Treatment of RA with humanized anti-IL-6 receptor antibody

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Arthritis Rheum. 2004 Jun;50(6):1761-9.

Treatment of rheumatoid arthritis with humanized anti-interleukin-6

receptor antibody: a multicenter, double-blind, placebo-controlled

trial.

Nishimoto N, Yoshizaki K, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T,

Hashimoto J, Azuma J, Kishimoto T.

Laboratory of Immune Regulation, Graduate School of Frontier

Biosciences, Osaka University, Suita-City, Osaka, Japan.

norihiro@...

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.

PMID: 15188351

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