What I would like to have heard from the neurologist who diagnosed me 30 years ago. and all the others since, 'I will treat you as I would treat myself". I am 64 now with EDSS 6/6.5 and have never fitted a profile along the way which has allowed treatment. So now described as SPMS. I wish you the very best with this approach. And I'm glad I did the Nataliszumab trial for 2 years + as it may turn out to be the only treatment I will get!
Dr. Giovanni, what about a study of those who early in their diagnosis adopt a holistic, anti-oxidant, anti-inflammatory lifestyle that includes diet, movement, stress management, sleep and social connections compared. I am thinking of Dr. Wahls and Dr. Stancic. Both went on the conventional treatment, continued to decline. But once they adopted an anti-inflammatory, nutrient dense lifestyle, they turned things around. In fact, Dr. Stancic marked her 20th anniversary of her diagnosis by taking a 20 mile walk with friends. This blows my mind as I can only do 1.5 to 2 miles right now. To me, if one takes the best in class treatments, but continues with an inflammatory lifestyle, why should improvement be expected? From what my layperson brain has learned, our bodies our geared towards healing if given the right environment and inputs, namely homeostasis based upon nutrient dense inputs, frequent movement, positive thinking, appropriate sleep, elimination of negative stress and frequent cognitive challenges to promote "fire and wire" hormetic lifestyle challenges. I would love to see such a study.
I wouldn't rely on single anecdotal case reports to treat my MS. I have seen too many people take this route who regret it later. And many people who think they are doing well comeback many years later with progressive MS.
You have to realise there is a reporting bias in relation to pwMS doing well with aggressive lifestyle management strategies; for every one that does well there are an order of magnitude more that don't do well. Lifestyle interventions are complimentary treatment and not an alternative treatment for MS.
Thank you Doctor. I have a visit with my neurologist Dr. Jennifer Graves at UCSD next month. I will explore if I should be on any treatments. A year ago, my neuro, Dr. Revere Kinkel, said there where no meds that would be helpful, including Ocrevus. Thank you!
A sobering read. A related question for those of us who already had many silent lesions at point of diagnosis: do you think there is any benefit to knowing how long we have probably had MS? I nearly asked my neurologist at the last appt, but wasn't sure if there was an upside to finding out (save for satiating my curiosity)...
It is very difficult to define how long the presymptomatic phase of MS is. Data suggests it can be up to 10 years. What we can say the more lesions you have the more likely it is you have had quite a long presymptomatic or prodromal phase.
I was wondering if there’s a study showing early activity / relapses in first few years after onset of MS with long term prognosis of disability? I’m sure I’ve seen it somewhere but can’t locate it now.
Scalfari et al. Early relapses, onset of progression, and late outcome in multiple sclerosis. JAMA Neurol. 2013;70:214-22. doi: 10.1001/jamaneurol.2013.599.
Objectives: To investigate the relationship among attacks in the first 2 years (early relapses), secondary progression (SP), and late disability in multiple sclerosis (MS).
Design: Cohort study with follow-up of 28 years.
Setting: Referral MS center.
Patients: Patients (N=730) with relapsing-remitting MS diagnosed according to Poser criteria, from the database of the London Multiple Sclerosis Clinic, London, Ontario, Canada.
Main outcome measure: Long-term evolution of patients with high (≥ 3 attacks) and early (within the first 2 years of the disease) frequency of relapses. In the total SP population and in patients grouped by numbers of early relapses, we assessed the predictive effect of latency to progression (time to SP) on times to attain cane requirement (Disability Status Scale score of 6 [DSS 6]) and bedridden status (DSS 8).
Results: Among the group with frequent early relapses (n=158), outcomes were variable. Although 103 (65.2%) experienced rapid conversion to SP MS (median duration, 5 years) and rapidly attained DSS 6 and DSS 8 scores (7 and 17 years, respectively), the remainder (n=55) did not enter the SP phase, despite adverse early relapse features. Among the total SP population, longer latency to progression was associated with lower probability of attaining DSS 6 (odds ratio, 0.76 [95% CI, 0.69-0.84] and 0.44 [95% CI, 0.37-0.52] for 5- and 15-year latency, respectively) and longer times to severe disability. The same association between time to onset of SP and late outcomes was observed even in patients matched by number of early attacks. However, duration of the relapsing-remitting phase did not influence the times from SP onset to DSS levels.
