IBD Therapy Horizon Consists of new Agents, Improved Applications
ORLANDO — Brian G. Feagan, MD, FACG, from the Robarts Research Institute at the University of Western Ontario, discussed current anti-TNF therapy options for inflammatory bowel disease and the need for new agents during a presentation at Advances in Inflammatory Bowel Diseases 2018.
“We’re approaching a quarter century of experience with TNF antagonists. TNF antagonists, you could argue, are yesterday’s drugs,” Feagan said during his presentation. “Unfortunately, gastroenterologists don’t change quickly. We’re subjects of habit and there have to be compelling reasons for us to change. The first reason to change is that these drugs are far from perfect when it comes to efficacy.”
According to Feagan, current agents such as Humira (adalimumab, AbbVie) and Remicade (infliximab, Janssen), have a “significant Achilles heel” in the form of risk for serious infection.
Currently, only infliximab has had one dedicated, randomized trial for fistulizing Crohn’s disease, with all other support from observational data, such as a subgroup analysis from the GEMINI II clinical trial of vedolizumab.
“I’ve never been a strong advocate of observational data to determine efficacy, but many people find these studies comforting and there have been some surprising results from these studies,” Feagan said, then referring to recent data from the Victory consortium.
Focusing on vedolizumab, Feagan advocated for its remarkable promise of safety even in early disease, because it is a gut-selective agent with no increased risk for infection according to randomized control trials and following real-world data.
“Vedolizumab has an unprecedented safety record,” he said. “It’s effective in both [ulcerative colitis] and CD for induction and is highly effective for maintenance. Its onset of action is slower in CD and you have to deal with that if you want to use this agent.”
While speaking about “horizon agents,” Feagan covered a new study of subcutaneous vedolizumab and a new agent, etrolizumab, an antibody designed against both alpha-e beta-7 and alpha-4 beta-7.
Results from a recent study showed that subcutaneous application of vedolizumab following induction therapy with a standard regimen of two doses of intravenous vedolizumab was not significantly different from standard intravenous application at week 52 for the endpoint of remission in UC.
Regarding etrolizumab, multiple clinical trials should be “coming off the drawing board of the next year,” he said, and “may be a greater difference in efficacy and side effects,” due to the formula being less selective than vedolizumab.
“Combination therapy is one futuristic concept ... and is probably the way to go with a new generation of agents,” Feagan concluded. “Identification of high-risk patients is a critical step and treating to a specific target is also an important concept.” – by Talitha Bennett
Reference: Feagan B. Positioning Inhibitors of Lymphocyte Trafficking. Presented at: Advances in Inflammatory Bowel Diseases; Dec. 13-15, 2018; Orlando.
Disclosure: Feagan reports that the is a consultant for Abbott/AbbVie, ActoGeniX, Akros, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics Inc., Avir Pharma, Axcan, Baxter Healthcare Corp., Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharma, Roche/Genentech, gICare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Hakko Kirin Co Ltd, Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestle, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, VHsquared Ltd, Warner Chilcott, Wyeth, Zealand, and Zyngenia. He has received grant and research support from Abbott/AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, and UCB Pharma. He is also on the board of directors for Robarts Clinical Trials Inc.