New Meds—New Hope for IBD
1.4 million Americans suffer from inflammatory bowel diseases –like Crohn’s and ulcerative colitis. Constant diarrhea, abdominal pain, and intestinal bleeding are just some of the symptoms these patients endure. Now, there’s a new therapy for people who have tried everything.
A year ago, Megan Johnson would never have been able to enjoy a beautiful day.
“I was wheelchair-bound,” Megan told Ivanhoe.
Megan has ulcerative colitis. This 29-year-old suffered from constant diarrhea, bleeding, malnutrition, and severe pain.
“I just said if this is my life, I don’t want it. It’s too miserable,” Megan said.
When doctors suggested removing her intestines –Megan found UCSD Gastroenterologist William Sandborn.
“It’s always surprising to me how much inflammatory bowel disease can impact a patient’s life,” William Sandborn, MD, Chief of Division of Gastroenterology, University of California, San Diego, Director of UC San Diego Inflammatory Bowel Disease Center, told Ivanhoe.
In inflammatory bowel disease, immune cells travel to the colon and make chemicals that cause inflammation. Most treatments target the chemicals after they attack, but a new therapy, called Vedolizumab, stops cells before they attack.
“It really acts to stop the diseases before they even start,” Dr. Sandborn said.
In a clinical trial, patients who had infusions of Vedolizumab every four or eight weeks, went into remission.
“I can’t even remember the last time I felt this good,” Megan said.
Megan is excited about this new option. She knows every day without pain is a good day.
The new drug was tested in patients with both ulcerative colitis and Crohn’s disease. It could be approved and available for use in 2014. Another benefit is the therapy is targeted, so side effects—like weight gain, nausea, and headaches—are less common.
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic intemperate of all of the organs in your digestive tract. This usually includes Crohn's disease and uncreative colitis, and is known to be very painful and uncomfortable. Crohn's disease causes inflammation in the digestive tract and spreads along the tissue. The effects of this disease are severe diarrhea, malnutrition, and abdominal pain. Ulcerative colitis is another inflammatory bowel disease that is long-lasting. The symptoms of this disease develop over time, but it only affects the lining of the large intestine. (Source: http://www.mayoclinic.com/health/inflammatory-bowel-disease/DS01195)
CAUSES: Doctors have not pinpointed the specific cause of IBD, but they are sure that stress and a poor diet are not the main factors. Researchers are now focusing on hereditary and the immune system as leading causes. If one or both of your parents has IBD, then chances of you having it are greater than if they didn’t. Researchers suggest that genetics may play a role in developing the disease. The immune system is another target for triggering IBD. Researchers believe that bacterium, or a virus, also prompts inflammatory bowel disease. (Source: http://www.mayoclinic.com/health/inflammatory-bowel-disease/DS01195/DSECTION=causes)
SYMPTOMS: Symptoms of IBD come and go, and they may vary between each patient. Symptoms may include:
• Loss of appetite
• Weight los
• Blood in stool
• Urgency to have a bowel movement
• Abdominal cramps
• Iron deficiency (Source: http://www.webmd.com/ibd-crohns-disease/crohns-disease/inflammatory-bowel-syndrome)
NEW TREATMENT: Vedolizumab is being tested to treat the symptoms of inflammatory bowel disease. This treatment’s purpose is to put the disease in remission so the patient will be able to live a healthy and normal life outside of the bathroom. Though the drug is not FDA approved yet, it has been tested on patients with Crohn's disease and ulcerative colitis. Common side effects of treatments for the disease are weight gain, headaches and nausea. However, Vedolizumab has not shown any listed side effects. (Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557917/)
William J. Sandborn,, MD, Professor of Medicine and Chief, Division of Gastroenterology, Director of UCSD IBD Center, University of California San Diego and UC San Diego Health System, talks about new medications available for patients with IMB.
IBD stands for several different diseases and affects a lot of people, right?
Dr. Sandborn: Yes, Inflammatory Bowel Disease is actually an umbrella term and it encompasses both Crohn’s disease and ulcerative colitis. It’s kind of half of each.
