33 Comments
Oct 17, 2021Liked by Gavin Giovannoni

I’m 64 and on Ocrevus for 3 1/2 years. (Tysabri for 5 years prior to that.) Blood tests done 1 day prior to my last infusion show no CD19 B cells so it’s doing what it’s supposed to do. However, it also is causing an ever increasing drop in my IgG and IgM levels both of which are now slightly below the range low point. I’m very unhappy about this and live in fear of serious infections. My neuro talked to an immunologist who told her my IgG and IgM levels aren’t at a low enough point to be of concern just yet. Really?!? I’m convinced that Ocrevus is why I’ve gone from never getting sick to colds every winter as well as a horrible six week pink eye infection in both eyes last fall, my first ever UTI and a slew of other strange malfunctions that went away months after they appeared. I’m still classified as RRMS 20 years since diagnosis and my MRI’s have been stable.

I don’t know what I’m going to do about all this just yet. My next followup with my neuro will be next month. This will definitely be a topic of discussion. It feels like there isn’t a really great option for us older folks. Especially since most drug trials don’t include us so we don’t have good data to use in making decisions. We either risk MS decline or significant infection and even death. I had the Covid vaccines but as you might have guessed, did not develop antibodies.

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Oct 16, 2021Liked by Gavin Giovannoni

I'm on Tecfidera, which I thought was classed as immunomodulatory but I agree that it is immunosuppressive. I've been on it 3 1/2 years and since starting it I've had every cold going when I used to never get sick. I currently have what is known in London as The Cold (because it is so bad). I had to pull out of Manchester Marathon halfway through because I couldn't breathe enough and I was slowing down (ok I didn't have to pull out but I was getting off my target pace and I'm going to prioritise recovery so I can try again sooner for the Good For Age time I'm seeking).

I hate getting sick all the time! I was hoping the pandemic had changed people's behaviour but the speed at which this cold has spread around London means I'm obviously wrong!

My lymphocytes have only dipped below .5 once and my blood tests have been changed to every 6 months now. I hate needles! But it turns out I liked the reassurance of getting my blood test results and seeing lymphocytes up around 0.8-1 most of the time.

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Sarah, DMF is definitely immunosuppressive. Lymphocytes drop on average by about 30% and in some pwMS lower, there is an opportunistic infection signal and a herpes zoster (shingles) signal. I suspect a secondary malignancy signal will emerge after about 10 years of exposure (unknown-known), which is what happened with azathioprine.

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Oct 17, 2021Liked by Gavin Giovannoni

I’m horrified to read about the secondary malignancy risk from DMF - I didn’t sign up for that. I’d there no such thing as a safe effective DMT?

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author

This is not confirmed, but highly likely. You shouldn't be horrified this is to be expected with any immunosuppressive therapy. It is a basic principle of immunosuppression.

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Oct 18, 2021Liked by Gavin Giovannoni

What I'm horrified by is that this was never discussed - surely something my neuro or MS nurse should have told me? I also have no clue as to the actual size of the risk, which is a very important factor.

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Liz, this is what is in the label: https://www.medicines.org.uk/emc/medicine/28593#gref

Carcinogenesis

Carcinogenicity studies of dimethyl fumarate were conducted for up to 2 years in mice and rats. Dimethyl fumarate was administered orally at doses of 25, 75, 200 and 400 mg/kg/day in mice, and at doses of 25, 50, 100, and 150 mg/kg/day in rats. In mice, the incidence of renal tubular carcinoma was increased at 75 mg/kg/day, at equivalent exposure (AUC) to the recommended human dose. In rats, the incidence of renal tubular carcinoma was increased at 100 mg/kg/day, approximately 2 times higher exposure than the recommended human dose. The relevance of these findings to human risk is unknown.

The incidence of squamous cell papilloma and carcinoma in the nonglandular stomach (forestomach) was increased at equivalent exposure to the recommended human dose in mice and below exposure to the recommended human dose in rats (based on AUC). The forestomach in rodents does not have a human counterpart.

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Nov 13, 2021Liked by Gavin Giovannoni

I was previously on Tysabri for 4 years in total, with a years break on Fingolimod. I had HSCT nearly 3 years ago and thankfully have been in remission since. I have had MRI scans annually but I don’t know if my neurologist will continue that now. I had some blood tests in June this year and my lymphocyte level had dropped slightly (1.2) but still just within normal limits. My immunoglobulin levels have never been checked. Is this important? Apart from monitoring for secondary cancers, (should these be done more frequently than at the standard intervals?) should anything else be monitored now?

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Your lymphocyte counts are normal and hence your immune system should be fully competent. There is no need to have screening for cancers more frequently than that proscribed by your national programmes.