Conclusions: Our results indicate dissociation between early inflammatory attacks and onset of the SP phase and further question the validity of relapse frequency as a surrogate marker for late disability. Among the group with frequent early relapses, we observed a large variability of outcomes, ranging from one extreme to the opposite.
Interesting study. Seems like a high stakes roll of the dice what future awaits those who relapse frequently in the first 2 years. May I ask if you have a secretary we could reach out to regarding paying for a private consultation? If it’s easier to reply by email I’m on jcarrvocalist@gmail.com
This model of treating pwMS seems to differ from many other sectors of the NHS; cancer, strokes come to mind. Why is this? NICE or health politics? It seems so hard to change. What it must do to people who deteriorate knowing they may not be eligible for the treatments that could conserve the health they still have, such as upper limb function.
Hello Doctor: A side question- The 4 graphs you present of long term results for beta 1b from 2012, if I am reading correctly, show a slightly better outcome for a dose smaller (50 ug), than for the standard dose which was 250 (.25 mg). Am I correct? I know at one point there was a "more is better" study which failed to show benefit. I always believed the interferon 1b Betaseron dose to be stronger than Avonex and therefore more effective.
I was on 1b for 23 years, and the mantra back then was the earlier you start the better off your'd be. Yet, it still gets pushed aside. I'm currently "intermittent cane" due to MS gait + flat naturally low arch foot = PTTD or some version of that. No complaints, I certainly agree with quick treatment, because if your plan is improved survival and you are paying attention, you have no other choice.
Does starting out with Tysabri help in this instance?
I’m a healthy (bar MS) 35M who was diagnosed last year and chose Tysarbi due to covid.
I have no clue how long Ms has been with me probably years, also EBV positive, but how late is too late for treatment?
I’m looking to move to Mavenclad however next month, can’t take the daily headaches from Tysabri anymore and like the idea of an IRT option (too nervous about Lemtrada), wise option?
I’m in Australia and unfortunately can’t get HSCT though my neurologist has pushed Lemtrada a few times.
So what i want to know is how manny years interferon treatment save the patient to reach disability milestones
Aparently this study from Novartis just came out, saying that a more potentdrug(fingolimod)
Saves you only 3.5years against placebo
Now imaging you tell your naive patient ,i have this very good drug that you have to take for the rest of your life ,it will give you liver issues possible heart issues and you will gain 3,5 years more before reach edss 6 Professor if you were that patients will you take it?
New study details the ways patients with multiple sclerosis develop impairment
Treating patients with DMTs delayed these times significantly by 3.51 years (95% confidence limit: 3.19, 3.96) and by 3.09 years (2.60, 3.72), respectively
The cost for Gilenya oral capsule 0.5 mg is around $9,980 for a supply of 30 capsules, depending on the pharmacy you visit. Prices are for cash paying customers only and are not valid with insurance plans.
Out of interest if someone was diagnosed and put on DMF before Oclizumab was licensed, should they ask about switching to that now as it’s more effective?
No not necessarily. It is horses for courses and if you are a super-responder to DMF why switch? The issue is about getting your disease under control (NEIDA). Interestingly, DMF has some off target effects in relation to brain and metabolic health that may target some of the components of smouldering MS.
As I was breastfeeding when I first saw my MS nurse, I was offered a beta interferon DMT. My son self-weaned the week before I first injected with Plegridy, but my nurse will not swap treatments the whole time the side effects are manageable, and they are waiting for new baseline MRIs in June followed by a year of waiting to see if this changes. I feel like I should be pushing for a more highly effective DMT, but already feel that I won't be listened to.
I assume your MS team are waiting see if you are a responder or non-responder. In my experience about 20% of pwMS treated with interferon-beta remain NEIDA over a 4-5 year period with the remainder needing to be escalated. This is the maintenance-escalation approach to managing MS, which is still quite common.
