A single 400 mg injection of Cimzia ( Certolizumab pegol, CDP 870 ) every four weeks was effective in maintaining control of the signs and symptoms of Crohn's disease following induction therapy, according to pivotal phase III research presented this week at the annual meeting of the American College of Gastroenterology.

The study, entitled PRECiSE 2, found that a significantly higher proportion of patients who responded to an induction regimen of 400 mg Certolizumab at weeks zero, two and six, were able to maintain clinical response and achieve remission by week 26 when given a single injection every four weeks, compared to those treated with placebo.

Crohn's disease is a chronic inflammatory bowel disorder that affects approximately one million people in the US and Europe alone.
Because there is no cure, treatment is focused on suppressing the inflammatory response that is at the root of its cause.
Certolizumab is a biologic agent that has been designed to inhibit the production of tumor necrosis factor alpha ( TNF-alpha ), a protein involved in the inflammation process.

The PRECiSE clinical trial program is composed of four studies ( PRECiSE 1, 2, 3 and 4 ).
In addition to PRECiSE 2, the detailed results of which were presented at ACG Meeting, PRECiSE 1 is a 26-week double-blind, placebo-controlled trial, and represents the first long-term fully placebo-controlled clinical trial of a biologic in Crohn's disease.

PRECiSE 1 successfully met its primary endpoints with statistical significance. As expected from a study with such a challenging trial design, top-line results were of lower magnitude than observed in the PRECiSE 2 trial.
The detailed analysis of the PRECiSE 1 data is still ongoing.
PRECiSE 3 and 4 are both 24-month, open-label trials for patients who participated in either PRECiSE 1 or 2, assessing the longer-term safety and tolerability of Certolizumab, and are currently ongoing.

The 26-week PRECiSE 2 study was designed to assess the safety and efficacy of Certolizumab 400 mg for the maintenance of clinical response after open-label induction therapy in patients with mild to moderate Crohn's disease. Those who responded by week six were randomized to receive either a once-monthly maintenance dose of Certolizumab 400 mg or placebo.

Clinical response was defined as a 100 point drop in the Crohn's Disease Activity Index ( CDAI ), which measures the disease severity by taking into account a number of factors such as intensity of symptoms, medication and general well-being.
The primary endpoint was the percentage of patients at week 26 with a C-reactive protein ( CRP, a marker of inflammation ) level > 10 mg who maintained a clinical response after successful induction.
Major secondary endpoints included remission ( CDAI < 150 ) in those with a CRP level > 10mg, and response and remission in the overall treatment population.

Sixtyfour percent of the 668 patients enrolled in the trial responded to induction therapy by week 6. Those who responded were randomized to receive maintenance treatment with either Certolizumab ( n=216 ) or placebo ( n=212 ); 62.8 percent of patients receiving Certolizumab maintenance 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 C-reactive protein ( CRP ) status or prior exposure to anti-TNF therapy; 47.9 percent of patients receiving Certolizumab maintenance therapy were in clinical remission at week 26, compared to 28.8 percent with placebo.

Adverse events were mostly mild to moderate with the most common being headache ( maintenance: Certolizumab 6.9 percent; placebo 6.6 percent ).
Serious non-Crohn disese-related infections were observed in both the Certolizumab ( 3 events ) and placebo ( 2 events ) treatment groups.

Crohn's disease is a chronic disorder that causes inflammation of the gastrointestinal tract, most commonly at the end of the small intestine ( the ileum ) and beginning of the large intestine ( the colon ). Common symptoms include diarrhea, fever, abdominal pain and weight loss. Although it can occur at any age, it primarily impacts young adults between the ages of 15 and 35. Because it is a chronic illness, patients experience an ongoing cycle of symptom "flare-ups" and periods of remission, when symptoms disappear or are controlled.

Certolizumab is unique anti-TNF therapy in that it is a humanized antibody Fab' fragment chemically attached to polyethylene glycol ( PEG ).
PEGylation increases the plasma half-life of certolizumab to approximately two weeks.

Source: UCB, 2005


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