AB0562 A double-blind, placebo-controlled, multicenter trial of tocilizumab in moderate to severe active RA patients with inadequate response to methotrexate in korean population

• Published in: Annals of the rheumatic diseases Vol. 71; no. Suppl 3; p. 670
• Main Authors: Lim, M.J., Park, S.H., Shim, S.-C., Baek, H.J., Yoo, D.-H., Kim, H.A., Lee, S.K., Lee, Y.J., Park, Y.E., Cha, H.-S., Park, W., Song, Y.-W.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2013; BMJ Publishing Group LTD
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2012-eular.562

Background Interleukin-6 (IL-6), a proinflammatory cytokine, is thought to play a major pathological role in rheumatoid arthritis (RA). Tocilizumab is humanized anti IL-6 receptor monoclonal antibody which has been shown to improve signs and symptoms of RA. Objectives To investigate the efficacy and safety of tocilizumab in a Korean population. Methods This clinical trial was a 24-week phase III, randomized, double-blind, placebo-controlled, multicenter trial with two treatments arms and conducted from October, 2009 to October, 2010. The eligible patients had moderate to severe active RA, inadequately responding to MTX (or DMARDs). Tocilizumab at a dose of 8mg/kg or placebo were administered in a blinded manner, intravenously every 4 weeks, with stable dose of methotrexate (MTX) or other DMARDs. Results Total of 80 patients completed 24 week’s treatment with 40 patients in each treatment arm. At week 24, proportions of ACR 20, ACR 50, DAS28 remission and EULAR response were significantly higher in Tocilizumab group than in placebo group (p <0.0001, p=0.0002, p=0.0002 and p<0.0001, respectively as shown in Table 1). The mean hemoglobin level was increased and the rheumatoid factor titer was decreased in Tocilizumab group, compared to those of placebo group (p=0.0002, p=0.0055, respectively). Adverse drug reactions were more frequent in Tocilizumab group than in placebo group as follows; increased SGPT (21%), granulocytopenia (17%), leukocytopenia (15%), hypercholesterolemia (13%), pharyngitis (13%), and increased SGOT (10%). There were more incidences of serious adverse drug reactions in Tocilizumab group than in placebo group, but it was not significant (p=0.0548). Table 1. Parameters of RA activity Tocilizumab groupPlacebo groupP Proportion achieving ACR2061.7%16.7%<0.0001 Proportion achieving ACR5029.8%2.1%0.0002 Proportion achieving ACR704.3%2.1%0.617 Mean changes in DAS28 - ESR3.211.16<0.0001 Proportion achieving DAS remission42.5%3.3%0.0002 Proportion achieving EULAR response<0.0001 Good53.2%2.1% Moderate31.9%33.3% Mean changes in Hemoglobin0.920.110.0002 Mean changes in rheumatoid factor53.829.390.0055 Conclusions In Korean population, administration of tocilizumab 8 mg/kg in combination with MTX (with or without other DMARDs) reduced RA activity significantly. Most of RA activity parameters including ACR 20, ACR 50, DAS 28 remission and EULAR response were achieved more frequently in Tocilizumab group than in placebo group. Tocilizumab was generally well tolerated since no safety issue was observed during the study. This study was financially supported by JW Pharmaceutical Co. (KFDA clinical trial-146). References Maini RN, et al. Arthritis Rheum. 2006;54(9):2817-29. Jones G, et al. Ann Rheum Dis. 2010;69(1):88-96. Disclosure of Interest None Declared