ARD online First, published on March 17m, 2009 as 10.1136/ard.2008.105197

Objective: IL-6 is a key cytokine in the pathogenesis of rheumatoid arthritis. Tocilizumab is an anti-IL-6 receptor antibody inhibiting the action of IL-6. This study (AMBITION study) evaluated the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA who had not previously failed methotrexate or biologics treatment.

Methods: 24 week double-blind parallel group study with randomisation of 673 patients to either tocilizumab 8 mg/kg every 4 weeks or methotrexate (initial dose 7.5 mg/week with titration to 20 mg/week within 8 weeks, oral drugs), or placebo for 8 weeks followed by tocilizumab 8 mg/kg. Primary end point was the proportion of patients achieving ACR 20 response at week 24.

Results: In the intent to treat analysis tocilizumab was superior to methotrexate, achieving a higher ACR 20 response (69.9 versus 52.5%; p<0.0001), and DAS 28<2.6 rate (33.6 versus 12.1%) at week 24. There was a non-significant difference of serious adverse events between the two groups (3.8% for tocilizumab versus 2.8% in methotrexate), whereas serious infections were found at a rate of 1.4% for tocilizumab versus 0.7% under methotrexate. The side effects of neutropenia and increase in total cholesterol were higher in the tocilizumab group. There was a lower incidence of ALT elevations under tocilizumab.

Conclusions: Tocilizumab monotherapy appears to be superior to methotrexate monotherapy with a rapid improvement in RA signs and symptoms. There appears to be a favourable benefit-risk ratio in patients who have not previously failed methotrexate or biologics treatment.

Comments: This study of tocilizumab showed for a first time that in the direct comparison with methotrexate a monotherapy with a biologic substance is more effective. With regard to side effects, there appears to be an increased rate of serious infections under tocilizumab. Furthermore, the extent and severity of other side effects such as neutropenia, cholesterol elevation and transaminases elevation will have to be carefully observed in long-term studies or post surveillance investigations.

Beat A. Michel

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