Amazing discoveries was the name of the punk band of which professor and gastroenterologist Nanne de Boer (1978) was the singer in his teens – a nod to the then popular program on sales television channel Tel Sell. “The host of that, Mike, said everything Isn’t it amaaaaazingwhether it was a mediocre juicer or a completely unnecessary fitness machine.” The band no longer exists, but De Boer did not let go of that Tel Sell slogan until the day of his inaugural lecture last month.
Amazing drug discoveries was the title of his inaugural lecture: a sneer at the pharmaceutical industry that continually uses new (often more expensive) medication without necessarily being more effective. And that is exactly what he wants to defend against with his chair ‘effective and optimal use of medication for inflammatory bowel disease’. Because as a gastroenterologist at the Amsterdam UMC, he has seen for years that one drug after another is being conjured up for patients with chronic, inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease, while the effectiveness rate does not really improve. “Twenty years ago we said for every medicine: it works for about 1 in 3 patients, and that is still the case.” That is precisely why it is time to take a different tack, De Boer emphasizes – for example through the ‘rediscovery’ of medicines such as thioguanine, which came into vogue shortly after the Second World War.
How would you define ‘chronic inflammatory’?
“In short, they are inflammatory diseases in which the body unfairly attacks its own intestines, i.e. autoimmune disorders. The English term is IBD, inflammatory bowel diseasenot to be confused with the more innocent irritable bowel syndrome or irritable bowel syndrome. Severe flare-ups can be alternated with relatively calm periods, but if you have such a disease it never goes away. Ulcerative colitis is limited to the colon; Crohn’s disease is common in the last part of the small intestine, but can in principle appear anywhere in the digestive tract. With both diseases you see symptoms such as blood in the stool, diarrhea and often fatigue. They are called benign because they won’t kill you, but there is nothing good or nice about them. They are often accompanied by embarrassment. I have a distorted worldview because in my field, poop is often discussed, but in general, feces is still a taboo subject. Wrongly, because intestinal health concerns everyone.”
I had to spend weeks in the basement of the university hospital looking at intestinal infections under a microscope
And the number of intestinal patients worldwide is increasing.
“There are now around 100,000 IBD patients in the Netherlands. The increase seems to be slowly leveling off here, in contrast to countries where industrialization is now rapidly emerging – think of India, for example. We don’t yet know why: stress, nutrition, particulate matter? It is extremely interesting and important to investigate that. Worldwide we are now heading for around 9 million IBD patients.”
Initially, De Boer came into contact with IBD “out of laziness” while studying medicine in Maastricht. “I was too late to register for my internship and then had to spend weeks in the basement of the university hospital looking under a microscope at intestinal infections of patients with Crohn’s disease. At first I complained, but at the end of that period I was sold.”
In 2003, he started a PhD project into the effectiveness of thioguanine, a ‘forgotten’ anti-inflammatory drug that was developed in 1950 for the treatment of leukemia. “In the 1970s, related medications were used against colitis and Crohn’s disease, but they had relatively many side effects. This turned out to be much less with thioguanine, so we wanted to have the drug officially reregistered.”
It took quite some time…
“Yes, that turned out to be quite a challenge, partly because the Medicines Evaluation Board wanted additional studies. Ultimately, it took until 2022 until the use was officially approved. At a friendly price; that was our condition when we joined forces with drug manufacturer Teva for the redevelopment. That is not self-evident with such drug rediscoveries. Take the anti-gout drug colchicine for example. When it turned out that it was also effective in heart patients, prices suddenly went through the roof.”
Then why bet on it? rediscovery?
“Because new medicines are often expensive and not necessarily better. Then a new protein or molecule is discovered and hey, there comes a new drug that affects it. Research has shown that it works better than a placebo, but that is the wrong question. You should see whether it works better than the existing medication. And then the answer is: not at all or hardly at all. We are still left with the fact that IBD medicines only work for roughly 1 in 3 patients.”
Photos Jagoda Lasota
And what about other treatment methods?
“We are certainly looking at that as well. You should not procrastinate for too long if a drug does not work; it is better to get on with it, even if that means having to operate. For a long time, this was seen as a failure by gastroenterologists – the surgeon can solve it – but now we see that the disease can indeed be put to rest if you remove the appendix or the end of the small intestine. As a human being you have more than four meters of small intestine, so if you remove the last 10 centimeters of it, you have you still have a lot left, although that is not always a solution – the disease can come back. We have not yet discovered the perfect treatment method, which is why it is so important to explore new paths, for example drug rediscovery.”
In addition to the rediscovery of medication, De Boer also advocates reissuing: putting unused medicines back on the market that are returned to the pharmacy. “They are now thrown away as standard – that is not only a financial waste, but also extremely bad for the environment. Not to mention the medicines that people throw away themselves at home or flush down the toilet. And the healthcare sector is already so polluting… Of course, not every medicine is suitable for reissue: sometimes we work with, for example biologicals which must be kept very strictly at certain temperatures. But many other medications are simply available in tablet form. Fortunately, the European rules regarding reissuance have just been relaxed, so I certainly see room for improvement.”
You are also involved in putting one together essential medicines list for the World Health Organization (WHO). What does that mean?
“Good treatment guidelines are not available everywhere – that is why I am now involved in compiling one essential medicines list for WHO, especially for IBD patients. Such a list prescribes which medicines must be available to everyone, anywhere in the world, at low prices – and therefore sustainably where possible.”
According to your colleague, you were called the ‘yes-but PhD candidate’ at the time: you did not shy away from discussion. That rebellious side still seems to be in you.
Laughing: “Maybe that’s the punk in me. It’s not without reason that the VU carillon played a song by The Clash prior to my inaugural lecture.”
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