Note from CCFA's National Scientific Advisory Committee:
Early intervention enables potential for prevention of long term complications

Early Crohn's treatment with certolizumab pegol enhances outcome

Last Updated: 2010-03-29 14:28:02 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The response of Crohn's disease to certolizumab pegol is particularly good when treatment starts soon after diagnosis, multinational trial data suggest.

Clinicians have been reluctant to use tumor necrosis factor (TNF)-alpha blocking agents, including certolizumab, in patients with early disease because of uncertainty over the risk-benefit ratio, the investigators note in their March 16th online report in the American Journal of Gastroenterology.

They explain that certolizumab pegol is a Fab' anti-TNF-alpha agent that is PEGylated to increase its half-life. Unlike similar agents for Crohn's disease, it does not induce apoptosis in cultured peripheral blood lymphocytes and monocytes. Also, because certolizumab pegol binds univalently to TNF-alpha, it avoids the formation of large immune complexes through cross-linkage seen with full antibodies.

Their report describes a post hoc analysis of the randomized PRECiSE 2 trial, in which patients who responded to 400-mg subcutaneous injections of certolizumab pegol at weeks 0, 2 and 4 either continued the injections (n = 215) or received placebo (n = 210) every 4 weeks from week 8 to week 24.

Overall, 151 (70%) in the active treatment group and 109 (51%) in the placebo group completed the trial.

For the current study, Dr. Stefan Schreiber, from Christian-Albrechts University, Kiel, Germany, and associates analyzed rates of response (i.e., a decrease of at least 100 points in the Crohn's Disease Activity Index score) and remission (a decrease of at least 150 points) according to patients' duration of Crohn's disease at baseline.

Stratified by duration of disease, response rates with active treatment vs placebo at 26 weeks were as follows:

-- less than 1 year since diagnosis, 89.5% vs 37.1%

-- at least 1 year but less than 2 years, 75.0% vs 50.0%

-- at least 2 years but less than 5 years, 62.2% vs 36.4%

-- more than 5 years, 57.3% vs 32.7%

The authors saw a similar trend for disease remission.

"The proportions of patients achieving response... and remission on maintenance therapy at week 26 were inversely related to disease duration," the authors write.

They add that "both rates decreased in a stepwise manner with increasing disease duration."

On regression analysis, shorter disease duration was an independent predictor of response to certolizumab pegol at week 26. Other significant predictors included no history of resection or infliximab use, and no corticosteroid use on entry.

The researchers note that penetrating or stenosing complications increased with disease duration. On the other hand, there was a tendency toward fewer serious adverse events with shorter disease duration.

Dr. Schreiber and his associates believe the benefit-risk ratio for using an anti-TNF-alpha "may well be acceptable" in early disease.

They conclude that their findings "warrant further prospective studies of anti-TNF-alpha treatment in early CD (i.e., disease duration less than 1-2 years) and before corticosteroid treatment is started, with examination of efficacy and potential for disease modification."

Am J Gastroenterol 2010.