Certolizumab Shows Safety, Efficacy for Crohn's Disease
COPENHAGEN — A new, anti-tumor necrosis factor antibody was safe and effective for treating Crohn's disease for 26 weeks in a study with over 400 patients.
Certolizumab pegol was better than placebo for maintaining responses following induction in Crohn's disease patients, Stefan Schreiber, M.D., said at the 13th United European Gastroenterology Week.
A second Crohn's disease study of certolizumab (Cimzia), a pegylated form of a humanized antibody fragment, is in progress. Patients from both studies will continue to receive the drug for 2 years to gather further safety information. UCB, the Belgium company developing Cimzia, plans to submit all the data early next year to the Food and Drug Administration to apply for a new-drug approval.
Certolizumab is the third anti-tumor necrosis factor (TNF) antibody to be tested on patients with Crohn's disease. Infliximab (Remicade) is already approved for this indication. Adalimumab (Humira) is approved for treating rheumatoid arthritis and psoriatic arthritis, and is being studied in Crohn's disease.
Certolizumab and adalimumab are both administered by subcutaneous injection, making them more convenient treatments than infliximab, which must be administered by intravenous infusion. Studies are underway to assess certolizumab in rheumatoid arthritis.
The study reported by Dr. Schreiber began with 668 patients who had a Crohn's disease activity index (CDAI) score at baseline of 220–450 points, indicating active disease. All patients received three 400-mg doses of certolizumab, given at 2-week intervals. Following the induction phase, 428 patients (64%) had a clinical response, defined as a 100-point or better drop in their CDAI score. The fraction of patients who responded to certolizumab was similar in size to the fraction who responded in prior studies of infliximab and adalimumab.
The responders were then randomized to a maintenance regimen of 400-mg certolizumab injected every 4 weeks or placebo for an additional 22 weeks. After 26 weeks of treatment, 63% of patients who continued on certolizumab and 36% of patients on placebo remained responders, with at least a 100-point improvement in their CDAI score compared with baseline, said Dr. Schreiber, professor of medicine and gastroenterology at Christian-Albrechts University in Kiel, Germany.
Similar responses were seen in patients who entered the study with high serum levels of C-reactive protein, in patients who were on immunosuppressive drugs at baseline, and in patients who had previously failed treatment with infliximab.
The percentage of patients who reached remission, defined as a CDAI score of 150 or less, was 47.9% of those maintained on certolizumab, compared with 28.6% of those who received placebo. In addition, 60% of patients maintained on certolizumab had an improved quality of life, compared with 43% in the placebo group.
The rate of serious adverse events was similar in the two groups, and certolizumab was generally well tolerated, said Dr. Schreiber. One patient treated with the drug developed active tuberculosis.
An antibody reaction to certolizumab developed in 8%. Allthough not yet assessed, the major potential impact is that the antibody might blunt the drug's benefit. Certolizumab has a lower protein content than infliximab and adalimumab and is the only pegylated agent.
