Lol, of course pharmaceutical companies are complaining about offering objective information about their, and other, DMT's! They are in it for profit; effective marketing drives profit, and is inherently biased, by design. Objectivity removes marketing hype, taking away that power of biased influence, so naturally anything that puts distance between their marketing spin (bias) and their product will be of concern to them.
Their concern is duly noted.
Now please proceed with this desperately-needed, accessibility-friendly essential tool for pwMS in making major decisions concerning their health that literally may have of life-or-death consequences for them. The stakes can't get much higher for patients receiving this succinct, objective presentation of DMTs.
Yes, the stakes are equally high for their profits. Pick your side: profit or peoples' lives. The ethical choice is clear.
Bravo to you for so carefully crafting this most useful tool for pwMS! 👏
"do they have a case?" - they're entitled to their feelings.
I think we're beyond this, if we want patients making decisions on what risks are and are not acceptable then the risks need to be shown warts and all - including the risk of doing nothing and the risk of gradually ramping up treatment while accruing brain damage as opposed to hitting hard from the outset.
And neurologists need to be more honest about "lesions". Particularly when lesions "heal" and when they are or are not "expanding". Perhaps explaining that the neurons inside lesions stop functioning once the lesions are formed and are essentially holes in the brain where there used to be functioning neurons. I think that might sway the more cautious to opt for treatment given the damage they're accruing.
I believe healthcare professionals and the people with MS who are being treated with DMTs are better able to judge their efficacy than the pharmaceutical companies.
I know, bashing pharma is cheap and gives ultimate satisfaction to some but it would also be great to appreciate that without pharma people with MS would still be on steroids only.
Sorry for this but a bit more balanced view and an appreciation that we all may have a biased view would help to work together to get better.
A proposal for the content of the cards I have is to separate effects on relapses and progression. There is sufficient evidence to justify this and it may help people with MS to change a bit the focus from relapses to progression.
contribution of pharmaceuticals in MS by virtue of their creation. Nobody here is doubting or even minimizing those contributions.
Separating data as you suggest would make this a much-less useful tool for those disabled by MS, undermining the very intent of aiding the MS patient in decision-making.
I like the layout and readability of these cards, especially if comparing just a few for discussion with one’s doctor, or for doctors to give to patients when recommending of course. I was surprised by the higher cancer risk in Tysabri over Ocrevus since I’d thought that was just the opposite.
I think this is based on the emerging link between natalizumab and CNS lymphomas. With regards to ocrelizumab the potential link between breast cancer has not been confirmed in post-marketing studies. Overall the risk of cancer on natalizumab and ocrelizumab is low.
As natalizumab blocks CNS immune surveillance there is always a concern that it will create a sanctuary for CNS tumours and potentially for systemic cancers that metastasise to the CNS (breast, small cell lung, melanoma, renal cell and colon cancers. Saying this many metastatic cancers use VLA-4 the adhesion molecule that natalizumab inhibits to cross into the brain.
1) I think it's awesome that this has gotten on the radar of pharma companies, and that they CARE how they're being perceived in this forum! 2) They probably don't have a case until they do head-to-head trials on high efficacy DMTs, which they won't and shouldn't (waste of money, hard to get statistical power) do. 3) Are you going to publish the network analysis?
Samjoo IA, Worthington E, Drudge C, Zhao M, Cameron C, Häring DA, Stoneman D, Klotz L, Adlard N. Efficacy classification of modern therapies in multiple sclerosis. J Comp Eff Res. 2021 Apr;10(6):495-507. doi: 10.2217/cer-2020-0267. Epub 2021 Feb 23. PMID: 33620251.
A logical assumption would be that if I would have one relapse every year, I now only get two in three years (and I should be fine with those two, because that's what I chose for).
This number is the result from having ARR as a primary end-point in the clinical trial.
But I understood from your earlier information that that is not the way an MS patient should think about this. Let's say that a patient would want to strive for zero new relapses. I would think that would still be possible with this medication, however, the chance for this is lower than with higher efficacy drugs.
Do you think there is a better way of communicating this than saying: "X reduces relapses by about 30%...."
Do you have an article or podcast that I can refer people to who want to know more about this? I have the feeling it is still a big misconception among both patients and doctors.
