Dr. Kane: The 5-ASA agents are the first-line therapies for inflammatory bowel disease, whether it’s Crohn’s or colitis. And how do I describe 5-ASAs? They are like the Swiffers of IBD management. They work at the lining of the intestine. So they come along and they Swiffer up all those bad proteins that cause inflammation. If you take those away, then the colon or the intestine can heal itself. So these are medicines that are not very well-absorbed into the bloodstream. They are not steroids. They only work at the layer of the lining, the inside lining of your intestines.

5-ASA is the active ingredient. Asacol [mesalamine] is 5-ASA for the colon. It got its name because that’s the predominant part of the GI tract that ASA works on. Well, azathioprine [Imuran] doesn’t follow the same pattern, but azathioprine is 5-ASA along with sulpha. So patients who are sulpha-intolerant can’t be on azathioprine. But it’s the oldest drug that we have, and it works great if you particularly have problems with your joints because the azathioprine is used to treat rheumatoid arthritis. Colazal [balsalazide], so that’s Asacol for the colon. It’s just switched around, and that’s what Salix makes. Dipentum [olsalazine] is two molecules - ‘Di’, of 5-ASA ‘pent’, put together so Dipentum. Pentasa [mesalamine] and Rowasa [mesalamine], are enemas of 5-ASA. And Canasa [mesalamine] suppositories are Canada’s version of ASA.

The enemas come in 4 grams. Well, 4 grams of 5-ASA is like taking somewhere between eight and 12 pills. So nobody wants to do an enema. But really enemas are a very efficient way of delivering 4 grams of medicine to the directly inflamed lower part of the intestine.

So when do we use the 5-ASAs? They are first-line. They are used when patients have mild to moderate ulcerative colitis or Crohn’s disease to put people into remission. And once you’re there, you continue taking that medicine to maintain your remission. And it can be used in Crohn’s disease after you’ve had an operation to keep you in remission. And it can be used even if you haven’t had an operation for medical treatment.

What are some of the benefits of 5-ASAs? Well, they’re extremely well-tolerated because they’re not absorbed as much as some of the other drugs. So they have very few side effects. They’re relatively inexpensive. And that’s because you’re taking into account also you don’t have to go in to have blood tests to make sure that the levels are okay or because of side effects. The 5-ASAs can be the pill form, or they can be rectal, and they are safe for all ages and for pregnant patients.

There’s always a risk when you put something in your mouth. These are all, fortunately, very rare allergies and side effects. If you have severe disease, these drugs will not work. So it may be that you’re wasting your time taking a handful of pills if your disease is particularly active. And they are not helpful after steroids. So if you needed large doses of steroids to get your disease under control, the 5-ASAs are not necessarily to keep you well, following that steroid taper.

Pentasa releases pretty much starting in the duodenum and delivers medicine throughout the small intestine and throughout the colon. So it’s a very good drug for if you have Crohn’s disease or ulcerative colitis because it delivers medicine to the entire GI tract. Asacol opens in the terminal ileum and delivers medicine to the terminal ileum and throughout the colon. So it’s a drug that’s very good for Crohn’s disease and ulcerative colitis. Azathioprine, Dipentum and Colazal are drugs that are colon-specific. They require the bacteria that live in your colon in order to release the drug.

So if you don’t have colon these drugs are not going to be very helpful. They don’t release until they get into the colon, and they work throughout the entire colon. And then you have the Canasa suppositories, which work just in the rectum.

So why would your doctor give you enemas or suppositories? [They would] not [give them] because they’re mean but because you're having a lot of symptoms that suggest that your rectum is very sick. And the best way to treat that is to deliver medicine directly to that inflamed area. You’d have taken a whole bunch of pills in order for them to release the medicine way down low. So they really do make a very good choice for initial disease management when you have proctitis.

It turns out that pharmaceutical companies do hear you. “I have to take so many pills during my day. Can’t you make pills that have more medicine in them?” And low and behold, we do. Pentasa, which used to be just 250 milligrams, so you had to take upwards of 16 capsules a day, now comes in a 500-milligram capsule. So you’ve reduced the pill count by 50 percent. You’re going to deliver those 4 grams in eight capsules day. And the size of the capsule is not appreciably bigger, and it is not appreciably more expensive. So I think we’ve got a win-win situation there. And the Canadians have instead of just a 500-miligram suppository a 1-gram [suppository]. So, again, you’ve doubled the dose that you can deliver to your rectum and actually, has been available since February 28, 2005. But they seem to be very convenient because you can deliver twice as much in one suppository, so people don’t have to do twice a day. They just have to do it once a day.

