Prof G, you have emphasized many times MS is inflammatory from beginning to end and neurodegenerative from beginning to end. In other words there is no such thing as truly “inactive” MS. Therefore how can you ethically justify ever not putting someone with MS on a DMT? Aren’t you basically saying you’re OK with your “inactive” patients sustaining more brain damage than necessary simply because the DMT won’t have as much impact for them as for “active” patients? People with cancer are regularly given expensive drugs or treatments that extend life by only a few years or even a few months, why wouldn’t we apply the same thinking to saving brain in MS?
The NHS has quite strict and well-defined treatment guidelines that only allow the treatment of active MS, which is the simple answer. Then there is biology may patients have an inactive MS and a very good prognostic profile who may never need DMTs. These patients are very rare but if you monitor and wait they get self-select and the majority of patients end up on DMTs.
Another interesting article, thank you. I am 64 and recently had a contrast mri to see if my ms was active. It isn’t but when I asked does that mean it will never reactivate, the answer was almost certainly not.
I didn’t get diagnosed until I was 53 and had no problems until I was 62 and this article has helped me understand why my disability is getting progressively worse.
I was struck down with Ramsay Hunt at 62 syndrome and think the Tecfidera had possibly suppressed my immune system and from that time I’ve really noticed a physical decline. I’m now off the DMT.
Thanks for helping us all understand this awful disease!
Re: "Tecfidera had possibly suppressed my immune system>"
Herpes zoster is more common on DMF (Tecfidera) than what is expected based on the background rate. DMF reduces CD8+ antiviral T-cells, which explains why zoster is common.
At what point do you think that it’s too late to benefit from lemtrada? Walking is hard and definitely painful. You could easily tell that something is wrong with me because I stagger and have no balance. I couldn’t run if my life depended on it.
I don’t use a wheelchair, walker, or cane regularly but did need to use a wheelchair in the airport. My last definite relapse was about 10 months ago. I have had too many lesions to count since I was diagnosed.
My neurologist looked at my last MRI with me and she thinks that many of them intertwine together. That for quite a few of them, it’s really impossible to tell if you’re looking at 1 very large lesion or 9 smaller ones that are so close that you can’t see the space between them.
Have you had patients like me? If so, would you think that there’s any chance that lemtrada could be worth starting? Thank you so much for everything that you do.
The risks start to outway the benefits of alemtuzumab the longer you have had the disease, the older you are and the more comorbidities you have collected. This is why I have a preference for using a milder, less risky, IRT such as cladribine in older subjects.
Thank you for answering. 39, no other health issues except for being a bit underweight, diagnosed for 6 years, but actually had it for at least 13. Would that be too risky for you to think the benefits might outweigh them?
Get a new neurologist. It’s 2021. With all of the highly effective anti-inflammatory therapies available, including HSCT, preventing new lesions and relapses is the bare minimum that a neurologist can and should be doing for an MS patient. The fact that you are still getting lesions and relapses after six years and your current neurologist still hasn’t even bumped you up to Lemtrada is disgraceful.
She had me fill out the paperwork and have the blood work for it the day before I asked this question. I just wondered if it was too late for me now.
I started with tysabri and I actually did do pretty well on that. I was already having a horrible relapse when I was diagnosed and that relapse from hell was still very active started tysabri since my first neurologist (I’ve moved twice since then) ordered another MRI a few days before starting. He always showed them to me with, I guess, a projector that showed them on his wall. It was lit up everywhere.
This was after I’d already had 2 rounds of solumedrol in less than a month. The radiologist had diagnosed me in his report :( the same day that I had an MRI that my family doctor ordered. He called me at 7pm that night, told me to go to his office at 8am the next morning for solumedrol. He’d sent the images to a neurologist an hour away who he respected. That I would have 5 days of that in his office and was scheduled to see the neurologist in a week.
I’d never even been to a neurologist before. Less than 6 months before then, I’d been climbing ladders to pick apples! The neurologist did a spinal tap because he said that my (pretty crappy) insurance required it, did blood work and paperwork to start tysabri as soon as possible, and ordered 5 more days of solumedrol.
He’d wanted to admit me but my ex husband (we’re actually still married because he’s drug it out for 2+ years) did not want that to happen because he thought that I needed to be home to watch our kids and pick them up from school. So I went home and waited. The neurologist called the insurance company himself and pushed them into approving tysabri a week later.
