KOL: IBD

Expert Profile

Section 1: Current IBD/Colitis Therapy

1.1. How would you describe the current IBD/Colitis patient journey?

When thinking how you should start a new patient on treatment, you want to think about what is the disease? Is this Crohn’s disease or ulcerative colitis? Secondly, you want to think where is the disease? So, what’s the anatomic location. And then the third thing to think about is how severe is the disease in that anatomical location?

If you have a patient who already has had a diagnosis of inflammatory bowel disease, so they are a returning patient, you will think of one extra thing, which is what has been their disease history? Meaning that if they’ve had a very easy course in the past, they’ll likely have an easy course in the future. If they’ve had a torrid course in the past, they’re likely to have a torrid course in the future. So those are the main things that people think about, and organize in their mind as a doctor, over maybe 20, 30 seconds, when they first are thinking about what they’re going to say to a patient.

Most patients have already been diagnosed because this is a recurring disease. The great burden of disease, if you like, are in follow up patients. But in terms of a new patient, then the diagnosis is usually not made by the GP. It may be suspected by the GP, but to make it a diagnosis of inflammatory bowel disease, to be honest, you really need, ideally, an endoscopy plus the biopsy result; that’s called histology. Or, in some cases, it’s acceptable enough to have more surrogate measures, such as an MRI scan, you probably would need something like an MRI scan to demonstrate some abnormal pathology radiologically, but even then the correct thing would probably be to then push on to endoscopy to get tissue, to really confirm the diagnosis. And, as GPs don’t do the endoscopies, it would be unusual for this to be a firm diagnosis made in GP land.

1.2. What are the main bottlenecks in IBD/Colitis patient journey?

Thinking about a patient journey. And to answer the question, we’re going to make a mythical patient, and just imagine the patient. The patient gets their first symptoms, so they develop inflammatory bowel disease. The first bottleneck, or shall we say delay, against optimum treatment would be for the patient to recognize that they need to see a doctor.

The second delay will be getting to see their family doctor. As you know, with COVID, people use it as an excuse, many different people, to, as it were, delay other things. So, then they’ve got to see the GP. The GP may make an accurate diagnosis of IBD, but probably won’t. But the GP will probably send the patient off for some tests, blood test and a stool test. The stool test will probably be raised; that’s called calprotectin. At which point the GP will make a referral through to their local secondary provider, saying, “I think this patient needs to be seen in your clinic. I think they may have inflammatory bowel disease”, or something like that.

So already the delays are: A, the patient recognizing and visiting the doctor, B, getting the doctor’s new appointment, C, being sent off for a blood test and a stool test, D, coming back to see the doctor to be given those results. Then the letter has to be written to the hospital. And then the delay is usually somewhere in between two and three months to be seen, which obviously these days is going to be a remote consultation; that doesn’t matter in inflammatory bowel disease at all, I don’t think.

Then they will have a remote consultation and the secondary care provider will then say, “Okay, I think you need tests.” Now, what will those be? They’ll probably do some extra blood tests; they may repeat the stool test. But the diagnostic test to make the diagnosis, as I mentioned to you, would probably be an endoscopy, maybe a scan as well. When I say endoscopy, I’m meaning almost always colonoscopy, which is up the bum. You might do a limited colonoscopy; that’s called a flexible sigmoidoscopy. But, broadly speaking, these are all called endoscopy. It would be unusual in inflammatory bowel disease to have to through the mouth. Most people think of endoscopy as something through the mouth, only because 30, 40 years ago, when it was first being produced, as it was discovered, that’s how people called it.

Then they get referred from their clinic to have their colonoscopy. Delays, at the moment, because of all the PPE and all that sort of stuff, maybe two months. Three or four months, if you’re unlucky, in certain centers. So, then they get a colonoscopy. Let’s say that, there and then, the person who’s doing it can usually make a diagnosis, but it slightly depends on how empowered they feel, that’s the doctor. And also, to what extent they can be bothered. I’m sorry, I’m talking very bluntly, just as it is. If it’s Friday afternoon and they’re exhausted, are they going to want to have a 20-minute conversation talking about the implications of having Crohn’s disease or colitis? No, particularly if there are other emergencies. What they’ll say is, “Oh, I’m sorry, I’m just the guy doing the endoscopy. You’d better go back to the clinic and speak to those people.”

You might leave with some treatment, but you probably won’t. And, unfortunately, we’re more and more in silo mentality in hospitals nowadays. And so, they’ll probably be then sent back to the clinic, another two or three month delay, where they will probably see a different doctor, who will read the notes from the first doctor, and read the notes from the endoscopy, tell them maybe a bit about what they’ve got, and start some treatment.