In the attack ms trial are you referring to randomising patients before they have finished the MS diagnostic pathway to treatment meaning a CIS diagnosis vs. delayed access due to not having a CDMS diagnosis?
Yes, it is before the diagnostic tests are completed and the patient is told the diagnosis, counselled and started on a DMT. On average this takes about 8 weeks and may be longer because of having to update vaccines etc. These are not a problem with natalizumab.
I definitely agree that more effective treatments should be used first. At the moment there is no treatment for myelin repair so it’s better to prevent the damage and disability. It’s not just about length of life but quality of life. I was diagnosed with CI syndrome in 2008 and DMTs weren’t offered until I had another relapse 18 months later. Copaxone had horrible side effects and probably wasn’t any better than placebo. 18 months later I had one relapse after another which left me being pushed in a wheelchair for about 5 months because I had difficulty using my left arm as well as the difficulty walking. Unfortunately my neurologist at the time refused to see me and had failed to look at the reports that a registrar wrote in my notes about me. My MS nurse helped to get me MRI scans and get me reclassified as Rapidly Evolving RRMS so I qualified for Tysabri. Tysabri was brilliant and my EDSS dropped to 1. Unfortunately after 2 years I moved to a different area and my new neurologist persuaded me to change to Fingolimod because of the PML risk. Once again the side effects were awful and I relapsed, putting me back in a wheelchair and causing me difficulty using my right arm. I took myself off Fingolimod and persuaded the neurologist to put me back on Tysabri. My EDSS dropped to 3. Once again after 2 years he tried to persuade me to come off Tysabri. I was told that I didn’t qualify for HSCT in the UK so my husband withdrew the money from his pension fund for my treatment in Moscow. I’ve been in remission for 3 years now and have an EDSS of 1, however during the time messing about on useless drugs, with horrible side effects had a massive affect on my QOL and I had to give up my business.
Interest stuff. I have an appointment with my Neuro tomorrow and 'Treatment Inertia' is something I will mention, along with 'Smoldering MS'. Wish me luck! I feel I am a sitting duck waiting for something symptoms to occur. Can there be an MSer that is asymptomatic, and evidence that they can manage without DMTs?
My last 2 MRIs have noted inactive lesions so I can understand why my annual MRI was cancelled this year. It seems that NHS PCTs all have different views on MRI frequency.
I am lucky to say I feel that I am in rude health thankfully at the moment.
Yes, there is a small group of untreated pwMS who end up having benign disease. In hospital based cohorts this is less than 5% of patients with the figures dropping further with 40+ years of follow-up. I always say the given sufficient time the majority of pwMS will become disabled. I am hoping this will change with a more proactive approach to managing MS.
Improved. We don't have data yet at EDSS 10.0 for individual DMTs, but overall survival and life expectancy has improved. Sadly though pwMS are still having to live for decades with disability and poor quality of life. We can and will do better; if only ......
I have been offered nothing except pain relief, I have now moved to secondary progressive ms and have been told it is of the smouldering type and therefore nothing can be done!! Just keep on keeping on. Thankyou so much for your newsletters and podcasts xx
What I would like to have heard from the neurologist who diagnosed me 30 years ago. and all the others since, 'I will treat you as I would treat myself". I am 64 now with EDSS 6/6.5 and have never fitted a profile along the way which has allowed treatment. So now described as SPMS. I wish you the very best with this approach. And I'm glad I did the Nataliszumab trial for 2 years + as it may turn out to be the only treatment I will get!
If only we knew 30 years ago what we know now things would almost certainly have been different.
Dr. Giovanni, what about a study of those who early in their diagnosis adopt a holistic, anti-oxidant, anti-inflammatory lifestyle that includes diet, movement, stress management, sleep and social connections compared. I am thinking of Dr. Wahls and Dr. Stancic. Both went on the conventional treatment, continued to decline. But once they adopted an anti-inflammatory, nutrient dense lifestyle, they turned things around. In fact, Dr. Stancic marked her 20th anniversary of her diagnosis by taking a 20 mile walk with friends. This blows my mind as I can only do 1.5 to 2 miles right now. To me, if one takes the best in class treatments, but continues with an inflammatory lifestyle, why should improvement be expected? From what my layperson brain has learned, our bodies our geared towards healing if given the right environment and inputs, namely homeostasis based upon nutrient dense inputs, frequent movement, positive thinking, appropriate sleep, elimination of negative stress and frequent cognitive challenges to promote "fire and wire" hormetic lifestyle challenges. I would love to see such a study.
