Gastroenterology Xagena

Inflammatory bowel diseases: biological therapies

IBD ( inflammatory bowel diseases ) is a term referring to several chronic diseases that cause inflammation of the intestines, including ulcerative colitis and Crohn's disease.
Symptoms for both conditions are very similar and it is often difficult for physicians to differentiate between the two.
The most common symptoms of both ulcerative colitis and Crohn's disease are diarrhea, abdominal pain, fever, fatigue and weight loss.

“ Crohn's and ulcerative colitis are serious and complex diseases with varied treatment options.
Unfortunately, the available therapies are not effective in many patients.,” said John Johanson, of the University of Illinois. “ These findings deliver promising news for patients who do not respond to currently available therapies and is a much needed step in improving the lives of people suffering from IBD. ”

The studies below analyzed patient response based on the Inflammatory Bowel Disease Questionnaire ( IBDQ ), the Crohn’s Disease Activity Index ( CDAI ), which measures the severity of a patient’s disease and the Mayo score for ulcerative colitis.

Treatment of Crohn’s disease by oral administration of Alequel, a mixture of autologous colon extracted proteins: a patient-tailored approach

This study from Hadassah Hebrew University Medical Center and Enzo Therapeutics applies concept of personalized treatment option to gastroenterology and explores the safety and efficacy of a personalized treatment for Crohn’s disease by oral administration of Alequel, a protein-containing extract manufactured from tissue removed from a patient’s own colon.

Thirty-one patients with moderate to severe Crohn’s disease were enrolled in the 27-week randomized, placebo-controlled, double blind trial and received either placebo or the study drug, which was prepared from extracted colon proteins.
Trial participants were monitored for response based on the Crohn’s Disease Activity Index ( CDAI ) and Inflammatory Bowel Disease Questionnaire ( IBDQ ).

Clinical remission rates observed during the trial were 58 percent for patients receiving Alequel, compared to 29 percent for patients on placebo.
A clinical response was seen in 67 percent of the participants receiving the drug compared to 29 percent of those that took placebo.
Of the patients taking Alequel, 43 percent experienced an improvement in their overall quality of life compared to 12 percent of the placebo patients.

“ The notion of personalized therapy is an exciting new model for treating patients and is especially applicable in Crohn’s disease, where a misfiring of the body’s immune system is believed to be related to the inflammation observed with this condition,” said Dean Engelhardt, study investigator from Enzo Therapeutics. “ The results shown with Alequel tell us that we may now have a well-tolerated, personalized treatment alternative for patients with active Crohn’s disease. Based on the promising nature of these results, larger confirmatory trials are being pursued.”

Induction maintenance of clinical remission and response in subjects with Crohn’s disease treated with fully human anti- TFN-alpha monoclonal antibody Adalimumab

Researchers from the Mayo Clinic assessed the long-term efficacy and safety of Adalimumab ( Humira ) in an open-label study of patients with active Crohn’s disease. Results showed that Adalimumab’s efficacy increased over time, while maintaining a strong safety profile.

Adalimumab, which is currently approved to treat rheumatoid arthritis, has also shown positive results for Crohn’s disease in previous clinical trials.

Study findings demonstrated that the rate of clinical remission increased from 5.5 percent at baseline to 33.2 percent after six months of treatment and the rate of clinical response improved from 40.5 percent at baseline to 78.2 percent after six months of therapy.

Adverse events were mild to moderate in severity.

Overall, a progressive increase in clinical response and clinical remission was seen in patients receiving Adalimumab, as one-third of study participants were in clinical remission at the end of six months.

Adalimumab is a fully human monoclonal antibody that targets tumor necrosis factor-alpha ( TFN-alpha ), a protein produced by the body's immune system that is thought to contribute to the inflammation in Crohn’s disease and ulcerative colitis.

A total of 220 patients participated in the study, receiving 40mg of Adalimumab every other week for one year.
This study only includes data from the first six months of the study.
Trial participants were assessed for clinical remission ( defined as a CDAI1 ) and mucosal healing ( defined as an Endoscopy sub-score of 0 or 1 ).

“ Given that anti-TNF agents like Infliximab appear to be effective in treating Crohn’s disease, it made sense to explore its use in ulcerative colitis as well,” said Dr. William Sandborn of the Mayo Clinic and lead investigator of the ACT II trial. “ I am pleased to say that the ACT I and ACT II results suggest that Infliximab is an effective and well-tolerated treatment for ulcerative colitis. This is very encouraging news for a patient population that has few treatment options.”

Source: Digestive Disease Week ( DDW ), 2005