Andrew B. Grossman, MD, a Pediatric Gastroenterologist and Co-Director of Center for Pediatric Inflammatory Bowel Disease at Children’s Hospital of Philadelphia talks about some of the treatment options for kids and adults with IBD.
Interview conducted by Ivanhoe Broadcast News in November 2017.
Your undergraduate work and your med school work?
Dr. Grossman: I completed my undergraduate degree at Duke University and my MD is from Rutgers Robert Wood Johnson Medical School, New Jersey.
How did you get into IBD, what was it that fascinated you about that portion of medicine?
Dr. Grossman: I was always interested in a career in pediatrics but certainly wanted to be pursuing an avenue where I was taking care of children with chronic illness and could improve quality of life both through medical, psychological, social means. I was always interested in GI; I developed that in medical school I think because the pathology and the physiology made sense to me. But then as I pursued that further I really enjoyed caring for the children with IBD. I thought there was a big difference that could be made and really found a lot of fulfillment in doing so.
For adults who have IBD it’s a spooky, scary thing. So for kids when they come in how do they present as a patient and emotionally how does it impact them?
Dr. Grossman: The presentation can be very similar to the adult presentation, particularly in that the gastrointestinal symptoms can be similar. Abdominal pain, diarrhea, vomiting, weight loss and those type of issues; fevers, fatigue … The difference is that in children there can also be growth failure. So sometimes they’re not even having symptoms but in fact they’re just failing to grow and it’s hard to figure out why. But the presentation can often be similar although often it can be a bit more severe in children who present.
Are the kids aware of what’s going on, how does it impact them emotionally?
Dr. Grossman: So it’s interesting, I think it depends on the presentation. For those who truly weren’t having abdominal symptoms but they weren’t growing or maybe didn’t have the same energy as their peers it’s a big surprise when we finally realize what it is that’s causing these symptoms. For those who are having more obvious symptoms it’s very difficult. Most kids don’t want to use the bathroom in school; these are children who have to use the bathroom multiple times a day. They have pain and they don’t understand why. So in a sense while it’s scary it’s sometimes also liberating to get an answer and to finally have a treatment plan.
So by the time the children get here and they see you they’re already significantly ill I’m assuming?
Dr. Grossman: Often they are yes. It’s pretty rare that we meet someone who has mild symptoms, although that does sometimes happen but generally they’re quite ill. And generally you had to have the condition for a while before it becomes clinically apparent enough that the referral is made.
So when they come in and you diagnose them and you work with them, I know that one of the medications that you give them has been very effective, can you talk about that a little bit?
Dr. Grossman: There are different medications that can be effective. The ones that we tend to be using the most now particularly for Crohn’s disease are the biological therapies including Remicade and Humira. Remicade is given intravenously, the Humira is given as a subcutaneous injection and these are medications that really block one of the inflammatory proteins in the blood stream and in the bowel that contributes to a lot of the inflammation. And we found that these medications are often quite effective in improving symptoms, in helping exact better linear growth and also improving quality of life.
When you get this to them either through IV or subcutaneous, how long does it take for the medication to take effect for them and is it a recurrent type of treatment?
Dr. Grossman: It is different for every patient, there are some who state that they start to feel better as the intravenous infusion is going in, there are others where it might take a few days and there are even others where it takes a few treatments. For the intravenous Remicade, the typical schedule is you get three infusions in six weeks which is called the loading dose and then typically it’s every eight weeks thereafter. For subcutaneous Humira, there are several injections the first time then you receive it every two weeks and ultimately we hope for it to be one injection every two weeks. However, what we’ve learned with these medications is every patient is different regarding how they clear the medications and how much of the medicine they need. So it’s not uncommon for us to have to give the medications at higher doses or even more frequently.
You’re talking about some of the kids; their systems absorb the medication differently? So that’s another thing that you have to figure out is how much of a dosage they need.
