Michael Nurmohamed has been a member of the Dutch Medicines Evaluation Board (MEB) since 2020. And he is no stranger to this organization; thirty years ago, he joined the MEB as a clinical evaluator. Since then, the MEB has always fascinated him, Prof. Nurmohamed: ‘The Medicines Evaluation Board is where it happens’. In daily practice, Prof. Nurmohamed sees many patients with various types of joint diseases, autoimmune diseases and connective tissue diseases. The finding that rheumatoid arthritis and cardiovascular symptoms are related is something that has preoccupied Prof. Nurmohamed throughout his career. In this article, Prof. Nurmohamed takes us through his experiences at the MEB, his fascination with inflammatory diseases and cardiovascular complaints, and his plans for the future.
Prof. Nurmohamed’s road to the MEB
Three decades ago, when Prof. Nurmohamed finished his doctoral studies, he noticed an advertisement as a clinical evaluator at the Medicines Evaluation Board (MEB). Prof. Nurmohamed: "My interest was piqued immediately, I applied and was hired. In the months that followed, I kept myself busy preparing registration files and reports. At the time I found it a very interesting place to work, the Medicines Evaluation Board is where it happens".
While working for the MEB, Prof. Nurmohamed became more distant from the patient. Prof. Nurmohamed: "After a good conversation with a friend, I realized, the patient is what matters. Then I started training as a rheumatologist and successfully completed it. About 15 years ago I came in contact with the MEB again, they were looking for an internist to join their board and I applied for that position. However, I was rejected because I am not an internist. Unfortunate, but legitimate comment'.
About seven years ago, Prof. Nurmohamed ran into Prof. Hazes. Prof. Nurmohamed: "She was working for the MEB at the time and I expressed my interest to her back then. When she quit her position, she nominated me and that is how I ended up back at MEB some 25 years after my first encounter."
The MEB’s function
The Medicine Evaluation Board (MEB) is an independent authority that regulates the quality, effects and safety of medicines and promotes the proper use of medicines for the right patient. The MEB assesses the balance between the efficacy and the adverse reactions and risks of medicines and also examines whether the quality of the medicine is satisfactory and remains so. In the event of a positive opinion, the MEB authorizes the medicines for the Dutch (and/or European) market. The Board has a maximum of 17 members, including the chair. The members are medical specialists, hospital pharmacists, professors and others. They are leading experts in the medicine or pharmaceutical field who fulfil their role of Board member alongside their day jobs. Michael Nurmohamed has been a member of the MEB since 2020.
The common origin of rheumatoid arthritis and cardiovascular disease
When Prof. Nurmohamed finished his doctoral research, he noticed that rheumatoid arthritis and cardiovascular disease regularly occurred at the same time. Prof. Nurmohamed: "I then applied for a grant to investigate this extensively. For this study, we compared 350 patients with rheumatoid arthritis with healthy subjects and patients with diabetes from the Hoorn study. Eventually, a large national and international line of research emerged from this study; we have just published the 20-year data.
From this research, very relevant information has emerged over the years about the relationship between rheumatoid arthritis and cardiovascular disease. Prof. Nurmohamed explains, "Today we know that joint rheumatism and atherosclerosis are both inflammatory diseases. That inflammation spreads throughout your body, this also causes your coronary arteries to become inflamed and eventually clogged. For people with rheumatoid arthritis, the risk of heart disease is doubled compared to the general population: half of this chance increase is caused by the inflammation, the other half by traditional cardiovascular risk factors for heart disease (including high blood pressure and smoking)."
Traditional risk factors
The 20-year data from the combination study between rheumatoid arthritis and cardiovascular disease were recently published. This shows that where the risk of heart-and-vascular disease for rheumatoid arthritis patients was twice as high in the past, today this has been reduced to 50 to 60 percent. The reason for this significant decrease: joint rheumatism is well treatable, the influence of inflammation on cardiovascular disease has therefore decreased. Nowadays, especially traditional cardiovascular risk factors contribute to the development of cardiovascular diseases in rheumatoid arthritis patients. Prof. Nurmohamed: ‘A big challenge awaits us in the coming years, how are we going to influence the traditional risk factors? With good lifestyle you already achieve a lot, but people have to take it on themselves.’
