Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.

Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R; OPTION Investigators. Collaborators (76)Tate G, Maldonado-Cocco JA, Scali J, Taylor A, Hanrahan P, Nash P, Smith M, Smolen J, Koeller M, Smolen J, Eberl G, Dunky A, Zamani O, Simon JC, Scheinberg MA, Yaneva D, Oparanov B, Karastatev D, Atkins C, Beaulieu A, Bell M, Haraoui B, Marin L, Thorne JC, Zummer M, Khraishi M, McKendry RJ, Pandith V, McCarthy T, Lau CS, Li E, Mok CC, Kahan A, Wendling D, Bardin T, Nguyen M, Claudepierre P, Berenbaum F, Puechal X, Alten R, Fiehn C, Heilig B, Hellmich B, Lange U, Lorenz HM, Rubbert-Roth A, Wendler J, Czirijak L, Hodinka L, Szekanecz Z, Molad Y, Nahir M, Rosner I, Rubinow A, Abu Shakra M, Elkayam O, Marcolongo R, Bagnato G, Triolo G, Trotta F, de Vita S, Ramos-Remus C, Lugo GE, Abud-Mendoza C, Pineca C, de la Torre IG, Pacheco C, Leong KH, Koh DR, Rovensky J, Dudler J, Villiger P, Lothrenoo W, Asavatanabodee P, Nilganuwong S, Totemchokchaiyakarn K. SourceDivision of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. josef.smolen@meduniwien.ac.at Abstract BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. FINDINGS: The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p