I'm guessing they are hoping you use relative efficacy as opposed to absolute efficacy. Now where have I come across that issue recently with regards to a controversial drug? Lol 😆
Thanks for replying. I of course have my pharma glasses on, but I cannot sense an hommage to Pharma in the comment thread. In any case these cards are very useful if balanced. To have it vetted by more than very few people, though obviously extremely knowledgeable, would add credibility.
Samjoo IA, Worthington E, Drudge C, Zhao M, Cameron C, Häring DA, Stoneman D, Klotz L, Adlard N. Efficacy classification of modern therapies in multiple sclerosis. J Comp Eff Res. 2021 Apr;10(6):495-507. doi: 10.2217/cer-2020-0267. Epub 2021 Feb 23. PMID: 33620251.
In the context of drug company reactions and being bearers of “pressure and influence”- To skip the main gist of the post, which by the way is fantastic, when considering influences it is useful to keep in mind where the influencers place their influence attempts- Besides doctor’s office tables and the doctors themselves (I suppose), there are the ads in online resources and written materials provided by “societies” etc., and other sources such as Multiple Sclerosis News Today. Let’s not also forget about, in The US, commercials on television (do they still call it that?).
I think your ratings are important for people to discuss with their neurologist, and have a conversation that can lead to better understanding about their treatment.
Of course drug companies are going to complain. Too bad! These cards are amazing. I've never had access to this kind of information when changing DMTs. I have been, or am on, a total of four DMTs and there are things about each drug I never knew, particularly the effectiveness on a number scale and the response to vaccinations. As much as I love the cards, it's discouraging to realize what a poor job my health care providers have done in terms of informing me of basic information about my treatment.
Actually, directly and indirectly a good amount of the pharmas are contributing to confounding information...
This article is from September of last year, but there was a newer article, just a few days ago in the journal Science, warning that the paper mills are now bribing editors at the big journals. Mostly because papers can be tied to a public company, and subsequently responsible for 'pumping up' their stock.
I've been dx in 2022, 46 yo, started with Tecfidera and after 6 months, due to active lesions, switched to ofatumumab. all good in the best of all possible worlds, my last MRI now shows no active lesion, but I feel all chapters slightly worsened.
my neuro doesn't like the word "progressive" - she says it's too early to make a call. but without MRI activity and continuous deterioration (my EDSS went from 3 to 4.5 in ab. 18 months) I feel like she ran out of options. haha, too bad for me.
PS. why not combine DMF with ofatumumab? what could possibly go wrong?
I don't like to speak out of turn but am gonna do it anyway:
With anti-CD20 therapies like ofatumumab and the rest (and any of the immune depleting / reconstituting therapies potentially) it helps to bear in mind WHERE you're taking your meds. Whether you eat them, inject them under the skin or infuse them into a vein, they all go into the "peripheral" blood (eventually in the case of oral meds).
Our brains and spinal columns are protected by the blood-brain barrier which only allows stuff across that is seen as necessary. When you use an anti-CD20 you're depleting B-cells outside the brain and spinal column. It can take anywhere between 18 months and 2 years for these changes to be reflected inside the brain, once the B cells and T cells die off in there. So - you may still get some "episodes" of lesion formation in there after you start treatment, until you're about 2 years in, unfortunately. These episodes are likely to be less severe than they would have been had you not been on treatment.
Once you're 2 years in, disease activity is supposed to stop and if it doesn't, your neurologist is likely to suggest a stronger treatment.
Also once you're 2 years in then you get a better idea that what you're experiencing MIGHT be smouldering MS / progression and you can try to get your neurologist to act accordingly with add-on therapies (if they're open to them - not sure what add-ons we have at the moment, I think that would be a question for Prof Giovannoni to address...)
thank you, Simon. I started ofatumumab in July, 2023 and last MRI is from December, so I'm about 5-6 months in - if Kesimpta would have been ineffective, then alemtuzumab (this being an option of last resort, procedurally speaking). but seeing the MRI, my neurologist adviced me to go on with the current anti-CD20.
Prof. Giovannoni has said it many times here: once "progression" is on the table, there isn't any miracle to be expected. maybe I'm not employing the correct mindfulness techniques, haha, maybe is dairy, maybe my ancestors, maybe is just sheer randomness.
Lol, of course pharmaceutical companies are complaining about offering objective information about their, and other, DMT's! They are in it for profit; effective marketing drives profit, and is inherently biased, by design. Objectivity removes marketing hype, taking away that power of biased influence, so naturally anything that puts distance between their marketing spin (bias) and their product will be of concern to them.
