The FDA Approves Actemra for Rheumatoid Arthritis

By Brenda Goodman

01/11/10 The U. S. Food and Drug Administration (FDA) has approved tocilizumab, brand-named Actemra, a new kind of biologic drug to treat patients with moderate to severe rheumatoid arthritis (RA) that has not been well controlled by other medications.

Actemra is the first drug to block a protein called interleukin-6 (IL-6), which is overproduced in the joints of people who have rheumatoid arthritis.

According to Daniel Furst, MD, a rheumatologist at the University of California at Los Angeles who has been involved in the clinical trials of tocilizumab, the drug, which is given once monthly by intravenous infusion, is “powerful and rapidly acting,” but he also says that because of significant safety concerns, it should still be used with great care.

“You never get something for nothing,” Dr. Furst adds. “Here’s a drug that’s going to be very effective, but it’s also going to have consequences.”

In clinical studies, some people taking tocilizumab experienced serious side effects including elevated LDL or “bad” cholesterol, high blood pressure, elevated liver enzymes and gastrointestinal perforations – holes in the lining of the stomach or intestines.

“Actemra’s recommended use is limited to patients who have failed other approved therapies because of serious safety concerns that were noted in clinical studies,” says FDA spokesperson Karen Riley.

And because of those concerns, the FDA is requiring the drug’s manufacturer to continue to monitor the long-term safety of tocilizumab with ongoing clinical trials.

“Specifically, the FDA wants to evaluate the impact of elevated LDL cholesterol and blood pressure seen in some patients in shorter-term trials on the cardiovascular health of patients treated with Actemra,” Riley says.

Tocilizumab appears to be the first biologic drug to increase cholesterol. That’s a significant concern for people who have rheumatoid arthritis because the systemic inflammation caused by the condition already increases the risk of cardiovascular disease – nearly doubling the risk of a heart attack within 10 years of diagnosis.

In one clinical trial, in fact, about 2 percent of patients on tocilizumab saw their LDL cholesterol climb by about 100 points.

"Rheumatologists are likely to need to be much more attentive than they ever have been in the past to their patients' lipid levels on this drug," says Jeffrey R. Curtis, MD, a rheumatologist at the University of Alabama at Birmingham, who was involved in the clinical trials of tocilizumab.

“You have to watch this drug,” Dr. Furst agrees. “But with regular blood tests, it’s a drug that can be handled pretty comfortably.”

It’s been a long wait for tocilizumab in the United States. It had previously been approved in other countries, including Japan, the European Union, Mexico, Brazil, India and Australia.

An expert panel first voted to recommend approval for tocilizumab in July 2008, but six months later, the FDA delayed the drug’s approval, asking for more data.

Tocilizumab is a monoclonal antibody that blocks the protein interleukin-6, or IL-6, which is something of a double agent in the immune system, acting to both spur and calm inflammation. Beyond the joints, IL-6 acts in many other parts of the body including bone marrow, muscle cells and the lining of the blood vessels.

Most other biologics drugs for RA, including adalimumab (Humira), etanercept (Enbrel), infliximab (Remicade), golimumab (Simponi), and certoluzumab pegol (Cimzia), block the inflammatory protein tumor necrosis factor alpha or TNF-alpha.

Three more biologics used to treat RA work to interrupt other parts of the immune response. Anakinra (Kineret) blocks the inflammatory signal interleukin-1, or IL-1, abatacept (Orencia) prevents certain immune system cells, called T-cells from being activated, and rituximab (Rituxan) helps to eliminate immune system cells called B-cells, which are thought to be overly active in autoimmune diseases.

According to Roche, the drug’s manufacturer, tocilizumab will be available to patients starting the week of January 18, 2010.