Dr. Korzenik: Osteoporosis is an important thing, as mentioned. And what this means is some thinning of the bones. The bones can be more fragile, and the thing we worry about then certainly is [that] maybe that someone’s bones will be more susceptible to fractures, particularly in the spine. If you get a compression fracture in the spine, that can cause a lot of chronic pain, and so we want to try to prevent that as much as possible. We want to think ahead because you may be young now and your bones might be pretty good, but we want to do something now to prevent you from having a fracture 20, 30 or 40 years from now.

So what are the risk factors? Steroid therapy is an important risk factor, so it’s just one among many reasons why we want to limit your exposure to steroids. Smoking is a risk factor for osteoporosis. Active disease, particularly in Crohn’s disease, is an important risk factor, so getting the disease under good control will decrease the risk. And particularly in women, smaller stature, smaller bones to begin with, a family history, and also postmenopausal women are at increased risk as well. So all of these things have to be factored in.

There are now good ways of screening to be able to deal with osteoporosis. There are bone density scans. One’s called the DEXA, or also there’s the heel scan that you can have as an initial screening. It’s important to control the disease, as mentioned. Weight-bearing exercises give important information to our bones to grow and remodel themselves, so that’s very important in itself. And it’s also important that if you’re on steroids and other things, there’s some evidence that calcium and vitamin D can decrease the bone loss. And there’s a variety of medications that have been developed called bisphosphonates. Actonel [risedronate] and Fosamax [alendronate] are two of them that can be very effective at minimizing bone loss. There are now other medications that can actually even increase bone density. So it’s important to be screened, not just to know about it, but because there’s something to do about it to try to prevent any further bone loss.

So, how do we treat it? This is really in part what we think of as the heart of things. We, as physicians, tend to focus a little too much perhaps on medications, but there are lots of other things here. Certainly, emotional support is critical in getting someone through and dealing with this and coping with these diseases. The medication part is just one aspect. Surgery is critical. We’ll talk about that. And nutrition is vital. It is again an area where much more research is needed, but we do have some guidelines that can be helpful.

Dr. Korzenik: When we think about inflammatory bowel disease, what are we trying to do? Well, a lot of what we’ll talk about today are the medications, but there are a variety of things we want to do. We obviously want to get the acute flare under control so that the person can get on with their [life]. We want to relieve the symptoms. But in addition to relieving the symptoms, we want to get that inflammation under control. We want to treat any complications we might have from the disease itself, and we want to have a treatment that’s pretty nontoxic. We don’t want to create more troubles by the treatment than we have with the disease to begin with. And once we’ve gotten someone out of that acute inflammation, we want, above all, to be able to maintain them in health. It’s not enough to just treat it as an episodic disease, “Oh, you’re having another flare, let’s treat this. We’ll put out that fire, and we’ll see you at your next flare.” We want to keep someone doing well over the longer haul.

There are a variety of other things that we really need to do that is part of medical management. Part of it is addressing [these] whole psychosocial is sues. How do you deal with friends and family and colleagues? How does it interfere with your work? How does it interfere with your own sense of yourself? [There are] a whole host of things that are very important to take into account, and in a perhaps more positive way, to think about what are the good things about having inflammatory bowel disease? And it may seem like “I can’t imagine anything that’s good about it,” but in a lot of ways you wouldn’t be the person you are today if you hadn’t had this. And, it’s been said that which doesn’t kill us, makes us stronger. And it’s lent important things to your character. [It contributes to] your ability to recognize and value the important things in life.

In addition, it’s important to keep in mind this cancer is sue. Nutritional defects are important. And part of this also, in terms of management, is education and learning as much as you can about these diseases.

So what should you expect as somebody who is dealing with these diseases? I think many of our medical centers may fall down a little bit in terms of getting quick access or referral to primary care, from primary care to a specialist. Often, the primary care doctor says, ”Well, you’re not dealing with anything too much. We can deal with this here quite well,” but at a certain threshold he has to be ready to say, “All right, maybe we should send you to a specialist.” And hopefully that will happen quickly when the time is necessary. Once you have a diagnosis, it’s important for you to work with your physician to learn as much as you can about it. In busy practices, often it’s unfortunate that the line is, “Well, you have inflammatory bowel disease. That means you have inflammation in your bowel, and it’s a disease, and these are the medications you take, and we’ll talk about it more next time.”

