S8E25: Webinar Highlights – Medication with Dr Jonny White

Dr Jonathan White (00:00)

It’s always, I think it’s always worth having that discussion about, okay, where do we go next? If this one doesn’t work and if I open this door, does it close other ones to me? I think that that is a really reasonable thing to ask.

 

Regina Beach (00:51)

Today’s episode features audio from the Medication and MS Making Sense of Your Options webinar, part of the Living Well with MS webinar series. Dr. Jonathan White, Overcoming MS program facilitator and medical advisor, and myself, Regina Beach, explore the complex world of MS medications and treatments.

 

Dr Jonathan White (01:13)

So first thing to say is that I’m not a neurologist and I don’t claim to be, but I am a practising UK doctor. I work as the medical advisor for Overcoming MS, alongside my job as a facilitator for them. My real job is as an obstetrician and gynaecologist within the NHS in the UK. My area of interest is in recurrent pregnancy loss and early pregnancy care.

 

I myself had a lived experience of MS from my own diagnosis in 2015 and I’ve been following the Overcoming MS program for, I’d say about 48 hours after that time and I’ve been doing so ever since. I’ve spoken and written now fairly widely on the rule of medication and lifestyle modification in MS. But as I said, it’s a professional and personal passion, but it’s not my absolute day job.

 

So what I thought we would cover today, and for those of you who may have heard me talk about this before, a lot of it will be similar, but it changes every time I do it. And that’s the nature of the beast with this. The landscape of medication changes at just a rapid, rapid pace.

 

So I think it’s important to start off by recognising where we as an organisation are coming from, that we are absolutely pro-medication as part of someone’s holistic management for MS when it’s right for them. There traditionally has been perhaps a perception among some people and healthcare professionals that we may have been anti-medication. That’s never been the case at all. George Jelinek has said while the drug only approach is not good medicine, the medications have a significant role.

 

As part of an integrated preventive medicine strategy to assist recovery for many people with MS and I couldn’t agree more. Many of you will be familiar with the Overcoming MS Program and the seven pillars it contains. Medication is absolutely a key aspect of that. But as I said, may not be right for every person and everyone’s MS. I think our role in that is to help support and guide in making those decisions and giving you that trusted information and time and space to come to a decision that you’re comfortable with.

 

A lot of people will think medication is synonymous with DMTs or DMDs, but there’s much more to medication and MS than just that. And if you think in three broad circles, there’s the DMTs, there’s medication for relapses and there’s treatments for symptoms. And all of those things interact with each other and they intersect around lifestyle choices. So for example, you may need medication to treat symptoms to then allow you to be in a place whereby you can have the headspace or the cognitive ability or the energy to then do the research to make the consideration about which DMT to take, which prevent relapses and so you go round and round.

 

The balance of those things changes throughout our MS and throughout our health course.

 

So if we go to steroids first of all, they are used in the treatment of acute relapse. So an MS relapse is defined as new or worsening symptoms lasting 24 hours or more, occurring at least 30 days from the start of a previous relapse. So that means you can only technically have one relapse a month or 12 in a year. And there mustn’t be another reason for symptoms. So for example, stress, infection, a raised temperature, all things that can bring about old symptoms or what we call pseudo relapse.

 

So steroid in this instance is short for corticosteroid, which is a natural group of hormones made within the liver of the body, synthesized from cholesterol largely that we get from our diet.

 

We’re using steroids to shorten recovery time from an individual relapse, but it does not have an effect on the disability that you would be left with from that relapse with a long-term course of MS. So it doesn’t change your prognosis or trajectory. It just shortens that healing time. And it is prescribed usually for three to five days, It’s usually methyl prednisolone 500 to 1000 milligrams.

 

And it can be oral or intravenous. It used to always be intravenous. That meant admission to hospital and all of the change in routine and the risk of infections. There’s no evidence that it’s superior to have it intravenously.

 

Steroids in this case act by suppressing the immune system. So there’s no good and bad, and I know I’ve written bad on that, but it reduces the pro-inflammatory signals of the immune system. And it also makes white blood cell membranes more pliable and less sticky. So they’re less likely to clump together and attack at the site of injury. It will significantly reduce the swelling around MS lesion, often within hours of the dose, if you look on MRI, and it then allows better nerve transmission, which can help with the symptoms.

 

But the reason we don’t use it in the long term is that it can cause weight gain, fluid retention, infections because the immune system is dampened, it really damages the stomach lining and can cause ulceration and bleeding, can cause muscle weakness, depression or psychosis, cataracts and osteoporosis. So you don’t want to take it long term, but they are absolutely safe and effective if they’re used in short courses.

 

So moving on then to the DMTs.

The first generation of those came into being and practice in the mid 1990s in this country. And those were the injectables interferon, but interferon and Copaxone. They had a modest effect on relapse rate reduction. And when they say modest, it generally means about a third reduction. So if you were to have three relapses in a year, they were reducing by 33%, which meant you would have two rather than three relapses compared to placebo.

 

At the time of licensing, was very little known about their effects on disability progression in the long term, and they came with really significant side effects, more so interferons, where you felt you had flu-like symptoms often for 24 to 36 hours after a dose. And if you take it three times a week, that’s over half your week feeling pretty miserable.

 

2000s then, the second generation started to become available and those tend to be infusions, injections and tablets. They have a better effect on relapses and there is evidence with some of them for the slowing of disability accumulation. And in 2019, the first treatments for progressive MS were released and continue to be so.

 

If I can perhaps look at this from the neurology perspective, of MS up until the mid 1990s being a disease of very often inevitable progressive decline where there was no meaningful treatment, and we now have treatments that are very effective at reducing relapse rates and turning off that inflammatory activity less so at the minute on slowing progressive disability but we are definitely seeing more of that and as a result, less secondary progressive MS. And the consensus of a major group of MS charities from the Brain Health Report in 2015 and last year was that early treatment is the key to MS care. So rather than that traditional wait and see approach, was often and can sometimes still be used, there’s now a trend towards really aggressively treating MS at an early stage to no evidence of disease activity or NEDI or sometimes NEIDI for inflammatory.

 

And that’s where they’re coming from. When I say they, I mean neurologists and MS teams. They’re not the enemy, they are there. Some people find this a very difficult subject where they feel pressurised and if they don’t want to make that decision, then almost cut adrift. But just, I suppose, from their perspective, they now have treatments they find are very, very effective, but they’re not the ones that have to weigh out the personal risk, benefit profiles and side effects of that. It can be a very difficult decision to come to.

 

Gavin Javonone and others talk about flipping the pyramid of MS whereby you, rather than building up the efficacy of a DMT, you start high and you try to induce almost reconstitution of the immune system or remission of the MS. So you’re what we call flipping the pyramid.

