Jan 18: Two year anniversary of my Last Dose

[EPguy]

Today is the 2-year anniversary of my last dose of IFN. My post last year, link below, covers it well and I got the courage to read it today. I know that post has helped at least someone reduce the risk of my fate.

healthunlocked.com/mpnvoice...

In particular context of Sjogren’s and a year to learn from here and elsewhere, I’ve concluded my experience was one-of-a-kind to date. This is good for other IFN users. I’m not aware of any published case histories or member reports here of a single IFN dose instantly causing permanent personal mayhem via Sjo. For others there seems to be a graduated warning over weeks or months. Plenty of time to get any worries checked. But please do get them checked, whether it’s emergent with IFN or pre-existing the IFN.

One notable item I had forgotten is how high the Sjo risk is with IFN in the “ANNEX I” of the Bes Euro label “SUMMARY OF PRODUCT CHARACTERISTICS”

I wrote, “In the Euro label Sjo is the only (non-thyroid) A-I (autoimmune) listed as “common” (1-10% pts) on page 9 (34 and 46) here”

It follows that, while the severity is not reported, the "common" cases here were not like my experience since it was approved for marketing. Sjo is a unique autoimmune in this "common" class, even closely related Lupus is not a listed Bes risk in this reference. My impression from anecdotal posts here is the Sjo incident range in this report is plausible.

ema.europa.eu/en/documents/...

This report does not specify the gender of the Sjo pts. But so far all the related case reports I found and member experience I recall here have been women, which follows the 90% of Sjo pts that are women. The 10% that are men on average get a more severe disease expression (on average being the important qualifier) so as the lone representative male with IFN related Sjo my extreme experience may fit well. I have zero family history of autoimmune disease. But either gender can and do get strong presentations.

In sum, Sjogren's risk is significant with IFN, and suggests careful attention, but my crash and burn remains unique to date.

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I continue to suspect the botched flu vax I got is tied to this outcome as I've posted. Disasters usually require a sequence of unlucky and unlikely events- this fits in my opinion. My husband discussed it today, he had told me to wait on the flu vax, but my GP said one week spacing was fine. I now know it’s not.

You should discuss with Dr my two suggestions (my opinion) for safest vax strategy:

1- As I’ve posted before: Do not get vaccines one week apart. Same day or preferably two weeks+ is safer. This is common knowledge among some, but not enough, practitioners. I got them at the same pharmacy and they did not screen for this. With three Fall vaxes these days it’s highly and newly relevant.

2- A new advice from an old memory- Be sure to fully expose your shoulder to the care giver. It’s the caregiver’s fault if they don’t insist on this but it’s the pt’s problem. My flu vax was misplaced (one of the steps in that sequence of events).

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On Sjo treatments, there are now 5 promising therapies in phase 3, up from zero recently. I’ve contacted all 4 of the distinct trials near me. But the MPN and/or the Rux exclude me. I would switch to HU if it could get me these treatments. It would be worth risking a rise in VAF and the extra sides I had. There are possibly curative cell trials that I would qualify but they considered and passed on the Sjo indication. “It’s not serious enough”, a still too common perception. So I await approval in coming years and hope to hold up in the meantime.

If you have or know someone with Lupus, the close Sjo relative, there are numerous early cell trials ongoing, one with breakthrough status. This is all just starting the past year. It could be worth inquiry, these show potential for a durable remission or even cure. I think Sjo will get a cell trial at some point. These are distant relatives to the new CAR-T therapies in study for CALR.

[hunter5582]

Thank you for continuing to post your saga with Sjo. It is a cautionary tale that anyone undergoing the serious treatments used for MPNs needs to heed. While the treatments like Besremi and jakafi are significant steps forward, they also come with risks. You have made the point on multiple occasions to pay attention to how your body is reacting and take action when something seems wrong. That is excellent advice.

Wishing you success on finding a more successful way to treat the Sjo while managing the MPN. Your posts about what you have experienced and learned continue to inspire and inform. Looking forward to seeing more.

[EPguy in reply to hunter5582]

Thanks for the support. Extrapolating my experience to one possible conclusion, a pt on IFN at low risk for Sjo (ie male, no family history of A-I) may be at higher risk for an exceedingly unlikely severe event with minimal warning. Even if there is something to that two things follow: the odds are vanishingly small it will happen, and in contrast for most pts those body reactions will give clear and timely warnings, and with timely action the adversity is likely to be reversible. We've seen here that non-A-I "Last Dose" events are also possible so the body attention you note is a good broad concept.