Really what’s important is learning as much as you can about it, preparing yourself when you go to a visit with your physician to have a list of questions, things that you want to make sure because there’s certainly a phenomenon that we all go through. We go to visit the doctor, and you have a whole lot of things you want to take care of and think about. And when you leave, you suddenly realize your 10 questions that you had in mind, you forgot eight of them. So it’s important to keep something with you when you go to see the doctor.

In terms of long-term follow-up, continuity of care is really important as many of you, I’m sure, recognize in terms of developing a good relationship with your physicians, so that they know you, you know them, they know when you’re complaining or having some problem, and you don’t do that lightly. Or they know how to handle it if you’re having a particular crisis, and they know your family, and they know what you’re going through. They know and you know what things are important to you, what things you’re trying to accomplish in your life, and how you want to get on with your life with things that are of value to you. So all these things are important and important to keep in mind. You don’t have to sacrifice them in your medical care.

When you go into a hospital, it’s a different set of factors altogether because part of the problem that happens increasingly with the way that most practices are structured is you have a close relationship with your gastroenterologist and your primary care doc. A crisis happens, you get hospitalized, and then you don’t see your gastroenterologist. Somebody else has taken over. And it’s an unfortunate way that many of our practices are structured because of the realities of trying to do too much. But you should see your gastroenterologist, hopefully. But you should expect in your hospitalization to have a staff that understands what you’re going through; understands what your disease is, and if things are not going well at that particular place, are ready and willing and able to transfer you where you need to [be]. There should be good communication. You should have a good understanding of what’s going on. Your family should understand that, as well as availability of what your various choices are and to the full set of care. So it’s not just a gastroenterologist that takes care of you, but it’s involvement of dietitians, social workers, psychiatrists and surgeons.

Dr. Korzenik: So what are we going to do with therapies? The most benign of the various therapies we use and could be quite effective, particularly in ulcerative colitis, are called the 5-ASA - aminosalicylate acid agents. These go by a variety of names: Asacol [mesalamine], Azulfidine [sulfasalazine], Colazal [balsalazide], Dipentum [olsalazine], Pentasa [mesalamine], Rowasa [mesalamine] and Canasa [mesalamine]. The important thing about these is they’re all the same active ingredient. They’re just different delivery systems. They [use] different ways of getting the active ingredient to where you want it in your intestine so that you can get the disease under control.

Other [medications] we use [are] antibiotics, Cipro [ciprofloxacin] and Flagyl [metronidazole] in particular for Crohn’s. Not so much for ulcerative colitis. Steroids [are used as well]. ACTH we don’t use so much anymore, but it used to be used. That’s the hormone that stimulates your own body’s production of steroids. Other ones go by the name of Medrol [methylprednisolone], prednisone, Cort enemas, and Cortifoam are other forms of steroids. Different immunologic agents, including Imuran or azathioprine, Azasan also, another trade name for azathioprine. Purinethol [mercaptopurine], Neoral or cyclosporin, methotrexate or other drugs, and we’ll go through some of these, and then, more recently, Remicade [infliximab].

Dr. Korzenik: The 5-ASA agents, or the aminosalicylates, are used to induce remission in both mild and moderate ulcerative colitis. Once you’re in remission, these can be quite effective in maintaining remission in ulcerative colitis, and we do use them to some degree in Crohn’s disease. But they’re a little bit more controversial, both for medical treatment to maintain remission, as well as after surgery we sometimes use them to keep someone in remission and prevent them from flaring up after that.

Now what are the benefits? Generally, they’re very well-tolerated, about 95, 96 percent of people tolerate them without any troubles. The side effects are relatively few. We say relatively inexpensive, but that’s really a relative term. I’m not sure everyone would agree with that. And there are a variety of ways of delivering them. It’s also safe at all ages, and so we rely on them a good deal. There are rare allergies and side effects. In severe disease, it’s not clear that they have much of a role. And after steroids, they probably don’t have that much of a role, particularly at least in Crohn's disease.

So what are the differences between them? Pentasa [mesalamine] is something that’s delivered throughout the small bowel, so it’s especially formulated to release itself throughout the small bowel and throughout the colon. So it can be used for Crohn’s and ulcerative colitis. Asacol [mesalamine] is just in the last part of the small bowel, as well as throughout the colon. Azulfidine [sulfasalazine], Dipentum [olsalazine], Colazal [balsalazide] are specifically just to the colon. Rowasa [mesalamine] is an enema, which can go up sort of the left side of the colon, and Canasa [mesalamine] is a suppository, which just treats the rectum.

