Thank you Prof G, this is an interesting topic because some countries mostly use interferons.
Is there an explanation for why some people still have flu-like symptoms after each injection even after several years of taking Rebif? Can taking antipyretics 3 times a week for several years be harmful?
Re: "Is there an explanation for why some people still have flu-like symptoms after each injection even after several years of taking Rebif?"
This is unusual, but it does mean the drug is binding to its receptor and stimulating a type 1 interferon response. Persistent flu-like symptoms exclude NABs.
Re: "Can taking antipyretics 3 times a week for several years be harmful?"
In most people no. Many people with arthritis take NSAIDs for decades without problems. However, upper GI bleeding is more common in people infected with Helicobacter pylori so it maybe worth getting screened to make sure you Helicobacter pylori negative.
Hi Prof G, a bit late to this but, I am taking Plegridy after much effort spent trying to get a higher efficacy treatment. I’m now unsure as to whether to keep going or try to switch.
I thought IFN-beta treatments were moderate efficacy and the result of that would only be apparent after the damage was done. Therefore treating early with the highest efficacy treatment was the best option, particularly as measure that might indicate a suboptimal response i.e. BVL weren’t commonly used.
Your article seems to suggest that there are some people for whom IFN-beta is an effective treatment long-term that doesn’t carry the risks of others and that it’s possible to understand who those people are?
Hello Doctor-, there may be something here (?). Back in the day when I developed MS (early 1990’s), there was nothing but Swank Diet, steroids and “Bee stings”. Then along came Betaseron (1994ish) and we all, in the MS “Men’s Group”, believed we were saved! Then, slowly, interferon variations appeared, then totally different DMTs. A single inconvenient option to save yourself became a crapshoot (seemingly) on how to move forward with no inconveniences whatsoever (and perhaps), some avoidance of the truth.(But, I digress…)
So I was deteriorating, clinically and with X-ray and/or MRI by 1995, and I started Betaseron 1b as it became available. Walking became at times very difficult (got my custom wheelchair), periods of blindness in one eye and then the other, head and body shakes/numbness- making driving, hand writing and other activities difficult. Weak legs and balance issues. Episode or two of unexpected bladder “difficulties” at the wrong time in the wrong place. Doctoral graduation and dream job, [ADA lawsuit]. Trying to find a partner. These were trying times.
Within all this I switched my Doctor to an MS specialist who also advocated quick (within 2 or 3 days) intravenous steroid use in order to reduce disability. So those were my treatments (including Betaseron and Swank) for the next 23 or so years. Last steroid use was 1999. Interferon side effects have always been acceptable in terms of the trade-off (in my mind), which was active MS. A few flu reactions every year easily resolved with ibuprofen, and no significant injection reactions but for one (in 23 years). No enhancing lesions since. No new lesions ID’d via MRI since; OTHER THAN on my spine when I switched to Avonex (a weaker interferon, [I believe] for a year. (I had moved far away, and the change was based on a new doctor’s recommendation that it might help me teaching!?.) I insisted on going back on Betaseron though he thought Novantrone or some other med. was indicated. (So I learned that you have to be your own advocate). Ever since then, again, MRI showing stability. All symptoms very gradually improved from 1995 to 2003, and I arrived at a new “normal”. Subcutaneous shots every two days, no problem! (Within this, in about 2005, a visit with a new doctor, (the previous had seemed to stop caring), allowed for a check of antibodies, which came back +, and he commented that he wasn’t even sure I had MS, given my new MRIs. [his explanation for why I was doing well]). So good-bye to this doctor as well. Next Doc for 10 years was head of Neurology Dept. at a medical teaching university in Philadelphia and his philosophy was “if it’s not broke, don’t fix it”. Somewhere during this period it was impressed upon me that (especially if doing well anyway) antibodies did not rule out a benefit with Betaseron.
I did have a 3 day hospital stay of antibiotics and “watching”, due to infection where I routinely “jabbed” myself in the buttocks with Betaseron.