Dr. Kane: Steroids are the atom bomb of anti-inflammatories. They just shut down your entire immune system. So, of course, your IBD is going to get better. These are not Swiffers. These are cannons that are just attacking your entire immune system and shut it down. So we have ACTH, which is a very old, old-fashioned formulation of steroids not used very much anymore. Medrol [methylprednisolone] is an oral form and comes in very convenient packs. So you see asthmatics taking Medrol dose packs, or your physician may have prescribed a Medrol dose pack for you because you have a mini-flare, and you just need six days of steroids, and then you're off. Prednisone is what we usually use. Cort enemas, so that’s cortisone in an enema form. So that’s an enema that’s hydrocortisone, and then there’s Cortifoam, which is a foam preparation. It’s like shaving cream. It’s a foam that’s got hydrocortisone in it. [It] can be better tolerated when you insert it into the rectum. But another steroid is Entocort [budesonide], which is cortisone for the enteric system. The enteric system is the small bowel, so Entocort is a steroid that does have more topical therapy than systemic, meaning that it’s safer to use than Prednisone, but it’s not as strong. So if you have very severe Crohn’s disease, Entocort may not work. But if you have mild, milder to more moderate symptoms, then Entocort may be better than prednisone.

We don’t like patients to have to take the atom bomb of anti-inflammatory [steroids]. We want to try to sort of target different parts of the immune system so that the whole thing isn’t shut down. Azathioprine comes in generic, and it comes in two brand names: Imuran and Azasan. The cousin to azathioprine is 6-MP. It comes in generic form, but it also comes in a brand name: Purinethol. And why should you be on a brand name rather than the generic? Sometimes, your body can tell the difference. So if you use the brand name, you are getting a consistent drug every time. The generics work, but there are differences between the different generics. So you have to be mindful that your doctor is prescribing either the same brand name for you all the time or the same generic for you all the time. Cyclosporine is a drug we borrowed from the transplant surgeons because it is a drug to help prevent [transplant] rejection. So it does suppress the immune system. And some patients need that. And methotrexate [is] another drug we stole from the rheumatologists because it’s very good for the joints. So patients who have a lot of joint symptoms have Crohn’s disease. Methotrexate can be a very good choice for them. And then we have Remicade [infliximab], which is FDA-approved for Crohn’s disease. And the big buzz at our international meeting two weeks from now is that Remicade seems to work for ulcerative colitis also, and by the fall we’ll have FDA approval for ulcerative colitis also. [Medical editor's note: At the moment, however, it is only approved for Crohn’s disease.]

So what are the names of the steroids you might hear? Prednisone, hydrocortisone, budesonide [Entocort], Medrol, Decadron [dexamethasone] [are some of them]. The list goes on. You can get steroids in pill form, in IV form if you’re in the hospital or in enema form. And they are used to induce remission in patients who have moderate to severe disease.

But somebody who is well on steroids is not in remission. That person is well on steroids. Remission is somebody who was on a therapy that is not a steroid. There is no maintenance benefit to steroids.

What are some of the benefits? Well, it induces remission, it works really fast, and it’s really cheap, so it’s the quick fix. So it’s very tempting for gastroenterologists when they have an unhappy sick patient in the office or on the phone. And you can deliver it by pill or by the cort enema or the Cortifoam [hydrocortisone].

But the risks far outweigh the benefits. There is no long-term benefit, and there are numerous side effects. As you all are very aware of, you get puffy and fat in your face, hypertensive, your blood sugars go up, you get osteoporosis, acne, cataracts, mood swings and, in kids, growth retardation.

Cyclosporine: This is a drug that should not be used without a net. It’s a great drug if it’s used in the right hands. It’s very effective in severe ulcerative colitis. It may be effective in Crohn’s disease and works very rapidly. So within a few days of IV cyclosporine, we can put people into remission. The problem with cyclosporine is that it can cause kidney damage. It can increase risk for infections. It can cause seizures. It can cause high blood pressure, and there is a thought that it can actually cause cancer. Now, all of those things are very scary. If cyclosporine is used in the right hands, it’s a very good drug.

Methotrexate [is], again, a very good drug, used in the right hands. Many decades worth of data for rheumatoid arthritis [is available]. It’s very useful in Crohn’s to help people get off of steroids. And it’s given once a week as an injection. So for people who don’t like to take pills every day or can’t remember to take pills, you just take a shot once a week. You do have problems with flulike symptoms the day of the injection, so usually we have our patients do it on Sundays when they can just sit around and watch either baseball or football. Rare side effects are liver disease and pneumonia, which your doctor will monitor for, and this where people who don’t know what they are doing will run into trouble. This is a drug that is used the obstetricians to cause abortions. It cannot be used if you are attempting pregnancy, let alone being pregnant. [It also] damages sperm. So this is not a drug that I recommend to my 22-year-olds or my 30-year-olds who have just entered a marriage or who are thinking about having kids.