In addition to taking them as oral forms, we have them as topical forms, meaning taking them as an enema. And the attractive idea behind that, even if you don’t think the idea of an enema is all that attractive, is that you’re treating the inflammation directly. You’re putting the drug exactly where you want it to be. You’re not relying on the GI tract to bring it down there. It may be a little variable. You know where the inflammation is. The likelihood of any general side effects is even lower, and it’s right there. And if someone has just disease right there in the rectum or a little bit on the left side, it’s a really good choice. It’s not necessarily condemning you to a lifetime of enemas, but it’s a way of delivering it directly there and hopefully seeing if it’s going to work.

A lot of these pills are things that certainly if you were taking the older pill of Pentasa, you were taking a full dose of 4 grams a day, which is the appropriate dose, and your doctor prescribes 16 pills. You say, “Oh my god, I can’t take 16 pills.” Well, we say, “You know, it’s all one medication. It’s just that we can’t deliver it in a tiny, little package. We have to give you a lot of these little ones.” Well, the good news is there’s now a 500-milligram pill. So instead of taking 16 pills, you’re taking eight, which is a great improvement. And also, for many of you who might be taking it as it was originally developed as a four-times-a-day drug, that all of these we really have moved, almost all of them, for the most part we have moved them to twice-a-day drugs. Both [have been changed] in the recognition that it’s awfully hard, even if you’re not feeling well, to remember to take a drug three times a day. And so then switching them so, to say for Pentasa four pills twice a day, is probably fine for most people. Canasa also is now available in a larger size, so it could be [taken] once a day in the evening with the same efficacy and safety as the 500-milligram suppository. So that’s all good news and small advances, but important advances.

Dr. Korzenik: Steroids are both friends and foes. And they are things that can be quite effective, both at inducing remission in ulcerative colitis and Crohn’s. They are not effective in maintenance. So we really try to limit how long someone is going to be on these. As effective as they are in getting someone under control, they also can be quite effective at causing a lot of side effects.

So, if the benefit is that it brings about a fast remission, then I would say that I tend to use it a lot more around the holidays when somebody’s got a crisis, or you really want to get them better, or they’ve got graduation or a wedding or something like that. You need something that’s going to kick in quickly. It is good for that, but it’s got its problems. There are no long-term benefits. There are lots of side effects. We [doctors] worry about things like osteoporosis, the risk of cataracts. What I think a lot of people who take them worry about more is some of the changes in how you look. It might make your face look puffed up. It might give you mood swings. It might make it difficult to sleep. My mother has asthma and has just gone on some steroids for that, and she never wants to go on them again. Mood swings, making her feel miserable, and so many people will be on them and feel like they have done great wonders but “I don’t care, I never want to go on them again.” Other people tolerate them better, but regardless, in any way, it’s important not to be on them for long periods of time.

Again, it’s good for mild to moderate Crohn’s. It’s good for fistulas, and there have been several good studies to suggest using it after surgery, when there’s no evidence of disease. But using it for even just three months can reduce the recurrence rate even a year later or even a little bit beyond that. They are not effective in ulcerative colitis. [With] Flagyl, it’s important to keep in mind that if you’re on it for a long period of time, if you get any tingling in your hands or feet, stop it. [If] it’s hurting your nerves, call your doctor. It can give you a terrible taste in your mouth, and it can make your tongue kind of coated. It can give you yeast infections, and some people can’t tolerate alcohol. Cipro can also give yeast infections.

One thing to keep in mind because it’s unusual, people wouldn’t think it’s an antibiotic that can cause it. It can give injury to your tendons, particularly your Achilles tendon. You can get pain there. You can even get a rupture of your tendon there. It’s important to keep that in mind because you wouldn’t think of it. One thing to keep in mind with Cipro, also that can happen a little bit more commonly, particularly if we ever get warm weather, at least in Boston, we’re still praying for it is that you can get a little bit of sun hypersensitivity. So you go outside. You get more of a sunburn than you would normally, and that can be due to the Cipro.

Dr. Korzenik: We then jump to immune modulators, things that are going to try to hopefully change the natural history of the disease and really get this under control and really keep you in a long-term remission. These are drugs such azathioprine, Imuran, Azasan, that’s also another name for it, and Purinethol - 6-MP. These are used in a variety of people. Often if there is severe disease, people are steroid-dependent or need something more significant than steroids are able to handle. The things that are important to keep in mind about these medications are that they can be extremely effective, but they have to be well-monitored. So they’re a two-edged sword. If you don’t monitor them closely, they can cause all sorts of troubles. If used safely, they’re great. So it’s important to keep that in mind. So they can be steroid-sparing.

