The Future of IBD Is Personalized Medicine
PHILADELPHIA—Following the lead of other specialties and pursuing a personalized medicine approach for patients with inflammatory bowel disease (IBD) will allow for better treatment options, said Stephen B. Hanauer, MD, during The J Edward Berk Distinguished Lecture today at the American College of Gastroenterology Annual Meeting 2018.
“Personalized medicine has become a catch word throughout the medical field…We have to follow other specialties, like oncology, where diagnosis is no longer clinical but rather based on molecular genetics,” said Dr Hanauer, professor of medicine at Northwestern University Feinberg School of Medicine, during his lecture. “Only with that kind of comprehensive approach are we only going to be able to make greater strides in treatment for our patients.”
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IBD has remained a complex disease. As of 2018, more than 200 gene mutations have been identified as associated with ulcerative colitis (UC), Crohn disease (CD), or a combination. However, a majority of the population with one of the 200 mutations do not have IBD.
Rather, 15% of patients with IBD have one of the recognized mutations.
Factors such as diet, genetics, environment, immune system, and the microbiota all affect and can modify underlying genetics. Studies have researched the impact of various factors on genetics and IBD. Still, only 20% to 40% of remissions are reported.
“We have a number of opportunities to improve the outcome to an 80% response rate,” Hanauer said.
The evidence to improve outcomes is related to diagnosis, more research, prognosis, and targeted treatments.
There is a need for optimization in the diagnosis of IBD. In 2018, the field still does not know how to define UC and CD, according to Hanauer.
“We will have to fill in the gaps in order to develop a more comprehensive approach to diagnosis,” he said.
Although more than 200 genes are associated with UC and CD, they can be seen in other diseases as well. Serology data has provided insight and have already determined the influence of microbiome and how it can be affected by diet. Changes in the diet can lead to prone inflammatory environment in the intestine.
“As a result, we are left in the middle a lot, where patients are often named as indeterminate colitis,” he said. “So, we have to consider genes.”
Omics Research, Biomarkers >>
Difficulties in Omics Research
Hanauer pointed out many different challenges with Omics research, including:
- Poor quality and difficulties in standardization of electronic medical record integration,
- Majority of research are cross-sectional studies,
- Patients are concerned with privacy and data security, and
- Lack of standardization of all steps in biomarker discovery, but this is difficult to achieve in practice.
“It will take continued teamwork and collaboration,” Hanauer said.
Need for Biomarkers
Identifying and applying biomarkers relevant to key areas in precision medicine in IBD are of upmost importance.
Currently available IBD biomarkers are not used clinically because they are not simple, accurate, easy to perform, or rapid, as well as lack clinical utility and inconsistent validation in independent cohorts.
Difficulties with prognosis are often related to the lack of biomarkers. Hanauer said current prognoses are typically based on clinical markers and, therefore, do not give proper insights to underlying disease behavior.
“Currently, markers are demonstrating what we already know in that patient population,” he said.
“We need to identify the self-phenotypic of individuals before they develop IBD but certainly at the time of diagnosis, which will improve categories of therapies and alternatives,” Hanauer said. “I anticipate more sequential or combination therapeutic approaches.”
Mucosal healing is currently the best discriminator between placebo and drug therapy—the most sensitive marker—in clinical trials that predict long-term course of disease, according to Hanauer. However, mucosal healing is difficult to achieve.
“We haven’t identified a specific mucosal healing definition that will fit our needs,” Hanauer said.
Critical Enablers in Precision Medicine
According to Hanauer’s presentation, enablers exist in terms of available data, analyses performed, and outcomes. Currently, data on microbiome and genetics, algorithms and integration of data sets, and disease activity and susceptibility are just a few enablers.
Other enablers will need to be incorporated into newer mechanisms to approach IBD. These include large-scale prospective cohorts and patient-reported data for newer data sources, advances in computational power and innovative access to new ideas for more in-depth analyses, and applying disease outcomes, activity, behaviors, and therapeutic response in clinical trials.
Identifying and incorporating biomarkers into the design of clinical trials will also be vital for advancing treatment of IBD and pursuing precision medicine. Potential solutions for more biomarkers include:
- Data-driven approaches such as network interference,
- Prospective studies with multiple time points,
- Standardized method of simple acquisition, and
- Use of homogenous patient subsets and studies of subjects with no prior medical therapy.
Hanauer SB. Fake news and alternative facts on personalized medicine in IBD. The J. Edward Berk Distinguished Lecture presented at: American College of Gastroenterology Annual Meeting 2018; October 5-10, 2018. Philadelphia, PA. https://www.eventscribe.com/2018/ACG/agenda.asp?day=10/9/2018&theday=Tuesday&h=Tuesday%20%20October%209&BCFO=P|G. Accessed October 9, 2018.