Medications that block tumor necrosis factor alpha (TNF-a), a pro-inflammatory cytokine important in the pathogenesis of RA, were among the first to be developed and approved for the treatment of RA. Several anti-TNF-a medications including Enbrel, Humira, and Remicade are currently marketed for the treatment of RA.

Actemra (tocilizumab) differs from currently marketed biological response modifiers that block TNF-a, since it targets interleukin-6 (IL-6), a cytokine that is also over-produced in the joints of RA patients.

Il-6 is believed to contribute to inflammation, swelling and joint damage and possibly the anemia and platelet elevation counts seen in RA.

Actemra is a humanized anti-human IL-6 receptor monoclonal antibody that works by competitively blocking the binding of IL-6 to its receptor. In essence, it inhibits the deleterious effects of IL-6, which lead to inflammation and proliferation of inflammatory cells and the destructive organ potential in RA.

Multiple clinical trials have examined the efficacy and safety of Actemra.

The largest of these trials was the OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate RespONders), a three-arm, randomized, double-blind, controlled study designed to compare the safety and efficacy of Actemra plus methotrexate with methotrexate plus placebo in RA patients who had an inadequate response to methotrexate alone.

Results from the OPTION trial demonstrated that rheumatoid arthritis (RA) patients not only achieved greater improvement of symptoms but also a higher quality-of-life with Actemra compared with methotrexate, a commonly used RA treatment.

In the OPTION trial, which was a three-arm, double-blind, controlled Phase III study, 623 patients were randomized to receive Actemra intravenously (either 4mg/kg or 8mg/kg) every four weeks plus methotrexate weekly or placebo infusions plus methotrexate weekly. The study was conducted in 73 trial sites in 17 countries outside the United States.

A rapid decrease in disease activity was seen as early as two weeks in a greater proportion of patients treated with Actemra plus methotrexate, with 27.5% achieving clinical remission by 24 weeks.

Additionally, results showed that 80% of patients in the Actemra plus methotrexate group responded with moderate to good improvements in RA symptoms, compared with 35% for those treated with placebo and methotrexate at 24 weeks.

The OPTION trial also assessed physical function and quality-of-life at baseline and every four weeks thereafter. Patients receiving Actemra achieved significantly greater improvement in areas of fatigue and mental function at 24 weeks, and achieved normal levels of hemoglobin (red blood cell count)and C-reactive protein (CRP), a marker of inflammation due to RA, compared with patients receiving placebo plus methotrexate. In addition, platelets, blood cells that often increase in number during the inflammation that accompanies RA, seemed to drop as well.

According to Dr. Nathan Wei, “The advantage of Actemra is that it offers treating rheumatologists another weapon in our arsenal for treating rheumatoid arthritis. Nowadays, it is my expectation that when I see a patient with rheumatoid arthritis, I can count on getting them into remission. It may be only a short time into the future that we will be able to cure this disease.”

Roche, the manufacturer of Actemra in the United States, announced that the Arthritis Advisory Committee of the U.S. Food and Drug Administration (FDA) by a near unanimous (10-1) vote recommended approval of Actemra (tocilizumab), a novel interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody, for reducing the signs and symptoms in adults with moderate to severe rheumatoid arthritis (RA).