 

And the theory and early evidence would suggest that that is a very effective way of preventing long-term disability, certainly through relapse associated worsening, which is RAW or raw. Another big topic, is smoldering associated worsening or SAW. And at the minute, we don’t have really effective medications for that. So there is huge scope within medication and treating MS to use lifestyle strategies to reduce that smoldering effect which affords neuroprotection and stops that damage and accidental loss that we often get that leads to progressive symptoms. So there’s room for both. Taking a DMT or DMD usually nearly always will involve monitoring for safety and efficacy, which is often blood tests, clinic visits, neurologists, MS nurses, infusion centers, ideally MRI scans, which comes with the scans which I personally know very well.

 

It’s impossible to predict an individual’s response to any particular drug. So there is no good way of doing that. You can’t say this person is going to do really well if they take X. But what we do know is that if you respond well and early to a particular drug, in terms of relapses and disability progression, that is a good way of predicting your long-term progression at 10 years. So if you respond and you have no evidence of disease activity and no relapses in the first 6 to 12 to 18 months, that’s a really good sign for the medium to longer term. So I’m going to go through the main classes now individually.

 

So the interferons.

They came online 2002, they were self-injectable, somewhere once, twice, three times a week. As I said, about a 33 % reduction in relapses versus placebo. Interestingly, some of the longer term data did show that there was a modest effect on disability progression. So you could look at that positively and say, well, even the medications that weren’t as effective still had a benefit in the longer term. But as I said, the side effects often made it very difficult to take and they have largely been overtaken by the new generation. Capaxone, really interesting drug if you like, I suppose the history of science because they were originally designing capaxone to induce MS in mice and then by a twist of fate like penicillin almost, they found that it prevented it in mice. So it mimics myelin, it tricks. Myelin is the fatty protein covering nerves that is attacked by our immune  systems in MS.

 

And capaxone and glutiromer tricks the immune system into reducing inflammation and in early stages promoting remyelination. It doesn’t suppress immune systems. You don’t need to monitor your blood. It’s usually a daily injection, but it often doesn’t cause much of side effects for people other than injection site reactions. Its effects are similar in terms of relapse rates to that of interferons.

 

The longer you use it, the better it seems to work. And it was the first drug licensed in MS for pregnancy and breastfeeding, which I’ll touch on later. And they’re both interferons and compaction licensed to treat clinically isolated syndrome, which is the first presentation of MS symptoms and active relapsing remitting MS. So briefly to explain this, it’s a bit of a tongue twister. Active MS means two or more relapses in the last two years and or new MRI lesions.

 

And these are ways of stratifying people for its health economics who needs certain treatments. Highly active MS is relapses after treatment for a year or two or more severe or disabling relapses in previous year and new lesions on two consecutive MRI scans.

 

Fingolimod or Gilenya was the first oral treatment for MS. I mean, that’s a giant leap forward that you can take a tablet rather than having to inject yourself. And it was once a day, which we know really helps with compliance. It’s licensed for highly active relapsing remitting MS, but is often used in many places for active MS and a first line treatment. It is a really unusual action because it reversibly will trap immune cells in the lymph nodes or the barracks of the little foot soldiers of the immune system so that it can’t get out into the system, cross the blood-brain barrier and can’t attack myelin, but it doesn’t suppress your immune system overall. So it doesn’t increase your risk then of infections, which is one of the major side effects of these drugs. Reduces relapses by 50%, 52%. So that’s gone from 33, we’re up to now 50. So you can see that the significant increase in its efficacy.

 

And in one study from the initial data, the risk of disability progression was reduced by around 30%. The first dose is always given in hospital because there is a risk of a slow heart rate. If it doesn’t happen on the first dose, it won’t happen with any subsequent one. And there is potential for rebound disease activity when you stop it, which means that if you stop the tablet, often your MS will go back to the point that it was at before you started and in fact may actually go further and worsen.

 

You absolutely must not become pregnant taking Fingolimod There’s a significant risk of fetal abnormalities and you need to have about two months washout before becoming pregnant, which is relevant when three and four patients are female and many of those will be in the reproductive phase of their lives.

 

Tecfidera or BG12 dimethyl fumarate and was previously a treatment for psoriasis and actually spray put into shoes and on furniture to prevent mold growth, which was nice and was licensed in 2013. It is twice daily capsule. Really interestingly, it has anti-inflammatory but also neuroprotective effect and acts in a way like fasting does, promotes a certain pathway that mimics fasting, which is another really interesting area. Reduces relapses by 50% and there’s evidence of reduction in disability progression from two of the early large studies. Can be tricky to take for some. One of the major side effects was flushing. I took Tecfidera myself for many years and whilst it worked well for me, it was pretty funny being a gynaecologist that used to flush regularly. It often will cause stomach upset and there is a risk of upper respiratory and urinary tract infections and 10% of people will stop the treatment because of this.

 

Blood tests are taken every three months to ensure that your white blood cells don’t drop too low and that your liver and kidney functions are normal. And there are low numbers of cases now, and as I said, it’s been on the market for long time, of something called PML, progressive multifocal leukoencephalopathy, which is something we’re going to talk about in much more detail in a moment or two regarding another drug. I feel it’s important that I mention there have been in the single figures last time I checked the number of cases around the world with Tecfidera.

 

Obagiol or Teriflunomide has been around since 2014. It’s a once a day tablet, still very popular in the United States because many of the insurance companies will cover it. It reduces relapses by 30%. So around the same as the first generation, many through disability accumulation. About 10% will suffer side effects. Nearly all of them, it’s respiratory and you’ll retract infections.

 

Hair loss and alopecia is a really relevant concern with Abaju and transient raising liver enzymes, also pins and needles, nausea and vomiting. You’re advised to limit alcohol, not completely avoid it, but to completely avoid live vaccines. And I think this is probably the most limiting thing about Aubagio, given the number of people who may wish to become pregnant. There’s a 24 month risk of birth defects after stopping treatment. So it takes two years to get fully out of your system. If you were to become pregnant in that period, there are treatments that we can use to wash it out quicker, but it’s not a situation that you would wish to find yourself in.

 

Natalizumab was the first of the really effective high efficacy drugs. It’s often known as Tysabri or Tyruko now. And I know there’s lots of that. That was the first of one of the biosimilars. So when they come off patent after 10 years, these medications can be made by any company and they in theory should be exactly the same. But there have been published data now to show that Tyruko certainly does not behave like Tysabri for some people. And in fact, there have been some significant issues with it.