I was on that for a bit longer than a year. I had 3 MRIs during that time.
The inflammation had calmed down I guess because the lesions stopped glowing when I had an MRI after the 3rd dose. Nothing changed in MRIs after that.
Then my jcv antibodies went up to a bit over 4. I’d moved and the new neurologist changed me to Gilenya. That was okay until I relapsed and had a large new lesion close to my brain stem.
Then I moved again (ex loved moving) and my current neurologist put me on ocrevus. I had 3 doses of that and had horrible reactions every single time. At the time, I’d actually wanted mavenclad but no one knew when it would be approved. Guess what? It was approved days before my first half dose of ocrevus.
I’m crying now. Sorry. It’s like I won a reverse lottery in life. I really wish that I’d started with lemtrada but I didn’t know anything about it. I was shaken and had gotten so sick in a short window of time.
My first relapse was about 13-14 years ago, but none were very bad. I was diagnosed as being a stressed out young mom who didn’t get enough sleep. Seriously. I was given prescriptions for Xanax and sleeping pills. That was horrible.
Sorry for that novel! It’s such a long story. I would have loved hsct but it isn’t FDA approved here and I didn’t have $50k to go have it somewhere else. I really did want that in the beginning and applied for a trial that (I think that he was known as Dr. Burt?) was doing in Chicago back then. That trial ended. So here I am. Fun times.
Anon, I take it that you would do lemtrada if you were me? Please send me some prayers (or good vibes if ya don’t do prayers, I hope that I didn’t offend you by saying that) that it won’t make me worse.
Absolutely, I would do Lemtrada if I were you. The most likely side effect is thyroid issues, which are fairly easy to manage with a pill. There is no pill to manage brain damage. Considering how many lesions you already have, I would be even more inclined to throw caution to the winds and do cyclophosmamide (i.e., HSCT) to try to rescue as much neurological function as possible. Here is case report of someone who presented to hospital with over a hundred lesions and recovered almost all neurological function after rescue therapy with cyclophosmamide: https://www.frontiersin.org/articles/10.3389/fneur.2021.696807/full
I'm a different case, but honestly, considering the long list of possible other side effects from Lemtrada (which might be a lot rarer than just thyroid issues, but still happen) and the higher efficacy of HSCT, while seemingly having less long-term risks makes me lean more towards HSCT than Lemtrada. I might be overlooking something, but whenever people say that you can just get thyroid issues from Lemtrada, I wonder just how often the other stuff like ITP and kidney failure, lymphoma or a stroke after infusion happens.
I would like to know this too Amy. I was lucky to have Lemtrada as first DMT very early in the disease and have done very well. You sound like my sister who has probably had MS for years before diagnosis and has so many lesions they can’t be counted. She has just started needing walking sticks and is prone to falls. I would love to stop her progression. She’s on Tecfidera and 50.
Similar to Lynn - same age - slowly deteriorating SPMS, but never had a DMT. Recently requested Siponmod...in your view is it better to not have inflammation and not be eligible or to be eligible and take Siponimod? If it's possible to say!
I would need much more information to make a call to be on a DMT or not, including a neurological examination, MRI and other blood work, not to mention knowing the patient's profile and social circumstances etc. Neurology is still more an art than a science.
Thanks Prof G, can you explain what T2 lesions and enhancing lesions are, are there other types of lesion in MS that pwMS might experience and what do they indicate in terms of disease severity, prognosis and symptoms? Thank you
When you develop a new lesion on MRI it typically enhances, appears white, on the so-called T1 scans. This enhancement is due to leakage of gadolinium across a leaky blood-brain barrier. Gd-enhancement typically lasts for 3-4 weeks and indicates that the lesion is actively inflamed. In comparison, T2 lesions are the white blobs that are seen on a T2 scan. These tend to remain in about 80% of new lesions after Gd-enhancements disappears. As these accumulate over time they are can be used as an integrator or marker of disease activity between two-time points. The lesion load refers to the number or volume of all the bright T2 lesions on the T2-weighted images.
I will do a longer newsletter in the near future on interpreting your MRI.
