David T. Rubin, MD: Undaunted in his quest to improve the lives of patients with inflammatory bowel disease and other digestive ailments

Patients come through his door looking for answers and relief. The symptoms that began as a nuisance have turned painful and chronic. Their bodies have turned on them.

David T. Rubin, MD, is a world-renowned expert on the treatment and research of inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis. He’s a tireless educator — in classrooms, at conferences and on Twitter, where he’s known as @IBDMD — and an ardent advocate for people living with IBD. His preeminence was recognized in 2020 with the Sherman Prize, one of the most prestigious awards in his field. Becker’s Healthcare recently named him to its list of Crohn’s disease can involve any part of the GI tract from the mouth to the anus, while ulcerative colitis attacks only the large intestine. In addition, Crohn’s can be patchy, appearing in one place but not another; ulcerative colitis is continuous in its distribution.

“Treatments are aimed at turning off the inflammation,” Rubin said. “And we’ve made great progress in managing these conditions. When I started my training, we basically had no treatments. Now there are more than 15 available, effective and safe treatments.

Biological therapies for inflammatory bowel disease

That includes the revolutionary development of biological therapies for IBD. Biological therapies are proteins that are made in living cells. There are now three classes of biological therapies available for Crohn’s disease and ulcerative colitis.

The first class, the anti-TNF class, includes drugs that block the body’s signals that fight infection or cause inflammation. By targeting the inflammatory protein called TNF, anti-TNF therapies can shut down inflammation broadly across the body. These drugs are also used to treat rheumatoid arthritis, psoriasis and other inflammatory conditions.

Another biological antibody therapy selectively targets the white blood cells on their way to the bowel. The newest antibody class targets a different inflammatory protein called IL-23, and works in IBD and psoriasis.

“The strategy is to turn down the overactive immune response long enough so that the body can take over and then heal,” Rubin explained.

The latest treatment for inflammatory bowel disease

The newest treatment focus is on synthetic targeted small molecules, which work on specific enzymes or other mechanisms of inflammation. These molecules are small enough to be delivered as pills and be absorbed into the bloodstream.

Finally, 5-ASA therapies, which Rubin has been studying for years, were first developed in the early 1950s to treat arthritis. These therapies don’t suppress the immune response, but are believed to affect the immune activity in the lining of the bowel.

With so many options, it would seem that patients with Crohn’s disease and ulcerative colitis can live worry-free, even if a cure isn’t found. But then the human body proves again why it is such a marvelous example of biological engineering.

“Remember that we’re not treating the cause of IBD, we’re treating the result of it,” Rubin said. “The immune system of the gut is there to protect us. It still thinks there is a threat. So, it can be just a matter of time before it finds a new pathway and the inflammation returns.”

As a clinician-scientist, Rubin attacks these problems from all angles, pushing our understanding of biology and disease in his research while analyzing and assessing the stream of information coming from his patients. Each patient’s unique biology might provide a special insight into how IBD works.

“So these are the things — I’m not making this up — they literally keep me awake at night,” said Rubin. “Is this the patient who is going to be the key to what we’re trying to find?”

There’s one more complication. Rubin and his colleagues across IBD research and treatment may be dealing with multiple diseases.

“It might be because what we call Crohn's disease and ulcerative colitis are more like 50 different diseases that all look similar, but the body can only express itself in certain ways,” Rubin said.

Microbiome research

Eugene Chang, MD, is the director of the Chang’s lab was well-positioned then to be among the first groups to receive grants from the National Institutes of Health's Human Microbiome Project.

Chang, a frequent collaborator with Rubin, studies how the gut microbiome affects IBD. He considers the microbiome to be like another organ of the body, though one that is acquired early in life instead of inherited.

“The human microbiome has changed rapidly in just the past hundred years,” Chang said. “It is influenced by diet, lifestyle and xenobiotics, like antibiotics, that are so common now. So our microbiome is much less diverse. There are certain microbes that have disappeared in many populations. It is a real disturbance in the normal evolutionary pressures that would determine which microbes we match to our own needs, for example, in immune or metabolic systems.”

Chang said the consequences have not been good, creating a mismatch between us and our microbes. “I think that underpins the increase in these new age disorders, such as inflammatory bowel disease, but also other autoimmune and inflammatory disorders, such as asthma or rheumatoid arthritis,” he said. “But we’re still just scratching the surface of the science.”

Chang said he first met Rubin because they had the same mentor, Joseph B. Kirsner, MD, PhD, who is considered the grandfather of modern IBD research and treatment and put the University of Chicago on the map as an IBD pioneer.

“I remember Kirsner saying, ‘You need to meet this really bright, superstar medical student,’” Chang said, though he didn’t really get to know Rubin until he joined the faculty.

Chang said Rubin’s many talents make him a “quadruple threat.”

“He’s an outstanding clinician, a wonderful educator — my gosh, you should listen to him give a talk — and an outstanding clinical investigator,” he said. “And finally, I think he is a superb section chief. He has vision, he gets things done, and knows how to select the right people for key tasks.

“David really is a remarkable individual.”

Game-changing care

Rachel Hendee’s story captures the recent history of IBD treatment in a nutshell. Diagnosed with severe Crohn’s disease at age 14 in the mid-1990s, she had surgery to remove part of her small and large intestines just a year later at the University of Wisconsin-Madison hospital. Her ongoing care was still through a specialist in her hometown of Freeport, Ill., about 115 miles northwest of Chicago, but he began sending her to UChicago Medicine for regular checkups to monitor her condition.

“During those first five or six years, I did OK, but the disease always came back,” Hendee said. “This was before there were very many options so I went through all those available at the time.”

In the late 1990s, Remicade (the first anti-TNF therapy) was approved, and Hendee said she was the first in Freeport to receive it.

“Remicade was a miracle drug,” she said. “I had never felt so good in years.” The medication meant Hendee was able to go away to college to earn an undergraduate degree. It even meant she could go to China for a year to teach English.

But her health declined precipitously when she returned. She started cycling through drug protocols that would only work for short periods, and underwent 10 surgeries and countless smaller procedures. Despite her difficult health situation, she still managed to return to school and earn a degree as a physician assistant. About seven years ago, she transferred her care full-time to UChicago Medicine and became Rubin’s patient.

When you’re in an appointment with him, you feel like you’re his only patient.

“That was a game changer,” Hendee said. She appreciated how he approached her care, how he was willing to try new medications and had the reputation, expertise and Twitter platform to successfully appeal to her insurance company to pay for it. Finally, though, in 2019, when her body fought off another round of medications, she and Rubin decided the best course of action was to have her colon removed.

“I’ve probably felt the best I have in the 25 years since I was diagnosed,” she said. “The sad irony was that I had surgery at the end of December and in March was feeling better and finally wanted to go out and be social and the pandemic hit.”

Hendee, now a physician assistant in colon and rectal surgery at another Chicago hospital, says her early diagnosis and experience played a big role in her career decision. It maybe isn’t so surprising that she often sounds like her doctor and mentor.

“One of the most important things newly diagnosed patients need to know is that it will get better and that they will be able to enjoy a long life,” she said, adding that it helps when they see her in her white coat and hear it from her. Hendee said her own expertise in the field has only increased her admiration for Rubin. When she learned about the Sherman Prize, she decided to nominate him for the award.

“Dr. Rubin really is amazing,” she said. “I think that quite possibly he is the busiest person I know, but when you’re in that appointment with him, you feel like you’re his only patient.”