 

It’s a monthly infusion. It’s licensed for very active MS, reduces relapses by 70%. So again, we’re really pushing on now versus placebo and slows progression disability by 42%. Lots of people have been on this for a very long time and it’s kept them very, very well. The side effects of the drug itself are usually minimal, but it’s the risk of PML that I spoke about a moment or two ago that is really significant here.

 

PML relates to a completely harmless virus, the John Cunningham JC virus, that 50 to 70% of us in the population will have or will be positive for. If you’re not positive for it, your risk of PML is very, very low. It’s around one in 10,000. But if you do develop it, the potential for severe disability or death is very high. It’s one in four. So the problem is that you could be negative when you start treatment, but become positive. And at that point then, there are some very difficult discussions because what they’ll have to do is monitor the levels of the virus in your system. And as the levels get higher, the risk increases of PML. And so at that point, you may have to have discussions with your neurologist about changing and moving off Tysabri, which can be difficult to do.

 

Because as I said, around fingolimod, there is a 10% chance of rebound disease where things get worse. And it is very difficult to work out which of the other DMTs you should change over to, to avoid this iris (virus?) or immune reconstitution inflammatory syndrome. Fingolimod was certainly one of them. Ocrevus or Ocrelizumab has become another one, but individual practicing clinicians will have their own preferences and be able to guide on that.

 

And I think these are really, really important things to consider. So this is very effective medication, but what happens if I have to stop?

 

Lemtrada. So if I’d have been giving you this presentation 10 years ago, many, many of us would have been offered this drug. I was offered it in my own diagnosis of 2015. It’s really gone down in popularity, although it still remains a very effective drug. You’ll see why it’s gone down in popularity. It’s licensed for active and very active relapsing reminiscence. It binds to B and T immune cells, they’re two of the… I suppose the key soldiers of the immune system and it destroys them. It’s almost like a mini stem cell transplant. It’s what’s called Immune Reconstitution Therapy, IRT, because it destroys your immune system and it reboots itself. It’s given as an infusion over five days and then 12 months later as a three day course. Up to 50% require third or fourth. Some have had a fifth course and it requires four years of monthly blood tests after that last dose. So that’s not insignificant.

 

Very effective in terms of relapse rates. There is evidence for a reduction in disability. Females are advised to avoid pregnancy for around four months after a treatment.

 

But here’s the problem, side effects and secondary immune issues are a really big issue here. At the time of the infusion, it’s things like headaches and rash, hives, nausea, vomiting, which is usually manageable. About a third will develop an autoimmune thyroid disease whereby they need treatment for that. 1 to 3% will develop a, what’s called a thrombocytopenia, which is a platelet condition. It can cause bleeding and may need monitoring and treatment.

 

And then in 2019, there were new reports of really rare, very serious side effects around the immune system, liver, heart and blood vessels. And so the European Medicines Agency and the FDA following suit really have changed the criteria so that you can only use it if two other DMTs have proved ineffective or you run out of options. As I said, though, it’s still very popular with neurologists because they see how well it works, but it does need to be monitored really carefully. A lot of the side effects, if you do develop them, are not reversible.

 

Mavenclad was approved in the UK in 2018. It was already an anti-cancer drug as many of these have been in the past. It’s a tablet you take for five days, you repeat it after a month and then again after 12 months. And there’s no follow-up data certainly past five years that shows that people remain in remission and don’t require any other DMT after that. Reduces relapse rates by almost 60% against placebo, reduces risk of disability progression by around 30%. One in four will end up with severe lymphopenia, which is a drop in their white blood cells, which can then increase the risk of infections, reactivation of things like herpes virus and shingles. So there are regular monitoring and blood tests.

 

Both men and women need to avoid pregnancy for six months after their last dose.

 

Ocrevus is really popular now and many will have heard of it. It was the first medical treatment for primary progressive MS and is also used in relapsing remitting. It’s an infusion that you’re given two weeks apart and then every six months. And in primary progressive MS, the initial data showed the 12 week disability progression rates were reduced by around a quarter versus placebo. And you might say, well, 12 weeks is only three months and I’m going to have primary progressive for the rest of my life. Is that really significant? Well, yes, it was because it was the first one that was ever shown to do that. And the 12 week confirmed disability progression scores were a really good way of objectively measuring that. So there is continued data still, and that does hold up over the medium term, certainly. In relapsing remitting MS, it reduces your relapses by 50% compared to interferon. So it’s quite hard now to compare apples and oranges because some were against placebo and now they’re what’s called non-inferiority trials because it’s not really ethical to give people placebos and MS when you know that other  drugs are effective so they usually compare them to the less effective ones.

 

Ocrevus was one of the first drugs that showed a reduction in brain atrophy rates. And that’s important because brain atrophy essentially is loss of brain tissue. All humans do that as they age, but unfortunately in MS that rate is significantly higher. So often a metric that we use now in these trials is checking how the drug affects the rate that the brain tissue is lost. There is an increased risk of unusual chest infections, some urine infections, and there are concerns over possible cancers. But there’s no direct evidence that it causes cancers. It’s a theoretical because you’re suppressing the B cells within the immune system. It’s worth saying that ocrevus comes from a treatment designed to treat cancer. So it was used for lymphomas and leukemias when it was something called Rituximab, and the Swedish still use that very regularly in treatment of MS, and there is no direct evidence that it increased the risk of cancer, particularly breast cancer, which was a concern. A review from a couple of years ago now is showing that it is either equally or more effective than all the other DMTs and that its side effect profile is as favourable as any other DMT.

 

Braumvi, which is ubituximab came online last year. It’s a very similar drug. It’s given in the same way and works in the same way. I think it’s important that people understand there are still quite strict criteria as to who can get Ocrevus in primary progressive MS. And that’s again about health economics and also a lack of data as to who it works best for at the moment. So it will vary depending on where you are, but there is commonality there. And what I would say is that the NICE criteria are having had symptoms of primary progressive MS for 15 years or less. Relatively, although 15 years is long time, but relatively new diagnosis rather than 30, 35 years of MS that you should be able to walk 20 metres or more with or without walking aids. So that gives you an EDSS, which is a scoring scale for disability, although it’s very crude and controversial of 6.5. And you have to have evidence of inflammatory activity and an MRI scan.

 

So really what that looks like is that you have had primary progressive MS for not an enormous length of time, that you still have some lower limb function and that you have inflammatory activity in an MRI scan because these are the people that it should work best for. But of course we need treatment options for everybody living with MS at every stage, should they wish to use them.

 

Kesimpta is Ofatumumab and it’s a really interesting drug because it’s the first B-cell depleter, so that all of these are anti-CD20s, that you can give yourself at home. So it’s self-injected every four weeks, reduces relapses by up to 60 % versus Aubagio over two and a half years. It reduces disability progression by a third compared to Teriflunomide or Aubagio, and it’s safe to conceive on Kesimpta.

