Patient Selection and Safety With TNF Inhibitors - Episode 2
Marla Dubinsky, MD: There are some classic symptoms that belong to the group of inflammatory bowel diseases [IBDs]. I should note that IBD encompasses or is an umbrella term for 2 specific disease states. One of them is ulcerative colitis, and the other one is Crohn disease. We used to think of them as 2 very distinct buckets, mainly because Crohn was originally found at Mount Sinai by Dr Crohn and his colleagues Dr Oppenheimer and Dr Ginzburg. The condition was first reported in 1932 and was called “regional enteritis.” It was really terminal enteritis just at the end of the small bowel, and then it evolved to show that Crohn could actually occur anywhere—from the mouth to the anal canal. What’s different versus ulcerative colitis is that ulcerative colitis is restricted to the colon.
Since there are a lot of genes and a lot of bacteria and a lot environmental factors, there are multiple kinds of Crohn. We have started to understand the genetics around it. We have started to see that these 2 historically distinct subtypes are probably closer than we thought, especially because there’s a group of patients with Crohn disease who have disease isolated to the colon. This is like a Crohn colitis, which looks very similar to ulcerative colitis. So people confuse the term. I think the direction that we’re going is determining where the disease is located. Forget whether it’s Crohn or ulcerative colitis. Is it colon only? Is it small bowel plus colon? Is it small bowel only? Then you can choose your treatments based more on location. Location drives symptoms.
Someone who has colon involvement, or colitis, typically has urgency, which means they rush to go to the bathroom. They may have rectal bleeding, an increase in bowel frequency—so more trips to the restroom—and cramping associated with a bowel movement that is often relieved after a bowel movement. Sometimes when they eat they have to run to the bathroom. So there’s this distinct colon inflammation that you sort of get a feel for when you ask a patient about symptoms. You can say, “Oh, that’s classic left-sided colitis symptoms,” and we treat accordingly. That’s sort of an easier example of a colitis description. Some patients wake up at night as well. It really affects quality of life, especially with urgency. On occasion there are accidents if the patient can’t find a restroom or make it in time. So it’s very disruptive.
How do these diseases affect patients’ quality of life? I’ll tell you that colon inflammation really affects life because, often, they’re in the bathroom in the morning. It’s hard for them to get out of their house because they may run to the restroom, think that they’re finished, and stand back up and have the sense that they still have to go. We call that tenesmus, which is incomplete evacuation. It’s sort of this spasm of the rectum. That’s extremely stressful. This is not to say that Crohn symptoms are not stressful and do not affect quality of life, but they’re different. Small bowels are where you absorb your nutrients. Often, the distinction between Crohn and ulcerative colitis is that Crohn affects all 4 walls of the bowel. Ulcerative colitis affects only the inner lining, which is called the mucosa.
Because Crohn can affect all 4 walls, inflammation in all 4 walls creates somewhat of a constriction. And so patients may have pain when eating because of what we call swelling inside the bowel. But also, when you go in with an endoscope and actually find these ulcerations, they can be quite deep in Crohn disease. With ulcerative colitis, because it’s just the inner lining, it’s sort of a smattering of, almost raw… sort of like a sore throat. There is continuous inflammation from the rectum, heading north into the colon.
Crohn disease looks different—almost as if you used a rake. You sort of have these linear ulcerations that are more complex forms of Crohn. So patients may have abdominal pain, weight loss, fatigue, and anemia. Patients lose iron through their stool. Alternatively, they’re just absorbing their food and they’re not absorbing their iron. Abdominal pain and change in stool frequency are the characteristic patient-reported symptoms that we get. For patients with ulcerative colitis, stool frequency and rectal bleeding are the 2 main issues. So those are what we focus on when we ask for symptoms. Even in drug trials, those are the symptoms that we are looking for. So those are important symptoms.
One thing that affects the quality of life significantly in Crohn patients—which, again, differentiates it from ulcerative colitis—is something called peritoneal disease. So perianal fistulas, abscesses, ulcerations, and fissures. Obviously, that’s very painful, to sort of have a fluid-filled collection of infection in your bottom area that often requires surgery for drainage. There may be constant drainage through these tunnels, or what we call fistulas, around the anal canal area.
What’s also interesting about Crohn disease is that because it’s all 4 walls, the way the body tries to heal itself is by creating scar tissue. That’s all right when you have a wound on the outside. You want wounds to close. You want scars to develop. However, this is not really the case in the intestinal tract. Again, as you get inflammation, the body sort of heals by itself. It will sense if we’re not providing enough biological therapy and anti-inflammatory drugs to them. Then the body starts to create scar tissue. So not only do you have some inflammation that constricts the lumen of the bowel, but you also have scar tissue. That can result in bowel blockages, for example, and patients have a lot of pain.
You may also have this tunneling that we describe around the perianal area. Patients may have it in the bowel wall because of the 4 walls, and then things get complicated. And so, our philosophy is to explain what the natural history of the disease is to patients and tell them why we need to focus on getting them the right therapy.