The case could be made for humanized monoclonal antibodies being the greatest development in gastroenterology, if not medicine, in the last decade.
It’s a simple argument: since receiving US Food and Drug Administration (FDA) approval in the mid-2010s, therapies like ustekinumab and vedolizumab have ascended to significant status in treatment regimens for common diseases like inflammatory bowel disease.
But what’s a tool without its user? The greatest development to come in gastroenterology since 2010 has been the major change in disease-treating mindset.
Historically, treatments for ulcerative colitis and Crohn’s disease have targeted symptom management in an effort to improve the quality of life of patients.
But a new way of thinking about disease treatment in gastroenterology has been more impactful than any of the new drugs that have come on board. David Rubin, MD, told MD Magazine® the impact of disease monitoring in gastroenterology—the effort to understand l disease onset and pathology in patients—has been more important than any other innovation this decade.
This collective effort from clinicians, the University of Chicago Chief of Gastroenterology, Hepatology, and Nutrition said, has led to more objective endpoint achievements, significantly better patient outcomes, and even reduction of recurrence in diseases such as Crohn’s.
“I think we've made great progress in understanding the natural history and risks of recurrence and preventing it from coming back,” Rubin said. “And it also is a key component to understanding the chronic nature of the disease and monitoring patients over time, so that we can keep them well.”
With both new objectives and treatments in hand, gastroenterologists have taken a more algorithmic approach to medicine—“target to treat.” Physicians are treating to assess a target, and sequentially assess disease activity, while adjusting therapies to change patient’s conditions, driving the better outcomes.
Another emerging theme has been the concept of shared decision-making and convenience in disease management, Rubin said. He often highlights this new embrace in his lectures on the history of irritable bowel disease (IBD), marking the change as a true sign of progress being made.
“When you ask patients, ‘Would you rather take your medicine once a day or twice a day? Would you rather get it as an injection you do yourself or an infusion where you go somewhere else?’” he prosed. “As soon as you start talking to people about convenience, you know, you've really made progress in managing the condition.”
Rubin likened the change to that seen in rheumatology—a new emphasis on changing the natural course of diseases. That’s led to the recognition of the data and therapies achieve such objective endpoints.
“We hadn't really used it in IBD previously—and with some of the newer therapies, like the ustekinumab trials for ulcerative colitis, by using endpoints like the way the bowel looks with the scope and how it looks under the microscope, we're actually pushing the field forward to a disease modifying goal,” he explained.
At one time in the field’s history, physicians were fixed on symptom control with just a limited pool of drugs. The ceiling for patient improvement was being lowered immediately. Disease modification strategy, and a bevy of treatment options has raised it back up.
However, with a bevy of treatment options, patients can stay on effective medications or switch off of ineffective medications.
"In the prior era, we were really stuck because a lot of patients had to live through the natural history of their disease progression, and ended up with a lot more surgeries and disability," Rubin said. "When we had newer therapies, being able to use those therapies effectively and cycle patients effectively has really changed the natural course of the disease for many people."
While a change in mindset was welcomed, new therapies also emerged in the last decade that helped patients.
In October, for the fourth time since 2009, the FDA approved a new indication of ustekinumab, as part of the UNIFI trial. The phase 3 study showed the drug’s ability to induce remission in more than 40% of patients at 1 year.
The UNIFI trial consisted of an initial induction study and a maintenance study to assess the safety and efficacy of the treatment. During the induction study, patients received ustekinumab 6 mg/kg intravenously. Following the induction phase, patients were monitored for 8 weeks and received ustekinumab 90 mg subcutaneously every 8 weeks for 44 weeks.
Investigators observed 19% of patients receiving ustekinumab achieved clinical remission during the induction study. It also provided rapid relief of symptoms in 58% of patients during the eight-week study.
Vedolizumab, approved in an intravenous formulation 5 years ago, also had an effective decade for treating both ulcerative colitis and Crohn’s disease.
Rubin explained that vedolizumab, which is a monoclonal antibody targeting α4β7 integrin, could ultimately usher in a new class of treatments.
“What [vedolizumab] did is it demonstrated to us that we could have therapies that were gut selective or targeted the bowel predominantly, and that we didn't have to use systemically immunosuppressive strategies,” Rubin said. “That started to get us to a much more directed or precision approach to thinking about our management.”
Another way these new treatments are met with optimism is that might eventually replace the need for corticosteroids.
“The biggest unmet need in inflammatory bowel disease is really a replacement for corticosteroids in our therapeutic armamentarium,” Stephen B. Hanauer, MD, professor of medicine at Northwestern University Feinberg School of Medicine, told MD Mag at ACG. “Even with our most effective biologic therapies, or even with the novel immunomodulators such as tofacitinib, still only about 30% of patients have a steroid-free remission.”
Another area where progress has been made is treating postoperative patients in monitoring, scoping and predicting disease recurrence, while managing these conditions. When patients have surgery, Rubin explained, doctors are able to essentially reset the disease, particularly for those with Crohn’s disease.
Historically, when someone has surgery from Crohn’s disease, the disease will come back at the same rate it developed in the first place. However, the advent of new therapies and treatments increases the chance of controlling the disease and preventing it from coming back.
With progress made in several different areas of gastroenterology, Rubin said that 1 disease that has not had the progress since 2010 is pancreatic cancer, which still has an incidence that matches its prevalence.
Within IBD specifically, there has not been a great deal of progress made in perianal disease, which features the worst quality of life of all IBD situations.
As for the next era of gastroenterology, Rubin says there are several ongoing trials trying to find therapeutic biomarkers.
“That means treatments that are chosen based on markers in the disease that tell us that the patient will respond more likely to that therapy, or that the patient will be less likely to respond to that therapy,” he said. “I think that that's going to be the most important advance that occurs."
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