Drs. Genovese and Nasonov have received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000 each).
Rheumatoid Arthritis Clinical Studies
Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: The tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study†
Article first published online: 29 SEP 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 10, pages 2968–2980, October 2008
How to Cite
Genovese, M. C., McKay, J. D., Nasonov, E. L., Mysler, E. F., da Silva, N. A., Alecock, E., Woodworth, T. and Gomez-Reino, J. J. (2008), Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: The tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis & Rheumatism, 58: 2968–2980. doi: 10.1002/art.23940
ClinicalTrials.gov identifier: NCT00106574.
- Issue published online: 29 SEP 2008
- Article first published online: 29 SEP 2008
- Manuscript Accepted: 27 JUN 2008
- Manuscript Received: 7 FEB 2008
- F. Hoffmann-La Roche Ltd.
To examine the efficacy and safety of the humanized anti–interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA).
A total of 1,220 patients were randomized (2:1 ratio) in the phase III, double-blind, placebo-controlled, multicenter TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy) study. Patients remained on stable doses of DMARDs and received tocilizumab 8 mg/kg or placebo (control group) every 4 weeks for 24 weeks.
At week 24, the proportion of patients achieving a response according to the American College of Rheumatology criteria for 20% improvement (ACR20) was significantly greater in the tocilizumab plus DMARD group than in the control group (61% versus 25%; P < 0.0001). Secondary end points including 50% or 70% improvement (ACR50/70), the Disease Activity Score in 28 joints (DAS28), DAS28 remission responses (DAS28 <2.6), European League Against Rheumatism responses, and systemic markers such as the C-reactive protein and hemoglobin levels showed superiority of tocilizumab plus DMARDs over DMARDs alone. Seventy-three percent of patients in the tocilizumab group had ≥1 adverse event (AE), compared with 61% of patients in the control group. AEs leading to withdrawal from the study were infrequent (4% of patients in the tocilizumab group and 2% of those in the control group). Serious AEs occurred in 6.7% and 4.3% of patients in the tocilizumab and control groups, respectively, and serious infections occurred in 2.7% and 1.9%, respectively. Elevations in the alanine aminotransferase level, from normal at baseline to >3-fold the upper limit of normal, occurred in 4% of patients in the tocilizumab group and 1% of those in the control group, and elevated total cholesterol levels were observed in 23% and 6% of patients, respectively. Sixteen patients started lipid-lowering therapy during the study. Grade 3 neutropenia occurred in 3.7% of patients receiving tocilizumab and none of the patients in the control group, and no grade 4 neutropenia was reported.
Tocilizumab combined with any of the DMARDs evaluated was safe and effective in reducing articular and systemic symptoms in patients with an inadequate response to these agents.