Dr. Kane: Antibiotics: The two that we use most often [are] Flagyl [metronidazole] and Cipro [ciprofloxacin]. We use antibiotics for mild to moderate Crohn’s disease for patients who have fistulas and abscesses. And there’s actually data to suggest that if you go on antibiotics after you’ve had an operation for Crohn’s disease, that it may actually deter the recurrence of Crohn’s disease. Antibiotics do not work in ulcerative colitis. So we’ve sort of given up that. Flagyl, unfortunately, can cause a coated tongue, yeast infections, and numbness and tingling or inflammation or damage to the nerves if taken long term. So if you start to feel some tingling and numbness in your fingers or toes and you’re on Flagyl, you should tell your doctor. It’s not that your hand has fallen asleep. It may be a complication of this drug. Cipro the same thing - you can get yeast infections and particularly in woman, and, interestingly, it can cause tendon injuries. If you’re apt to be a runner or jogger and you take long-term Cipro, you may end up with injury from that.

Dr. Kane: The immune modulators are drugs that we use not to wipe out the immune system like steroids, but to try to tamper its effect. They are very good for long-term maintenance of both ulcerative colitis and Crohn’s disease. And they can also help to dry out fistulas. They are meant for patients who are on steroids, who may be stuck on steroids or who want to try to avoid steroids.

One of the complications is that patients need to be monitored by blood tests when they are on these drugs - and why is that? Well, because they can work too well - and not just decrease the activity of your white blood cells - but actually kill of your white blood cells. And you’re not going to know that. It’ll happen that you’ll stub your toe, or you’ll get some kind of paper cut, and it gets infected, and it’s not healing. And it’s because you have no white blood cell count to mount a response. And people can get into a lot of trouble if they have no white blood cells. So we use them quite a lot for patients who need to be spared of steroids.

They are very good for long term. They are the marathon drugs, not the sprinters, but the marathon drugs. And they are relatively inexpensive when you think about some of the other things that we may use. We do have to monitor blood counts, and that requires long-term monitoring. This is a reaction that can happen years after you’ve been on this medicine. So every three months, you have to have blood count, regardless of how long you’ve been on this medicine. And there are patients who occasionally get allergies to this medicine. They can develop fevers, rashes or inflammation of their pancreas, which is called pancreatitis.

[There is a myth that] immune modulators are dangerous drugs used to treat cancer. The fact is that they have been used in the past, and are still used, to treat cancer. They treat leukemia. These drugs are used in 15 to 20 times the dose of what is given to inflammatory bowel disease. We are not trying to kill off your white blood cells. We are trying to just get them to calm down. So these are not dangerous drugs used to treat cancer in the doses that we give to inflammatory bowel disease patients. No, they do not cause cancer. They are used to treat cancer in the very high doses, and we’ve used these drugs for a lot longer than three years, and we have not had problems with patients staying in remission. These are the marathon drugs. These are drugs that take months to kick in. At first, they don’t seem to work, but it’s the dose and time that you’ve been on them that makes a difference.

The other myth is that they must be stopped before or during pregnancy. And we are fortunate enough to have enough data now, most of it coming out of Mt. Sinai from Dr. Present, that says that they can be used during pregnancy to keep the mothers well. Those moms just have to be monitored a little bit more carefully.

[Remicade] does induce and maintain remission. It rapidly relieves symptoms because it is an antibody that attacks and neutralizes this protein, and you can allow patients to get off of their steroids, and it can be effective while other therapies have failed. This is an intravenous therapy. So patients can have reactions to the infusion. They can develop antibodies to the antibody. And how does that happen? Your body says, “Okay, you’re giving me this foreign antibody, and I don’t know what this is, and I don’t like it, so I’m going to form an antibody to counteract the antibody that you’re being given.” So you can become immune or allergic to Remicade. Because of the protein that Remicade specifically targets and does away with, it can allow tuberculosis (TB) to reactivate, if you have been exposed to TB and maybe never even knew it. And, again, this is very expensive therapy. Anywhere from $4,000 to $10,000 per infusion is how much it costs.