Moved again. It wasn’t until 3 or 4 years ago, after my leg/foot hurt, that I learned of smoldering and SPMS. It was quite depressing. I switched to Ocrevus, primarily to try and head off anything I could. Covid then came along and was decimating Italy, and while my Doc was on sabbatical, it was up to me to terminate Ocrevus before my 3rd dose. I researched what I could, and I did in March of 2020, not get re-infused. I have since, not been on any DMT. It’s nice not being tied to a routine injection; I had forgot what that was like. Just had an MRI of brain, cervical and thoracic spine. Brain and cervical are (once again) stable, and perhaps something going on at one spot in thoracic spine (which seldom gets MRI’d- so no comparisons). That’s Jan 2022 back to 2018.
This is just a summary! I’m 64 now and believe I’ve avoided the worst of it. There is visible atrophy and I don’t think instantaneously on all things like I once did. Walking OK (no running since 1995), foot problem based on changes from a naturally low foot arch, combined with prior MS gait. (In other words, it was not new MS activity [probably]) causing pain in 2018. What would I have done in the past if in 1995 there were lots of treatment options? I don’t know. Try to pick the “right one”, I suppose. As it stands, back then I had no choice and “went with it”. Worked out OK. Everything does not work like new now. I may not make it to 80, or if I do, it won’t be without issues (like a fully functioning bladder like a young man). But really, at this point, who cares?! I’m happy with the outcome so far.
If I had to do it all over again, I would probably try reconstitution therapy.
One question after all this, however. Is there any evidence or discussion that acquired kidney cysts without a family history can be the result of Betaseron or Ocrevus? I haven’t found anything.
Thank you Dr. Giovanni. You briefly mentioned EBV in today's note. What do you think of the application of Thymosin Alpha One and Thymosin Beta Four for managing EBV?
Since MS seems like such a "holistic" type condition, would a holistic, lifestyle medicine approach be the most effective means of managing it? My story is diagnosed with aggressive RRMS 4.5 years ago in the States, put on Tysaberi and stayed on it for 6 months. Then I stopped it. From there on I follow OMS. No relapses thank God but two recent pseudo-relapses due to viruses (one Covid). In August last year I felt really crappy. I hired a functional medicine practice and through blood work they identified elevated EBV antibody levels. Theymosin was prescribed and I have felt so much better. Also working on my microbiome health. Your Smouldering Theory makes so much sense to me! Thank you, sir.
Hi Prof G and thanks so much for this information. I always appreciate your posts but especially this one. I am 67 and been on Ocrevus since 2018. Diagnosed 10 years ago. Started off with Gilenya for 18 months until breast cancer showed up. After BC treatment I used IVIG, Tysabri and now Ocrevus. Because I didn’t get a response after three vaccines, I skipped the next infusion due to delta and omicron. My MS specialist decided I should bridge over to Plegridy which I start next week. I was also lucky to get Evusheld (emergency use authorization by the FDA) when it was available in my area. I don’t know if I’ll go back to Ocrevus. At my age, so many things to consider.
Yes, age is a hot topic in MS, in particular immunosenescence and its interaction with immunosuppressive therapies. Not to mention ageing being one of the mechanisms driving smouldering MS.
In a similar situation with O and vaccine response. Had to "move some mountains" to finally getting a dose of Evusheld. Hopefully protective against Omicron...
Re: "Since when was beta interferon deemed safe in pregnancy? Always wonder who first makes these decisions and on what evidence."
For quite a few years now. The MS community usually moves first on this based on pregnancy register data and then the regulators (EMA, MHRA, FDA, etc.)>
A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited.
Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far.
If clinically needed, the use of Rebif may be considered during pregnancy.
Breast-feeding
Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated.
Rebif can be used during breast-feeding.
Fertility
The effects of Rebif on fertility have not been investigated.
The Nabs are due to oxidation products and protein aggregates. The Biogen scientists were just better at the details and making sure they got the production right.
Thank you Prof G, this is an interesting topic because some countries mostly use interferons.
Is there an explanation for why some people still have flu-like symptoms after each injection even after several years of taking Rebif? Can taking antipyretics 3 times a week for several years be harmful?
Re: "Is there an explanation for why some people still have flu-like symptoms after each injection even after several years of taking Rebif?"
This is unusual, but it does mean the drug is binding to its receptor and stimulating a type 1 interferon response. Persistent flu-like symptoms exclude NABs.
Re: "Can taking antipyretics 3 times a week for several years be harmful?"