Dr. Grossman: It really is important. It’s been pretty clear from the medical literature and our own experience that for these medications to work best, you have to have enough of the medication still in the system at the time of the next treatment. There are individual patient-specific variables that affect the clearance of it, but there are also disease specific variables as well. For example, the more inflammation there is, or the lower the serum albumin levels are, the faster you’ll clear it.
So the inflammatory protein that is at the root of this, do you know the cause of that and how did you determine that it was an inflammatory protein?
Dr. Grossman: This would be so much easier to treat if it was a single inflammatory protein that we could always target. The problem is this is a very complicated disease where every patient is different. You have to have a genetic predisposition and also some environmental trigger (which we usually can’t figure out on an individual basis). This causes dysregulation of the immune system which results in this unfettered inflammation and thereby ulceration, contributing to the clinica problems that the patients are experiencing. It’s not the same inflammatory proteins for everyone., The one that is neutralized by these biologic medications is called TNF alpha, While these have been effective, unfortunately there’s not a one hundred response rate to this medication, or any medication.
If they are genetically predisposed, are you saying that when the parent has come in they have some idea because they have it themselves or it could be generationally?
Dr. Grossman: No. So it’s actually even more complicated than that. The genetic predisposition occurs in many people in the population, many of them don’t even end up having Crohn’s disease or ulcerative colitis. If you have identical twins, if a disease was purely genetic then there would be one hundred percent concordance between identical twins, we don’t see that in Crohn’s disease at all. So you have to have a genetic predisposition but there are hundreds of genes that could be involved. It seems that there has to be some form of environmental trigger; so while many of our patients do have a family member who has inflammatory bowel disease and in particular our youngest patients tend to have a family history, it’s by no means universal.
When you think about that environmental trigger and I know you haven’t determined it … Could be multiple triggers, but I’m sure you speculate as a physician, are you talking about things like pesticides?
Dr. Grossman: Maybe, maybe. We certainly know that where you live in the world makes a difference. If you live in the part of the world like this or in more westernized environment you are significantly more likely to develop an inflammatory bowel disease than if you do not. And if you come from a different environment, say sub-Saharan Africa and you move to the United States, your risk begins to approximate that of those from the United States not that of where you came, so it must be environmental. Now while we’ll never know from an individual patient what the trigger was, we certainly know it at a population level what triggers may be. The westernized diet is probably contributing and I would say maybe undoubtedly it’s contributing likely through changes in the individual microbiome. We know smoking is a risk factor, we know frequent antibiotic use is a risk factor. Certain infections predispose you. Use of NSAID anti-inflammatories may be a risk factor. So there are multiple risk factors that there could be, but the bad news is that living here and having the diet from here is probably one of the biggest risk factors.
We are advanced as a society but we have all of that processed food and those medications. So part of what you’re telling me and I’m sure this wouldn’t be a preventative but people could at the very least with their kids follow a great diet that’s good for the gut. Could you go into that a little bit?
Dr. Grossman: I think it certainly couldn’t hurt and we definitely talk to families who have one family member with inflammatory bowel disease about dietary changes that would not only benefit the patient but also the first degree relatives. So the components of the diet that are problematic are still being figured out but it really does seem that it’s the processed components of the diet. Certainly the use of emulsifiers; what allows a food to have a long shelf life. The difference between the hummus you make at home and the hummus you buy in the supermarket and how long they last. We think that a lot of red meat in the diet is probably problematic. But there have been some realizations that what we used to think was wrong. For example, we used to say everyone should be on a low fiber diet and now it seems that fiber is actually helpful and probably well tolerated in most instances. The bottom line is there’s so much that’s in our food supply that’s problematic. The best that one could have a whole food diet, more fruits, more vegetables, more lean meats, less processed food, less foods with emulsifiers, less of the sugars probably the better. But that can be incredibly hard for anyone to do, particularly in a pediatric population.
So you advise these parents and these kids, they go on a special diet pretty much what you just defined, if they didn’t do that and you still treated them with the medication, how much does that impact whether or not they get better?
