IBD therapies ‘still plateauing’ despite progress: Combining drugs may help break ceiling
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Despite the considerable progress made in the care of inflammatory bowel disease, current therapies are “still plateauing” in terms of response and remission, according to the keynote speaker at the Crohn’s and Colitis Congress.
However, combining therapies with “complementary mechanisms of action” may offer one strategy to help overcome this therapeutic plateau.
“We have come a long way,” Jean-Frederic Colombel, MD, professor of gastroenterology at the Icahn School of Medicine at Mount Sinai, told attendees. “You have to realize that 30 years ago, we basically only had steroids. Obviously, the world has changed, and we have so many different therapies, targeting different pathways in IBD, with both biologics and small-molecule drugs. However, although these drugs are great and we are making progress, we are still plateauing.
“In clinical practice, we are plateauing on blocking the progression of disease, especially blocking the progression to surgery,” Colombel added. “There is a high risk of surgery in patients with ulcerative colitis.”
Colombel highlighted recent data from Tsai and colleagues published in Clinical Gastroenterology and Hepatology, which found that the 10-year risk for surgery for ulcerative colitis dropped from 15% in the years prior to 2000 to 9.6% in the years after biologic therapies were introduced.
“What can we do to break this ceiling?” Colombel asked. “The big problem is that there is a huge gap between knowledge and clinical practice. The care of IBD has become very complex with the concept treat-to-target, tight control, therapeutic drug monitoring, positioning and prevention of side effects. Many people are lost.”
One possible strategy to “break the IBD therapy ceiling” involves the identification of rational combinations of therapies with complementary mechanisms of action.
“What does that mean? In a nutshell, if you are taking two of these drugs, where the mechanism of action is overlapping, you have low probability of improvement because you are basically targeting the same point,” Colombel said. “But what we need to do is find complementary modes of action so that the combination will be more effective and will have the highest chance of success.”
In a recent commentary in Gastroenterology, Colombel and colleagues noted that among the many strategies tried to maintain/enhance response or remission — including tight control, therapeutic drug monitoring and multiple drug sequencing — rational drug combination offers the most practical approach, and one which other specialties have already begun to explore.
“We have been amazed to see that rheumatologists and dermatologists are already exploring these associations between drugs used in their clinical practice,” he said. “In IBD, so far, we have almost nothing. But it is coming.”
Colombel noted that combination therapy use in other specialties have uncovered at least one “red flag” notably, the risk of increased serious infections — but this only means that if “we want to do these combinations, we need to know how the drug works.” Overcoming the treatment plateau using rational drug combination will require additional research examining individual drug mechanisms, as well as their potential impact on intersecting biological pathways.
“I’m making this plea to explore combination therapies in IBD,” Colombel said. “It is coming, and you will see more data on this in the coming months.”
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