Prof G, you have emphasized many times MS is inflammatory from beginning to end and neurodegenerative from beginning to end. In other words there is no such thing as truly “inactive” MS. Therefore how can you ethically justify ever not putting someone with MS on a DMT? Aren’t you basically saying you’re OK with your “inactive” patients sustaining more brain damage than necessary simply because the DMT won’t have as much impact for them as for “active” patients? People with cancer are regularly given expensive drugs or treatments that extend life by only a few years or even a few months, why wouldn’t we apply the same thinking to saving brain in MS?
The NHS has quite strict and well-defined treatment guidelines that only allow the treatment of active MS, which is the simple answer. Then there is biology may patients have an inactive MS and a very good prognostic profile who may never need DMTs. These patients are very rare but if you monitor and wait they get self-select and the majority of patients end up on DMTs.
Another interesting article, thank you. I am 64 and recently had a contrast mri to see if my ms was active. It isn’t but when I asked does that mean it will never reactivate, the answer was almost certainly not.
I didn’t get diagnosed until I was 53 and had no problems until I was 62 and this article has helped me understand why my disability is getting progressively worse.
I was struck down with Ramsay Hunt at 62 syndrome and think the Tecfidera had possibly suppressed my immune system and from that time I’ve really noticed a physical decline. I’m now off the DMT.
Thanks for helping us all understand this awful disease!
Re: "Tecfidera had possibly suppressed my immune system>"
Herpes zoster is more common on DMF (Tecfidera) than what is expected based on the background rate. DMF reduces CD8+ antiviral T-cells, which explains why zoster is common.
At what point do you think that it’s too late to benefit from lemtrada? Walking is hard and definitely painful. You could easily tell that something is wrong with me because I stagger and have no balance. I couldn’t run if my life depended on it.
I don’t use a wheelchair, walker, or cane regularly but did need to use a wheelchair in the airport. My last definite relapse was about 10 months ago. I have had too many lesions to count since I was diagnosed.
My neurologist looked at my last MRI with me and she thinks that many of them intertwine together. That for quite a few of them, it’s really impossible to tell if you’re looking at 1 very large lesion or 9 smaller ones that are so close that you can’t see the space between them.
Have you had patients like me? If so, would you think that there’s any chance that lemtrada could be worth starting? Thank you so much for everything that you do.
The risks start to outway the benefits of alemtuzumab the longer you have had the disease, the older you are and the more comorbidities you have collected. This is why I have a preference for using a milder, less risky, IRT such as cladribine in older subjects.
Thank you for answering. 39, no other health issues except for being a bit underweight, diagnosed for 6 years, but actually had it for at least 13. Would that be too risky for you to think the benefits might outweigh them?
Get a new neurologist. It’s 2021. With all of the highly effective anti-inflammatory therapies available, including HSCT, preventing new lesions and relapses is the bare minimum that a neurologist can and should be doing for an MS patient. The fact that you are still getting lesions and relapses after six years and your current neurologist still hasn’t even bumped you up to Lemtrada is disgraceful.
She had me fill out the paperwork and have the blood work for it the day before I asked this question. I just wondered if it was too late for me now.
I started with tysabri and I actually did do pretty well on that. I was already having a horrible relapse when I was diagnosed and that relapse from hell was still very active started tysabri since my first neurologist (I’ve moved twice since then) ordered another MRI a few days before starting. He always showed them to me with, I guess, a projector that showed them on his wall. It was lit up everywhere.
This was after I’d already had 2 rounds of solumedrol in less than a month. The radiologist had diagnosed me in his report :( the same day that I had an MRI that my family doctor ordered. He called me at 7pm that night, told me to go to his office at 8am the next morning for solumedrol. He’d sent the images to a neurologist an hour away who he respected. That I would have 5 days of that in his office and was scheduled to see the neurologist in a week.
I’d never even been to a neurologist before. Less than 6 months before then, I’d been climbing ladders to pick apples! The neurologist did a spinal tap because he said that my (pretty crappy) insurance required it, did blood work and paperwork to start tysabri as soon as possible, and ordered 5 more days of solumedrol.
He’d wanted to admit me but my ex husband (we’re actually still married because he’s drug it out for 2+ years) did not want that to happen because he thought that I needed to be home to watch our kids and pick them up from school. So I went home and waited. The neurologist called the insurance company himself and pushed them into approving tysabri a week later.
I was on that for a bit longer than a year. I had 3 MRIs during that time.