I wouldn't rely on single anecdotal case reports to treat my MS. I have seen too many people take this route who regret it later. And many people who think they are doing well comeback many years later with progressive MS.
You have to realise there is a reporting bias in relation to pwMS doing well with aggressive lifestyle management strategies; for every one that does well there are an order of magnitude more that don't do well. Lifestyle interventions are complimentary treatment and not an alternative treatment for MS.
Thank you Doctor. I have a visit with my neurologist Dr. Jennifer Graves at UCSD next month. I will explore if I should be on any treatments. A year ago, my neuro, Dr. Revere Kinkel, said there where no meds that would be helpful, including Ocrevus. Thank you!
A sobering read. A related question for those of us who already had many silent lesions at point of diagnosis: do you think there is any benefit to knowing how long we have probably had MS? I nearly asked my neurologist at the last appt, but wasn't sure if there was an upside to finding out (save for satiating my curiosity)...
It is very difficult to define how long the presymptomatic phase of MS is. Data suggests it can be up to 10 years. What we can say the more lesions you have the more likely it is you have had quite a long presymptomatic or prodromal phase.
Sad read for us who have left it too late and are now secondary progressive...
But we say it is never too late to treat and manage MS holistically.
I was wondering if there’s a study showing early activity / relapses in first few years after onset of MS with long term prognosis of disability? I’m sure I’ve seen it somewhere but can’t locate it now.
Scalfari et al. Early relapses, onset of progression, and late outcome in multiple sclerosis. JAMA Neurol. 2013;70:214-22. doi: 10.1001/jamaneurol.2013.599.
Objectives: To investigate the relationship among attacks in the first 2 years (early relapses), secondary progression (SP), and late disability in multiple sclerosis (MS).
Design: Cohort study with follow-up of 28 years.
Setting: Referral MS center.
Patients: Patients (N=730) with relapsing-remitting MS diagnosed according to Poser criteria, from the database of the London Multiple Sclerosis Clinic, London, Ontario, Canada.
Main outcome measure: Long-term evolution of patients with high (≥ 3 attacks) and early (within the first 2 years of the disease) frequency of relapses. In the total SP population and in patients grouped by numbers of early relapses, we assessed the predictive effect of latency to progression (time to SP) on times to attain cane requirement (Disability Status Scale score of 6 [DSS 6]) and bedridden status (DSS 8).
Results: Among the group with frequent early relapses (n=158), outcomes were variable. Although 103 (65.2%) experienced rapid conversion to SP MS (median duration, 5 years) and rapidly attained DSS 6 and DSS 8 scores (7 and 17 years, respectively), the remainder (n=55) did not enter the SP phase, despite adverse early relapse features. Among the total SP population, longer latency to progression was associated with lower probability of attaining DSS 6 (odds ratio, 0.76 [95% CI, 0.69-0.84] and 0.44 [95% CI, 0.37-0.52] for 5- and 15-year latency, respectively) and longer times to severe disability. The same association between time to onset of SP and late outcomes was observed even in patients matched by number of early attacks. However, duration of the relapsing-remitting phase did not influence the times from SP onset to DSS levels.
Conclusions: Our results indicate dissociation between early inflammatory attacks and onset of the SP phase and further question the validity of relapse frequency as a surrogate marker for late disability. Among the group with frequent early relapses, we observed a large variability of outcomes, ranging from one extreme to the opposite.
