VIENNA – Vedolizumab, a second-line biologic for treating patients who have ulcerative colitis or Crohn’s disease and don’t respond to an anti-tumor necrosis factor drug, is gaining traction with experts who have used the drug investigationally for several years and consider vedolizumab to be their first-line biologic for ulcerative colitis. But they agree that for Crohn’s disease the available data support using vedolizumab as a second-line agent.
“I think vedolizumab [Entyvio] is a first-line biologic for ulcerative colitis. Full stop,” said Dr. Brian G. Feagan during a talk at the United European Gastroenterology Global Congress. He cited his 12-year experience using vedolizumab, which has compiled a strong record of efficacy as well as safety for ulcerative colitis.
Dr. Brian G. Feagan
“It’s the promise of a reduced risk of systemic adverse events, especially secondary infections,” by using vedolizumab instead of a drug that blocks tumor necrosis factor (TNF), said Dr. Feagan in an interview.
“For Crohn’s disease, vedolizumab seems to have a slower onset of action, so for sicker Crohn’s patients you may want to choose a TNF blocker,” said Dr. Feagan, a gastroenterologist and professor of medicine at the University of Western Ontario in London, Ont. “For Crohn’s disease you could use vedolizumab first in some patients and an anti-TNF first line in other patients.”
Another gastroenterologist experienced in using vedolizumab to treat inflammatory bowel diseases largely agreed. “Vedolizumab is a first-line biologic for ulcerative colitis, For Crohn’s disease, the anti-TNF drugs are still the way to go,” said Dr. Paul Rutgeerts, a gastroenterologist and professor of medicine at Catholic University in Leuven, Belgium.
Dr. Paul Rutgeerts
Dr. Feagan and Dr. Rutgeerts as well as others cite a fundamental difference in the way vedolizumab mitigates autoimmunity compared with TNF blocking drugs as the likely explanation for why vedolizumab seems to work much better for ulcerative colitis than it does for Crohn’s disease.
As spelled out last year in an editorial by Dr. Fabio Cominelli (N. Engl. J. Med. 2013;369:775-6), vedolizumab specifically blocks the integrin that directs leukocytes to the gut musoca, and this limited, gut-specific action may explain why the drug has such a favorable adverse effect profile as well as why it is less effective at inducing remissions in Crohn’s disease, which can hit any site along the entire gastrointestinal tract and cause transmural fistulas and multi-organ involvement. In contrast, ulcerative colitis is limited to the superficial mucosa of the large bowel.
“With ulcerative colitis it is only the mucosa. Crohn’s disease is more of a transmural disorder that involves the entire wall of the gut so you have more need for systemic action, which is better delivered by anti-TNFs” than by vedolizumab, Dr. Rutgeerts said in an interview.
Perhaps vedolizumab’s only major drawback as first-line biologic treatment for ulcerative colitis and even for some Crohn’s disease patients is its high cost, especially at a time when the price for the anti-TNF drug infliximab has begun to fall following introduction of biosimilar infliximab in Europe and its expected appearance soon in the United States.
“The cost [of vedolizumab] is very high,” especially when administered every 4 weeks, which seems to be the dosage many patients need to maintain long-term responses and remissions, Dr. Rutgeerts said.
“Now we have biosimilar infliximab, which is cheaper than vedolizumab” and hence more attractive, at least for cost, noted Dr. C. Janneke van der Woude, head of the inflammatory bowel diseases unit at Erasmus University in Rotterdam, The Netherlands. She also noted that many patients prefer subcutaneous drug treatment with the anti-TNF agent adalimumab over intravenous treatments, which is the route for vedolizumab.
Two-year data show durable efficacy, safety
Vedolizumab demonstrated its ability to safely maintain remission in responsive patients with inflammatory bowel disease in results from long-term treatment and follow-up of patients enrolled in the pivotal phase III trials that supplied the data that led to vedolizumab’s marketing approval earlier this year in both the United States and in Europe.
Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.