The molecule of this drug is an antibody directed at a substance called beta seven integrin. Integrins are molecules that act with adhesion molecules allowing white cells to leave the blood vessels, enter the soft tissue, and cause inflammation. Beta 7 integrin is found on molecules α4β7 and αEβ7. These molecules interact with two different adhesion molecules called MAdCAM, which is found in the gut, and E-cadherin, which regulates the white blood cells to leave the blood vessels.
Etrolizumab was study in a group of about 120 patients with moderate to severe ulcerative colitis. This trial was a randomized, placebo controlled, double-blind study with three treatment options. The first treatment option was four infusions of the placebo. The second treatment option was 300mg of Etrolizumab at weeks 0, 4, and 8 and a placebo infusion at week 2. The third treatment option was a dose of 420mg of Etrolizumab at week 0 and 300mg of Etrolizumab at weeks 2, 4, and 8. The goal of the study was remission of ulcerative colitis at week 10. Remission is defined as a Mayo score of 2 or less. The Mayo score is a combination score based on number of bowel movements per day, how much rectal bleeding the patient is having, what the colitis looks like after endoscopy, and the physician's assessment of the colitis.
At the end of the study, none of the placebo treated patients were in remission, 21% of the patients in the lower dose of Etrolizumab were in remission, and 10% of the patients at the higher dose were in remission. The researchers also looked at serious adverse events. The rate of serious adverse events was 12% in the placebo treated patients, 12% in the lower dose of Etrolizumab patients, and even lower for the patients that received the higher dosage of Etrolizumab.
The results of the study show that the phase two trial was positive and the study will continue to phase three.
Read the full study online here.
For more information about IBD, visit mayoclinic.org/ibd.
Dr. Loftus is a gastroenterologist at Mayo Clinic.