TNF Blocker May Help Crohn's Disease

ORLANDO—Endoscopic improvement occurred in more than 60% of Crohn's disease patients after 10 weeks of treatment with a pegylated biologic agent, certolizumab pegol. The study was the first prospective, phase III, multicenter, open-label study of the drug in such patients.

The tumor necrosis factor (TNF) blocker also led to improved clinical scores and histologic response among patients with moderate to severe disease.

The investigators showed that Cimzia (certolizumab pegol) was associated with endoscopic improvement in 62% of patients at week 10.

They also assessed endoscopic remission, defined as a Crohn's Disease Endoscopic Index of Severity (CDEIS) score decrease of at least 7 points from baseline.

“We confirmed clinical efficacy, with 42% of patients in remission at week 10,” said Dr. Jean-Frederic Colombel, a hepatogastroenterologist at Centre Hospitalier Universitaire de Lille (France). He is a consultant and on the advisory board for UCB Pharma, which initiated and analyzed the study.

Cimzia was approved by the U.S. Food and Drug Administration in April 2008 for the reduction of signs and symptoms of Crohn's disease and the maintenance of clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

In the study, 51% of the initial 89 participants were on immunosuppressant therapy and 42% were taking corticosteroids. Participants started with a CDEIS score of 8 or greater, ulcerations in at least two segments, and a Crohn's Disease Activity Index (CDAI) score between 220 and 450. “This is one of the most severe populations studied,” Dr. Colombel said at the annual meeting of the American College of Gastroenterology.

The primary outcome, change in CDEIS scores, showed improvement from a mean of 15 at baseline to 8 at week 10. This was “highly significant,” Dr. Colombel said. He presented these first, 10-week results of the ongoing endoscopic Mucosal Improvement in Patients with Active Crohn's Disease (MUSIC) study, and said the 54-week results are pending.

Mean duration of Crohn's disease in study participants was 8 years, mean age was 30 years, and 30% were men. A total of 71 patients (80%) experienced an adverse event during the study in an intent-to-treat analysis, including 37 patients with a drug-related event. Nine participants discontinued treatment before 10 weeks—two citing lack of efficacy, and seven because of adverse events.

Participants received subcutaneous injections of certolizumab pegol 400 mg at weeks 0, 2, and 4 and then every 4 weeks. After week 10, depending on CDEIS response, some patients switched to injections every 2 weeks, Dr. Colombel said.

A meeting attendee asked about the rationale for increasing administration to every 2 weeks. “The induction regimen is the same used in clinical practice,” Dr. Colombel said. “For this short-term data, we did not escalate the dose. For the long-term data, there is evidence that you can go from every 4 to every 2 weeks. That is what we are doing with the 54-week data.”

At baseline, 92% of the patients had deep intestinal ulcerations; this percentage decreased to 42% at week 10. In addition, 5% had superficial lesions detected at study entry, and this increased to 31% at week 10, Dr. Colombel said.

Compared with baseline, histologic Crohn's disease scores decreased a mean of 2.7 points in the colon and 2.8 points in the ileum at 10 weeks. In addition, 46% of patients achieved clinical remission, defined as a decrease in CDAI baseline scores of 150 points or more by 10 weeks.

A meeting attendee asked if the single-arm study design is a limitation. “Good question,” Dr. Colombel said. “It's quite difficult to put patients in a placebo-controlled study because anti-TNF is available, and they need three endoscopies in 1 year.

“What we also plan to do is look at videotapes in a blinded way, and do the same thing with histology—which will significantly improve the value of the data,” he added.

ORLANDO—Endoscopic improvement occurred in more than 60% of Crohn's disease patients after 10 weeks of treatment with a pegylated biologic agent, certolizumab pegol. The study was the first prospective, phase III, multicenter, open-label study of the drug in such patients.

The tumor necrosis factor (TNF) blocker also led to improved clinical scores and histologic response among patients with moderate to severe disease.

The investigators showed that Cimzia (certolizumab pegol) was associated with endoscopic improvement in 62% of patients at week 10.

They also assessed endoscopic remission, defined as a Crohn's Disease Endoscopic Index of Severity (CDEIS) score decrease of at least 7 points from baseline.

“We confirmed clinical efficacy, with 42% of patients in remission at week 10,” said Dr. Jean-Frederic Colombel, a hepatogastroenterologist at Centre Hospitalier Universitaire de Lille (France). He is a consultant and on the advisory board for UCB Pharma, which initiated and analyzed the study.

Cimzia was approved by the U.S. Food and Drug Administration in April 2008 for the reduction of signs and symptoms of Crohn's disease and the maintenance of clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

In the study, 51% of the initial 89 participants were on immunosuppressant therapy and 42% were taking corticosteroids. Participants started with a CDEIS score of 8 or greater, ulcerations in at least two segments, and a Crohn's Disease Activity Index (CDAI) score between 220 and 450. “This is one of the most severe populations studied,” Dr. Colombel said at the annual meeting of the American College of Gastroenterology.

The primary outcome, change in CDEIS scores, showed improvement from a mean of 15 at baseline to 8 at week 10. This was “highly significant,” Dr. Colombel said. He presented these first, 10-week results of the ongoing endoscopic Mucosal Improvement in Patients with Active Crohn's Disease (MUSIC) study, and said the 54-week results are pending.