 

And safe to breastfeed. So side effects wise, it’s again, always about infections. It’s always about injections, site reactions. And around a fifth will get headaches or flushing. And that first initial dose, because you have to take it regularly for a month. It’s once a week rather than once a month for the first loading period. Very often will cause some flu-like symptoms, but most will not experience that when they inject regularly.

 

Siponimod or mayzent was the first treatment for secondary progressive MS, which is the condition that certainly 50% of people with relapsing remitting MS will develop by the 25 year mark. That number is going down, but there are a significant number of people who live with SPMS who have never had a treatment option and still are not meeting the criteria for that. It’s a once a day tablet. It’s very similar to Fingolimod. So it’s one of the tablets that you must take in hospital monitoring your heart rate, watching for low white blood cells and all of those sorts of things as well as swelling in the back of the eye. There is some really nice early data about reducing the risk of disability at six months and brain atrophy rates, but it needs longer term study and while that is happening, very few people will be eligible for it and that’s a recurring problem.

 

Zeposia proof for active relapsing remitting MS in 2021. It’s a once daily tablet, again, similar to Fingulamod, similar side effect profiles and risks.

 

You’re seeing a recurring theme here. It’s again, very similar to Fingolimod. It’s for active relapsing  MS. It’s a single once daily tablet. Reduced relapse rates by around the same. Again, evidence of slowing of brain atrophy and improvement in fatigue, which we’ll cover in a moment or two, and similar side effects. So, as a brief run through of, of the current licensed DMTs. At any one time, there are some that are coming on and going off. It usually sits around between 13 and 15 different options. No one patient with MS will ever be offered all of them, but quite often you’re told, probably in your case, it’s two or three, here the leaflets go and make that choice.

 

What I would recommend in that instance actually is using a decision-making tool, obviously speaking to your MS care team. One that I have found really helpful in the past is that of the MS Trust in the UK. They have a decision-making guide and it’s an interactive tool. It lays out things really, really clearly in a really usable way. And I find it personally quite helpful. Some people think graphically and for me, I often do. So the DMT pyramid is a way for me to sort of conceptualize this.

 

Thinking at the bottom, you’ve got the Copaxone’s, interferons, about 30% reduction in relapse rates. Up above them, the orals, fingolimod, Tecfidera, teriflunomide reducing relapses by 50%. And then you’ve got the 70 % reduction from the usually infusions or injections or cladribine, which is that course of oral tablets that you take twice.

 

It’s worth knowing for those of you who may be considering pregnancy or if that’s in the long-term future for you, the association of British neurologists have really, really helpful guidance on this now. The take home message of that is that, and this is as an obstetrician, I feel confident in saying this, we generally overstate the risks for obvious reasons. It’s a high stakes game.

 

It’s not ethical to test medications on unborn foetuses. So it takes a long time to collect data on people using medication. So we see this in all sorts of conditions. There was a really helpful German paper on this a few years ago now, and it really showed that DMTs did not increase pregnancy complications, miscarriage, small babies, pre-term birth or stillbirth. But what we thought about Fingolimod was true, and that it did increase the risk of congenital abnormality.

 

Maybe some data pointing at reduced birth weights with, if you continued your DMT into the third trimester, mainly with Tysabri. But as a whole, that they were much safer to be pregnant and to breastfeed on. But as I said, the ABN guidance there is really, helpful. So where does this leave us? These are difficult decisions to make. It might not be the right choice for everybody.

 

But it is important to think about especially in early aggressive disease when the inflammatory load, new lesions in your MRI is high. And because the new DMTs are really good at treating that and that might just get you to the even keel where, if you’re thinking about using lifestyle alongside this, it gives you that protection whilst all that effect within the body and from the cell level up is really maximising. So questions that I maybe have asked myself and thought about when I’m trying to make this call is, when should I start? Do I go for it now? Do I hit this hard? Do I build up and see, or do I watch and wait? Which one should I take? What are my options? What am I being advised? What benefits can I expect? Because what you need to remember about a DMT is this is about preventing relapses and disability largely, not about making you feel better on a day-to-day basis. In fact, some of them make you feel worse, certainly in the short term. What are the risks? What are the potential side effects? How does this fit into my lifestyle? If I travel for work, do I need a fridge? Can I travel with needles? How do I get a supply if I’m away? How often do I have to have an MRI or a blood test? How often do I have to go and see my nurse or my neurologist? I’m thinking about starting a family. How do I do that? Where?

 

What does it look like? When do I change medication? Stop, reduce my medication? When do I have to start again? My breastfeeding on this? These are all really, really difficult, intensely personal decisions.

 

So if we then briefly move on to some of the symptom relief treatments and you know, you could spend a long time talking about this because MS can affect so many things. I was talking to a patient today about bladder symptoms and I haven’t covered bladder stuff directly, you know, bowel bladder, sexual function, these are all very relevant. And I’ve neglected to mention them. And I think that really says something that these more intimate symptoms are often not covered well. And that’s something that I think we all need to get better at advocating for,  and I’ll certainly consider when I revise the presentation again. But baclofen is certainly one to consider and to think about. This is a first-line treatment for spasticity. So spasticity is that tight contracted feeling within a muscle or a group of muscles. It’s really, really common in people with MS. It is a GABA receptor agonist. So it reduces nerve cell transmission. So it causes muscle relaxation. It’s an oral tablet, a low dose that you increase slowly to balance side effects and benefits because obviously if you relax a muscle it makes it bit weaker so you have to balance them being able to function versus the terrible pain and stiffness and disruption of spasticity. It can be given as a pump into the spinal cord directly for relatively severe cases. Around 45% will suffer side effects and often that is disturbance to sleep, worsening dizziness and worsening fatigue.

 

You must not stop it suddenly. If you want to come off it, please tell your care team because it can cause seizures and hallucinations. So it needs to be reduced slowly.

 

Fampridine or Fampyra , a really interesting drug. Access to this has been far too patchy for far too long. It’s a twice daily tablet, blocks potassium channels, so it improves the efficiency of nerve transmission. And it was initially designed to increase walking speed. The problem with it was, that it was always felt to be non-cost effective. So it was very hard to get publicly. But what we know is that for a third of patients, it will significantly increase their walking speed. And there may be additional benefits to hand and cognitive function. You also know within a matter of weeks if it’s going to work. So it’s not like you have to take up two years to get full effect. You’ll know within a month or so, if it’s not working, then it could be stopped. But nonetheless, many people have to privately fund it and that comes at significant cost. So there are sometimes finance and payment plans available through the pharmaceutical companies. Side effects, just to mention briefly, UTIs, dizziness, headache, back pain, insomnia, nausea and vomiting, all the usual not so fun things. Fampridine really, really interesting though, and is being studied, I think, with the MS register in the UK, in Swansea University. It’d be really interesting to see what that data shows about its efficacy and if we can get more access from more people.