They are relatively inexpensive. They can be very effective for long-term maintenance, meaning years. But it can lower your blood count, so you have to keep that monitored to make sure, even if you’ve been on it for a while. There is a small risk of infections that you wouldn’t have gotten otherwise. And, occasionally, you can get allergies to them. Usually, if you’re going to get an allergy to them, you’re going to get them the first three weeks, maybe up to eight weeks after you start it. If you’ve been on it for a long period of time, it’s extremely unlikely you’re going to develop some of these other problems. One of the things about it when you start them is that they take a long time to kick in. It’s not like steroids where you can feel better in a matter of days. This can take two to even six months to kick in. So you have to be patient with them, and so it means we have to do other things while we’re trying to get them to be kicked in.

Because Imuran was used initially to treat cancer, people think, “Oh, this is a cancer drug. This is chemotherapy. It’s going to cause all sorts of things.” The way it was used in cancer is different than it is used in ulcerative colitis and Crohn’s. There is, out there, the thought that it can cause cancer. That’s not supported with good scientific evidence. People also thought, “You shouldn’t be on it for more than three years.” That’s not the case. Now we have data on people being on it for decades and staying in remission and doing quite well. As I said, it takes a while to kick in, so it has to take patience. It’s got to be at the right dose and for the right duration, as with any medication. But unlike other medications, this takes a little longer.

I think we all feel comfortable that it is safe during pregnancy. The real sort of guiding principal for pregnancy is a healthy mother makes a healthy baby. A number of important studies, one landmark study by Dan Present, did find that they’re safe in pregnancy in a large number of pregnancies, so that is giving us increased confidence.

Cyclosporin, I’m just going to touch on very briefly. It’s something we just use typically for severe ulcerative colitis. It’s is another medication that is available also for certain subgroups of Crohn’s patients.

Methotrexate is probably something that is slightly underutilized in the Crohn’s population. In places like Canada, they tend to use it more as a second-line agent. Here, we tend to use it as third- or fourth-line agent. It’s been used for many decades in rheumatoid arthritis. It’s been demonstrated in good studies that it can reduce the steroid need in patients with Crohn’s and keep people in remission over a long period of time. It’s given as an injection typically at the full dose once a week. Currently, there’s sort of a national shortage for the injectable form, and so we’re using just oral pills. You can use the oral form, particularly at the lower maintenance dose. It’s generally really quite well-tolerated, but it is something that absolutely cannot be used in pregnancy, and that’s no question about it. [It is] absolutely contraindicated [cannot be used] in pregnancy, but otherwise it can be quite safe and can be effective, and it’s something again, as I mentioned, that can be underutilized.

Dr. Korzenik: Biology therapy means things such as antibodies or using proteins to modify the disease based on a better understanding of the disease. And Remicade is the first of probably many that are coming down the line. This blocks the immune system by blocking a particular protein that’s important in inflammation. It rapidly relieves the symptoms, typically within two weeks, but sometimes people [have their relief] in days. Occasionally, people even talk about in hours, but if you haven’t responded right away, don’t give up hope. We give at least two weeks, sometimes even a little bit more than that.

[Remicade has] been effective at getting people off of steroids, and it can be given over a long period of time in repeated cycles. So it’s not something you’d just use once or twice or a typical induction dose for say three doses. It’s not as if that’s the end of your therapy. You can then get it on repeated cycles every eight weeks. If you’re starting to lose response, [you can get treatment] every seven or six weeks. It does maintain remissions.

In Crohn’s, it rapidly relieves the symptoms. It’s very good for fistulas. It is steroid-sparing. It can be effective with other therapies. You can get infusion reactions. It is given as an [intravenous] infusion [either in the doctor’s office or at a special infusion center]. You can develop antibodies to the drug, and you may develop a resistance to the drug, which can be a problem. There can be a reactivation of tuberculosis, which can be a problem, so everyone has to be screened for that before starting. Remicade is also quite expensive.

Is [Remicade] effective in ulcerative colitis? Well, we don’t really know. There [are] some studies that suggest “Yes,” some studies that suggest, “No.” There are going to be two studies presented [in 2005] showing that Remicade is quite effective in ulcerative colitis. So it will open up a new avenue of therapy and will change our approach to ulcerative colitis to some degree [pending FDA approval]. Whether the insurance companies will catch up with us is another question, but I think many of us are already using this, and, for the most part, we haven’t had a big problem.

