Pioneering Care, Research, and Sustainability in IBD: An Interview with Dr Marjolijn Duijvestein

Dr Marjolijn Duijvestein, is a gastroenterologist and Head of the GI Clinical Research at the Radboud UMC, Nijmegen, the Netherlands.

How did you became interested in gastroenterology and inflammatory bowel disease?

I studied Medicine in Leiden, a nice university town near to the Hague. During my clinical rotations, I first did internal medicine followed by surgery and that is where I met a surgeon who did IBD surgery and I recall that I was always very excited joining him in the OR, especially for abdominal surgery. He said to me: “OK, why don’t you become a surgeon?” But then I thought to myself that I did not want anything to do with fractures. And sometimes I would even faint when I was in the OR! So, that was not really what my ambition was. We then chatted a little bit longer and then he pointed out to me that perhaps gastroenterology would be a very good option. But during my internal medicine training in a regional hospital, I had not seen that much of gastroenterology. But he told me, well, there’s a new young ambitious professor coming from Amsterdam. That new professor was Daniël Hommes and I reached out to him for my final clinical rotation which turned out to be a very interesting one. Subsequently, there was also a possibility to join the PhD group of himself and prof Gijs van den Brink. My PhD was on stem cell therapy for IBD. I performed translational lab work but also designed and performed a clinical study. So it was actually a surgeon that inspired me to become a gastroenterologist.

You recently did a presentation at the Radboud UMC Grand Rounds focused on customized patient care and sustainability and how they can enhance one another. How can physicians work in a “greener” way in their GI practice?

We know now (thanks to the work of Evelien Hendrix, using data from “My IBD Coach”¹¹) when we looked at the whole IBD patient journey, more than 50% of the whole carbon footprint is caused by hospitalization and around 29% by transportation of patients. So, if you would like to become a “green doctor”, you really need to treat your patients well (to prevent hospitalization). I think when you look at the IOIBD guidelines¹ and what our treatment targets are, we should not hesitate to treat our patients well and the best treatment will give you the best outcomes and in that way also less hospitalization. So, if you could think of a second step, which you could do differently is not always ask your patients to come into the hospital physically, for example by doing phone or online consultation or by trying to combine diagnostics, for example, a gastroscopy and a colonoscopy in one day. Also, try to do the lab work on the day of the consultation.

Also, we know from life cycle analysis (LCA) of colonoscopy performed by PhD student Dorien Oomkens¹² that transportation itself (both hospital staff and patients) has a major impact (76.5%). The total impact of 1 colonoscopy is 26 times that of an ultrasound. So intestinal ultrasound (IUS) is a very good alternative for colonoscopy both for the environment, but also for the patient as it is less invasive. You can train a gastroenterologist within a couple of months to do IUS. Of course you must have some exposure, but there is a great training program organized by IBUS⁹. So, in the case of inflammation, I would really recommend IUS instead of a colonoscopy, and I’m really happy that IUS also becomes an endpoint in many trials.

So, it’s treating your patients well, reducing less transportation, and using alternatives as IUS or fecal calprotectin instead of colonoscopy.

You recently shared some information also on the activities that you and others are doing to find smarter ways to monitor IBD, like a smart toilet seat. Can you tell me just a little bit more about that?

This is a pilot study that we’ve performed together here with One Planet Research Center/IMEC². They developed a smart toilet seat which tracks how long you are on the toilet seats, what your body temperature and your heart rate variability are. In a pilot study in Ulcerative Colitis patients with a flare performed by Lotte Hazeleger we saw that the number of toilet visits, as expected, go down once a new treatment kicks in. This device could be an alternative to daily diaries in clinical trials. The ultimate goal is to use this toilet seat as a passive way of monitoring the disease, so patients that are in remission, to find a flare before they actually notice it themselves. In addition, a beautiful study published³ a couple of months ago showed that a wearable can actually also predict flares.

Another tool under development is a smart pill which samples inflammation¹³ within the GI tract. We are now doing a pilot study in patients with ulcerative colitis and want to expand it to Crohn’s Disease patients.

What are some of the main challenges you face at your site or maybe within your country (the Netherlands) in doing clinical trials in gastroenterology?

One of the most difficult things is, of course, that there’s many times a placebo arm. For me, this makes it sometimes difficult to explain to a patient in a country where we have a lot of possibilities, why at that moment they should choose to go for a trial instead of receiving reimbursed treatment, which I can immediately start next day.

In addition, you usually have a washout period which is a couple of weeks. You can use steroids for a while, but I like to work as steroid free as possible.

For Crohn’s disease particularly the discrepancy between CDAI and also endoscopic abnormalities can be a challenge.

Also, the timing of the endoscopies is important as most patients don’t want to go undergo a second endoscopy within a couple of weeks. Fortunately, there are more and more trials now where you can use a video made during earlier endoscopy.

A key item is that I promote with my non-academic physicians in our region is that they should not only transfer patients to the academic centers once they’ve failed everything, because then for me it’s also more difficult to find an appropriate trial as many trials have a cap on how many biologics patients can be exposed to.

What are some of the ways to promote clinical trials more?

We need to infom patients better about why research is so important, and what the role of clinical trials is. The Dutch patient organization Crohn’s & Colitis NL⁴ developed a tool to make patients more aware of what trials are, what research is, what kind of research there is.

Many patients that I talk to recognize that the availability of their current treatments is the result of clinical trial participation by those who came before them and are willing to contribute to research themselves.

Outside of trial design, are there particular things that CROs and Sponsors could help you with?

I think one of the keys for a new study is to prepare very good training on the mechanism of action (MoA) of the new drug. I have worked with companies who could not tell me what the exact MoA of their drug was and if I (as a principal investigator) don’t understand the MoA of the drug being tested, how am I going to explain it to my team and my patients? I have seen videos and other digital materials that work very well here.

Is there a particular clinical trial that you have worked on or that you’re going to work on that you’re very excited about?

Yeah, there are several! First, what I really like is all the trials that we have done together with surgeons. One of them of course is the ACCURE trial which was published in the Lancet gastroenterology⁵. This was a positive trial where it showed that removing your appendix can protect you from relapses. I think that’s really a very original trial and well designed with nice outcomes.

What I really like now are the head-to-head trials, such as the REVAMP UC, Galaxy and VICTRIVAstudies^{6, 7,8}, where they combine different agents during induction and/or maintenance therapy. Also, the OMICROHN study¹¹ I think is one of the most interesting studies to look at in the near future to see if we could predict which drug works best for our patients, based on the epigenome. Also, I am curious to see what comes out of the different TL1A inhibitor studies.

Is there anything else you would like to share with the GI research community?

For the Grand Round I was looking again at the incidence numbers and it’s so strange to realize that IBD is now also seen increasingly in developing countries. So, I think we really need to better understand the influence of environmental factors, and of course our diet. It feels a bit strange that we focus on the effects of the immune response in patients with IBD, yet pay less attention to addressing the causes that actually trigger the inflammation. I don’t think that at the end of the day we’re going to be able to treat IBD as well as we possibly could if we were able to identify what triggers IBD or how to modify the environmental factors (like food, stress or sleep) of patients. I feel there’s a need for a more holistic approach of IBD

And for our physicians, it is important to also take care of yourself. We always hear in the airplane: you first have to take care of yourself before you take care of others. The same accounts for physicians, as shown in a collaborative article on burnout in gastroenterology of the UEG National Society committee that will soon be published in the UEG Journal.

High-quality IBD care requires balance: caring for patients, caring for ourselves, and caring for the planet—integrating medical and environmental dimensions into a truly holistic approach.

Many thanks, Dr Duijvestein!

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