BARCELONA, Spain—When used in combination with methotrexate (MTX), the experimental TNF-inhibitor certolizumab pegol (Cimziaâ„¢, UCB) may allow more RA patients to achieve remission more quickly than treatment with currently available TNF-blockers. The new research was presented at EULAR 2007 in Barcelona by Edward Keystone, MD, with the University of Toronto, in Ontario, Canada.1

"It could be cheaper, looks like it has a faster onset and clearly better for women of child bearing age which could put it ahead of the pack."—Edward Keystone, MD.
Given subcutaneously every 2 weeks, the new agent is the first PEGylated TNF-inhibitor to selectively target TNFα in inflamed tissue. PEGylation is the process of attaching strands of the polymer polyethylene glycol to drug molecules. This can improve safety and efficiency by changing a drug's conformation, electrostatic binding, or hydrophobicity, and can both improve absorption and distribution and decrease immunogenicity.

Certolizumab pegol is still an experimental agent, but Dr. Keystone hopes the drug will be available in "a couple of years."

In the phase III study, 982 patients who were previously treated for >e;6 months with MTX were randomized 2:2:1 to treatment with certolizumab pegol of three 400 mg doses every 2 weeks or placebo, followed by doses every 2 weeks of 200 mg or 400 mg or placebo. MTX therapy was continued as usual. If patients did not respond in 16 weeks, they were moved into a rescue arm.

59% ACR 20 Response

At week 24, 59.2% of patients receiving the 200 mg dose achieved an American College of Rheumatology (ACR) 20 response as did 61.2% of patients who received the higher dose, and 13.5% of patients in the placebo group (MTX alone) (P <.001 active vs placebo). There was a 25.4% response rate at week 8 in both active arms.

In addition, 37.5% of the patients in the certolizumab pegol 200 mg group achieved an ACR50 as did 40.6% in the 400 mg group, and 7.5% in patients taking MTX alone (P <.001 active vs placebo), the study showed.

At week 24, an ACR70 was achieved in 21.4% of patients taking certolizumab pegol 200 mg, in 20.7% of patients taking the 400 mg dose, and in 3.0% taking MTX alone (P <.001 active vs placebo). The higher dose of 400 mg every 2 weeks did not demonstrate any additional benefit.

"ACR50 was achieved by virtually all patients receiving certolizumab pegol by 16 weeks," Dr. Keystone said. "In all of the other TNF-inhibitors, patients usually plateau at 24 to 36 weeks, so we are seeing an earlier response. This translates into more RA patients getting closer to remission earlier in the game," he said.

"Patients achieve low disease activity at 4 months as opposed to 6 to 8 months," Dr. Keystone said. "If you achieve a 50% to 70% reduction in the first 4 months, that's significant. My patients will be closer to remission earlier than they were before."

Advantages cited

"One of the potential advantages is the concept that there may be a selective increase in uptake of these molecules within the inflamed joint," Dr. Keystone added.

The new agent does not cross the placenta or infiltrate breast milk. It is manufactured in bacteria, not in rodents, therefore reducing production costs.

"It could be cheaper, looks like it has a faster onset, and is clearly better for women of child-bearing age, which could put it ahead of the pack," Dr. Keystone said.

The proportion of patients who experienced an adverse event was 74.0 % and 76.1% in the certolizumab pegol 200 mg and 400 mg groups, respectively, and 57.7% in the placebo group. The majority of adverse events were mild to moderate and discontinuation caused by these events was low.

Another anti-TNF drug for the arsenal

"We know that switching from one TNF drug to another is beneficial, so to have more options is, in itself, beneficial," EULAR President Tore K. Kvien, MD, of Diakonhjemmet Hospital, in Oslo, Norway, told CIAOMed. "From a Scandinavian perspective, there is a strong focus on cost so if a new anti-TNF drug can create more competition, it would be beneficial."

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Reference

1. Keystone E, Mason D, Combe B. The anti-TNF certolizumab pegol in combination with methotrexate is significantly more effective than methotrexate alone in the treatment of patients with active rheumatoid arthritis: preliminary results from the RAPID 1 study. Presented at: EULAR 2007 Meeting; June 13-16, 2007; Barcelona, Spain. Abstract OP0016.