 

Fatigue. Fatigue is probably one of the best known symptoms of MS, possibly the most debilitating for lots of people. It affects three quarters of us. It can be physical, emotional, or cognitive. It’s probably the most debilitating symptom that I live with. And it’s usually cognitive for me. So I will suffer from cog fog if I, for example, talk nonstop for an hour. But it’s also totally invisible for lots of people and that can be really, really very, difficult to deal with. Primary or secondary? So primary fatigue is due to neuroinflammation damaged by MS within the brain itself. Secondary would be, for example, you have to get up overnight to pass urine three times. Therefore your sleep is disrupted. So you’re then tired the next day and that worsens your fatigue.

 

There are licensed medications, so Modafinil and Amantadine are the two most commonly used. They’re moderately effective, but it’s really worth saying, and there is evidence for this, that exercise, meditation and diet are actually more effective at treating fatigue than medication is. So it may be that you need, and this goes back to that Venn diagram at the start, it may be that adding in Modafinil gives you enough energy to then exercise or cook a little better in terms of energy reserve, which then improves your fatigue to the point where you don’t feel it’s necessary to take the medication anymore. And that’s how I sort of think of how these are interrelated.

 

Cannabis, I’m sure many of you will have heard of it for its use in MS. It’s been around for a long time in the MS community. Cannabis contains two active cannabinoid compounds, THC, CBD. THC gives you the high. CBD is the bit that MS benefits from if you like directly. So it improves pain, spasticity, muscle cramps and sleep. It is legal in the UK, but only on prescription from a specialist and it’s very difficult in Scotland. It can be easy to access, but it can be very difficult to get Sativex spray on prescription in many parts. Therefore, some people move to private prescriptions or more traditional sources. And if you are to smoke cannabis, then it gives you all the risk of tobacco smoking plus the narcotic effects, which then has concerns for mental health, memory loss, panic attacks, psychosis. The evidence is clear on this that 10% of people with MS the benefit from medicinal cannabis there’s no way 10% of people with MS have access to it at the minute.

 

Just to highlight a couple of things. Ibudilast is a drug that has been used in Japan for quite some time as a treatment for asthma, for stroke and actually for addiction, and it suppresses three inflammatory immune signals and turns on anti-inflammatory signals. It’s been given to people with primary progressive MS in a phase two study over two years. It was found to be safe and significantly reduced brain atrophy rates, which is one of the things that obviously is really, important with regards to progression of MS, we think. So the phase three trials now are ongoing to assess those effects on disability progression and cognition. It’s a really, really interesting medication.

 

Climastine, another one that’s been touted for a couple of years now.

 

It’s a 40 year old antihistamine. It costs cents or pennies, freely available certainly in the United States for hay fever. And the early studies there have shown that an increased nerve conduction speeds in the optic nerve, even if they had significant disability or MS for up to 15 years, and increased the amount of myelin being made in one area of the brain.

 

Side effects wise, same with any antihistamine, was drowsiness and fatigue, so it was given at high dose but at night to try and mitigate that. The explanation for increasing nerve speeds and more myelin on a scan obviously has to be repair or making of myelin, therefore remyelination. That’s often considered the holy grail with in MS treatment. If you can make more myelin or repair damaged myelin, then you could potentially reduce symptoms and reverse disability.

 

But that’s not the same as getting a cure.

 

The other thing that’s interesting about myelination and remyelination is there are little cells called OPCs, oligodendrocyte progenitor cells. So they are the little cells within our central nervous system that go along repairing damage to myelin. I think about if train tracks, railways were damaged, a team would go along and they’d repair the tracks, they’d grease them up again and the trains would be able to pass by safely and effectively. OPCs do the same thing.

 

And in early MS, they’re very effective and that’s how you tend to get good recovery from relapses if you have relapsing remitting MS. But over time and with aging, they somehow switch off or they’re not as effective. So there’s a lot of interest in if you could get stem cells into the brain, can you turn those OPCs back on to make more myelin? Which would then reverse symptoms. And the initial results again are promising, but the treatment here is some years away. The reason that there’s a green viper is that there is a compound within their venom that is currently being looked at to see if that will be effective. Another, I think really novel revolutionary trial is octopus or, and I’m not joking when I say this, platypus in Australia. And this is revolutionary because rather than the ponderously slow, it is really slow path to follow in clinical trials where you get ethical approval, design the trial, recruit, test, follow up of usually one drug. What’s happening here is they’re trialing many drugs at the same time in many places and they’re slotting in. So they’re getting early data saying that’s not effective. Let’s switch out and move to something else. So at the minute, what they’re looking at is Metformin, an anti-diabetic drug. So that mimics some aspects of fasting, arthalipoic acid, is a really high potency antioxidant, and placebo. And so that’s being analyzed right now. And they claim that this allows results three times faster than a traditional trial, which can only be a good thing.

 

Some of you might have heard of BTK inhibitors. feel that I really have to mention these. It’s a difficult topic because it’s one of the ones where you think there’s so much hope and positivity and then another trial will come out that really throws water on that fire. They’re Britten’s tyrosine kinase inhibitors. It’s a really interesting drug because it’s one of the only ones that can penetrate through the blood-brain barrier and get directly into your brain and spinal cord.

 

It’s being tested in relapsing, remitting and progressive forms of the disease. And early data was very, very promising and the FDA gave it breakthrough therapy status at the end of 2024, which meant that it had priority and felt it would be more likely to get licensed quickly. As I said, mixed results. So the Hercules trial tolerated first drug to slow progression in non-relapsing secondary progressive. So there wasn’t evidence of inflammation. It was actually stopping that the progressive effects of axonal loss and brain loss over time. But it didn’t have a benefit in relapsing or remitting MS, and it didn’t meet its primary endpoint in primary progressive MS. Whereas Fenebrutinib, which is related, obviously, did have positive results for both primary progressive and relapsing or remitting MS. So obviously, they need to then look very carefully at the data, try and work out why the discrepancy, which group of patients benefit from what drugs and etc. But really interestingly, and maybe you don’t find this interesting, but I find this fascinating, there was a publication just at the end of last week around, I think it was Tolerbritonib showing that its effect on disability prevention far outweighs its effect on relapses. So usually the two are linked.

