Author(s): Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA,
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Abstract OBJECTIVE: 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). METHODS: 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. RESULTS: 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 >or=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. CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00106574.
This article was published in Arthritis Rheum
and referenced in Rheumatology: Current Research