How do we administer Remicade? It’s intravenous, so we have nice happy nurses that put it together for us. But you have to be monitored when you get this medication or this therapy by nurses. Physicians are usually hovering somewhere, but it’s given over two to three hours in, either an infusion center or an office.

Dr. Kane: You have to weigh the benefits with the risks. All of the medicines and all the therapies, they all have a lot of benefits. They all carry their own risks. So it’s a question of what’s right for you, and what does your physician feel comfortable giving you based on that physician’s experience with the therapies?

Dr. Kane: What can you take when you’re in the pregnant? The 5-ASAs, steroids, most antibiotics are going to be okay. Imuran [azathioprine] and 6-MP are going to be okay if monitored during pregnancy. Methotrexate must be avoided, both in men and women. Fertility is normal if your disease is controlled. So nature has a way of taking care of you. If your disease is really active, you’re not going to have a great chance of getting pregnant, and there are many reasons for that. Pregnancy outcomes are normal if you have a healthy mom going into the pregnancy. And if you have active disease during that pregnancy, then your baby is at-risk for low birth weight or prematurity, but there’s no increased risk for birth defects. Let me say that again, no increased risk for birth defects if you have Crohn’s or colitis. All the medicines that I showed you that were safe for being pregnant and during pregnancy, you can also take when you want to breast-feed.

Dr. Kane: Nutrition: Malnutrition can occur for several different reasons. One is because you feel terrible and don’t want to eat. Nothing looks good, and it’s going to cause pain. But there are other people who are very overzealous about what they should and shouldn’t eat. And then they are left eating just dry rice cakes all the time and Gatorade. That’s not much of life, and then, of course, you’re going to lose weight if you’re eating dry rice cakes all the time. But you will decrease your absorption of nutrients if your smaller bowel is inflamed. The job of the colon is to absorb water. If your colon is inflamed, then you’re going to have diarrhea. But you’re not going have malnutrition. So you’re going to have loss of weight with Crohn’s disease more than ulcerative colitis. And it’s very interesting that patients who get Remicade [infliximab] for the first time they finally have their small intestine under control, and they start to gain weight. And they hate it because they didn’t realize that for years they could eat whatever they wanted, and they weren’t going to gain weight because it just went right through them. They weren’t absorbing [the food they ate]. And now, suddenly, they’ve joined the rest of the world and are absorbing every calorie that they are putting in their mouths, and they hate it. I would much rather deal with the battle of the bulge than battle of the Crohn’s.

Every patient deserves a professional nutritional assessment. Professional nutritionists do not work at the GNC. Your physician should know professional nutritionists. Again, not every woman smells the same in the same perfume so that the diet has to be tailored to individual needs but also preferences and tolerances. And dietary supplements are great, but show them to your doctor because lots of supplements are out there, and they contain all sorts of very scary and unnecessary things. And you spend a lot of money for stuff that you don’t need, and you will literally [urinate] away. How much vitamin C do you need in a day? [You need] 100 percent of the RDA. You do not need 4,000 percent of the RDA. So what’s going to happen? You’ll put it in your mouth, it gets filtered through your kidneys, and you will [urinate] it out. So don’t take 4,000 percent of the RDA.

Dr. Kane: A lot of gastroenterologists feel like they have failed their patients if they send them to the surgeon. My job as a physician is to help my patient the best way I know how and if I can’t do it with medicine, I’m going to do it with the knife. In Crohn’s disease, [some] gastroenterologists are very afraid of sending their patients to the surgeon because it’s going to come back. Well, it could come back, but now we understand how to decrease that risk of it coming back.

We have patients who have such bad strictures and narrowing in their small intestines that nothing other than pure liquid goes through that stricture, and patients are basically on a puréed diet and are miserable, and no amount of Remicade [infliximab] or 6-MP or steroids is going to undo that stricture. That’s what the surgeon does, is [he/she] takes out that piece of very bad strictured inflamed intestine. If you had three abscesses and you come to my office with a drain in place, and the patient says, “I’m on steroids and Remicade, and my abscesses aren’t getting better, and this drain has been in place for six months,” the first thing I do is call my surgeons. It’s like the leaky pipe in your basement, how many times can you put duct tape around that pipe before it just leaks out around that duct tape? You take out a piece, and that just continues to blow open. Surgeons have a very important role.

Why do we send somebody to surgery for ulcerative colitis? [We send them] when they develop a severe attack that we can’t control, when they are hemorrhaging, when they develop cancer, or they’ve been on every medicine, and they're still not well, and we’ve got to make them well. To say, “Well, I can’t have surgery because I only have the left side of my colon inflamed or abnormal.” [That's] wrong. It’s for the patients who have one of these scenarios that we take the colon out. In Crohn’s disease, the stricture - a fistula that keeps opening up, drains and is so large that sometimes we can’t tell the difference between a fistula opening and a normal natural opening, abscesses and unresponsive disease.

