Provide feedbackProvide feedback

« Back

Certolizumab pegol improves signs, symptoms of RA among patients with insufficient response to methotrexate, study data show

Friday, June 15 2007 | Comments
Evidence Grade 0 What's This?
The addition of certolizumab pegol to methotrexate reduces the signs and symptoms of active rheumatoid arthritis among patients who have had an insufficient response to methotrexate monotherapy, according to preliminary data from a recent study.

Certolizumab is a humanized, pegylated Fab fragment that targets tumor necrosis factor. Unlike conventional anti-TNF agents, which use the Fc region of immune globulin G as a weight, certolizumab uses a pair of 20,000 kb molecules. This appears to slow the body's clearance of the active compound from patients' blood, which prolongs its activity and may lead to differential accumulation in inflamed tissue relative to normal tissue.

In the double-blind, Phase III, RAPID1 trial, patients with RA who had insufficient disease control with methotrexate monotherapy were randomized to receive add-on therapy with certolizumab 200 mg (n=397), certolizumab 400 mg (n=394), or placebo (n=201) every 2 weeks for 52 weeks. Patients randomized to receive certolizumab at either dose received 3 initial doses of certolizumab 400 mg at 2-week intervals before initiating therapy with their randomized dose.

At 24 weeks, 59.2% of the patients in the certolizumab 200 mg group achieved a 20% response based on American College of Rheumatology criteria (ACR20) compared with 61.2% in the certolizumab pegol 400 mg group and 13.5% in the placebo group (P<.001 for active therapy vs placebo). ACR50 and ACR70 response rates showed a similar pattern, with rates of 37.5% and 21.4%, respectively, among patients in the certolizumab 200 mg group, 40.6% and 20.7% among those in the certolizumab 400 mg group, and 7.5% and 3.0% among those in the placebo group (P<.001 for active therapy vs placebo for both response criteria).

Overall, 74.0% of the patients in the certolizumab 200 mg group, 76.1% of those in the certolizumab 400 mg group, and 57.7% of those in the placebo group reported an adverse event; the proportions of patients who discontinued because of adverse events were 4.3%, 5.6%, and 1.5%, respectively. The majority of adverse events were mild to moderate in intensity, according to Dr. Edward Keystone, the lead researcher.

Unlike conventional anti-TNF agents, certolizumab is Fc-free, according to Dr. Keystone. Preclinical studies conducted in animal models of RA have suggested that the lack of the Fc region in the drug could make it less cytotoxic than current anti-TNF agents are and reduce transport across the placenta.

Certolizumab also differs from conventional anti-TNF agents in that efficacy plateaus at 16 weeks, rather than at 24 to 36 weeks with conventional anti-TNF agents, which leads to "an earlier, more robust response," Dr. Keystone said.

Furthermore, Dr. Keystone noted that the drug is manufactured in bacteria, rather than in mammals, which could make it more cost effective to produce relative to current anti-TNF agents. (Abstract #OP0016.)

This information concerns a use that has not been approved by the Food and Drug Administration.

Print  |  E-mail


Be the first to write a comment for this article!

You must be logged in to post a comment.