Interesting study. Seems like a high stakes roll of the dice what future awaits those who relapse frequently in the first 2 years. May I ask if you have a secretary we could reach out to regarding paying for a private consultation? If it’s easier to reply by email I’m on jcarrvocalist@gmail.com
This model of treating pwMS seems to differ from many other sectors of the NHS; cancer, strokes come to mind. Why is this? NICE or health politics? It seems so hard to change. What it must do to people who deteriorate knowing they may not be eligible for the treatments that could conserve the health they still have, such as upper limb function.
Hello Doctor: A side question- The 4 graphs you present of long term results for beta 1b from 2012, if I am reading correctly, show a slightly better outcome for a dose smaller (50 ug), than for the standard dose which was 250 (.25 mg). Am I correct? I know at one point there was a "more is better" study which failed to show benefit. I always believed the interferon 1b Betaseron dose to be stronger than Avonex and therefore more effective.
I was on 1b for 23 years, and the mantra back then was the earlier you start the better off your'd be. Yet, it still gets pushed aside. I'm currently "intermittent cane" due to MS gait + flat naturally low arch foot = PTTD or some version of that. No complaints, I certainly agree with quick treatment, because if your plan is improved survival and you are paying attention, you have no other choice.
Yes, very little difference between doses on survival. More evidence that MS is not relapses and MRI activity.
Does starting out with Tysabri help in this instance?
I’m a healthy (bar MS) 35M who was diagnosed last year and chose Tysarbi due to covid.
I have no clue how long Ms has been with me probably years, also EBV positive, but how late is too late for treatment?
I’m looking to move to Mavenclad however next month, can’t take the daily headaches from Tysabri anymore and like the idea of an IRT option (too nervous about Lemtrada), wise option?
I’m in Australia and unfortunately can’t get HSCT though my neurologist has pushed Lemtrada a few times.
Nice
So what i want to know is how manny years interferon treatment save the patient to reach disability milestones
Aparently this study from Novartis just came out, saying that a more potentdrug(fingolimod)
Saves you only 3.5years against placebo
Now imaging you tell your naive patient ,i have this very good drug that you have to take for the rest of your life ,it will give you liver issues possible heart issues and you will gain 3,5 years more before reach edss 6 Professor if you were that patients will you take it?
New study details the ways patients with multiple sclerosis develop impairment
Treating patients with DMTs delayed these times significantly by 3.51 years (95% confidence limit: 3.19, 3.96) and by 3.09 years (2.60, 3.72), respectively
https://medicalxpress.com/news/2022-02-ways-patients-multiple-sclerosis-impairment.html
https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/brain/PAP/10.1093_brain_awac016/1/awac016_supplementary_data.pdf?Expires=1647885550&Signature=p2eG38oibV9XY9ah45wxLlxNMznWE9OrVkUqAHf602pMFxzHP2QmqXHYdPGOkddJYGt-gSqRiOzQhsRPEg9bWk30p~jPej1TLqmXoXipNiViEhO6RdX1U3PpQrY~Vxt-JkRYY5n7XpO04AA0oEStJgHnWotvMt2z2bstRjt5lmzZO5eFaFqZByave3dbbV8fDQO5nrWUdEFX4kT7jrOAmeH2fCk16au5zJje3Yxm20d75WCNzJjuOVWTaUvLm~NL7EICmI1bAzMRmov9oKisgotp~z2mG5jQjjg2i1~KgHYxnsVynZXTzgI2YPrqjqKr4cet78CkvDDwI3YBoBJgMA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
Oh i forgot ye$ ye$
The cost for Gilenya oral capsule 0.5 mg is around $9,980 for a supply of 30 capsules, depending on the pharmacy you visit. Prices are for cash paying customers only and are not valid with insurance plans.
You may find this newsletter helpful:
https://gavingiovannoni.substack.com/p/research-big-data-and-smouldering?utm_source=url
Out of interest if someone was diagnosed and put on DMF before Oclizumab was licensed, should they ask about switching to that now as it’s more effective?
No not necessarily. It is horses for courses and if you are a super-responder to DMF why switch? The issue is about getting your disease under control (NEIDA). Interestingly, DMF has some off target effects in relation to brain and metabolic health that may target some of the components of smouldering MS.