The inflammation had calmed down I guess because the lesions stopped glowing when I had an MRI after the 3rd dose. Nothing changed in MRIs after that.
Then my jcv antibodies went up to a bit over 4. I’d moved and the new neurologist changed me to Gilenya. That was okay until I relapsed and had a large new lesion close to my brain stem.
Then I moved again (ex loved moving) and my current neurologist put me on ocrevus. I had 3 doses of that and had horrible reactions every single time. At the time, I’d actually wanted mavenclad but no one knew when it would be approved. Guess what? It was approved days before my first half dose of ocrevus.
I’m crying now. Sorry. It’s like I won a reverse lottery in life. I really wish that I’d started with lemtrada but I didn’t know anything about it. I was shaken and had gotten so sick in a short window of time.
My first relapse was about 13-14 years ago, but none were very bad. I was diagnosed as being a stressed out young mom who didn’t get enough sleep. Seriously. I was given prescriptions for Xanax and sleeping pills. That was horrible.
Sorry for that novel! It’s such a long story. I would have loved hsct but it isn’t FDA approved here and I didn’t have $50k to go have it somewhere else. I really did want that in the beginning and applied for a trial that (I think that he was known as Dr. Burt?) was doing in Chicago back then. That trial ended. So here I am. Fun times.
Anon, I take it that you would do lemtrada if you were me? Please send me some prayers (or good vibes if ya don’t do prayers, I hope that I didn’t offend you by saying that) that it won’t make me worse.
Absolutely, I would do Lemtrada if I were you. The most likely side effect is thyroid issues, which are fairly easy to manage with a pill. There is no pill to manage brain damage. Considering how many lesions you already have, I would be even more inclined to throw caution to the winds and do cyclophosmamide (i.e., HSCT) to try to rescue as much neurological function as possible. Here is case report of someone who presented to hospital with over a hundred lesions and recovered almost all neurological function after rescue therapy with cyclophosmamide: https://www.frontiersin.org/articles/10.3389/fneur.2021.696807/full
I'm a different case, but honestly, considering the long list of possible other side effects from Lemtrada (which might be a lot rarer than just thyroid issues, but still happen) and the higher efficacy of HSCT, while seemingly having less long-term risks makes me lean more towards HSCT than Lemtrada. I might be overlooking something, but whenever people say that you can just get thyroid issues from Lemtrada, I wonder just how often the other stuff like ITP and kidney failure, lymphoma or a stroke after infusion happens.
I would like to know this too Amy. I was lucky to have Lemtrada as first DMT very early in the disease and have done very well. You sound like my sister who has probably had MS for years before diagnosis and has so many lesions they can’t be counted. She has just started needing walking sticks and is prone to falls. I would love to stop her progression. She’s on Tecfidera and 50.
Thanks you, Dr. G!
This worries me too! I am virtually the same as above but since 2008 I think but it is still a worry that something is building about to pounce !
Hannah, not all neurologists agree with me so be prepared for pushback.
Similar to Lynn - same age - slowly deteriorating SPMS, but never had a DMT. Recently requested Siponmod...in your view is it better to not have inflammation and not be eligible or to be eligible and take Siponimod? If it's possible to say!
I would need much more information to make a call to be on a DMT or not, including a neurological examination, MRI and other blood work, not to mention knowing the patient's profile and social circumstances etc. Neurology is still more an art than a science.
Thanks for taking the time to reply. I will have to await my neuro appt, not too long :-)
Thanks Prof G, can you explain what T2 lesions and enhancing lesions are, are there other types of lesion in MS that pwMS might experience and what do they indicate in terms of disease severity, prognosis and symptoms? Thank you
When you develop a new lesion on MRI it typically enhances, appears white, on the so-called T1 scans. This enhancement is due to leakage of gadolinium across a leaky blood-brain barrier. Gd-enhancement typically lasts for 3-4 weeks and indicates that the lesion is actively inflamed. In comparison, T2 lesions are the white blobs that are seen on a T2 scan. These tend to remain in about 80% of new lesions after Gd-enhancements disappears. As these accumulate over time they are can be used as an integrator or marker of disease activity between two-time points. The lesion load refers to the number or volume of all the bright T2 lesions on the T2-weighted images.
I will do a longer newsletter in the near future on interpreting your MRI.