Actemra Is First Biologic Agent To Show Better Efficacy Than Methotrexate In RA

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Main Category: Arthritis / Rheumatology
Also Included In: Pain / Anesthetics;  Bones / Orthopaedics
Article Date: 17 Jun 2008 - 9:00 PDT

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PARIS: The interleukin-6 receptor inhibitor Actemra (tocilizumab) achieves significantly greater reduction in the signs and symptoms of rheumatoid arthritis (RA) than the current standard of care, methotrexate, according to two international clinical trials reported this week at EULAR 2008, the Annual European Congress of Rheumatology.

The phase III AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) trial randomised 673 patients with active moderate to severe RA, including a high proportion of patients with early disease, to Actemra (8mg/kg) or methotrexate.

Results showed significantly greater reduction in the signs and symptoms of RA at six months in patients treated with Actemra than in those given methotrexate. Nearly three-quarters (70%) of patients treated with Actemra achieved a 20% reduction in their symptoms (ACR20) after 24 weeks, compared to 53% of those treated with methotrexate. No previous biologic therapy has demonstrated superior efficacy to methotrexate in this key measure of RA symptoms by six months.

Nearly three times as many patients treated with the Actemra achieved remission of their RA - defined by the globally recognised measure of Disease Activity Score (DAS) 28 < 2.6 - compared to those taking methotrexate (34% vs 12%). Remission is the ultimate goal in the treatment of RA.

Reporting the results, Professor Graeme Jones, Professor of Rheumatology, University of Tasmania, Hobart, Australia and lead investigator of the study, said: "Tocilizumab demonstrated superior efficacy to methotrexate across a range of measures of RA signs and symptoms. It is the first and only biologic agent that has demonstrated clinical superiority compared to methotrexate as monotherapy."

Asked what treatment he would want to take if diagnosed with RA, Professor Jones said: "Last year, I would have said methotrexate plus an anti-TNF agent, starting on day one. But based on the new data with tocilizumab showing that, as monotherapy, it achieves equivalent efficacy, I wouldn't mind taking this from day one." He added that it had been easy to tell which patients were on Actemra in the trial, as their improvements in RA symptoms were so rapid and dramatic.

Results from a second major study with Actemra showed that the IL-6 receptor inhibitor was also highly effective in difficult-to-treat RA patients who had previously had an inadequate response to anti-tumour necrosis factor drugs (anti-TNFs).

The RADIATE (Research on Actemra Determining effIcacy after Anti-TNF FailurEs) randomised 499 patients with moderate to severe active RA and an inadequate response to at least one anti-TNF drug to Actemra (8 or 4mg/kg) or placebo, in combination with 10-25mg methotrexate.

Half (50%) of patients treated with Actemra (8mg/kg) plus methotrexate achieved an ACR20, compared with 10% of those in the control group. Disease remission (DAS28<2.6) occurred in nearly one-third (30%) of the Actemra-treated patients, compared to only 1.6% of those treated with methotrexate alone.

Professor Paul Emery, ARC Professor of Rheumatology, University of Leeds, UK, and principal investigator of the study, said: "These results are very promising for RA patients who need a variety of treatment options, particularly when they have failed to gain adequate pain and symptom relief with anti-TNF therapies." He noted that the findings were particularly remarkable considering that 12-18% of the study population had already failed to respond to three or more prior anti-TNF therapies.

Actemra is the first humanised monoclonal antibody that inhibits IL-6 receptors. IL-6 is a key mediator in inflammation. Overproduction of IL-6 leads to inflammation in the joints and joint damage associated with RA, and is involved in the systemic manifestations of the disease, including anaemia, fatigue and increased cardiovascular risk.

Written by Susan Mayor, PhD
Susan Mayor is a medical journalist who works in London, UK.
Susanmayor(at)mac.com
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