In today’s interview, we talk about chronic smoldering inflammation in multiple sclerosis (MS) – a process that affects many people with MS but often goes unnoticed for a long time. I speak with Dr. Boris Kallmann about how these slow, subtle changes show up, how they can be recognized, and which treatment options are available today – and may become available in the near future.
This episode was supported by Sanofi S.A.
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Introduction
Please introduce yourself briefly: Who are you and how did you come to work with MS patients and clinical research?
Dr. Boris Kallmann: My name is Boris Kallmann. I am originally from the northern part of Germany, near Göttingen, and then moved south for work—to Franconia, or Bamberg to be precise. I have been based there since 2007 and have set up my own practice, including an MS center.
Even during my time at the University of Würzburg, I was intensively involved with multiple sclerosis – both scientifically and clinically. I was particularly interested in questions relating to the blood-brain barrier and the immune system: How does the immune system change in MS? What role does it play in inflammation and the course of the disease?
What ultimately kept me interested in this topic is the complexity of the disease. MS can be researched in the laboratory, at the cellular level—but we can and must also provide intensive care for the people who live with this disease. It is precisely this holistic view that has motivated me to accompany MS patients over many years, to make decisions together, and to constantly ask myself: What can we do better today—and what can we perhaps do better tomorrow?
A practical view
You have been supporting many people with MS for years. What do you notice in people whose MS is slowly worsening—without them having relapses?
Dr. Boris Kallmann: This is a hot topic at the moment – almost a wave sweeping through the MS world. To be honest, though, it’s nothing new. Since I started working with MS in the mid-1990s, we have known that, in addition to acute relapses, there are also slow, insidious changes.
For a long time, our focus was strongly on relapses, i.e., acute inflammatory events. That was the right thing to do, because we have made enormous progress in this area and now have very effective therapies. At the same time, we may have lost sight of the fact that in some people, the disease can slowly worsen independently of relapses.
In the past, it was said that there is first a relapsing-remitting phase, and after ten to fifteen years, the disease progresses to secondary progressive MS. Today, we see that this is much more individual. Thanks to modern therapies, we can often significantly delay this development—but we cannot always prevent it completely. There are people who no longer have relapses but still experience slow changes.
Recognizing subtle changes
How do you recognize such slowly progressing courses in practice—and how often do they occur?
Dr. Boris Kallmann: First of all, I rely on my gut feeling – and on listening carefully. MS is not a disease with a thousand faces, as is often said, but a disease with great fluctuations. Those affected experience good and bad days, as everyone does, but with MS this is much more pronounced.
The big challenge is to distinguish between normal fluctuations and genuine, long-term worsening. A classic example is walking. Many people with MS report that walking becomes more difficult – their legs become weaker, stiffer, or less coordinated. I then ask specific questions: What exactly has changed? Over what period of time? What was still possible six months ago that is no longer possible today?
The same applies to other symptoms such as fatigue, concentration problems, or sensory disturbances. The time factor is crucial. That’s why it’s important for me to work with patients to determine whether their symptoms have been slowly worsening over a period of months.
My clear request is: take notes. Keep a diary, whether on paper or digitally. This information is extremely helpful in classifying developments.
Use of technologies for monitoring progress
Dr. Boris Kallmann: Almost everyone has a smartphone these days, and most devices already collect health data in the background—for example, step counts, walking distances, or even fall risks. You don’t necessarily need a smartwatch for this. The important thing is to actually use this data.
I’m not interested in the perfect day, but rather the average: the mean value for a month. If I see that this changes over several months, I can identify trends. Of course, external factors must be taken into account—weather, infections, stress—but basically, this data provides valuable information.
In addition, such tools can be motivating. Many people develop athletic ambition, set small goals for themselves, and thus remain more active. For me, that’s already part of the therapy.
Therapy goals for smoldering inflammation
What therapeutic options have you had so far for gradual worsening – and what realistic goals have you been able to pursue with them?
Dr. Boris Kallmann: We have more options than many people think. The first step is always your own attitude: What can I do myself? Exercise is key – regardless of whether someone can walk or is in a wheelchair. Training is not just about quantity, but above all about quality.
The second pillar is symptomatic therapy. Pain, spasticity, or other complaints can prevent movement – so we have to treat them specifically. There are many options here: classic medications, antispasticity drugs, but also cannabis, if used sensibly.
Another important point is physical therapy. Not as massage, but as active work. The goal is for those affected to continue training at home.
Then immunotherapies come into play. If we see that there is still inflammatory activity—such as new lesions on MRI—we should consider changing therapy. Good data shows that this can be useful.