At that point, they might then be referred on for follow-up, thereafter, to see one of our inflammatory bowel disease nurses; Europe doesn’t have them, but the UK does. And they are work horses, in a lot of departments, because they are committed, have a good work ethic, haven’t got burnt out from having done medicine for 20 years, and are not so proud that they feel it’s beneath them to be talking about the same thing every single time with the patients. I’m a great supporter of inflammatory bowel disease nurses; I think they’re doing an amazing job. And most of what we do is very formulaic, meaning that you can make a recipe and then anyone can cook the cake pretty much.

So from the time of feeling the symptoms you could, when you replay the recording, you will work it out, to the time of getting your first treatment could be of the order of six months, which is a bit crap, if you excuse the pun, if you think about it.

If you imagine, you are the patient. You ring up Bupa, you come to see me this evening. You say, “Okay, for four weeks I’ve had some blood out of my bottom, doctor; I’m a bit worried.” Let’s say. What happens to that patient? Well, I would then say, “Okay, you probably…” You’d take the story and then I’ll say, “You probably need a colonoscopy. Let’s do it next week.”

And so, then they would have it. I would know the patient because obviously you own more, at least you own the patients in that environment, as we did in the olden days. So, then you do the colonoscopy. You say, “Oh, I’ve seen this. I’m pretty sure it’s not cancer. I’m pretty sure it’s colitis. Here, take this treatment.” And you would provide the treatment. So within about a week or two, a patient would start treatment.

The system is not designed to institute the delays, but the system allows the delays to give it some flexibility, but it’s not very patient centered or patient friendly. It’s not Apple. It’s an equivalent provider who doesn’t think about the user as the center.

1.3. What are the greatest unmet needs around clinical use of IBD/Colitis?

Unmet need, in terms of doctors getting the diagnosis wrong, that’s not just an operational delay, but an intellectual delay, if you like. Usually most people end up with a scope, and most scopes: colonoscopies or flexible sigmoidoscopy, or possibly even imaging and MRI, would usually make the diagnosis fairly quickly. So, as long as the right tests have been done, you’ll get to the diagnosis. That’s not the same as with, say, some other diseases. Some diseases can be difficult to diagnose.

You’ve got diagnosis, then in terms of treatments, I think an unmet need is going to be getting the patient on to the right treatment. In most healthcare systems, there’s a gradation of therapies, both based on cost and on length of time in the market, which relates to cost, and also on side effects. But mainly it’s cost as the driver, which usually tries to give the patients the simplest, and the safest, and the cheapest treatment first, and then moving up slowly towards the opposite. Now, we know from several different IBD studies, that actually in IBD, you probably want to start with the most expensive, which may have some risks, albeit very rare, risks. And we call these biologic treatments.

The most famous study was called the SONIC study in Crohn’s disease, published in 2009 in the New England Journal of Medicine, but since then there’ve been equivalent studies now for colitis. We also know that if you use the more expensive biologic treatments, not only do you end up treating the patients better, you end up with less side effects. So really from a patient’s point of view, if I’m your advocate and talking to you as a patient, you and I are only going to be really interested, for you individually, in is this treatment going to work? And is it going to harm me or help me? From a national point of view, you’re worried about, can we afford to give 10,000 of these treatments, or a 100,000 to our population?

There is a tension already, automatically, in health care systems between the individual and the payer, and that tension still exists. And it often falls on the shoulders of the doctors to try and negotiate that conversation with the patients. Some doctors won’t necessarily be too honest because it’s a difficult one. Some doctors will say, “Why don’t we just follow the ladder because that’s what we’re told to do.” But the issue with guidelines or treatment ladders, is they don’t fit any specific patient because patient, a particular person, you, me, whoever, have many different facets to our lives, all of which will come into the decision as to what’s best in terms of a treatment. And that’s not necessarily going to be on one side of a piece of paper. So, there is that tension with cost, and what in America you’d call managed care, i.e. you have to follow this recipe. You can’t go off-piste.

Another unmet need would be, a true unmet need, in terms of treatments, and this impacts not on the pain, this is on you as a patient, is that there are not very good treatments for middle level disease. So, we’ve got quite nice treatments in colitis for mild disease. We have no real good treatments for mild Crohn’s. We have no real good treatments for mild to moderate Crohn’s. Quite often, one finds oneself in no man’s land, meaning that the patient’s not quite ill enough to go on to biologic treatment maybe, but you don’t have anything else. And the mild treatment doesn’t really work, certainly in Crohn’s disease that’s the case.

So, there is this unmet need of a sort of treatment for the middle severities. Now, what has tended to happen over the past 20 years is that with more data coming out, often from drug company funded studies, and there must be bias there of course, but with more data coming out, people are more and more comfortable about using biologic therapy. The threshold for using those has dropped. So, a moderate patient now, I will have no problem putting them on a biologic therapy. 10 years ago, it was only the severe ones. Actually, the moderate ones probably should have it because you want to do preventative rather than restorative care.

