Monthly injections of an investigational biologic for Crohn’s Disease appear to offer relief from symptoms and may induce remission, according to results of a phase III trial presented here today that compared the agent with placebo.

In the study, known as PRECiSE-2, a significantly higher proportion of patients who responded to an open-label induction regimen of 400 mg Cimzia (certolizumab pegol), a humanized anti-TNF PEGylated Fab’ fragment, were able to maintain a clinical response and achieve a remission by week 24, a Mayo-led team reported at the American College of Gastroenterology meeting here.

PRECiSE-2 stands for Pegylated antibody fRagment Evaluation in Crohn’s Disease: Safety and Efficacy. To be eligible, patients had to have moderate to severe disease, as defined as a Crohn’s Disease Activity Index (CDAI) of 220 to 450 points. CDAI measures the disease severity by taking into account the intensity of symptoms, medication and general well-being.

The primary endpoint was the percentage of patients at week 26 with a C-reactive protein of more than 10 mg/L who maintained a clinical response after successful induction. Major secondary endpoints included remission (CDAI of less than 150) in those with a CRP level of more than 10mg, and response and remission in the overall treatment population.

William J. Sandborn, M.D., of the Mayo Clinic and colleagues gave 668 patients with Crohn’s the induction dose at weeks 0, two, and four. At week six, the investigators randomized the 428 responders (64%), who had a decrease in baseline CDAI of at least 100 points, to receive monthly maintenance injections of either Cimzia or placebo every four weeks through week 24. Of those continuing on maintenance, 216 received Cimzia and 212 received placebo.

Among the 213 patients with CRPs of at least 10 mg/L, 61.6% in the treatment group had a sustained response in the maintenance phase, compared with 33.7% of those receiving placebo (p<0.001). Among patients in this stratum, 42.0% in the treatment arm experienced remission, compared with 25.7% of those on placebo (p<0.01).

In the overall group, 62.8% of those receiving Cimzia had a clinical response, compared with 36.2% of those on placebo (p<0.001). In this group, 47.9% of treated patients experienced remission, compared to 25.7% of those on placebo (p<0.001).

Adverse events were primarily mild to moderate, with headache occurring most frequently, in 12.6% of patients during the induction phase, and in 6.9% of the Cimzia patients, and 6.6% of placebo patients in the double-blind phase. One patient taking Cimzia died of a fentanyl overdose, and there were five serious infections that were unrelated to Crohn’s, three in the Cimzia group and two in the placebo group.

The patient who died of a fentanyl overdose in the treatment group was considered an anomaly and not related to Cimvia, Dr. Sandborn said. He said that although some patients with Crohn’s may be treated with narcotics for pain, it is not a typical way to manage their pain.

Of the five patients who developed serious infections, one in the treatment group developed tuberculosis, which is a known potential complication of all known biologic agents, he said. The remaining four patients, two in each group, had abdominal abscesses and other infections that often occur in Crohn’s and were not considered treatment-related, he said.

“We’ve known for some time that biologic agents such as Remicade [infliximab] are effective for inducing and retaining remission in Crohn’s Disease, but not all patients can use Remicade,” said Dr. Sandborn. Remicade is approved for the treatment of Crohn’s Disease.

He pointed out that Remicade is composed of 25% mouse monoclonal antibody, and some patients have allergic reactions to it, while 95% of Cimvia is of human origin and therefore may be less likely to induce allergic reactions. Also some patients quit responding to Remicade, and the fact that it is administered intravenously can also be a barrier. Cimvia is administered subcutaneously, and it may eventually be available for home use.

“We need more biologic agents with which we can treat Crohn’s Disease, and Cimvia has the potential to broaden our options,” Dr. Sandborn said.

The investigators found:

 
• 62.8% of patients receiving Cimzia therapy sustained an overall clinical response throughout the 26-week study period, compared to 36.2 percent with placebo.  
• The primary endpoints of PRECiSE 2 trial were met with statistical significance, irrespective of CRP status or prior exposure to anti-TNF therapy.  
• 47.9% of patients receiving Cimzia maintenance therapy were in clinical remission at week 26, compared with 28.8 percent with placebo.

The PRECiSE clinical trial program is composed of four studies (PRECiSE 1, 2, 3 and 4). PRECiSE 1 was a 26-week double-blind, placebo-controlled trial that met its primary endpoints with statistical significance. The detailed analysis of the PRECiSE 1 data is still ongoing, with results yet to be presented. PRECiSE 3 and 4 are ongoing 24-month, open-label trials for patients who participated in either PRECiSE 1 or 2, assessing the longer-term safety and tolerability of Cimzia.

The PRECiSE 2 study was funded by UCB Pharmaceuticals, which developed Cimzia.

Primary source: American College of Gastroenterology. 70th annual meeting. October 28-November 2, 2005. Honolulu, Hawaii.