Note from Nele:
If you would like to learn more about this topic, I discussed the benefits of physical exercise on the immune system and MS symptoms with Prof. Ulrik Dalgas in a separate podcast episode.
New therapeutic approaches & clinical trial experience
You are also actively involved in studies in your practice. What has been the latest development in research into progressive MS?
Dr. Boris Kallmann: We are gaining a better understanding that a large part of the progressive deterioration takes place directly in the brain and spinal cord. This is where the inflammatory cells are located, which many of our existing drugs are unable to reach.
This is precisely where new groups of active substances, which are currently being intensively researched, come into play. It is particularly exciting that several studies—including phase 3 studies—are already showing positive effects. This gives us hope that we will be able to influence these processes in a more targeted manner in the future.
Note from Nele:
If you would like to learn more about smoking, why it is beneficial to quit, especially if you have MS, and how you can succeed, listen to the interview with Dr. Claudia Marck, who used to be a heavy smoker herself.
BTK inhibitors and where they're used
BTK inhibitors give many people hope. How do they work—and how do they differ from previous therapies?
Dr. Boris Kallmann: BTK inhibitors, or Bruton’s tyrosine kinase inhibitors, attack on two fronts. On the one hand, they act on B cells in the blood, similar to well-known anti-CD20 therapies. On the other hand, they can cross the blood-brain barrier and act directly on local inflammatory cells such as microglia in the brain.
One point is particularly important to me because it is often misunderstood: studies have shown that BTK inhibitors are not inferior to the comparator therapy. This means that they are at least as effective as established drugs in combating classic inflammatory activity, i.e., relapses and new lesions.
In one study, for example, they were compared with teriflunomide. This showed a comparable anti-inflammatory effect – in addition to the effect on reducing disease progression. This is precisely what makes this class of drugs so interesting.
What makes them special is that these drugs reach areas that we have hardly been able to influence until now. Studies show that they not only slow down progression, but also have an anti-inflammatory effect that is comparable to established therapies.
You can find out more about the therapeutic concept of BTK inhibitors here:
Dr. Boris Kallmann:
Despite all the justified hope, I would also like to make it clear that there is no drug without possible side effects. In the studies on BTK inhibitors, changes in liver values were observed, among other things.
This means that great care must be taken, especially at the beginning. There will probably be close monitoring, particularly in the initial phase. And, of course, it will be necessary to carefully assess which patients are suitable for this therapy—especially those with pre-existing liver problems.
Healthcare, specialization, and rural areas
What is your estimate: Will this new class of drugs be widely used, or could patients benefit from additionally consulting specialized centers or study practices?
Dr. Boris Kallmann: I believe that these new drugs will initially be used rather cautiously. On the one hand, this is due to the guidelines issued by health authorities, which will specify very precisely for which patient groups they are approved.
On the other hand, it is because many colleagues understandably want to gain experience before routinely using a new class of drugs.
Especially in the beginning, the drugs will therefore probably be used more frequently in specialized centers—i.e., places where there is a lot of experience with MS and where close monitoring can be well organized. This applies in particular to the initial phase, when regular laboratory tests will be necessary.
Another point is the overall care situation. In some regions, there are a large number of neurologists, while in others – especially in rural areas – there are significantly fewer. In these areas, doctors often treat many different neurological diseases and have only a few MS patients. This makes it more difficult to implement new treatment concepts comprehensively right away.
That is why I believe good cooperation is crucial: between patients, local neurologists in private practice, and specialized MS centers. It can be very useful to involve a specialized center in the decision on therapy or new treatment, while long-term care continues to be provided close to home. In my opinion, this model works well and will become even more important in the future.
Note from Nele:
Many people affected tell me that this model—specialized advice on important therapy decisions and local support in everyday life—works well for them and gives them a sense of security.
Focusing on the future
What developments in the field of MS would you like to see in the next five years?
Dr. Boris Kallmann: My greatest wish is that we gain better control over the progression of the disease. If we can establish effective treatment options in this area, that would be a major step forward. We are still in the very early stages here. There are already two active substances—tolebrutinib and fenebrutinib—for which we have initial study data. But we will only see much more once these drugs are used in everyday practice.
It is quite possible that they will prove to have even more potential than we can currently deduce from the studies. That is why it is so important to systematically record data and closely monitor changes in the future.
In addition, I hope to see long-term progress in areas such as remyelination or even neuroregeneration—even if that will probably take several more years.
Farewell
What else would you like to share with our audience?
Dr. Boris Kallmann: Stay interested, stay informed, and take responsibility for your own health. MS manifests itself differently in every person—and the ways of dealing with the disease can be just as individual. Your podcast makes an important contribution to this by informing, motivating, and encouraging people.
See you soon and try to make the best out of your life,
Nele
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