Their concern is duly noted.
Now please proceed with this desperately-needed, accessibility-friendly essential tool for pwMS in making major decisions concerning their health that literally may have of life-or-death consequences for them. The stakes can't get much higher for patients receiving this succinct, objective presentation of DMTs.
Yes, the stakes are equally high for their profits. Pick your side: profit or peoples' lives. The ethical choice is clear.
Bravo to you for so carefully crafting this most useful tool for pwMS! 👏
And thank you from the bottom of my heart.
"do they have a case?" - they're entitled to their feelings.
I think we're beyond this, if we want patients making decisions on what risks are and are not acceptable then the risks need to be shown warts and all - including the risk of doing nothing and the risk of gradually ramping up treatment while accruing brain damage as opposed to hitting hard from the outset.
And neurologists need to be more honest about "lesions". Particularly when lesions "heal" and when they are or are not "expanding". Perhaps explaining that the neurons inside lesions stop functioning once the lesions are formed and are essentially holes in the brain where there used to be functioning neurons. I think that might sway the more cautious to opt for treatment given the damage they're accruing.
I believe healthcare professionals and the people with MS who are being treated with DMTs are better able to judge their efficacy than the pharmaceutical companies.
🎯
I know, bashing pharma is cheap and gives ultimate satisfaction to some but it would also be great to appreciate that without pharma people with MS would still be on steroids only.
Sorry for this but a bit more balanced view and an appreciation that we all may have a biased view would help to work together to get better.
A proposal for the content of the cards I have is to separate effects on relapses and progression. There is sufficient evidence to justify this and it may help people with MS to change a bit the focus from relapses to progression.
Thanks for the opportunity to share my view.
I think the cards pay homage to the
contribution of pharmaceuticals in MS by virtue of their creation. Nobody here is doubting or even minimizing those contributions.
Separating data as you suggest would make this a much-less useful tool for those disabled by MS, undermining the very intent of aiding the MS patient in decision-making.
Me thinks thou doth protest too much ;)
I like the layout and readability of these cards, especially if comparing just a few for discussion with one’s doctor, or for doctors to give to patients when recommending of course. I was surprised by the higher cancer risk in Tysabri over Ocrevus since I’d thought that was just the opposite.
I think this is based on the emerging link between natalizumab and CNS lymphomas. With regards to ocrelizumab the potential link between breast cancer has not been confirmed in post-marketing studies. Overall the risk of cancer on natalizumab and ocrelizumab is low.
As natalizumab blocks CNS immune surveillance there is always a concern that it will create a sanctuary for CNS tumours and potentially for systemic cancers that metastasise to the CNS (breast, small cell lung, melanoma, renal cell and colon cancers. Saying this many metastatic cancers use VLA-4 the adhesion molecule that natalizumab inhibits to cross into the brain.
Thanks so much for your clarification.
1) I think it's awesome that this has gotten on the radar of pharma companies, and that they CARE how they're being perceived in this forum! 2) They probably don't have a case until they do head-to-head trials on high efficacy DMTs, which they won't and shouldn't (waste of money, hard to get statistical power) do. 3) Are you going to publish the network analysis?
The network analysis is published.
Samjoo IA, Worthington E, Drudge C, Zhao M, Cameron C, Häring DA, Stoneman D, Klotz L, Adlard N. Efficacy classification of modern therapies in multiple sclerosis. J Comp Eff Res. 2021 Apr;10(6):495-507. doi: 10.2217/cer-2020-0267. Epub 2021 Feb 23. PMID: 33620251.
These are fantastic! Thanks for all the dedication to provide these as a resource for us to navigate the DMT field.
Looking good! And as for Pharma not liking them... I'm shocked 🤣
"X reduces relapses by about 30%...."
How should a patient interpret this information?
A logical assumption would be that if I would have one relapse every year, I now only get two in three years (and I should be fine with those two, because that's what I chose for).
This number is the result from having ARR as a primary end-point in the clinical trial.
But I understood from your earlier information that that is not the way an MS patient should think about this. Let's say that a patient would want to strive for zero new relapses. I would think that would still be possible with this medication, however, the chance for this is lower than with higher efficacy drugs.
Do you think there is a better way of communicating this than saying: "X reduces relapses by about 30%...."
Yes. I think we could add NEDA rates. But not all DMTs have this information available and they tend to define it differently.
