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Biologic therapy has revolutionized our approach to the treatment of rheumatoid arthritis (RA). Less than 10 years ago, the best we could hope for was to 'modify disease' or slow it down and also help with symptoms. Now the goal is to not only control symptoms, it is to get RA into complete remission. Biologics are protein-based medicines that are synthesized in a laboratory. They act like laser beams to target the immune abnormalities that are felt to cause RA.

First generation biologics such as etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) are known as TNF-inhibitors and have done wonders for many patients. Second generation biologic such as rituximab (Rituxan) which acts against B cells and abatacept (Orencia) which works on T cells are both welcome additions to the arsenal of weapons available to combat RA.

Cimzia (certolizumab) is an investigational TNF-inhibitor. It differs from the current crop of TNF-inhibitors since it is 'pegylated.' This means that a substance called polyethylene glycol has been attached to the molecule. This pegylation lengthens the half-life of the drug- meaning the drug stays in the system longer. Cimzia also has had a piece of protein removed from the molecule. The piece of protein that has been removed contained a small amount of mouse protein (yes... these drugs are often created using mouse proteins). By removing the piece of mouse protein, it is hoped that Cimzia will cause fewer adverse reactions.

A recent presentation on June 14, 2007 at the annual meeting of the European Congress of Rheumatology (EULAR) described data on Cimzia.

The team studied 2 dose regimens, which patients received subcutaneously as add-on therapy to methotrexate.

In a phase 3, multicenter, double-blind, placebo-controlled, parallel-group study, the investigators recruited 992 patients with RA who received either the study drug or placebo. The investigators wanted to know the rate at which people had a 20% improvement, as defined by the American College of Rheumatology criteria (ACR 20).

The patients, who had previously been treated for at least 6 months with methotrexate, were randomized to treatment with either pegylated certolizumab or placebo. Those on treatment received 3 400-mg doses every 2 weeks, followed by 200 or 400 mg doses of certolizumab pegol every 2 weeks. The patients continued methotrexate as usual. The investigators assessed the efficacy and safety parameters at 2-week intervals.

In an early analysis at 24 weeks, the investigators found that 581 patients completed the study: 259 of the 397 on 200 mg of the drug, 278 of the 394 on 400 mg, and 44 of the 201 on placebo. The ACR20 response rate was 59.2% in the 200 mg group, 61.2% in the 400 mg group, and 13.5% of those who received methotrexate and placebo. The proportion of patients who experienced a significant side effect was 74.0% in the 200 mg group, 76.1% in the 400 mg group, and 57.7% in the placebo group. The majority of adverse events were mild to moderate.

"Pegylated certolizumab adds significant benefit in reducing the signs and symptoms of RA in combination with methotrexate, compared to using methotrexate alone," said lead investigator Edward C. Keystone, MD, professor of medicine at the University in Toronto, and director of the Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, in Ontario.

Bottom line: Pegylated certolizumab works like a TNF blocker and appears to treat the signs and symptoms of RA. Whether it's better than the TNF blockers that are currently available is still no known. It is better than placebo.