Another unmet need is prediction. So, there’s an unmet need in terms of predicting lots of things. So, in inflammatory bowel disease, it’s quite hard to predict whether a patient will respond to a particular treatment. You’ll have a percentage, you’ll know that two-thirds respond, but is that patient in the one-third or the two-thirds? And so, we really do have a need for better, what are called biomarkers, meaning either a blood test or a stool test, hopefully not an endoscopy or a scan because those costs much more money. So simple measures to predict whether you as a patient would benefit more from drug A or drug B or drug C. And we don’t really have good markers for that just yet. They are being developed, but they’re not really being widely used yet.

Is that the patients are often taken off the treatments because they’re well, and this is a real problem now. If you’re lucky enough to get, say, half of your patients into a good place, the National Health Service tries to take them off to save money, and then of course they end up in trouble again. It’s almost like shooting yourself in the foot. And I think that does need to be a real understanding of the cost benefit, rather than the short termism. So that’s a very important thing. And that, unfortunately, is not easy because if you’re looking at a budget, you’re only going to look at one year. You don’t look at five years.

Section 2: Future of IBD/Colitis therapy

2.1. What new therapies could be seen for future IBD/Colitis?

The first trial, comparative blinded trial, between two biologics was reported in the New England Journal of Medicine a year and a half ago. It was Humira versus Vedolizumab and Vedo-1. And this was really interesting because we thought we would never power a study suitably to achieve a superiority outcome, but we did. We being the community, not me. And so, I think in the future, we’re going to start seeing a few more comparative studies. And those will enable us to construct, to some extent, a better ladder for knowing which one you use first. It will make the payers have to follow that because there’s good evidence then to say, “We should give you drug A, even though it’s a bit more expensive, because it’s better than drug B.” Whereas at the moment, we don’t have comparative studies, and therefore, the payers can easily sit back and say, “Well, you can’t tell me that the expensive one is better than the cheap one because the studies are in different populations”, and so on.

Another future need, and development, I think the biomarker, so talking about the ladder, that will come out, so we’ll have a better idea, probably pharmacogenomics. Genes will tell us that you should take drug A not drug B, or vice versa. So, we’re going to have, rather than having all the bespoke options, we’re going to have the cheap versions, but they’re just as good. So, we’re pretty sure the biosimilars are just as good as. So, therefore, drugs will get cheaper and gastroenterology will probably move from where it is now towards more like a rheumatology type of approach, where they have about twice the number, or more, of biologic therapies and they just mix and match them. So, there’s many more opportunities for patients.

The next point is that the number of therapies is increasing, and we know that. So, six years ago, there was one class of agents available, or eight years ago shall we say, and we now have three. We’re going to have five within 18 months from now. When I say class of agents, I don’t mean two different drugs which act in the same pathway. I mean drugs acting in totally different pathways. And that will provide, not just a wider range of therapies for patients, but it will also start to allow with, studies though, the mixing of patients.

2.2. What role could approved diets have in improving symptoms for IBD/Colitis patients?

Firstly, we are asking if there is any data that says that diets are effective in inflammatory bowel disease? Because if we have no data, you may as well go to the bus stop and ask someone what they think.

If we have reasonable data that says diet A is clearly superior to diet B, that would then be taken into guidelines. And I speak as the architect for the European guidelines for colitis, current ones. So that would then get into the guidelines and so on. Unless in the diet you’re going to put in some foodstuffs, like a special probiotic. Let’s say you’ve licensed; you’ve got the special probiotic. Maybe if that’s a component of the diet, then I have to go on Amazon and spend 100 euros or pounds to buy that special probiotic. That way you can get your reimbursement, maybe. Maybe the reimbursement will come as is occurring now in the irritable bowel syndrome arena with what are called the FODMAP diets, whereby the payers, certainly private providers as well as NHS, allow me to send patients to a dietician who talks through a diet called a FODMAP diet because there’s good science that that helps irritable bowel syndrome.

I think you’ve got historical parallels for reimbursement for dieticians. You’ve certainly got lots of evidence for the nutraceutical, 80 billion a year sales, which is not necessarily with a lot of evidence. Think of the probiotic yogurts or something like that that people buy, that may or may not be the right group of probiotics. But whether it’s going to be like 5,000 pounds a year special type of diet. I don’t see how that could work. And that is why, going back to the first thing, there’s no good research. Because if it costs 300 million to do a proper study of a drug or whatever it is, then your diet study is not going to get a look in. So, then you need to have Academia, or NIH, or something, taking that forward.