In most people no. Many people with arthritis take NSAIDs for decades without problems. However, upper GI bleeding is more common in people infected with Helicobacter pylori so it maybe worth getting screened to make sure you Helicobacter pylori negative.
i.e. pwMS doing well on IFN-beta (why change if you are doing well?).....doesn't this conflict with your general approach?
No we always treat-2-target so if you are there on an IFN-beta formulation why take on the risks of not getting there with another DMT.
Hi Prof G, a bit late to this but, I am taking Plegridy after much effort spent trying to get a higher efficacy treatment. I’m now unsure as to whether to keep going or try to switch.
I thought IFN-beta treatments were moderate efficacy and the result of that would only be apparent after the damage was done. Therefore treating early with the highest efficacy treatment was the best option, particularly as measure that might indicate a suboptimal response i.e. BVL weren’t commonly used.
Your article seems to suggest that there are some people for whom IFN-beta is an effective treatment long-term that doesn’t carry the risks of others and that it’s possible to understand who those people are?
Hello Doctor-, there may be something here (?). Back in the day when I developed MS (early 1990’s), there was nothing but Swank Diet, steroids and “Bee stings”. Then along came Betaseron (1994ish) and we all, in the MS “Men’s Group”, believed we were saved! Then, slowly, interferon variations appeared, then totally different DMTs. A single inconvenient option to save yourself became a crapshoot (seemingly) on how to move forward with no inconveniences whatsoever (and perhaps), some avoidance of the truth.(But, I digress…)
So I was deteriorating, clinically and with X-ray and/or MRI by 1995, and I started Betaseron 1b as it became available. Walking became at times very difficult (got my custom wheelchair), periods of blindness in one eye and then the other, head and body shakes/numbness- making driving, hand writing and other activities difficult. Weak legs and balance issues. Episode or two of unexpected bladder “difficulties” at the wrong time in the wrong place. Doctoral graduation and dream job, [ADA lawsuit]. Trying to find a partner. These were trying times.
Within all this I switched my Doctor to an MS specialist who also advocated quick (within 2 or 3 days) intravenous steroid use in order to reduce disability. So those were my treatments (including Betaseron and Swank) for the next 23 or so years. Last steroid use was 1999. Interferon side effects have always been acceptable in terms of the trade-off (in my mind), which was active MS. A few flu reactions every year easily resolved with ibuprofen, and no significant injection reactions but for one (in 23 years). No enhancing lesions since. No new lesions ID’d via MRI since; OTHER THAN on my spine when I switched to Avonex (a weaker interferon, [I believe] for a year. (I had moved far away, and the change was based on a new doctor’s recommendation that it might help me teaching!?.) I insisted on going back on Betaseron though he thought Novantrone or some other med. was indicated. (So I learned that you have to be your own advocate). Ever since then, again, MRI showing stability. All symptoms very gradually improved from 1995 to 2003, and I arrived at a new “normal”. Subcutaneous shots every two days, no problem! (Within this, in about 2005, a visit with a new doctor, (the previous had seemed to stop caring), allowed for a check of antibodies, which came back +, and he commented that he wasn’t even sure I had MS, given my new MRIs. [his explanation for why I was doing well]). So good-bye to this doctor as well. Next Doc for 10 years was head of Neurology Dept. at a medical teaching university in Philadelphia and his philosophy was “if it’s not broke, don’t fix it”. Somewhere during this period it was impressed upon me that (especially if doing well anyway) antibodies did not rule out a benefit with Betaseron.
I did have a 3 day hospital stay of antibiotics and “watching”, due to infection where I routinely “jabbed” myself in the buttocks with Betaseron.
Moved again. It wasn’t until 3 or 4 years ago, after my leg/foot hurt, that I learned of smoldering and SPMS. It was quite depressing. I switched to Ocrevus, primarily to try and head off anything I could. Covid then came along and was decimating Italy, and while my Doc was on sabbatical, it was up to me to terminate Ocrevus before my 3rd dose. I researched what I could, and I did in March of 2020, not get re-infused. I have since, not been on any DMT. It’s nice not being tied to a routine injection; I had forgot what that was like. Just had an MRI of brain, cervical and thoracic spine. Brain and cervical are (once again) stable, and perhaps something going on at one spot in thoracic spine (which seldom gets MRI’d- so no comparisons). That’s Jan 2022 back to 2018.
