Investigative Crohn's Disease Drug Shows Efficacy, Especially in Infliximab Non-responders: Presented at DDW
By Bruce Sylvester
WASHINGTON, DC -- May 25, 2007 -- Data from a Phase II study of an investigative agent for treating moderate-to-severe Crohn's disease suggest that it is efficacious and holds particular promise for patients who have already been exposed to infliximab treatment.
The findings were presented in an oral session here at the Digestive Disease Week (DDW) annual meeting.
Presenter and lead investigator William Sandborn, MD, gastroenterologist and professor of Medicine, Mayo Clinic, Rochester, Minnesota, United States, reported that short-term treatment with CNTO 1275 was generally well-tolerated and demonstrated a beneficial effect in moderate to severe CD patients, and this effect was most prominent in infliximab-experienced patients.
As background to the study, the researchers noted that, "The type 1 cytokines IL-12 and IL-23 are implicated in the pathophysiology of Crohn's disease (CD). In this 54-week study, the safety and efficacy of either a single intravenous (IV) infusion or four subcutaneous (SC) injections of CNTO 1275 were evaluated in patients with moderate to severe CD, including infliximab non-responders."
They enrolled 104 subjects (Population 1) who had moderate to severe Crohn's disease despite prior treatment with 5-ASA (azathioprine), antibiotics, corticosteroids, infliximab, and/or immunomodulators.
These subjects were randomised to one of four groups (approximately 25 patients per group).
· Group 1 received subcutaneous placebo at weeks 0, 1, 2, 3, and subcutaneous CNTO 1275 (90 mg) at weeks 8, 9, 10, 11.
· Group 2 received subcutaneous CNTO 1275 (90 mg) at weeks 0, 1, 2, 3, and placebo at weeks 8, 9, 10, 11.
· Group 3 received intravenous placebo at week 0 and intravenous CNTO 1275 (4.5 mg/kg) at week 8.
· Group 4 received intravenous CNTO 1275 (4.5 mg/kg) at week 0 and intravenous placebo at week 8.
Additionally, the investigators randomised those subjects (Population 2) who previously failed to respond or lost response to infliximab to open-label therapy in either Group 5 (n=14) with subcutaneous CNTO 1275 (90 mg) at weeks 0, 1, 2, 3, or to Group VI (n=13) treated with intravenous CNTO 1275 (4.5 mg/kg) at week 0.
The investigators defined a clinical response as a reduction from baseline in the CDAI (Crohn's Disease Activity Index) of >/= 25% and >/= 70 points.
The primary endpoint was the measure of clinical response for Population 1 at week 8 (intravenous and subcutaneous subjects combined).
The researchers reported that at week 8, 49.0% of patients in Population 1 receiving CNTO 1275 were in clinical response, as compared to 39.6% who had received placebo (P =.34).
At week 4 and at week 6, 52.9% of CNTO 1275 subjects were in clinical response, as compared to 30.2% of subjects receiving placebo (P =.02); 49.0% of patients receiving CNTO 1275 were in response at week 8 (using a measure of >/= 100 point CDAI reduction), as compared to 30.2% receiving placebo (P =.05).
For subjects with prior infliximab exposure in Population 1 (n=49), 59.1% who had received CNTO 1275 were in clinical response at week 8, as compared to 25.9% of those who received placebo (P =.02).
In Population 2, clinical response rates at week 8 for CNTO 1275 were 42.9% (subcutaneous ) and 53.8% (intravenous), respectively.
The investigators noted similar proportions of adverse events for CNTO 1275 and placebo patients.
No serious infections occurred in Population 1. Two serious infections occurred in Population 2, disseminated histoplasmosis (in a patient receiving prednisone (80 mg/day), azathioprine, and with ~3-years prior infliximab use) and a case of food poisoning.
Three patients reported injection site reactions in both the CNTO 1275 group and the placebo group.
The study was supported by Centocor, Inc.
[Presentation title: A Multicenter, Randomized, Phase 2a Study of Human Monoclonal Antibody to IL-12/23p40 (CNTO 1275) in Patients With Moderately to Severely Active Crohn's Disease. Abstract 272]
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