Maini RN et al. (2006) Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum 54: 2817–2829

Maini and colleagues have shown that tocilizumab (a monoclonal antibody against the interleukin-6 receptor) results in dose-related improvements in disease activity for patients with rheumatoid arthritis (RA). The efficacy of tumor necrosis factor inhibitors is increased by concomitant methotrexate, but the investigators found that the benefits of tocilizumab were similar with and without concomitant methotrexate.

This randomized, double-blind, 16-week trial included 359 patients with RA who had not responded adequately to ≥4 weeks of methotrexate. Patients received four infusions of tocilizumab 2, 4, or 8 mg/kg at monthly intervals plus either methotrexate or placebo once weekly, or four placebo infusions at monthly intervals plus methotrexate once weekly.

Improvements in RA activity were scored by the American College of Rheumatology (ACR) criteria. A 20% improvement (an ACR20 response) was achieved by 61% and 63% of patients who received 4 and 8 mg/kg of tocilizumab monotherapy, respectively, and by 63% and 74% of patients who received 4 and 8 mg/kg of tocilizumab plus methotrexate, respectively. A surprisingly high proportion (41%) of patients who received methotrexate without tocilizumab achieved an ACR20 response, however, which indicated that they had not yet fully responded to methotrexate at enrolment.

Tocilizumab was generally well tolerated: ∼50% of patients experienced an adverse event, although most were mild or moderate. Some tocilizumab-treated individuals experienced clinically significant increases in transaminase levels, which seemed to be exacerbated by methotrexate. Dose-dependent increases in bilirubin, cholesterol, and in neutrophils were also observed.