Personalizing Therapies: The Intersection of Drug Development and Complementary or Alternative Therapies for Ulcerative Colitis Patients

A robust pipeline of drugs has so far helped 30%-40% of patients. Clinical studies are exploring how non-drug therapies such as diet and cognitive behavioral therapy could help patients feel more in charge of their condition.
Dr. John Gubatan
Dr. John Gubatan
Stanford Gastroenterologist and Junior Researcher

People with ulcerative colitis yearn for a better quality of life. The cause of the chronic inflammatory bowel disease remains a mystery to scientists. But it is believed that it is tied to an immune system malfunction. The disease causes painful inflammation episodes called flare ups. Some of the symptoms include diarrhea, blood in the stool, and fatigue. These symptoms can make patients feel self-conscious, depressed, and socially isolated.  

Dr. John Gubatan is a Stanford Gastroenterologist and junior researcher. He thinks ulcerative colitis (UC) is a fascinating disease. Many factors can impact the disease such as environment, diet, genetics, and mental health. One area of interest is the connection between patients’ mental and physical health. There has been a steady stream of FDA approved treatments coming to market. But a treatment that works for everyone with the disease remains elusive. In an interview, he discussed how scientists are balancing the need for effective treatments with complementary or alternative therapies to improve patients’ quality of life.  

What are some of the treatments currently in development that should encourage people with this condition?

“A lot of the therapies target the immune system. They get more precise, targeting specific parts of it to reduce or halt inflammation. Certain treatments are intended to inhibit the faulty immune system’s response. Regrettably, they don’t work for everyone. These therapies are often only effective in 30%-40% of patients.  

The beauty of UC is we have a lot of treatments. Many different therapies target different parts of the immune system. More recently, there are targeted therapies that just focus on the immune system of the gut. We're fortunate in that almost every year or every couple of years, we have a new FDA-approved drug.

If you look at the clinical trial pipeline, there are many drugs being developed. Several are in advanced clinical trials (phases 2-3).

There are therapies in development that are designed to be less toxic. We're looking for more targeted therapies with fewer side effects that just target the gut.”

What drug alternatives are under development?

“Patients are interested in getting better but many don't want to be on drugs long term because of the side effects. That’s a hot topic in our field. Variability in response to approved therapies may also be influenced by other factors such as patient diets and stress. We're exploring diet, clinical trials with different diet types, and other approaches. That's where I think the field is going. Drugs are so important to improve inflammation.  But in the future, there will be some new therapies that offer combination therapy with or even alternatives to drugs – diet, lifestyle, and maybe even a fecal transplant.

A fecal transplant is when poop is transplanted from a healthy donor to another person to give them a healthy balance of bacteria.”

How does mindfulness play a role in treating ulcerative colitis?

“Medications improve inflammation, but some of these patients still have symptoms. Our field is opening up to non-drug options. Some studies explore the effects of mindfulness – teaching patients how to use breathing exercises to relax. Other clinical trials focus on cognitive behavioral therapy. This therapy helps patients to change the way they think to cope with stress. Clinical trials are assessing the effectiveness of these approaches for fatigue and mood symptoms of UC.”

What have you learned about ulcerative colitis patients through your work? What’s the ulcerative colitis patient experience?

“It's a journey. I think patients who get diagnosed are usually younger, they were previously healthier, they're at the prime of their life and boom! Suddenly, they have this chronic disease. It has a big impact on their lives – the side effects include diarrhea, bloody stool, weight loss. What I've learned is each patient is different. I also think it's important to have joint decision making between clinicians and patients.

Some patients are fine with treating their disease aggressively. They want the strongest therapies and they’re willing to live with side effects. Other patients don't like being on medications and we as clinicians must work with them to find a middle ground. But we have options if they want to decrease the dose later on or minimize it as they get better. It’s not ideal. I counsel them to show what the risks are, but it has to be based on what their values are. I'm fine with doing that cautiously.”

Do any patients stand out?

“I had one patient who went into the hospital with a very bad UC flare. She was not responding well. The doctors at the hospital pushed for surgery to remove her colon, which is a common treatment. Even though surgery was the right thing to do, the patient didn’t agree. After a long time in the hospital, she just got better with standard therapies, but it took some time. I think that's a humbling experience. We have clinical data and guidelines, but each patient is different. Doctors have to be open-minded and support the patient, even when they don’t agree with your therapy choice.”

Investigator Bio

Position:
Instructor of Medicine at Stanford University School of Medicine; Gastroenterologist at Stanford Health Care; Chan Zuckerberg Biohub Physician Scientist Scholar; Doris Duke Physician Scientist Fellow

Medical School:
Harvard Medical School

Residency:
Beth Israel Deaconess Medical Center, Harvard Medical School (Internal Medicine)  

Fellowship:
Stanford University School of Medicine (Gastroenterology)

Years researching ulcerative colitis:
7

Areas of interest:
Ulcerative colitis, Crohn’s disease, immunology, biomarkers, precision medicine, gut microbiome, vitamin D

Prior mentors:
Dr Alan Moss (mentor during residency at Harvard) currently Professor of Medicine at Boston University and Director of Crohn’s and Colitis Program at Boston Medical Center


Dr. Aida Habtezion (mentor during fellowship at Stanford) Professor of Medicine at Stanford University School of Medicine. Currently, Chief Medical Officer at Pfizer