RESEARCH - Effect of IL-6 receptor inhibition with tocilizumab in patients with RA - OPTION study

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Lancet. 2008 Mar 22;371(9617):987-97.

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, A, Hanrahan P, Nash P,

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.

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<0.0001 for 4 mg/kg vs

placebo). More people receiving tocilizumab than those receiving

placebo had at least one adverse event (143 [69%] in the 8 mg/kg

group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo

group). The most common serious adverse events were serious infections

or infestations, reported by six patients in the 8 mg/kg group, three

in the 4 mg/kg group, and two in the placebo group.

INTERPRETATION: Tocilizumab could be an effective therapeutic approach

in patients with moderate to severe active rheumatoid arthritis.

FUNDING: F Hoffmann-La Roche, Chugai Pharmaceutical.

PMID: 18358926

http://www.ncbi.nlm.nih.gov/pubmed/18358926

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