How many people suffer from this?
Dr. Sandborn: Overall, in the United States there’s probably in the range of one point four or one point five million people with inflammatory bowel disease. That’s kind of equally distributed between ulcerative colitis and Crohn’s so you know somewhere in the seven hundred and fifty thousand patient range for each of those two diseases.
What’s the difference?
Dr. Sandborn: So people always ask, what’s the difference between ulcerative colitis and Crohn’s disease? Ulcerative colitis involves only the colon and it always involves the lower colon or the rectum. So if you look in with a scope you’re going to see the end of the disease if you look in. Crohn’s disease involves the small intestine only in about a third of patients, the small intestine and the colon in about a third of patients and then the colon only in about a third of patients. Very often the rectum or the lower colon is skipped in Crohn’s disease. They’re both inflammatory conditions of the intestine, they can both lead to abdominal pain and to diarrhea and rectal bleeding. But the biggest difference in some ways between the two diseases from a patient perspective is what’s involved and the pattern of involvement of the large and small intestine is different.
Do you see a lot of patients with this and know that it can really change a person’s life?
Dr. Sandborn: It always surprising to me in a way how much inflammatory bowel disease can impact a patient’s life. I don’t mean surprising when you think about what they have if you look in with the scope and you see all the ulcers and bleeding it’s not that surprising that people would feel sick, but the magnitude of effect. If patients have a really active disease, they end up missing a lot of school and work and life activities—they’re constantly wondering where the bathroom is. Many of them if they have a really severe flare will sometimes have some accidents and if you have one accident, you know your focus on where the bathroom is, is just constant after that. It becomes the driving force in their life until they’re able to get in to remission.
Do you treat them both the same way with the same drugs?
Dr. Sandborn: The differences between ulcerative colitis and Crohn’s disease, we’ve talked a little bit about what areas of the bowel are involved, the other has to do with how much of the wall of the bowel is involved. So with ulcerative colitis most of the time, it’s just the most superficial layer or the lining of the bowel where as Crohn’s disease tends to penetrate through the entire thickness of the bowel wall. So with medications for ulcerative colitis sometimes we can almost create a salve or a topical treatment that treats the lining of the bowel. In Crohn’s disease, you really have to get drugs that penetrate deeply in to the wall of the bowel. Some medications like steroids and antibodies, tumor necrosis factor antibodies like Remicade or Humira, or Cimzia or Simponi seem to work with both diseases. Other drugs mesalamine products like Asacol and Lialda and Pentasa really work better for ulcerative colitis than for Crohn’s disease. Some of the drugs are in common and some are different.
Is this something that you will always do?
Dr. Sandborn: We sometimes will say that inflammatory bowel disease is chronic inflammatory bowel disease. That distinguishes it from an infectious colitis with e-coli or campylobacter or salmonella where you can have an inflammation of the intestine, you can have symptoms that look just like inflammatory bowel disease but it’s due to an infection and if you treat the infection the colitis is over. Ulcerative colitis and Crohn’s disease by contrast are chronic and that’s because we really don’t precisely know the cause. We think of them generally as autoimmune disease so that the patient’s immune system is attacking their own intestine. The therapies are really aimed at suppressing that inflammation of that self-inflammation where the patient’s immune system is attacking the intestines. Since we don’t know the cause, the therapies tend to be more suppressive. We will kind of have two phases of treatment. One is to put the disease into remission, to put out the fires so to speak. The other is to maintain the remission or keep the fire from coming back. Most of the treatments require, they work as long as you use them and then the fire tend to come back if you stop therapy.
Now there’s one new drug that treat both diseases?
Dr. Sandborn: We have an interesting new drug called vedolizumab that has just finished Phase III testing. It’s currently being reviewed by the Food and Drug Administration in the United States and by the equivalent to regulatory authorities in Europe. It’s anticipated that this could come into clinical practice in early 2014 and it’s an interesting drug because a lot of times a medication will be tested first for ulcerative colitis or first for Crohn’s disease and then eventually patients with the other disease will be tested with the drug. With this particular drug both diseases were tested in parallel so the stage Phase III programs were run kind of at the same sites at the same time. The regulatory authorities are considering both treatment indications at the same time. Which I don’t think has happened before in these diseases.