As I was breastfeeding when I first saw my MS nurse, I was offered a beta interferon DMT. My son self-weaned the week before I first injected with Plegridy, but my nurse will not swap treatments the whole time the side effects are manageable, and they are waiting for new baseline MRIs in June followed by a year of waiting to see if this changes. I feel like I should be pushing for a more highly effective DMT, but already feel that I won't be listened to.
I assume your MS team are waiting see if you are a responder or non-responder. In my experience about 20% of pwMS treated with interferon-beta remain NEIDA over a 4-5 year period with the remainder needing to be escalated. This is the maintenance-escalation approach to managing MS, which is still quite common.
In the attack ms trial are you referring to randomising patients before they have finished the MS diagnostic pathway to treatment meaning a CIS diagnosis vs. delayed access due to not having a CDMS diagnosis?
Yes, it is before the diagnostic tests are completed and the patient is told the diagnosis, counselled and started on a DMT. On average this takes about 8 weeks and may be longer because of having to update vaccines etc. These are not a problem with natalizumab.
So you are initiating treatment based on symptoms and neurological exam?
And MRI they have to have an abnormal MRI compatible with demyelination.
Is this study still recruiting?
I definitely agree that more effective treatments should be used first. At the moment there is no treatment for myelin repair so it’s better to prevent the damage and disability. It’s not just about length of life but quality of life. I was diagnosed with CI syndrome in 2008 and DMTs weren’t offered until I had another relapse 18 months later. Copaxone had horrible side effects and probably wasn’t any better than placebo. 18 months later I had one relapse after another which left me being pushed in a wheelchair for about 5 months because I had difficulty using my left arm as well as the difficulty walking. Unfortunately my neurologist at the time refused to see me and had failed to look at the reports that a registrar wrote in my notes about me. My MS nurse helped to get me MRI scans and get me reclassified as Rapidly Evolving RRMS so I qualified for Tysabri. Tysabri was brilliant and my EDSS dropped to 1. Unfortunately after 2 years I moved to a different area and my new neurologist persuaded me to change to Fingolimod because of the PML risk. Once again the side effects were awful and I relapsed, putting me back in a wheelchair and causing me difficulty using my right arm. I took myself off Fingolimod and persuaded the neurologist to put me back on Tysabri. My EDSS dropped to 3. Once again after 2 years he tried to persuade me to come off Tysabri. I was told that I didn’t qualify for HSCT in the UK so my husband withdrew the money from his pension fund for my treatment in Moscow. I’ve been in remission for 3 years now and have an EDSS of 1, however during the time messing about on useless drugs, with horrible side effects had a massive affect on my QOL and I had to give up my business.
The more I read about the NHS and its treatment of MS patients, the more I thank God that I wasn’t born in England.
Interest stuff. I have an appointment with my Neuro tomorrow and 'Treatment Inertia' is something I will mention, along with 'Smoldering MS'. Wish me luck! I feel I am a sitting duck waiting for something symptoms to occur. Can there be an MSer that is asymptomatic, and evidence that they can manage without DMTs?
My last 2 MRIs have noted inactive lesions so I can understand why my annual MRI was cancelled this year. It seems that NHS PCTs all have different views on MRI frequency.
I am lucky to say I feel that I am in rude health thankfully at the moment.
Yes, there is a small group of untreated pwMS who end up having benign disease. In hospital based cohorts this is less than 5% of patients with the figures dropping further with 40+ years of follow-up. I always say the given sufficient time the majority of pwMS will become disabled. I am hoping this will change with a more proactive approach to managing MS.
Has expected mortality increased or decreased with the introduction of newer highly effective therapies since these trial findings ?
Improved. We don't have data yet at EDSS 10.0 for individual DMTs, but overall survival and life expectancy has improved. Sadly though pwMS are still having to live for decades with disability and poor quality of life. We can and will do better; if only ......
Hopefully by the time we have longterm data for the highly effective therapies we will be looking at data for the add on therapies 🤞
I have been offered nothing except pain relief, I have now moved to secondary progressive ms and have been told it is of the smouldering type and therefore nothing can be done!! Just keep on keeping on. Thankyou so much for your newsletters and podcasts xx