Mean duration of Crohn's disease in study participants was 8 years, mean age was 30 years, and 30% were men. A total of 71 patients (80%) experienced an adverse event during the study in an intent-to-treat analysis, including 37 patients with a drug-related event. Nine participants discontinued treatment before 10 weeks—two citing lack of efficacy, and seven because of adverse events.

Participants received subcutaneous injections of certolizumab pegol 400 mg at weeks 0, 2, and 4 and then every 4 weeks. After week 10, depending on CDEIS response, some patients switched to injections every 2 weeks, Dr. Colombel said.

A meeting attendee asked about the rationale for increasing administration to every 2 weeks. “The induction regimen is the same used in clinical practice,” Dr. Colombel said. “For this short-term data, we did not escalate the dose. For the long-term data, there is evidence that you can go from every 4 to every 2 weeks. That is what we are doing with the 54-week data.”

At baseline, 92% of the patients had deep intestinal ulcerations; this percentage decreased to 42% at week 10. In addition, 5% had superficial lesions detected at study entry, and this increased to 31% at week 10, Dr. Colombel said.

Compared with baseline, histologic Crohn's disease scores decreased a mean of 2.7 points in the colon and 2.8 points in the ileum at 10 weeks. In addition, 46% of patients achieved clinical remission, defined as a decrease in CDAI baseline scores of 150 points or more by 10 weeks.

A meeting attendee asked if the single-arm study design is a limitation. “Good question,” Dr. Colombel said. “It's quite difficult to put patients in a placebo-controlled study because anti-TNF is available, and they need three endoscopies in 1 year.

“What we also plan to do is look at videotapes in a blinded way, and do the same thing with histology—which will significantly improve the value of the data,” he added.

ORLANDO—Endoscopic improvement occurred in more than 60% of Crohn's disease patients after 10 weeks of treatment with a pegylated biologic agent, certolizumab pegol. The study was the first prospective, phase III, multicenter, open-label study of the drug in such patients.

The tumor necrosis factor (TNF) blocker also led to improved clinical scores and histologic response among patients with moderate to severe disease.

The investigators showed that Cimzia (certolizumab pegol) was associated with endoscopic improvement in 62% of patients at week 10.

They also assessed endoscopic remission, defined as a Crohn's Disease Endoscopic Index of Severity (CDEIS) score decrease of at least 7 points from baseline.

“We confirmed clinical efficacy, with 42% of patients in remission at week 10,” said Dr. Jean-Frederic Colombel, a hepatogastroenterologist at Centre Hospitalier Universitaire de Lille (France). He is a consultant and on the advisory board for UCB Pharma, which initiated and analyzed the study.

Cimzia was approved by the U.S. Food and Drug Administration in April 2008 for the reduction of signs and symptoms of Crohn's disease and the maintenance of clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

In the study, 51% of the initial 89 participants were on immunosuppressant therapy and 42% were taking corticosteroids. Participants started with a CDEIS score of 8 or greater, ulcerations in at least two segments, and a Crohn's Disease Activity Index (CDAI) score between 220 and 450. “This is one of the most severe populations studied,” Dr. Colombel said at the annual meeting of the American College of Gastroenterology.

The primary outcome, change in CDEIS scores, showed improvement from a mean of 15 at baseline to 8 at week 10. This was “highly significant,” Dr. Colombel said. He presented these first, 10-week results of the ongoing endoscopic Mucosal Improvement in Patients with Active Crohn's Disease (MUSIC) study, and said the 54-week results are pending.

Mean duration of Crohn's disease in study participants was 8 years, mean age was 30 years, and 30% were men. A total of 71 patients (80%) experienced an adverse event during the study in an intent-to-treat analysis, including 37 patients with a drug-related event. Nine participants discontinued treatment before 10 weeks—two citing lack of efficacy, and seven because of adverse events.

Participants received subcutaneous injections of certolizumab pegol 400 mg at weeks 0, 2, and 4 and then every 4 weeks. After week 10, depending on CDEIS response, some patients switched to injections every 2 weeks, Dr. Colombel said.

A meeting attendee asked about the rationale for increasing administration to every 2 weeks. “The induction regimen is the same used in clinical practice,” Dr. Colombel said. “For this short-term data, we did not escalate the dose. For the long-term data, there is evidence that you can go from every 4 to every 2 weeks. That is what we are doing with the 54-week data.”

At baseline, 92% of the patients had deep intestinal ulcerations; this percentage decreased to 42% at week 10. In addition, 5% had superficial lesions detected at study entry, and this increased to 31% at week 10, Dr. Colombel said.

Compared with baseline, histologic Crohn's disease scores decreased a mean of 2.7 points in the colon and 2.8 points in the ileum at 10 weeks. In addition, 46% of patients achieved clinical remission, defined as a decrease in CDAI baseline scores of 150 points or more by 10 weeks.

A meeting attendee asked if the single-arm study design is a limitation. “Good question,” Dr. Colombel said. “It's quite difficult to put patients in a placebo-controlled study because anti-TNF is available, and they need three endoscopies in 1 year.

“What we also plan to do is look at videotapes in a blinded way, and do the same thing with histology—which will significantly improve the value of the data,” he added.