What does this drug do?
Dr. Sandborn: This drug has an interesting way that it works with the same mechanism of action. Most of the drugs that we have are really focused on, and to go back to this fire analogy, they are focused on putting the fire out. We talked earlier about autoimmune disease, what that really means is your immune cells, white blood cells, are made in your bone marrow, they go from the bone marrow to the bloodstream. Then in an autoimmune disease they’ll move from the bloodstream out into body tissues. So if you have multiple sclerosis they move into the brain, if you have rheumatoid arthritis they moved into the joints, if you have psoriasis they move into the skin. If you’ve got Crohn’s or ulcerative colitis they move into the small intestine or the colon and once those immune cells are present in the tissue of the autoimmune disease in high numbers or high concentration they start to make all kinds of chemicals and proteins that cause damage and inflammation. Many of the drugs that we have, for instance these tumor necrosis factor antibodies like Remicade or Humira are aimed at those chemicals or proteins that the immune cells make after they are already in the intestine-it’s kind of putting out the fire. The way the vedolizumab works is it keeps the blood cells from moving from the blood vessels out into the target tissue. Within the case of vedolizumab it’s very specific so the white blood cells for Crohn’s disease or ulcerative colitis to occur you need an excess of these immune cells or white blood cells in the small intestine or the colon and if you could block that selectively then you could treat the disease. Now, if you don’t block it selectively, white cells moving into tissues all over the body like the lungs or the brain or other places you might set the patient up for infection. Immune suppressing a specific organ without immune suppressing the rest of the body, we think that will be safer ultimately for patients in terms of infection and cancer risk and things like that. That’s really how vedolizumab works, it selectively or very narrowly blocks the white blood cells that go out into the gut tissue and cause Crohn’s and colitis from getting there. It prevents the fire.
Does it stop it before it can even get started?
Dr. Sandborn: It really acts to stop the diseases before they even start.
Are there any downsides that you’ve seen with the patient’s you have treated?
Dr. Sandborn: You know in the clinical trials with vedolizumab so far what we’ve studied are really with patients with what we say have moderate to severe ulcerative colitis and moderate to severe Crohn’s disease. These patients had also failed other therapies like steroids and immune suppressives such as azathioprine and these antitumor necrosis factor drugs like you know Remicade and Humira. These were really sick and refractory patients. They’re taking lots of other medicines that have many side effects. If you look at the clinical trials, you see some infections and some cancers that occur, but what you’re really interested in is whether these are occurring at a higher rate in the patients who get vedolizumab than in the patients who are sick and are getting all of these other medications as kind of background treatment. What we saw is you definitely can see some infections and side effects in the overall study but we didn’t see big differences between the patients who are getting vedolizumab and the patients who are getting all the other treatments.
Are IBD patients more susceptible to cancer and what type?
Dr. Sandborn: IBD patients overall have an increased risk or susceptibility to colon cancer if they have ulcerative colitis or Crohn’s disease of the colon. That’s the main thing that we see. and then some of the medications like azathioprine or the anti-tumor necrosis factor drugs like Remicade or Humana have been associated with skin cancers and sometime cancers of the lymph nodes or lymphoma. So far we’re not really seeing a signal for those types of cancer with vedolizumab. Inflammatory bowel disease patients have the disease related risk of colon cancer and then they had treatment related risk of skin cancer and lymphoma.
What does Megan have?
Dr. Sandborn: I first met Megan Johnson a couple of years ago, and she has ulcerative colitis that when I first met her was very, very severe. She was severely malnourished; in fact if I remember correctly, the day that I met her in the clinic she was in a wheelchair.
Is that what she said?
