Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial

• Published in: The Lancet (British edition) 2013, Vol.381 (9877), p.1541-1550
• Main Authors: Gabay, Cem, MD, Emery, Paul, MD, van Vollenhoven, Ronald, MD, Dikranian, Ara, MD, Alten, Rieke, MD, Pavelka, Karel, MD, Klearman, Micki, MD, Musselman, David, MD, Agarwal, Sunil, MD, Green, Jennifer, MSc, Kavanaugh, Arthur, Dr
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Adalimumab; Adult; Aged; alanine transaminase; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - therapy; Autoimmune diseases; Biological and medical sciences; Biological treatment; body weight; clinical trials; Cytokines; Diseases of the osteoarticular system; Double-Blind Method; Drug dosages; Drug therapy; Female; General aspects; Heart attacks; human resources; Humans; Infections; Inflammatory joint diseases; interleukin-6; Internal Medicine; intravenous injection; low density lipoprotein cholesterol; Male; Medical Science; Medical sciences; Medicin och hälsovetenskap; Medicinsk vetenskap; methotrexate; Middle Aged; neutrophils; patients; Rheumatoid arthritis; Rheumatology; Sensitivity analysis
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(13)60250-0

Summary Background Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab—an inhibitor of interleukin 6 receptor signalling—has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis. Methods We did this randomised, double-blind, parallel-group, phase 4 superiority study in 76 centres in 15 countries in North and South America, Australasia, and Europe. We enrolled patients who were aged at least 18 years, had severe rheumatoid arthritis for 6 months or more, and were intolerant to methotrexate or were inappropriate for continued methotrexate treatment. Patients were randomly assigned (1:1; block size of four) to receive tocilizumab 8 mg per kg bodyweight intravenously every 4 weeks plus placebo subcutaneously every 2 weeks or adalimumab 40 mg subcutaneously every 2 weeks plus placebo intravenously every 4 weeks for 24 weeks. Investigators, patients, and sponsor personnel were masked to assignment. The primary endpoint was change in disease activity score using 28 joints (DAS28) from baseline to week 24. This trial is registered with ClinicalTrials.gov , number NCT01119859. Findings We screened 452 patients and enrolled 326 patients. The intention-to-treat population contained 325 patients (163 assigned to tocilizumab, 162 assigned to adalimumab). Week 24 mean change from baseline in DAS28 was significantly greater in the tocilizumab group (–3·3) than in the adalimumab group (−1·8) patients (difference −1·5, 95% CI −1·8 to −1·1; p