ArticlesTocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial
Introduction
The introduction and uptake of biological disease-modifying antirheumatic drugs has substantially advanced the standard of care of patients with rheumatoid arthritis. Although most patients who are clinically eligible for such drugs also maintain current treatment with methotrexate (or another synthetic disease-modifying antirheumatic drug) as standard of care, up to 40% discontinue or are noncompliant with methotrexate because of toxic effects1, 2 or preference.3, 4, 5 Data from registries of biological drugs6, 7, 8, 9, 10, 11 and a US claims database12 suggest that roughly a third of patients take biological disease-modifying antirheumatic drugs as monotherapy.
Interleukin 6 is a key cytokine involved in the pathogenesis of rheumatoid arthritis,13 and increased concentrations of interleukin 6 correlate with disease activity in patients with rheumatoid arthritis.14, 15 Tocilizumab is a humanised monoclonal antibody that binds to membrane-bound and soluble forms of human interleukin 6 receptor,16 inhibiting signalling mediated by interleukin 6 and its inflammatory effects.17 Randomised, double-blind, controlled phase 3 studies have shown that combination treatment with tocilizumab and methotrexate or other synthetic disease-modifying antirheumatic drugs results in rapid and sustained improvement in the signs and symptoms of rheumatoid arthritis in several different patient populations.18, 19, 20, 21 Studies have also shown the efficacy and safety of tocilizumab as monotherapy.22, 23, 24, 25, 26
We compared the efficacy and safety of tocilizumab monotherapy with adalimumab monotherapy in patients with rheumatoid arthritis who were intolerant to methotrexate or for whom continuation of methotrexate was deemed inappropriate. This study is the first randomised controlled trial specifically designed to test the superiority of one biological disease-modifying antirheumatic monotherapy compared with another. Adalimumab is a fully human monoclonal antibody against TNFα that was chosen as a comparator to tocilizumab because of its status as a globally adopted, first-line biological therapy (in combination with methotrexate and as a monotherapy) in patients with rheumatoid arthritis who are refractory to non-biological disease-modifying antirheumatic drugs.
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Study design and participants
This randomised, parallel-group, double-blind, phase 4 study was done at 76 centres in 15 countries in North and South America, Australasia, and Europe.
Eligible patients were aged 18 years or older at baseline and had had rheumatoid arthritis for 6 months or more. Patients had to be taking methotrexate or have done previously, be unable to tolerate methotrexate, or be inappropriate candidates for continued methotrexate treatment in the judgment of the investigator. Patients previously treated
Results
Patients were enrolled between May 19, 2010 and June 21, 2011. 326 patients were enrolled in the study (163 in each group; figure 1). The intention-to-treat population consisted of 325 patients (163 in the tocilizumab group and 162 in the adalimumab group). One enrolled patient did not receive an adalimumab dose. The safety population consisted of 324 patients (162 in each group). One patient in the tocilizumab group had no safety assessments done after baseline. Baseline patient
Discussion
Comparison between biological monotherapies with different mechanisms of action is important because roughly a third of patients receive biological disease-modifying antirheumatic drugs as monotherapy.6, 7, 8, 9, 10, 11 Treatment with tocilizumab monotherapy led to a significantly and clinically meaningful greater improvement in DAS28 from baseline to week 24 compared with adalimumab monotherapy. Response rates were also significantly higher for tocilizumab for all secondary endpoints.
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Lead authors, contributed equally