Abstract
Objective. Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA. Methods. In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria. Results. Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients. Conclusion. Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.
| Original language | English |
|---|---|
| Pages (from-to) | 1761-1769 |
| Number of pages | 9 |
| Journal | Arthritis and Rheumatism |
| Volume | 50 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2004 Jun |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Rheumatology
Cite this
Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody : A multicenter, double-blind, placebo-controlled trial. / Nishimoto, Norihiro; Yoshizaki, Kazuyuki; Miyasaka, Nobuyuki; Yamamoto, Kazuhiko; Kawai, Shinichi; Takeuchi, Tsutomu; Hashimoto, Jun; Azuma, Junichi; Kishimoto, Tadamitsu.
In: Arthritis and Rheumatism, Vol. 50, No. 6, 06.2004, p. 1761-1769.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody
T2 - A multicenter, double-blind, placebo-controlled trial
AU - Nishimoto, Norihiro
AU - Yoshizaki, Kazuyuki
AU - Miyasaka, Nobuyuki
AU - Yamamoto, Kazuhiko
AU - Kawai, Shinichi
AU - Takeuchi, Tsutomu
AU - Hashimoto, Jun
AU - Azuma, Junichi
AU - Kishimoto, Tadamitsu
PY - 2004/6
Y1 - 2004/6
N2 - Objective. Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA. Methods. In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria. Results. Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients. Conclusion. Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.
AB - Objective. Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA. Methods. In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria. Results. Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients. Conclusion. Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.
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U2 - 10.1002/art.20303
DO - 10.1002/art.20303
M3 - Article
VL - 50
SP - 1761
EP - 1769
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 6
ER -