[Remicade] is an infusion. Mild infusion reactions can happen 10 to 20 percent, but more severe reactions are much less common. Occasionally, we have to stop infusions. Just yesterday, in fact, a patient of ours had a quite severe infusion reaction, but, fortunately, that’s pretty uncommon.

Dr. Korzenik: What’s the right therapy [for you]? We really try to weigh the risks and the benefits as with any decision in life. Will it control inflammation? Is it going to make you feel better? Is it going to let you get on with your life and do the things that you want to do in life? Is it going to keep you well? Is it going to prevent you from having a relapse? Is it going to reduce some of the complications, some of the extraintestinal manifestations? Will it be likely to reduce your chance of needing surgery? The other side of things is to know very well what the short-term side effects are. What are the long-term side effects? [Cost is important] as well. So, this is where your education really is an important is sue in terms of learning as much as you can about it and weighing these various things.

There are all of these medications, so [they each] have their own side effects. Some of them might be quite mild. Some of them are much more severe, and it’s important for you to know these things and then weigh things and decide what things are important to you. And there is this whole field of study called, “shared decision making,” where [you try] to get a sense from somebody, ”What are the things that are important to you? What are the complications you fear or are concerned about? How do you weigh these things, and how do you make a decision?” And then how do we, as a healthcare team, make that decision together?

Dr. Korzenik: IBD medications in pregnancy: The 5-ASA agents - the Asacol, Pentasa, Colazal - all those, are safe. They’ve been around for a long time, since the 1930s, and we have a lot of safety data.

Steroids are probably safe, but early on in higher doses there’s some low risk of a cleft palate. Keep in mind that it’s really during the first six to eight weeks or so at most that the baby is formed. After that, it goes from being a little fetus to a bigger fetus, and so it’s just that early period which is most vulnerable when all the different organs and the body are being formed.

Most antibiotics are safe. Imuran [azathioprine] and Purinethol [mercaptopurine] are safe. And Remicade [infliximab] is likely safe as well. We don’t have as much data on that as we’d like, but all the data we have so far suggests that it’s safe.

The one that is absolutely not safe is methotrexate. Now for some of the things, such as antibiotics, a lot of our safety comes from short-term use, meaning a week or two and not so much having someone on it for a month or two or three as we might do with Crohn’s. So some of these things have to be modified a little bit. But from our best knowledge, these are safe.

In IBD, it’s important to recognize that if the disease is controlled, fertility should be normal. In active disease, there’s reduced fertility. Pregnancy, though, outcomes are normal. So having ulcerative colitis or Crohn’s in itself doesn’t give you any higher risk for having any problems with birth defects. There can be a slight increased risk for low birth weight and sometimes prematurity, early delivery - but, otherwise, a healthy baby. What is very important though is if you’re thinking about getting pregnant, is that the typical saying is one-third of women get better, one-third get worse, and one-third stay the same. Well, that’s pretty close to what would happen if you followed women who weren’t pregnant. What’s most important is that you’re healthy when you get pregnant. And women who are healthy when they get pregnant have a much higher rate of staying better. Women who are ill when they get pregnant have a much [higher] likelihood of having a really rough pregnancy. So we don’t advise someone getting pregnant when they’re having a rough time. We want to get them in good shape [no inflammation]. Women who are ill when they get pregnant, have a much [higher] likelihood of having a really rough pregnancy. So we don’t advise someone getting pregnant when they’re having a rough time. We want to get them in good shape.

Dr. Korzenik: Malnutrition is an important is sue. Malnutrition can occur in IBD itself. Sometimes that’s when somebody doesn’t want to eat as much because they don’t want to have as much diarrhea. They’re trying to get out of the house and go about their lives, and sometimes that restriction can be a little bit too severe and lead to malnutrition and weight loss in itself.

For the most part, say with ulcerative colitis, most of your absorption takes place in the small bowel, and the colon itself is not where nutrition is absorbed for the most part. And so your nutrients are getting absorbed.

Even with Crohn’s, it’s the rare person who has their small bowel either resected or inflamed [so] that they’re having decreased absorption of the nutrients because of that. However, when there’s a lot of active inflammation, your body needs a little bit more nutrition. And it’s important to have a professional nutritional assessment. It’s also important to seek out a nutritionist who has experience, particularly in ulcerative colitis and Crohn’s, and understands the particular things that are important about diet and about dietary supplements.