Dr. Kane: Cancer: Nobody wants to talk about the big C. Well, when you have chronic inflammation that’s uncontrolled, the cells are trying to replicate and turn over. And every time that you create a new cell, there’s a chance that the DNA in that cell is abnormal and pre-cancerous. So the key is for us to try to keep your disease under control so that you’re not turning over cells all the time. Compared to the general population, you have a 20 times higher risk of cancer. If you put it into perspective, colon cancer is the second most likely cancer in America. So 20 times higher common is very common, but it’s something that we monitor for and we survey for.

How do we prevent it? Well, we know that if you stay on your medicines, you decrease the inflammation. Independently of that, we believe that 5-ASA medicines in particular can actually decrease your risk for cancer. So if you’re not on a 5-ASA yet, maybe you should talk to your doctor about being on one. We remove the colon if we find pre-cancerous changes, so we can prevent cancer if we find pre-cancer.

Dr. Kane: Where are we heading with research? Well, again, another company is coming up with an 800-milligram mesalamine tablet. So, again, 50 percent of the dose you will need. Targeted antibiotics: Salix has Xifaxan [rifaximin], which is an antibiotic that only works in the GI tract. It doesn’t work for the bladder. It doesn’t work for pneumonia, and it doesn’t work for the sinuses. It only works in the GI tract. That sounds pretty inviting. Biologics, other antibodies other than Remicade, [such as] Humira [adalimumab], which you may or may not have heard of yet. But, it has been used in controlled trials for Crohn’s [not FDA approved yet], as has Tysabri [natalizumab] [in clinical trials and not yet on the market]. And Leukine, which is sargramostim, which is an injectable therapy that actually stimulates your bone marrow to produce new white blood cells [is also not FDA-approved for Crohn’s yet].

In genetic research, we’ve identified certain genes that correlate with families and with certain clinical patterns, but we still have to identify more of them, and we have to try to decide if we can find ones that are protective against some of these bad things that I’ve already talked about. And we’d love to learn how to manipulate them so that we can prevent this or treat it. We want to understand some of the bacteria in the environment that are capable of causing this, how we can use bacteria to our advantage to maybe treat ulcerative colitis and Crohn’s disease, and try to better understand how bugs work with our immune system and our genetics to try to understand how this all happens in the first place.

The surgeons are busy. They want to try to make your outcome better. Twenty years ago, everybody had to have a permanent ostomy, and that wasn’t very acceptable. Now you have internal pouches, and the surgeons are working on perfecting this internal pouch and to try to prevent inflammation of that pouch, which we call pouchitis. Minimally invasive surgery [is being developed]. You can have your colon taken out, your entire colon taken out with a laparoscopic technique. So I have cat scratches that are bigger than some of my patients’ surgical wounds because of the way that the surgeons have been able to remove their intestines. And we’re trying to figure out what to do for those Crohn’s patients who have to have the surgery, how do we keep them well in the long term?

Clinical trials: There are patients who just have been everything, are intolerant to some things. And if you are asked to participate in a clinical trial, you are not a guinea pig. You are a patient who may be advancing science. Twenty years ago, Asacol [mesalamine] and Pentasa [mesalamine] were being studied for these diseases, and now they are first-line therapy. So these are trials where we’re trying to find a better, safer [treatment]. You are contributing to the advancement of management of these diseases.

Dr. Kane: For all of us, ulcerative colitis and Crohn’s are chronic diseases that require long-term medical therapy. Quality of life definitely is impaired but should be normal during remission. Life expectancy is the same. You are not going to die of this disease. Adherence to therapy decreases the risk of relapse and potentially for cancer.

Stay on your medicine. If you don’t like your medicine, are afraid of your medicine, it’s too expensive, it’s too cumbersome, tell your doctor because they’re not going to know. They’re not necessarily going to ask. They assume that you are doing what they’re telling you to do. And they’re not going to necessarily know that you’re not taking it or that you’re not taking it as regularly as you say. Don’t be embarrassed to say that it costs too much, and you can’t afford it. There are ways of managing those sorts of is sues, and only if you bring it up will it get addressed.

Surgery cures ulcerative colitis. I just said that we can’t cure this disease. Well, surgery cures ulcerative colitis, but most of the time we don’t need to send people to surgery. Surgery certainly treats complications and acute flares of Crohn’s disease.