Do you have an article or podcast that I can refer people to who want to know more about this? I have the feeling it is still a big misconception among both patients and doctors.
I'm guessing they are hoping you use relative efficacy as opposed to absolute efficacy. Now where have I come across that issue recently with regards to a controversial drug? Lol 😆
Thanks for replying. I of course have my pharma glasses on, but I cannot sense an hommage to Pharma in the comment thread. In any case these cards are very useful if balanced. To have it vetted by more than very few people, though obviously extremely knowledgeable, would add credibility.
Samjoo IA, Worthington E, Drudge C, Zhao M, Cameron C, Häring DA, Stoneman D, Klotz L, Adlard N. Efficacy classification of modern therapies in multiple sclerosis. J Comp Eff Res. 2021 Apr;10(6):495-507. doi: 10.2217/cer-2020-0267. Epub 2021 Feb 23. PMID: 33620251.
In the context of drug company reactions and being bearers of “pressure and influence”- To skip the main gist of the post, which by the way is fantastic, when considering influences it is useful to keep in mind where the influencers place their influence attempts- Besides doctor’s office tables and the doctors themselves (I suppose), there are the ads in online resources and written materials provided by “societies” etc., and other sources such as Multiple Sclerosis News Today. Let’s not also forget about, in The US, commercials on television (do they still call it that?).
I think your ratings are important for people to discuss with their neurologist, and have a conversation that can lead to better understanding about their treatment.
Of course drug companies are going to complain. Too bad! These cards are amazing. I've never had access to this kind of information when changing DMTs. I have been, or am on, a total of four DMTs and there are things about each drug I never knew, particularly the effectiveness on a number scale and the response to vaccinations. As much as I love the cards, it's discouraging to realize what a poor job my health care providers have done in terms of informing me of basic information about my treatment.
Actually, directly and indirectly a good amount of the pharmas are contributing to confounding information...
This article is from September of last year, but there was a newer article, just a few days ago in the journal Science, warning that the paper mills are now bribing editors at the big journals. Mostly because papers can be tied to a public company, and subsequently responsible for 'pumping up' their stock.
https://www.elsevier.com/connect/the-cost-of-fraudulent-research
I've been dx in 2022, 46 yo, started with Tecfidera and after 6 months, due to active lesions, switched to ofatumumab. all good in the best of all possible worlds, my last MRI now shows no active lesion, but I feel all chapters slightly worsened.
my neuro doesn't like the word "progressive" - she says it's too early to make a call. but without MRI activity and continuous deterioration (my EDSS went from 3 to 4.5 in ab. 18 months) I feel like she ran out of options. haha, too bad for me.
PS. why not combine DMF with ofatumumab? what could possibly go wrong?
I don't like to speak out of turn but am gonna do it anyway:
With anti-CD20 therapies like ofatumumab and the rest (and any of the immune depleting / reconstituting therapies potentially) it helps to bear in mind WHERE you're taking your meds. Whether you eat them, inject them under the skin or infuse them into a vein, they all go into the "peripheral" blood (eventually in the case of oral meds).
Our brains and spinal columns are protected by the blood-brain barrier which only allows stuff across that is seen as necessary. When you use an anti-CD20 you're depleting B-cells outside the brain and spinal column. It can take anywhere between 18 months and 2 years for these changes to be reflected inside the brain, once the B cells and T cells die off in there. So - you may still get some "episodes" of lesion formation in there after you start treatment, until you're about 2 years in, unfortunately. These episodes are likely to be less severe than they would have been had you not been on treatment.
Once you're 2 years in, disease activity is supposed to stop and if it doesn't, your neurologist is likely to suggest a stronger treatment.
Also once you're 2 years in then you get a better idea that what you're experiencing MIGHT be smouldering MS / progression and you can try to get your neurologist to act accordingly with add-on therapies (if they're open to them - not sure what add-ons we have at the moment, I think that would be a question for Prof Giovannoni to address...)
thank you, Simon. I started ofatumumab in July, 2023 and last MRI is from December, so I'm about 5-6 months in - if Kesimpta would have been ineffective, then alemtuzumab (this being an option of last resort, procedurally speaking). but seeing the MRI, my neurologist adviced me to go on with the current anti-CD20.
Prof. Giovannoni has said it many times here: once "progression" is on the table, there isn't any miracle to be expected. maybe I'm not employing the correct mindfulness techniques, haha, maybe is dairy, maybe my ancestors, maybe is just sheer randomness.