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That’s great, thank you for taking the time to reply.😀

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I broke through every medication from 2003 until 2011 when I went on natalizumab (Tysabri). Two years later I had to stop because too many JCV antibodies. Went on dimethyl fumarate (Tecfidera) after two years of glatiramier acetate (Copaxone) in 2015. It didn’t do much for me— probably because I was PRMS at this point. Stopped Tecfidera in end of 2016 and ended up in a nursing facility in 2017 when I developed sepsis because the doctors didn’t understand that I was immunocompromized from years of ‘tinkering’ with my immune system with MS drugs, and they gave me a course of methylprednisolone (Solumedrol) which blew up my ‘non-infection’ infection which was a UTI. While I was in the nursing facility I started ocrelizumab (Ocrevus) in 2019. I had to stop Ocrevus while I was getting Covid vaccinations—three in all—and I start Ocrevus again in December of this year. Problem is that I keep getting UTIs even right after a full course of antibiotics, so the UTIs are pretty much chronic now, and I have more profound disability that doesn’t get better with each infection. My nerves are constantly under attack and have no chance to recover or just calm down. It’s harrowing, and being in a nursing facility there’s never any sense of urgency from the staff, and I am considered a "troublemaker" because I keep pushing the staff to send me to the hospital so I can get antibiotics instead of waiting four to five days for a UA (urinalysis) result. Which most of the time doesn’t register much and I have to argue that the MS actually has an early warning system and I don’t have time to wait for the state appointed doctor to decide whether I really need another UA, and wait another week for the results. I have been through this about ten times, and you would think they would listen to me by now instead of just shaming me when I’m begging for help.

Yes.., being immunocompromized is horrible, and worse so when it’s caused by the stuff that is supposed to keep us MS'ers from being consumed by the disease. In some ways it’s like being a world leader, it’s interminable tough decisions.

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And I forgot… I blew through most antibiotics and I’m on carbapenems now. Not much left.

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Oct 17, 2021Liked by Gavin Giovannoni

I'm with rituximab since 2014. 7 years. The only opportunistic infection I have had was an herpes zoster on my neck about 4 years ago. It went away with treatment. Every winter if I don't take care of myself I catch a cold right away and it grabs my throat. Fever no. Now with the covid I take care of myself a lot and I have no contact with anyone. Waiting for the third dose because with 2 of pfizer I have not generated antibodies. Regards

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Oct 16, 2021Liked by Gavin Giovannoni

I've been on Tysabri for 12 yrs, just 3 small relapses but just tested positive for JCV (4.09%). Do I stay on Tysabri or switch to a safer DMT? Which one?

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Oct 16, 2021Liked by Gavin Giovannoni

See that Tysabri is classed as immunosuppressive but I thought it was immunomodulatory. If it is the former then there is more than JCV status to consider.

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Natalizumab is a selective immunosuppressive in that it prevents immune surveillance of the CNS, hence the infections such as PML.

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Oct 16, 2021Liked by Gavin Giovannoni

Incredibly usefully set out. It would help any pwMS to sort out treatments they might be offered. I was advised to have an immunomodulator in 2005, but hadn't a clear idea of what the difference between them and immunosuppressants was. The clinic (Centre Hospitalier Uninversitaire Renes) was very, very thorough but I hit a bit of a brick wall when I asked them to explain further. It was a case of "You just need to go on this; no need to know why." I therefore declined. This post would have helped me understand, not that much was available back then.

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Oct 16, 2021Liked by Gavin Giovannoni

I am on tecfidera. I am 57 and just got a terrible case of shingles.

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I was on fingolimod for about 18 months. I had to go on every other day dosing after developing lympfopenia during which time I had a relapse. I was then given aubagio. About a month later breast cancer was found on my yearly mammogram. I was 59. Don’t know if fingolimod caused it.

I consider myself lucky it was found early and I’m at 6 years since last chemo, surgery, and radiation.

Now on Ocrevus since 2018.

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Oct 16, 2021Liked by Gavin Giovannoni

When I was on Gilenya I developed ringworm and pink eye that both lasted for months and required multiple courses of treatment. I was 48 and despite working with kids for over 20 years, had never had either prior to the Gilenya. In addition my nails peeled excessively and nothing helped. As soon as I was switched to an every other day dose, my nails began to improve and since going off it completely, I’ve had no additional problems with any of the 3.

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Oct 16, 2021Liked by Gavin Giovannoni

I am now 47. I was diagnosed with MS in 2001 and did not have any medication or symptoms for years. In 2016 I started taking Tecfidera, but this was stopped in July 2020 after having breakthrough symptoms in order to start Ocrevous which started in November 2020. Now I have my 6 monthly Ocreovus infusions but tried to have my covid vaccines 2 months before infusions. I have only had my taken last week and do not know anything about my T or B cell counts. I have luckily stayed well apart from regular UTIs when I have to force my GPs to let me leave and check samples before they give a prescription for anti biotics. Should I be on continual low-level dose antibiotics due to my immunosuppressive Ocrevus? Do you think I am still at risk from covid due to the ocrevus? I do not have any other underlying health conditions and try to staff active and healthy (with my two teenage children). What else should I do to keep well? Thanks

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Jo, there are no right or wrong answers. We are all at risk of getting COVID-19. However, ocrelizumab-treated pwMS are at higher risk and also have blunted vaccine responses. The good news is that treatments are becoming available for COVID-19, which will help people like you. I tell my ocrelizumab-treated patients that they are vulnerable.

