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IL-6 blocker approved as second-line RA treatment.

The monoclonal antibody tocilizumab has received approval by the U.S. Food and Drug Administration for the treatment of moderate to severely active rheumatoid arthritis in adult patients who have failed one or more tumor necrosis factor blockers, according to an announcement made last month by the drug's manufacturer, Roche Holding AG.

Tocilizumab (Actemra) is the first interleukin-6 (IL-6) receptor inhibitor to be approved for the treatment of rheumatoid arthritis, and it can be used alone or in combination with methotrexate or other disease modifying antirheumatic drugs (DMARDs), according to the statement. The drug was co-developed by Chugai Pharmaceuticals and its parent company Roche.

The approval comes on the heels of an extensive clinical development program comprising five phase III trials as well as a resubmission of documents, including a proposal for a risk evaluation and mitigation strategy. The pivotal clinical trials include RADIATE (Research on Actemra Determining Efficacy After Anti-TNF Failures), OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy), AMBITION (Actemra Versus Methotrexate Double-Blind Investigative Trial in Monotherapy), and LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage).

In the RADIATE trial, 30% of patients who received tocilizumab in combination with methotrexate achieved disease remission compared with 1.6% of patients receiving methotrexate alone. Lead investigator Dr. Paul Emery, professor of rheumatology at the University of Leeds, England, and colleagues wrote that the findings were especially promising for that subset of rheumatoid arthritis patients who have failed to achieve adequate symptom relief with anti-tumor necrosis factor agents (Ann. Rheum. Dis. 2008;67:1516-23).

The results from the OPTION trial showed that 59% of the patients with rheumatoid arthritis who had incomplete responses to methotrexate achieved an ACR20 response following treatment with tocilizumab 8 mg/kg compared with 26% of patients treated with placebo, and 27% of the patients on tocilizumab achieved remission compared with 0.8% in the placebo group (Lancet 2008;371:987-97).

Similarly, in the TOWARD trial, 61% of patients who received tocilizumab 8 mg/kg achieved an ACR20 response at 24 weeks compared with 25% of patients treated with placebo plus DMARDs, and approximately 38% of tocilizumab-treated patients met ACR50 criteria for symptom improvement, compared with 9% of patients receiving placebo (Arthritis Rheum. 2008;58:2968-80).

The AMBITION study, in which 70% of patients who received 8 mg/kg achieved an ACR20 response at 24 weeks, was the first to show that treatment with a single biologic agent was superior to methotrexate alone for the treatment of rheumatoid arthritis at 6 months, according to a press release issued by Roche when the phase III results were released in 2008 at the annual Congress of the European League Against Rheumatism

Findings from LITHE, presented by lead investigator Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center in Dallas at the 2009 annual meeting of the American College of Rheumatology showed that, over a 2-year period, there was no radiographic progression or joint damage in 75% of rheumatoid arthritis patients taking tocilizumab 4 mg/kg plus methotrexate and 85% of those taking tocilizumab 8 mg/kg and methotrexate compared with 66% of patients taking methotrexate alone.

Among the serious tocilizumab-related adverse events that have been reported in the clinical trials are infections that lead to hospitalization or death, including tuberculosis, and bacterial, invasive fungal, viral, and other infections; gastrointestinal perforations; hypersensitivity reactions; and cellulitis, according to the press release.

In March 2009, Roche's Chugai Pharmaceuticals reported that, among nearly 5,000 rheumatoid arthritis patients in Japan who had been treated with tocilizumab between April 2008 and February 2009, 15 deaths occurred and the possibility of a link to the drug could not be denied, although the exact causes of the deaths were unknown, according to a press release from the company.
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Author:Mahoney, Diana
Publication:Family Practice News
Date:Feb 1, 2010
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