 

The better a drug is at stopping relapses, the better it will be at stopping disability progression. And the theory there is that it’s doing that because it’s stopping inflammation. But if the BTK isn’t doing much relapses, but it still has a profound effect on disability progression, it’s tackling what we call smoldering MS, which many will argue, and you’ll see this sometimes, is the real MS, whereby you’re getting degeneration over time. And if you can treat inflammation and degeneration, you’re going to get much better long-term outcomes. And so there are many people who are saying, well, perhaps you need to take one drug at one point and another different type of drug perhaps at another point in your MS or together at the same time. So that will be interesting.

 

Epstein-Barr virus, to very briefly talk about, this is fascinating. If you do not get Epstein-Barr virus, EBV, glandular fever, mono, it’s almost impossible for you to develop MS. But the problem is that 90 to 95% of us will be exposed to EBV during childhood or adolescence. Once you’re exposed, the virus is always there, it’s dormant within your central nervous system, and there is really fairly good early evidence that it is what drives MS activity. So it doesn’t cause it on its own, but if you then have the other things like the genetic makeup that’s prone to MS, lifestyle factors, vitamin D deficiency, et cetera, et cetera, that could be the final piece of the puzzle. So potentially, if you could prevent EBV with a vaccine like they did with HPV for cervical cancer, could you prevent MS? That would be phenomenal.

 

But also, if you gave people antiviral medications, would it treat MS? And so there are four drugs that are now in a phase three trial looking at that. Briefly around stem cell transplants, you will have probably seen stories like this in the media or your friends or family will have come to you and said, why have you not heard or thought about this? This is the cure for MS and some people certainly do consider it that. But it’s a very aggressive treatment option.

 

It’s similar to bone marrow transplant that you would use to treat leukemia. It is a complete destruction and reboot of the immune system and it is not widely available publicly. There are major clinical trials that people can have access to, but in very specific cases, which then leaves space for health tourism. It appears to work best for those who are Recently diagnosed active disease on MRI, aggressive in its nature but little disability at that point. You essentially give chemotherapy to get stem cells, which are little cells that can make any tissue in the body out of our bone marrow, collect them, you freeze your own.

 

You then give more chemotherapy to destroy the remaining immune system and then reinfuse your original stem cells. So it’s called autologous stem cell therapy.

 

But on average, that means one month in clinical isolation, the side effects of major chemotherapy, which many of us will sadly be aware of, through friends or loved ones. On average, it’s 6 to 12 months of recovery time. And in that 6 to 12 months, your symptoms of MS may be significantly worse. The mortality rate is actually now between 0.5 and 2%. And something as a gynaecologist that I don’t think has ever talked about enough is the 40% risk of premature ovarian failure, early menopause.

 

As it stands, there is evidence that it can halt the disease in the medium to long term, mainly to improvement in function, but it is not a cure. So health tourism, whereby you can be charged many tens of thousands of pounds with differing regulations, techniques, documentation, etc. fills that void and is a very dangerous thing in the wrong hands. So in summary, there are ever increasing options. And as somebody living with MS, I genuinely feel there has never been a better time to unfortunately be diagnosed with this condition, whereby more and more people with more forms of MS will have options for treatment. Still not everybody, it’s still not good enough, but it is improving all the time. We know that early treatment is shown to improve long-term outcomes. We have therapies for progressive MS.

 

But the more potent they are, the more significant the risks and side effects. There is no one size fits all. You need to discuss this with your MS team. You need to take time, trust resources. Stem cell transplants are not yet a cure. Other research projects are just as promising. So remyelination therapies, BTK inhibitors and EBV treatment show very, very real potential. So thank you for paying attention

 

Overcoming MS (43:49)

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Gina Beach (44:02)

Wonderful. Thank you so much, Johnny. There’s so much information to distill with this topic. So I think you’ve done a pretty good job And our first question is, what’s the best way or place to keep up to date with this landscape? Because as you said, it is ever changing.

 

Dr Jonathan White (44:20)

Yeah, I think that’s a really good question. Trust of resources is the first thing. So in the UK, I would use the MS Trust, the MS Society. Overcoming MS, we will always try and convey the most relevant and up-to-date information, but our focus is around lifestyle. And so we are a small charity that can’t be minute-to-minute, up-to-date on medication, although we are doing that on a very regular basis. So I think following the right people, can be very helpful. So Gavin G. Evenoni is incredibly up to date. He asks the difficult questions that will move this agenda forward. And you can subscribe to his Substack. MS Selfie is a really, really good resource as well. It depends how much you want to go down the rabbit hole because you could be reading Google alerts five times a day but it’s about trusted resources in a usable way.

 

Gina Beach (45:03)

Yeah, great. So we’ve got a question about someone choosing between cladribine, which you talked about as an immune reconstitution therapy, and a continuous B-cell depleter like Ocrevus. So is there a risk that a person will be ineligible for another DMT after mavenclad if their MRI doesn’t show new or enhancing lesions?

 

Dr Jonathan White (45:28)

Yes, potentially. It’s obviously, you know, specific to individual circumstances, but yes, there is. And it’s always, I think it’s always worth having that discussion about, okay, where do we go next? If this one doesn’t work and if I open this door, does it close other ones to me? I think that that is a really reasonable thing to ask, but that goes back then to, what I was saying about perhaps there being multi-phase treatments. So you may have a short course of anti-CD 20s and then you take something on a longer term basis or vice versa. And so I don’t know what that looks like in the next five years, but I do think that’s probably going to become a common practice.

 

Gina Beach (46:06)

Yeah, that’s great. I want to tag on another maybe good question. Does it have a PEML risk? To my knowledge, is hypothetical that no one has ever developed. Yeah. But maybe you can talk to the second part of the question, what happens after the second year? I know some neurologists are doing a third year, even though that’s recommended. What do you know about all of that?

 

Dr Jonathan White (46:27)

So PML risk theoretically possible, but I’m not aware of any significant data spikes that are saying, yes, you need to be very wary of it. That’s more of a Tysabri, certainly consideration there. With regards to second, third, you know, it’s really interesting that people talk about that almost being a reconstitution, a reboot and a medium term cure because there’s no data out to 7 and close to 10 years where people haven’t required another DMT. So who knows, who knows, but it certainly seems to be much more effective than a 58 % reduction in relapse rates we suggest. Interesting, and I think CloudRubin is gonna have a big role in the future.

 

Gina Beach (47:04)

I recently switched from Tysan to Drabin, so I’m really, really hoping to see them.

 

Dr Jonathan White (47:09)

Yeah, it’s very popular with neurologists now. They’re starting to think this might be a different way of hitting this. yeah.

 

Gina Beach (47:17)

Yeah. Is there evidence that any of these MS medications affect your gut microbiome? Should we be taking probiotics? Is there anything? I know that gastrointestinal symptoms are a side effect of especially the pills.