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Oct 17, 2021Liked by Gavin Giovannoni

Thank you. What would you say about continuing low level antibiotics use to decrease UTIs?

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Yes. In our centre, if you have three UTIs in a 12 month period or 2 UTIs in a 6 month period you should consider starting urinary antiseptics.

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thank you, I will chase this up!

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Oct 16, 2021Liked by Gavin Giovannoni

I've been on Fingolimod since 2016 and NEDA since then also. Apart from quite a few lingering coughs and colds it was fine. However, I developed a nasty bout of shingles in 2018 on my face and actually in my eye. It was incredibly painful. I have also developed around 6 Actinic Keratosis skin lesions which have been treated with Efudix cream. I've been waiting for an appointment for over a year with the Dermatology department but covid has really impacted the waiting list so I have no idea when I'll be seen.

After a very recent smear test I was told I have the HPV virus that has reactivated due to immunosuppression. This was discovered 18 months ago but I wasn't told. I'm still waiting to hear if I have any abnormal cells.

All in all at the age of 59 I am getting a bit exhausted with the constant self monitoring that goes with being on Fingolimod and I would like to come off it. Last time I discussed this with my neuro I was offered aubagio but due to where I've had previous lesions (brainstem land cervical) I was advised to stay on Fingolimod. I wasn't given any other options but I want to have the discussion again. The lack of antibodies against the covid vaccine has also got me to this point.

I feel very much that I'm dsmned if I do and dsmned if I don't.

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Oct 16, 2021Liked by Gavin Giovannoni

I was in a similar situation - started on fingolimod at age 63 after 11 years on copaxone. Like you, I stayed perfectly well MS-wise, but three years into was starting to get warts. Tolerable but annoying and unsightly. At the back of my mind was the risk of secondary malignancies. Coming up to my 70th birthday I asked the neuro if I was to be on fingolimod for life. I was given three choices - all, I was assured, being good choices, so it was up to me. 1 stay on fingolimod, 2 return to copaxone 3 cladribine. I did my homework, saw the neuro privately to discuss the ins and outs of each, then decided on cladribine. I've just finished round one, absolutely no regrets. The MS nurse also told me that at the neuro team's panel meeting to tick the boxes for approval of my change of meds, every member agreed it was the best choice in my circumstances. I wonder why you weren't given this option, so yes - definitely have a further discussion.

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Oct 16, 2021Liked by Gavin Giovannoni

Thank you. That's so helpful. I will do some research and definitely mention this.

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Oct 16, 2021Liked by Gavin Giovannoni

I was diagnosed in 2017, at 50 years old and started fingolimod. After some time, I became interested in changing meds because of immunosuppression, but my doctor would not approve a move to another drug. He did not want to rock the boat since I was not having issues.

In September of 2020 my insurance plan stopped allowing visits to this doctor so, I followed a recommendation and started seeing a new doctor. I did not realize it at the time, but it was all for the best. My new doctor changed my meds to cladribine and also referred me to additional doctors who have helped me with other issues that I was enduring. I start my second year of cladribine next January. My point is that I was really afraid to change docs and still a bit concerned about trying a new medicine, but the timing was perfect, (regarding Covid and immunosuppression)and I feel more hopeful about my health.

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Oct 16, 2021Liked by Gavin Giovannoni

I presume so, as I haven't had a relapse for years. I believe siponimod is the only DMT prescribable for SPMS, so if that's the case you've had the right advice. Was dx of SPMS made after tests?

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Oct 17, 2021Liked by Gavin Giovannoni

Yes, I'm in the UK and am seen in a centre of excellence (which I travel to) but locally I have seen MS friends receive care and advice of a much lower order. If I were you (and I know I'm not and everyone's circumstances are different) I would be paying for a one-off private appointment with a top-of-the-game neuro to get a second opinion on the SPMS. If it's not clear-cut, JUST MAYBE a neuro with a less rigid interpretation of the guidelines would offer cladribine.

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Oct 17, 2021Liked by Gavin Giovannoni

Hi Nellie- Just wanted to give you my 2 cents- I'm 64. I had pain, up to severe pain, also in my right calf, ankle, building over 3 years. Our assumptions, given a 35 year history with MS, was that it was MS. But no, it’s structural problems (PTTD, PTD, or peroneal neuropathy, inflamed nerve, or ?), contributed to by (in part) flat feet since birth. Pain was receptive to orthotics, but not simply or initially… I had to experiment and change things around for months; boots arches etc. Use of a compounded med with Elavil, Baclofen, Gabapentin, Ibuprofen, helped calm down the inflammation so I could then sense things more specifically. Ice pack in my sock. Hand held vibrators in rooms and car. All eventually in unison finally got the inflamation under control in 4 months. Just a tip to look at all possibilities (which you probably do), and good luck!

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