Dr. Grossman: That’s a good question. What we have shown is that the bad components of the diet increase your risk of developing inflammatory bowel disease. What has not yet been proven is if once you have inflammatory bowel disease and then you modify the diet could you then treat the disease that way? Studies are ongoing. However, we do treat many of our patients without medication with diet. I think it depends on the specific patient and there are certain patients for whom this would be more appropriate than others, but we do nutritional therapies. The bottom line is that for those who need medications or who want to pursue medications, they probably with a few exceptions can tolerate a regular diet. I do think there is probably a happy medium between a really poor diet, a perfect diet and maybe finding a happy medium makes sense as well. You know you have to remember that it is very important to try to modify the diet but these are children who are dealing with medical issues, who are dealing with the accompanying psychological barriers. To then limit their diet further is difficult; it really has to be a collaborative decision and you have to be careful not to be too limiting.
You talked about the child who is in school and has to go to the bathroom a lot, and then you treat them and they go back to school. Is there a significant change in that and their symptoms?
Dr. Grossman: Yes there can be. Our goal of treatment is normalcy; we want our patients to feel normal. Now it might be feeling normal while taking medications or while they’re on a special diet but the bottom line is we think it is achievable for most of our patients to go back to normalcy. And that is the first thing we say at the first visit after the diagnosis. We want you to play sports, we want you to be a good student. When it’s time we want you to date, we want you to have career aspirations, you’re going to have a family if you want to. And these are important things to establish from the beginning because it’s so scary to have a chronic illness. There are different levels of determining how a patient is doing. The first is are they clinically feeling better and that is of course our first goal. Are you gaining weight, are you feeling well, are you having pain, hopefully your diarrhea has resolved? The second is then determining if we’re actually achieving healing of the GI tract. We call this deep remission, not just clinical remission. Surrogate markers such as laboratory tests and stool tests help us evaluate for healing, but our ultimate goal would be for repeat procedures including endoscopy and colonoscopy tono longer looks like Crohn’s disease or ulcerative colitis but rather to look normal. That is sometimes achievable and is the ultimate goal.
Impact on lifespan overall and I’m sure that depends on the severity of the case, and any side effects of the medication that you’ve seen?
Dr. Grossman: There can always be side effects of medications and as you can imagine that’s one of the first things that we think about as practitioners and certainly one of the first things that parents are thinking about before starting these medications. All the medications we use have potential side effects and it’s important to distinguish between side effects, which are generally more common but less serious and risks, which are typically more severe but less common. Unfortunately, if you go on the internet you’ll find horror stories about many of these medications and it really requires a very good conversation between the family, the patient, and the provider to go through all these risks., The provider needs to know the data regarding these risks and then really emphasize when we’re recommending a treatment it’s because the risk of the disease is greater than the risk of the medications. But certainly each individual medication can have risks and can have side effects, no one more so than using steroids or prednisone. We do try in our practice to use as little steroid as possible and use these other therapies which are steroid sparing.
What does that medication do when it goes in IV, what is it literally doing inside of the body?
Dr. Grossman: It’s neutralizing tumor necrosis factor alpha, TNFalpha and preventing it from attaching to its receptor which contributes to the inflammatory cascade.. So that’s what it literally does and then probably has other effects on the immune system that aren’t as well understood to result in this improvement. At a less cellular level, but at a more pragmatic level, what it seems to do is heal the ulcers that we see and that’s what we really want.
Emotionally for you as a practitioner how fulfilling is it to see these children get better?
Dr. Grossman: It’s quite fulfilling when you see a child get better. I mean that’s why we’re all in pediatrics is because we want to make children better. And even in the timeframe that I’ve been doing this, our ability to make children better has been enhanced by the medications that have been developed but also a better understanding of how to use these medications. It’s quite fulfilling to see a sick child feel well. It’s quite fulfilling to see a very small teenage boy become big and strong and feel more confident. It’s quite fulfilling to be a part of that. At the same time I don’t want to pretend that every single one of our patients has it easy or that these medications always work; it’s also quite distressing for those who struggle so much. I think we’re inspired by the strength and by the courage of our patients and families but it is quite difficult for those where the medications are not as effective.
END OF INTERVIEW
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