Anti-IL-6 Receptor Antibody Therapy for RA - Veritas Medicine Viewpoint

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Veritas Medicine

Rheumatoid Arthritis

Viewpoint

Dr. Marvin Lee

08/06/2004

Anti-IL-6 Receptor Antibody Therapy for Rheumatoid Arthritis

Treatment of rheumatoid arthritis (RA) has been improved

dramatically with the development of the biologic response modifier

(biologics) class of medications. To date, biologic agents approved for

use in RA are directed against a class of molecules that drive

inflammation called cytokines. More specifically, two cytokines have

been targeted in therapy of RA: interleukin-1 (IL-1) and tumor necrosis

factor-alpha (TNF-alpha). There exist a large number of other cytokines

that have been implicated in the inflammation seen in joint tissues in

RA; the effectiveness of therapies directed against these other

cytokines remains an area of research. A Japanese group of

investigators recently tested a biologic therapeutic directed against

the receptor for the cytokine interleukin-6 (IL-6R) in patients with RA.

They reported the results from their clinical trial in the journal

Arthritis & Rheumatism1.

For this clinical trial, 162 RA patients were divided into three

groups receiving either monthly placebo, 4 mg/kg medication or 8 mg/kg

medication. The anti-IL-6 receptor biologic medication was a monoclonal

antibody called MRA administered by intravenous injection monthly for a

study period of 3 months. The investigators followed clinical responses

as measured by the American College of Rheumatology response criteria as

well as incidents of adverse events.

Clinical responses to administration of MRA were evident at both

doses with increased response noted in the higher dosing regimen.

Specifically, ACR 20%, 50% and 70% improvement responses of 78%, 40% and

16% were noted at 8 mg/kg of MRA, while responses of 57%, 26% and 20%

respectively were noted for 4 mg/kg treatment with MRA. These

contrasted with ACR response rates of 11%, 2% and 0% for placebo

therapy. It should be noted that of the 53 patients receiving placebo,

25 withdrew from the trial with the majority withdrawing for lack of

efficacy. Of the 109 patients treated with MRA, only 6 withdrew from

the trial. Adverse events were noted at similar frequency in placebo

and MRA treated patients. One patient treated with MRA died from the

rare syndrome of Epstein-Barr virus infection and the hemophagocytic

syndrome. Increases in blood cholesterol were also noted in a high

percentage (44%) of patients receiving MRA.

The authors of this randomized, double-blind, placebo-controlled

trial concluded that their results provide evidence for rapid reduction

in RA disease activity in response to treatment with the anti-cytokine

(IL-6R) directed medication MRA. They also conclude that these results

indicate an acceptable safety profile for this medication. They caution

that longer-term studies are required to further assess both efficacy

and safety. In particular, they intend to focus on cardiovascular

safety issues since elevations in blood cholesterol were common in this

study. Furthermore, they acknowledge that no radiographic measurements

of joint damage were included in this study and the effectiveness of MRA

in preventing joint damage will need assessing in the future. Overall,

these trial results provide encouraging initial information about a

possible new biotherapeutic treatment for RA. In addition to addressing

the issues outlined by the authors of this trial, future studies will

define the appropriate patient population and potential use of MRA in

combination with other medications used by physicians and patients with

RA.

Reference

1) Nishimoto, N. et. al. Treatment of rheumatoid arthritis with

humanized anti-interleukin-6 receptor antibody. 2004. Arthritis &

Rheumatism 50:1761-1769.

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