What Is Actemra?
How Does Actemra Work?
The therapeutic goal of Actemra is to block inflammatory responses. It does this by blocking interleukin-6. Actemra actually inhibits the interleukin-6 receptor, thereby blocking interleukin-6. This is the first drug to do this, making it a new treatment approach for RA. Classified as a cytokine, interleukin-6 is known to play a role in immune and inflammatory responses.
How Has Actemra Performed in Clinical Trials?
An extensive clinical development program of 5 Phase III trials was designed to evaluate Actemra. Four studies have been completed and reported meeting their primary endpoints (goals). A fifth trial, called LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage), is a 2-year trial that is currently underway. Preliminary first-year data is expected for LITHE in 2008.
The 5 Phase III trials for Actemra are known as: OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), TOWARD (Tocilizumab in Combination with Traditional DMARD Therapy), RADIATE (Research on Actemra Determining Efficacy after Anti-TNF Failures), AMBITION (Actemra versus Methotrexate Double-Blind Investigative Trial In Monotherapy), and LITHE.
What Was Learned About Actemra in the OPTION Study?
In the OPTION study, reported in the March 22, 2008 issue of The Lancet, 622 patients with moderate to severely active rheumatoid arthritis were randomized to receive 8 mg/kg Actemra, 4 mg/kg Actemra, or placebo intravenously every 4 weeks. Methotrexate was continued at pre-study dosages (10-25 mg/week). Study results showed that at week 24, there were more patients receiving Actemra who reached ACR20 than those on placebo. Of the study participants, 59% of patients in the 8 mg/kg group vs. 48% in the 4 mg/kg group vs. 26% in the placebo group achieved ACR20. Criteria for ACR20 include: 20% improvement in number of tender and swollen joints; greater than or equal to 20% improvement in at least 3 of the 5 following criteria:
- physician assessment of disease
- patient assessment of disease
- C-reactive protein
- Health Assessment Questionnaire
Another study published in The Lancet on March 22, 2008 concluded that Actemra is also effective for children with systemic juvenile arthritis -- a condition that is often hard to treat.
How Is Actemra Given?
Actemra is given intravenously (through an IV). In the OPTION study, it was given every 4 weeks.
What Side Effects Have Been Associated With Actemra?
According to drugmaker Roche, "The overall safety profile observed in the global studies of Actemra is consistent and Actemra is generally well tolerated. The serious adverse events reported in Actemra global clinical studies included serious infections and hypersensitivity (allergic) reactions including a few cases of anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension. Increases in liver function tests (ALT and AST) were seen in some patients. These increases were generally mild and reversible, with no hepatic injuries or any observed impact on liver function."
What Concerns Some Critics of Actemra?
Critics of some of the clinical trials involving Actemra believe not enough has been learned by comparing Actemra to placebo. Essentially, the critics said that it's reasonable to assume Actemra would be better than nothing, but more useful information would be gained by comparing Actemra to established treatments.
Is Actemra FDA-Approved and Available?
In November 2007, Roche submitted a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval for Actemra to reduce the signs and symptoms in adults with moderate to severe rheumatoid arthritis. On July 29, 2008, the Arthritis Advisory Committee of the FDA voted 10-1 to recommend approval of Actemra, but the FDA requested more information from Roche before it would grant final approval.
UPDATE: On January 8, 2010, Actemra was approved by the FDA for adult rheumatoid arthritis patients with moderate to severely active disease, who have failed one or more TNF blockers. The drug is expected to be available by January 18, 2010.
Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Smolen et al. The Lancet. March 22, 2008.
Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Yokota et al. The Lancet. March 22, 2008.
Roche Submits Application for FDA Approval of Actemra for the Treatment of Rheumatoid Arthritis. November 21, 2007. Roche Media News.