Dr. Sandborn: Yes, she was so malnourished and kind of run down and from severe colitis. We ended up making a variety of adjustments in her treatment and we tried a combination and she was receiving very high doses of steroids, prednisone, having a lot of side effects from that and it really wasn’t working. We ended up treating her with biologic therapy and an immune suppressive therapy and then she didn’t tolerate one of the immune suppressive therapies azathioprine and then we ended up switching over to methotrexate and that she ultimately didn’t tolerate as well. With the combination of all those medicines, she eventually went into remission and we’ve adjusted her biologic therapy and she eventually went into remission and has completely recovered and living and active life. She’s a vibrant you know active person.
Is she young?
Dr. Sandborn:Yes, she’s in her 20s I believe.
Is that strange to have such a young person have this?
Dr. Sandborn: With inflammatory bowel disease, the average age of onset is about 30. That means that half of people would get it in their teens and 20s. The first decade of life ten and below you can definitely see an onset even during those years but it’s not so frequent. The two most frequent decades where you might get it during your life are the teens and the 20s. Then about half the patients get it at age 30 and beyond, and I think the oldest patient that I’ve diagnosed was in their 90s. You could get it at any point in life but the highest hit rate if you will is the teens and the 20s. Megan’s onset was very typical.
I can’t even imagine being in the prime of your life and just being knocked down to where you don’t even feel like you can walk. Does it happen often?
Dr. Sandborn: You know a lot of times I meet patients for the first time when they’re in crisis and you know it’s a very common story to see someone who’s you know 18, 19, 20, early 20s in high school or college and is actually dropping out of classes. Then I’m seeing them because they’ve just dropped out of school because they can’t function and we need to get them healed up and back to school and back to life. Unfortunately it’s a pretty common story.
Is it pretty amazing to see someone like Megan?
Dr. Sandborn: It’s really exciting to see a patient that is headed down the path of missing their life just completely recover and come back with a vengeance if you will with a zest for living. She’s early in her life I expect in due course she may choose to have children and a family, career- all the things that sometimes get derailed if you’re ill and have you know devastating surgeries and things. If you can find a medicine that works for patients, all of their hopes and dreams and their potential to reach their own potential and to contribute to the world gets restored. For me it’s always very exciting to see a young person get their life back on track after they’ve been successfully treated.
How much should you take of his drug? Is it usually the same for everyone? Or is a twice a day?
Dr. Sandborn: Different drugs work differently. For orally administered drugs often they’re given once or twice a day. For the biologic medications, whether its anti-TNF drugs like Remicade, or Humira or Cimzia or Simponi or this new biologic drug vedolizumab that as we’ve discussed works differently they’re usually given either as an injection or an intravenous infusion. The injection drugs might be given every 2 to 4 weeks. The infusion drugs where you have to go in to an outpatient infusion center those are often given about every eight weeks. Vedolizumab for instance, in the clinical trials we’ve looked during the long term phase at every four-week and every eight week dosing. Both of those strategies work so I expect that the treatment strategy that will be used at least as the starting place in patients will be every eight weeks dosing.
Was that with an infusion?
Dr. Sandborn: Yes, and every eight week dosing with an infusion.
Now the clinical trial is over. Does that mean, Megan can’t get this drug, or can she continue on this drug?
Dr. Sandborn: Both, Megan’s actually currently taking a medicine that she has access to. The clinical trials are finished. The patients that participated in the clinical trials did well on vedolizumab are continuing it. There are not any current new clinical trials until the FDA and the regulatory authorities you know make decision.
Is Megan part of the clinical trials?
Dr. Sandborn: Megan, wasn’t part of this particular clinical trial, but she’s just a great kind of example of how sick someone can get from ulcerative colitis or Crohn’s disease and how an effective therapy can make them better. There are many patients like Megan who don’t respond to any of the medicines that we have currently and we think the vedolizumab will be a great option for some of those patients.
FOR MORE INFORMATION, PLEASE CONTACT:
William J. Sandborn, MD
Professor of Medicine and Chief, Division of Gastroenterology
Director, UCSD IBD Center
University of California San Diego and UC San Diego Health System
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