If we look at the role of the physician, there is still much to be gained. The cardiovascular risk management guideline specifically states that a risk profile should be made for patients with rheumatoid arthritis, but in practice this rarely happens. Prof. Nurmohamed: 'In my opinion, education could play an important role here. I also have ideas for an interesting Randomized Controlled Trial (RCT) in which I would like to compare rheumatologists, general practitioners and patients: to what extent do they perform the risk profile and/or does the patient ask for it themselves. I have not yet received funding for this study but I will definitely work on that."
Biologicals versus methotrexate
Prof. Nurmohamed has been a rheumatologist for 23 years and speaks with great passion and clear direction about the treatment taking place. Prof. Nurmohamed: “When a person is diagnosed with rheumatoid arthritis, the standard treatment protocol is started. By doing so, treatment begins with a low dose of methotrexate, this drug suppresses the immune system and inhibits inflammation. For seventy to eighty percent of patients, this drug works adequately.”
With greater understanding of the mechanisms of inflammation, biologicals have recently been developed, an addition to treatment with methotrexate when this drug does not work adequately. Prof. Nurmohamed says, "Inflammatory proteins are the culprit of the damaged joints in people with arthritis. Like the inflammatory proteins, biologicals are also proteins; they counteract the formation of the inflammatory proteins by binding to them and removing the proteins. Biologicals are offered to rheumatoid arthritis patients when they have responded inadequately to methotrexate and another drug, for example DMARD. Biologicals work well, however, there are also side effects: they suppress the immune system so the patient is more likely to get infections.”
Prof. Nurmohamed conducts research in the field of both medication types. Prof. Nurmohamed: "Soon a pharmacist within my group Renske Hebing will receive her PhD on a study of methotrexate and biologicals. Regarding biologicals, Renske Hebing is concerned with medication adherence. For methotrexate, we want to gain more insight into why it works for some people and not for others. To do this, Renske is looking at how methotrexate works in blood cells and the possible difference between using methotrexate in pill or injection form. This research is currently ongoing."
The future: lifestyle, depression, and heart failure
When Prof. Nurmohamed shares his plans for the future, he names several research directions, even despite emphasizing several times that at this point in his career, he is winding down in working hours. We can call him a real enthusiast and actioner. First of all, Prof. Nurmohamed mentions implementation research. Prof. Nurmohamed wants to do research on the role of education in cardiovascular diseases and rheumatism. Prof. Nurmohamed: "With a good lifestyle, you already achieve a lot."
In addition, the relationship between rheumatoid arthritis and depressive symptoms is something that interests Prof. Nurmohamed. Prof. Nurmohamed: "As described earlier during this interview, the same processes play a role in rheumatoid arthritis and cardiovascular disease, if we look at depressive symptoms, the same processes seem to be involved here as well. If we look at data from previous research, it has also been shown that patients with rheumatoid arthritis are more likely to have depressive symptoms. What I would like to look at is: is depression a problem in patients with rheumatoid arthritis? If so, can treating rheumatoid arthritis reduce depressive symptoms and cardiovascular disease?"
In addition, Prof. Nurmohamed is currently investigating heart failure in people with inflammatory diseases. Here, too, the question is: Does this occur more frequently together? Prof. Nurmohamed: "Here we are additionally investigating whether JAK inhibitors as drugs can improve cardiac function. In addition, we are looking at how JAK inhibitors affect the coagulation system in people with inflammatory diseases."
Get to know Prof. Nurmohamed
Prof. Nurmohamed is Professor of Rheumatology at Amsterdam UMC and Head of the Rheumatology Research Department at Reade. Furthermore, Prof. Nurmohamed holds several ancillary positions including Board Member of the Dutch Medicines Evaluation Board and Editorial Board Member of several renowned journals (e.g. Drugs, J Rheumatology, Plos One). One thing that is certain about Prof. Nurmohamed is that he loves a good challenge, July 1, 1994 is a date he will never forget, on this day he accepted the challenge of receiving his doctorate and getting married on the same day, both of which Prof. Nurmohamed successfully completed. Twice a year Prof. Nurmohamed travels to Bonaire to work on the outpatient clinic, this gives him a lot of energy. In addition, experimenting with his own salt aquarium is a great hobby, breeding anemone fish is a challenge for the future.
Text: Esmée Vesseur
Curious to learn more about rheumatoid arthritis?
- Altered gene signatures are detectable in synovial biopsies of individuals at risk of rheumatoid arthritis, which are associated with development of disease months to years later (December 2022)
- Interview with Lisa van Baarsen in MedNet's rheumatology newspaper (October 2022)
- Accelerated innovation driven by COVID-19 in rheumatoid arthritis research (August 2022)