 

Dr Jonathan White (47:31)

Yeah, it’s interesting. The direct answer is no, not in and of themselves. Although things like tech for Dera, which is the little green pill activates on a called an RF to you, which is a pathway similar to fasting. So maybe they don’t directly how you know, they shouldn’t have a negative effect on your microbiome. If anything, having an anti-inflammatory effect should be a good thing. But probiotics is a difficult thing to say in the second part of that question. The evidence is very mixed about their efficacy, but where we definitely see things lining up and coming together is around gut health, fibre, prebiotics, all of those things, feeding your microbiome the right foods. Guess what? Whole food, plant rich diets tend to do that pretty well. And if you’re doing that, then the microbiome tends to take care of itself. And there’s really interesting resources on that.

 

A good one would be Zooey in the UK where they talk about the… Is it 30 plants a week?

 

Gina Beach (48:27)

But it’s really easy to do because it’s grains and it’s spices and herbs and it’s all your fruits and veg. And we have several great podcast episodes and webinars on how to increase your gut flora, the good gut buds. So do check those out. So one thing we didn’t talk about is GLP-1s, weight loss medications like Moderna and Wigot.

 

Dr Jonathan White (48:30)

Exactly.

 

Gina Beach (48:52)

So what’s the relation with that in MS? Do they cause vision problems? Are there risks for us if someone wants to take them? I know this is a super, super popular right now.

 

Dr Jonathan White (49:03)

I think the short answer is we simply don’t know because we don’t have any data to say, you know, MS is relatively uncommon condition. We don’t have enough people who’ve taken GLP-1s with MS yet. In theory, if you are obese, very overweight, then a reduction of your body mass index would be a beneficial effect for your MS, would have a beneficial effect for your MS. But the medications directly themselves, I don’t,  we just don’t know if they benefit MS directly. I suppose you could go back to saying, well, metformin, which is an anti-diabetic drug, which has fasting, mimicking effects, has benefits. GLP ones also have that. So that’s indirect, we, so we don’t know. But yes, there are risks, side effects, as you said, vision loss. There’s the fact that you don’t just lose fat, you lose bone and muscle on these. That’s something osteoporosis, osteopenia is a big risk for people with MS. You certainly wouldn’t want to increase that risk and you also don’t want to lose muscle mass because obviously that is really important from a functional perspective. This is not a simple black and white yes or no and the jury is out. I’m sure as I said to you earlier we’ll get thousands of questions about that over the next couple of years.

 

Gina Beach (50:11)

And hopefully we’ll maybe we’ll have some answers, but, you know, talk to your talk to your team and see what’s right for you.

 

Dr Jonathan White (50:17)

Yes, I think use with caution at the moment would be my gut feeling.

 

Gina Beach (50:21)

We’ve got a question about low dose naltrexone. How do we use it? How do we get it? How is it prescribed?

 

Dr Jonathan White (50:27)

Yeah, low-dose naltrexone is really interesting. So Naloxone is a drug that’s used to reverse opioids, morphine, for example, overdose. It’s been used off-license in very, very low doses for a very, very long time in MS. indeed. I suppose the problem is there’s no money to be made in it. So it’s not patentable. So therefore the quality of studies is always going to be an issue, a little like vitamin or vitamin D.

 

Gina Beach (50:41)

of condition.

 

Dr Jonathan White (50:52)

People can access it usually through private prescription is the way that people do that. And there are certainly physicians within the UK that will prescribe it. There are websites and you can contact them and give them a medical history or perhaps a call and they will prescribe it for you and it’s relatively low cost. But yes, your family doctor or neurologist is very, very unlikely to do that for you.

 

But there are ways private avenues to explore to do that. And it certainly appears to be safe. For some people it works very well.

 

Gina Beach (51:21)

Yeah, so if you’re interested, find a prescriber, try it.

 

Dr Jonathan White (51:25)

Physician, heal thyself. Yeah, just you have to go out and find. Yeah.

 

Gina Beach (51:29)

So if you are stable on your DMT, you stay on it forever?

 

Dr Jonathan White (51:36)

Yeah, it’s a million dollar question. With some of the anti-CD20s, for example, ocrevus, there certainly are now people that are coming off ocrevus after a period of stability and seeing that they remain in remission in terms certainly of clinical and MRI activity. Maybe not that subclinical activity that we can’t easily recognise, but that they do maintain stability off any drugs. People with cladribine, which is obviously a short course, Lemtrada, they remain stable off DMTs. For others, it’s a really difficult thing because you take it for years and years, you feel well and you think, well, what do I do now? So it’s a very individual thing. You really need to discuss this with your MS team. I think what is worth bearing in mind is that as we age with our MS, generally the DMTs are less effective over time. And I remember there were studies about five to seven years ago when they were saying the average age of over 63 I think it was that really they weren’t contributing a great deal but these were in the first in the earlier stages and actually I think the New York drugs we just don’t have the answer to that question.

 

Gina Beach (52:44)

We don’t, but I will say that in a webinar with Dr. Boster, he recommends staying on a DMT if it’s working for you forever, because the risk, if you come off and you rebound or you relapse, is much worse than just staying the course.

 

You

 

Dr Jonathan White (52:59)

And that is the balance. It’s the unknown. But the other side that Dr. Bosser doesn’t have to consider is he’s not being exposed to the risks of the medications, which are unknown for some people in the longer term. So it’s again intensely personal.

 

Gina Beach (53:13)

Yes. So again, talk to your team and make that decision for yourself. So what about the newbies? So you get diagnosed, it’s really overwhelming. They give you the leave. Yeah. Should you ask your neurologist when discussing treatments?

 

Dr Jonathan White (53:26)

So the first thing I would say is do not be pressured into making the decision that day. There’s no need to do it. You’re going to have MS for rest of your life. A couple of days, a few weeks is not going to make a material difference. It’s very unlikely to. So take the time, find the trusted resources. So, you know, go to a decision-making tool like the MS Trust one that I said, or we have some freshly published things on our website around DMTs, which can hopefully simplify things for you.

 

Take the information leaflets, speak to your MS nurse, perhaps write out a pros and cons list. Add in your personal circumstances to this story. The most relevant often being, am I a reproductive age female who may be considering starting a family in the next three to five years? And only when you have satisfied yourself with those, and I think it’s fair to say you may never be completely, because it is an unknown, but trust your gut on this. If you,

 

can see yourself doing this and making that choice, going down that road, then remember, yes, you may be on it for the long term, rest of your life, but nothing is set in stone. And if you need to change or reassess, then do that. If you decide that you don’t want to take a DMT at this point of your MS, again, don’t rule it out forever. And please continue to engage with your MS team. Go for the scans to pick up changes early, for example. There’s no price for being stubborn about this.

