Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.
Details
Serval ID
serval:BIB_C0C9DF5BB672
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.
Journal
Lancet
Working group(s)
OPTION Investigators
Contributor(s)
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.
ISSN
1474-547X (Electronic)
ISSN-L
0140-6736
Publication state
Published
Issued date
2008
Volume
371
Number
9617
Pages
987-997
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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<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.
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.
Keywords
Antibodies, Monoclonal/administration & dosage, Antibodies, Monoclonal/adverse effects, Antibodies, Monoclonal, Humanized, Arthritis, Rheumatoid/classification, Arthritis, Rheumatoid/drug therapy, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Quality of Life, Severity of Illness Index, Treatment Outcome
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Create date
26/04/2013 10:40
Last modification date
20/08/2019 16:35
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