This is just a summary! I’m 64 now and believe I’ve avoided the worst of it. There is visible atrophy and I don’t think instantaneously on all things like I once did. Walking OK (no running since 1995), foot problem based on changes from a naturally low foot arch, combined with prior MS gait. (In other words, it was not new MS activity [probably]) causing pain in 2018. What would I have done in the past if in 1995 there were lots of treatment options? I don’t know. Try to pick the “right one”, I suppose. As it stands, back then I had no choice and “went with it”. Worked out OK. Everything does not work like new now. I may not make it to 80, or if I do, it won’t be without issues (like a fully functioning bladder like a young man). But really, at this point, who cares?! I’m happy with the outcome so far.
If I had to do it all over again, I would probably try reconstitution therapy.
One question after all this, however. Is there any evidence or discussion that acquired kidney cysts without a family history can be the result of Betaseron or Ocrevus? I haven’t found anything.
And thanks for everything Dr. G.
Tom
Re: " Is there any evidence or discussion that acquired kidney cysts without a family history can be the result of Betaseron or Ocrevus?"
To the best of my knowledge no.
Thank you Dr. Giovanni. You briefly mentioned EBV in today's note. What do you think of the application of Thymosin Alpha One and Thymosin Beta Four for managing EBV?
Since MS seems like such a "holistic" type condition, would a holistic, lifestyle medicine approach be the most effective means of managing it? My story is diagnosed with aggressive RRMS 4.5 years ago in the States, put on Tysaberi and stayed on it for 6 months. Then I stopped it. From there on I follow OMS. No relapses thank God but two recent pseudo-relapses due to viruses (one Covid). In August last year I felt really crappy. I hired a functional medicine practice and through blood work they identified elevated EBV antibody levels. Theymosin was prescribed and I have felt so much better. Also working on my microbiome health. Your Smouldering Theory makes so much sense to me! Thank you, sir.
Re: Thymosins
I have no idea on their utility in MS, but will do some reading about them.
Thank you Dr. Giovanni. I am just an N of one, but they have been very helpful to me.
Hi Prof G and thanks so much for this information. I always appreciate your posts but especially this one. I am 67 and been on Ocrevus since 2018. Diagnosed 10 years ago. Started off with Gilenya for 18 months until breast cancer showed up. After BC treatment I used IVIG, Tysabri and now Ocrevus. Because I didn’t get a response after three vaccines, I skipped the next infusion due to delta and omicron. My MS specialist decided I should bridge over to Plegridy which I start next week. I was also lucky to get Evusheld (emergency use authorization by the FDA) when it was available in my area. I don’t know if I’ll go back to Ocrevus. At my age, so many things to consider.
Re: "At my age, so many things to consider."
Yes, age is a hot topic in MS, in particular immunosenescence and its interaction with immunosuppressive therapies. Not to mention ageing being one of the mechanisms driving smouldering MS.
In a similar situation with O and vaccine response. Had to "move some mountains" to finally getting a dose of Evusheld. Hopefully protective against Omicron...
Hope so too. Best wishes!
Do Avonex and Plegridy have low NABs because dose is low and only once a week/fortnight? Versus say Rebif 44, high dose, high frequency.
Since when was beta interferon deemed safe in pregnancy? Always wonder who first makes these decisions and on what evidence.
Wonder how many people have managed to stay on Rebif when SPMS? Always thought it was weird you could remain on it, yet can't start new when SPMS.
Re: "Since when was beta interferon deemed safe in pregnancy? Always wonder who first makes these decisions and on what evidence."
For quite a few years now. The MS community usually moves first on this based on pregnancy register data and then the regulators (EMA, MHRA, FDA, etc.)>
For example, the following is the text from the SmPC of Rebif: https://www.medicines.org.uk/emc/product/8211#gref
4.6 Fertility, pregnancy and lactation
Pregnancy
A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited.
Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far.
If clinically needed, the use of Rebif may be considered during pregnancy.
Breast-feeding
Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated.
Rebif can be used during breast-feeding.
Fertility
The effects of Rebif on fertility have not been investigated.
Thanks for info, it's all there, I should have looked.
The Nabs are due to oxidation products and protein aggregates. The Biogen scientists were just better at the details and making sure they got the production right.