 

So, yeah.

 

Gina Beach (54:44)

Yeah, and I would say most people do change their DMTs. I am on my third. Absolutely, so there’s no shame as well as starting something and then it doesn’t work for you and then finding something else.

 

Dr Jonathan White (54:45)

Reach out.

 

Yeah, and reach out, LiveWell Hub. You will always find people within our community who have made that decision. Yeah, I mean, I’m on my second one and it’s not an easy decision.

 

Gina Beach (55:04)

No, it’s not. A tag on to this question is how soon post diagnosis should someone expect to be on a DMT? What is this early treatment time scale? Sometimes people think I should be on it right now, but I know for me it was it was probably three or four months after my diagnosis that I was prescribed DMT.

 

Dr Jonathan White (55:24)

Yeah, and it can take time, waiting lists and logistics and staffing and et cetera, et cetera. Can take, it can take weeks or months. Some people will be offered a DMT the day they’re diagnosed with MS. Some people are now being offered DMTs before a diagnosis of MS actually with clinically isolated syndrome and in certain studies done in England. Generally speaking, assuming the diagnosis is correct and timely, the wait and see approach is really now a thing of the past and it would be unusual for you not to be offered a DMT if your MS made that appropriate. So you’ll often find within that first, I would say, three to four months, I would certainly expect most people to be offered a treatment of some kind.

 

Gina Beach (56:04)

So we have a question about steroids. This person is confused about whether long term steroid use would damage the nervous system. And I think my understanding is that it would damage your bones.

 

Dr Jonathan White (56:17)

Yeah, the side effects of steroids long term just mean that they’re not, you know, it’s not safe to use them in the longer term that they will affect, you know, your eyes, your gut, your bones, lots of things. They used to give course of pulsed steroids before they had many of the DMTs, but really they’re only places in short term bursts for individual relapses. They’re not something to be taken for the long term and they don’t, you know the way that we use them currently, they don’t have a benefit in terms of residual disability they’re very good at turning off acute inflammation but no we wouldn’t take them long term.

 

Gina Beach (56:51)

I’m going to another question on steroids. The Overcoming MS website says that oral steroids are as effective as IV steroids, but they might damage the gut lining or you might need to take something for that. So can you talk about that and whether we should choose one the other if one is better or worse?

 

Dr Jonathan White (57:10)

So, if you take them orally, then yes, they may damage the stomach lining. You’re often given a medication like a Omeprazole or Lansoprazole, PPI, to protect it. But if you’re given it intravenously, it can also do that. So it’s the nature of the drug itself, not as well as it directly being in the stomach. So I’m not sure that I would put myself through hospitalisation or regular infusions just to get around that because there’s no guarantee. But if you are taking it orally, you should absolutely be covered with something like a Omeprazole. You definitely wouldn’t want to take five days of mithalpred on an empty stomach with no cover. It would do bad things.

 

Gina Beach (57:48)

Great. So besides the high JC virus titer, do there would be another reason to switch from Tysabri to Ocrevus?

 

Dr Jonathan White (57:57)

I suppose breakthrough disease activity would be one. So if you were having relapses after a time on the medication, and it’s worth saying that all of these medications have a lead in time. So nearly always six to 12 months before you can realistically establish how well they work. But I suppose new disease activity and MRI relapses or disability progression, side effect profile. But most people don’t have issue taking it. It’s the risk of JC virus and PMV.

 

Gina Beach (58:24)

That’s why I had to come off it because I was,  so I extended my dose to six weeks and then a few years it was like, well, maybe we should switch you.

So if people cannot take high efficacy DMTs due to comorbidities, what are your recommendations? What are the like highest effective maybe pills or other options for people?

 

Dr Jonathan White (58:45)

Yeah.

 

general rule, it’s Aaron Boster’s or not mine, is take the most effective one you can, whether that be from a side effect point of view or insurance point of view, which obviously is thankfully something we don’t have to consider in our country. So a really good middle of the road. If you think about the pyramid, 50 % reduction in relapse rates, moderate effect and disability, that’s something like Fingolimod. It’s something like Mavenclad technically, but I would consider that to be into the higher bracket and I think a lot of neurologists are considering that too. Yeah, so generally speaking, it’s tablets or the middle of the road drug. Yeah.

 

Gina Beach (59:21)

And then can you talk about Ty Sabri’s correlation with an elevated risk of melanoma?

 

Dr Jonathan White (59:26)

Yes, so the guidance on that is that if you have a personal or close family history of  melanoma, so that nearly always means first-degree relative, mother, father, brother, sister, then you shouldn’t use Tysabri. But otherwise, if it is the general population risk, it’s not something you need to be overly worried about.

 

Gina Beach (59:45)

And go to your dermatologist if you’re concerned about anything and get, you know, get it checked out. So why isn’t Tysabri approved for primary progressive MS if it reduces progression by 42 %?

 

Dr Jonathan White (59:58)

because it’s doing that by being really effective at inflammation, not degeneration. And that’s the problem. So that’s where BTKs fill the gap because their effect is over and above just turning off inflammation. So relapse associated worsening, Tysabri is your boy. It works really well, turns off inflammation. Therefore the progression you would get from the relapse doesn’t happen, but it’s not doing very much. We think at the minute for the smoldering,

 

the hot embers that are burning away underneath the real MS. That’s where BTK inhibitors seem to make a difference. And they’re the first ones that have really been showing that. At the minute, the best way to prevent smoldering MS that we have, that we can see, is neuroprotection. And guess what, folks? Exercise, diet. Gina and I have a bit of vested interest in this, so we’re biased, but that’s where lifestyle is incredibly important. So, yes.

 

Gina Beach (1:00:52)

Yeah. How is aggressive MS categorized? Is it by number of lesions? I know you said it was multiple relapses despite being a disease modifying therapy. Can you expand on that?

 

Dr Jonathan White (1:01:05)

Yeah, so it’s not usually the actual number of lesions, the actual effect of an individual lesion is dependent on so many things and depending where they are in the brain. Parts of the cerebrum have huge reserve and you may not notice any symptoms, whereas the lesions high in the spinal cord will cause enormous amount of symptomatology. So it doesn’t tend to be just that, that we talk about aggressive. It’s much more the frequency of relapses. So how often you’re getting new episodes of symptoms, how severe and debilitating those symptoms are, and where your residual disability is after those new onset of symptoms. Or if you have progressive MS, a diagnosis like primary, how fast are you progressing? So yes, it’s not really the amount of lesions.

 

Gina Beach (1:01:49)

Great. Thank you for that. Thank you for answering all of these questions. It’s been really, really wonderful to have you.

 

Dr Jonathan White (1:01:55)

Thank you.