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Russell D. Cohen, MD, Professor of Medicine, Director, Inflammatory Bowel Disease Center, Co-Director, Advanced IBD Fellowship Program.
Researchers and physicians have made great strides toward finding new, more effective treatments for Crohn's disease and ulcerative colitis, known collectively as inflammatory bowel disease (IBD). In just the past year, scientists have learned a great deal more about how the microbiome-the collection of bacteria and other microorganisms living in the intestines-affect the development of disease, and doctors have seen promising results from new types of medications.
UChicagoMed: What happened in the past year to turn the tide against Crohn's and ulcerative colitis?
Russell Cohen: I think that's a great question, and much has happened since you spoke to Dr. Rubin, in various realms. So the first realm is basic science. Thanks to patients who agree to let us take additional samples when we do colonoscopies or other types of tests, our scientists have been able to make some very interesting discoveries in inflammatory bowel disease, particularly ulcerative colitis. It hasn't been published yet, but we've been learning more about the role the microbiome has in these conditions.
As you may already know, the first Crohn's gene was discovered here in 2001, simultaneously with another group in France. For many years it was felt that this was a genetic condition and there would be a genetic breakthrough. However, that's changed. As our understanding has expanded, we've been able to do more genetic screening with larger groups. For example starting around 2010, you could test 10,000 genes at once-but be careful what you wish for, because now there are 150 Crohn's genes. It was a lot easier to study when there were five than 150 of them. So the attention now has shifted more toward the microbiome. We really think that our researchers are on to something with this, and we're focusing our attention on not just treating patients, but potentially leading towards possible cures for some patients.
What have they been studying about the microbiome?
We used to think that the microbiome was always the same, and it's just that the way your body's immune system was reacting to it that was different. That still may be part of it, but it may actually be that the microbiome either initially, or maybe even as a response to your body's immune system, changes, and perhaps more insidious creepy-crawlies begin to thrive inside you. Just like everything else in biology, biological diversity sometimes leads these creatures to change how they express their own genes based on what your body is doing to them. So it may be shaped in part by the type of stuff that's already inside you.
Are we getting to the point where we can now manipulate the microbiome as a treatment?
We know that changes in the microbiome may be due to our diet. Certain components of your diet may change the microbiome itself, or the particular organisms might change how they behave and how they interact with your immune system. It's been no secret that we don't see inflammatory diseases such as Crohn's and colitis in the developing world, but as you go from developing to developed nations, guess what? These diseases start taking off. There something called the hygiene hypothesis, which we thought meant that when you clean up and start having modern plumbing and living in less crowded conditions, you get fewer infections but more immune diseases. But it actually may be due to diet and other changes in the environment-industrialization perhaps-that changes the microbiome.
What other advances are helping us beat Crohn's and colitis?
There has been an explosion of new treatments. Some are pills, which is new because we haven't had a new pill in IBD treatment for many years. For many years now, since 1998, the big breakthroughs in inflammatory diseases have been Remicade (infliximab), Humira (adalimumab), and that family of drugs. They're still dominant, but there are other families of inflammatory blockers or promoters that are gaining ground in inflammatory diseases, including ours. It's always helpful when the drugs are already on the market, so we have a few drugs on the market for rheumatoid arthritis and psoriasis that we're able to get for our patients. There are others that are still completely investigational, and we're one of the leading centers doing those studies.
What makes these new drugs different?
So there are different pathways of inflammation, different ways it happens in the body. In 2014, one pathway had a drug Entyvio (vedolizumab), which blocked white blood cells from attacking the bowel-it's a very bowel-specific, almost a designer drug. That was a big breakthrough then, it still is now. We are hoping to have another big breakthrough of a drug that's on the market for psoriasis called Stelara (ustekinumab) which blocks different things that cause inflammation. It's very successful in psoriasis and it looks like it will be successful in Crohn's disease. Hopefully it will be approved this year.
Is that common for drugs that are approved for one usage to be used to treat others?
Some of these diseases share the same inflammatory pathways, meaning they cause inflammation the same way. When one makes a breakthrough, we're quick to run over there and try it on your patients too, because we're always looking for things to work. However, sometimes the reverse happens. So for example, there was a new drug on the market that looked promising, and when they gave it to the Crohn's patients they seemed to do worse, so they actually had to stop the trial. Now what's difficult in biology is sometimes it's a dose issue. Sometimes, some diseases are helped at a lower dose and made worse at a higher dose, or vice versa, so it can get a little complex.
Is it realistic to say we can cure Crohn's or ulcerative colitis, or would you even call it a cure?
I think we're not there yet. For certain patient populations it's going to be closer than for others. We certainly don't want to give people false hope, but we're hoping that some of the breakthroughs in the lab and some of these new medicines may be able to afford that word "cure" to some people. But I have to be clear: if the problem is that your immune system is not acting appropriately, you have to be careful about trying to fix it. You need your immune system, and you want it to work well, and you don't want to end up doing permanent damage from a breakthrough advance, medication or otherwise. Maybe the immune system is doing what it should be doing, but the patients are suffering and a lot of the damage by the immune system is not reversible. So ideally, we would be able to discover triggers in people, and have the immune system stop doing that every time we stop the medicines.
For a patient who is newly diagnosed, do they have a different prognosis now than they would have five or ten years ago?
Absolutely. For many years, unfortunately, the only effective treatments were steroids, prednisone or similar. And prednisone works well and works fast, but unfortunately it stops working long-term and has horrible side effects. Until the breakthrough therapies, we had some other effective agents, but not for people who were very sick. Starting around the late 90's or 2000's, we were able to make a big breakthrough for that patient population, and now we have a lot more options of expanding into different families of medications.
We've also been able to educate our colleagues about how treating someone with effective medicine early makes a big difference, particularly with Crohn's disease. Crohn's disease causes scarring in the bowel, so constant inflammation creates scar tissue. Once you get scar tissue, the medicine can only help a little bit and you really need a surgeon to cut the bad part out, and then it comes back again. But let's say you got to someone early in childhood or teenage years-maybe you could prevent that and make them more receptive to medicine. Or, let's say you do have surgery. I mentioned that Crohn's comes back, but that gives you an opportunity to prevent it from coming back.
So do you think we're really winning the battle against Crohn's disease and ulcerative colitis?
I think we're certainly making a turn in the racetrack, but I don't know if it's the final length. It would probably be a little facetious to think we're hitting the final length for anything in life, but it certainly is a major turn that's been happening over the past few years, with our better understanding of the triggers of the microbiome, as well as the explosion of other potential treatments for patients with inflammatory diseases.
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Russell Cohen, MD, is a renowned gastroenterologist with clinical expertise in inflammatory bowel disease (IBD). Under his leadership, a multidisciplinary team of specialists in gastroenterology, surgery, pathology and radiology provide comprehensive care for patients with Crohn's disease and ulcerative colitis.See Dr. Cohen's Bio