Vedolizumab Brings Endoscopic Remission in Some Patients With Crohn's Disease

By Will Boggs MD

July 24, 2019

NEW YORK (Reuters Health) - About 1 patient in 8 experiences endoscopic remission of Crohn's disease after completing 26 weeks of treatment with the gut-selective monoclonal antibody vedolizumab, according to results from a phase 3b single-group study.

"(These) data are in line with other biologics," Dr. Silvio Danese from Humanitas University, Rozzano, Milan, Italy told Reuters Health via email.

Rather than targeting clinical symptoms alone, the new Crohn's disease management paradigm aims for both endoscopic healing and symptomatic remission.

Dr. Danese and colleagues in the VERSIFY study tested vedolizumab in 101 patients with moderately-to-severely active Crohn's disease. Everyone received vedolizumab infusions on day 1 and at weeks 2, 6, 14, and 22, and a subset of 56 patients received infusions at weeks 30, 38, and 46. The primary endpoint was endoscopic remission (defined as a Simple Endoscopic Score for CD of 4 or less) at week 26.

Twelve patients (11.9%) achieved the primary endpoint, according to the July 4th Gastroenterology online report.

Among the 56 patients followed for 52 weeks, 9 (16.1%) were in endoscopic remission at week 26 and 1 additional patient was in endoscopic remission at week 52 (for a total of 17.9%).

Endoscopic remission rates at week 26 were higher in TNF-antagonist-naïve patients than in patients who had failed TNF-antagonist treatment (19.6 versus 5.5%).

Endoscopic remission rates were also higher in patients with moderate rather than severe endoscopic disease activity at baseline and in patients with shorter disease duration.

In the 26-week study, 24.4% of patients achieved histologic responses and 41.6% achieved clinical remission. Among patients followed through week 52, 20.5% had histologic responses and 50.0% achieved clinical remission.

Health-related quality of life showed clinically meaningful improvements over the course of the study, and treatment-related adverse events affected 11.9% of patients during the first 26 weeks and 5.4% of patients during the second 26 weeks of the study.

Fifteen patients in the first 26 weeks and 7 patients in the second 26 weeks discontinued treatment prematurely for perceived lack of efficacy, and 2 and 3 patients, respectively, discontinued because of adverse events.

These findings "support vedolizumab as a first-line biologic therapeutic option," the researchers conclude.

Dr. David T. Rubin from University of Chicago Medicine and Biological Sciences, Chicago, Illinois, who has also investigated the use of vedolizumab for treating inflammatory bowel disease, told Reuters Health that the low endoscopic remission rates are "a reality of such deeper endpoints in Crohn's disease. They are hard to get, and harder to get in patients who have been resistant to prior therapies, which is the case for clinical trials, and further demonstrated that the patients in this phase 3b study who had previously exposure or failure of anti-TNF therapies did worse than those who were naïve to these treatments."

"It is of interest that the histological endpoints were better than endoscopic, but this has been reported with ulcerative colitis, too, and may be a result of a differential response between endoscopy and histology, but may simply be differences in the sampling or scoring systems and doesn't necessarily mean that patients really achieve improvement in histological endpoints while maintaining endoscopic activity," he said in an email.

"While it is known that vedolizumab achieved its clinical endpoints in 6-10 weeks, this assessment shows the time to 'deeper' endpoints is longer," he added. "This has implications for clinicians managing patients in several important ways: first, to not give up on the therapy too soon or else you may be underestimating the benefit that can be achieved with vedolizumab; and second, when to reassess for objective evidence of improvement."

Takeda Development Center Americas, Inc. sponsored the study, employed 2 of the 10 authors, and had various relationships with the other 8 authors. Dr. Rubin has also received funding from Takeda.


Gastroenterology 2019.