Last Updated: July 18, 2007

NEW YORK (Reuters Health) -- Certolizumab pegol is a safe and effective treatment for moderate-to-severe Crohn's disease, according to the results of two related studies reported in the July 19th issue of The New England Journal of Medicine.

Like drugs such as infliximab and adalimumab, certolizumab works by blocking tumor necrosis factor-alpha (TNF-alpha). Unlike the older agents, however, certolizumab is an Fab' fragment of an anti-TNF monoclonal antibody so it does not induce complement activation, antibody-dependent cytotoxicity, or T-cell/monocyte apoptosis.

The two studies, Pegylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECISE) trials 1 and 2, looked at the use of certolizumab pegol in 638 adults with moderate-to-severe disease who were followed for 26 weeks, lead author Dr. William J. Sandborn, from the Mayo Clinic in Rochester, Minnesota, and colleagues note.

The studies were funded, in part, by UCB Pharma, which hopes to market the drug as CIMZIA.

According to a related editorial by Dr. James D. Lewis, from the University of Pennsylvania in Philadelphia, the studies shared many features, but had one key difference. The common features included disease severity of the study group, the use of the Crohn's Disease Activity Index to evaluate the treatment responses, the same dose of certolizumab (400 mg), and stratified randomization of patients based on the CRP level.

The difference between the trials was that PRECISE 1 randomized patients to receive certolizumab or placebo at the beginning of the study, while in PRECISE 2, all patients were given three doses of the drug and if they showed a response, they were then randomized to receive continued treatment with the drug or switch to placebo, Dr. Lewis notes.

In PRECISE 1, patients given certolizumab rather than placebo at weeks 0, 2, 4 and then every 4 weeks had significantly higher response rates at weeks 6 and 26. For instance, at week 26, the response rate in the certolizumab group was 35% compared with 27% in the control group (p = 0.02).

By contrast, no significant differences were seen between the groups in remission rates at week 26. Serious side effects, including infections, were uncommon with certolizumab and occurred with similar frequency as with placebo.

The findings from PRECISE 2 suggest that continued certolizumab therapy after successful induction therapy is effective in maintaining the treatment response and achieving remission. For instance, 62% of patients who continued the active drug had a maintained response at week 26 compared with 34% of those who changed to placebo. The corresponding remission rates were 48% and 29%.

While the current findings are encouraging, certolizumab may not be the most effective anti-TNF agent for patients with Crohn's disease, Dr. Lewis suggests in his editorial. Ideally, a trial would be conducted comparing the various agents, but unfortunately this is unlikely to happen, he adds.

"Rather, the choice of therapy will probably be driven by other factors, such as perceived relative effectiveness, economics, and convenience for patients," he concludes.

Date Posted: July 20, 2007