I still try to post analyses etc here but it is harder to do than before. I just did a nice quick summary of the promising new 3 Jak-i's but it was in a reply and the parent post got deleted. I'll try to reproduce it for a top post if I can.

[EPguy in reply to hunter5582]

I should add there is one risk factor I do have I forgot to note. A history serious mononucleosis. Reactivation of EPV (Epstein-Barr Virus) is increasingly recognized as a strong association with various A-I diseases, Sjo being one.

"Chronic or recurrent EBV infection of epithelial cells has been linked to systemic lupus erythematosus and Sjögren’s [syndrome]Disease, whereas chronic/recurrent infection of B cells has been associated with rheumatoid arthritis, multiple sclerosis and other diseases"

pmc.ncbi.nlm.nih.gov/articl....

On the Sjogren's forum an informal survey had near 100% of respondents with this history.

If may follow that IFN + serious EBV history increases Sjo risk. EBV is also associated with MS, but that is not an explicit IFN risk.

[hunter5582 in reply to EPguy]

Interesting that there is a possible link to mononucleosis. I had mono 50 years ago, accompanied by staff and strep infections. It was the sickest I have even been in my entire life. Certainly something to bear in mind.

I definitely agree with your other point about combining vaccines. I no longer dop that after combining flu and pneumonia several years ago. I never had such a broad reaction to vaccines. Not sure if the IFN had anything to do with it but i will not take the chance ever again. I will always space vaccines at least two weeks apart going forward.

All the best.

[EPguy in reply to hunter5582]

EBV is in almost everyone. But the distinction between none, regular or severe mono seems to be the diff. So we both fit the severe set and potentially that added risk. There are reports that Dipyridamole can prevent EBV reactivation:

sciencedirect.com/science/a...

but my Drs are not ready to Rx it. We know clinical practice trails research considerably, note hems who still think VAF doesn't matter.

From my understanding, combining (same day) vax is still better than 1 week spacing. But why risk even extra discomfort, 2 weeks + is better.

[Mieshie]

thank you very much for this update. Your continued thoughtful analysis of how and why sjo happened is appreciated. I followed your vax recommendations last fall, even adding a third week between them. Can’t be too careful! :). Bless you EPguy.

[Hopetohelp]

Very informative, thank you, and a lesson to be learned for us all regards timing of vaccinations and autoimmune warnings with interferons. I do hope your condition will improve and that you get received for a trial eventually

[RoundTheWorld]

Thanks EPGuy for your generosity in sharing your experience in the hope that it helps others. Wishing you improvement and/or manageability of both diseases.

[Jellybean129]

Thanks for your informative post, EP. It’s very interesting to read there are trials going on for hopefully upcoming treatments. Sjogrens seems to be a very misunderstood disease and often just associated with dryness and not the systemic damage. Your reaction to INF was obviously rare but I wonder if there are more out there who just haven’t made the link.

I am one who has taken heed of your warnings re IFN and Sjogrens. Since we last ‘chatted’ I have seen my GP, who basically passed the buck to the haematology team (“I could refer you to reumatology but the waiting list for an urgent appointment is currently one year”).

Next stop haematology: after endless calls and reminders for them to call me I got a call back from the specialist nurse. To say I was shocked and disappointed is an understatement. She advised me to continue with the Pegasus (your bloods are great on it) and brushed aside all the concerns I had over my increasing symptoms. When I mentioned the caveat on the data sheet about autoimmune symptoms and interferon the reply was “well they always have to put these statements in to avoid lawsuits”. I told her I would not take any more Pegasus until my symptoms have been checked out and that was that. Her disinterest was quite simply shocking to me - all I got was “it’s your choice”. The fact that I couldn’t even get to talk to a consultant really angered me. I know these people cannot go by what we ‘feel’ and need a confirmed diagnosis but the sheer lack of empathy and downright disinterest had me speechless.

On the run up to Christmas I don’t think I had ever felt so ill and depressed. It came to the point where I realised I was never alone - one of the family was on constant watch, discreetly. I was erratic, severely brain fogged to the point I cold barely string a sentence together and so full of pain it was a struggle to get through the day.

I have finally found a Sjogren’s expert and am now trying to arrange a private appointment to see her. She is a long distance away but worth the journey if she can get to the bottom of things. I have spent a lot of time looking through Sjogrens advocate (thank you for the recommendation) and now feel better armed to be my own advocate in this, and in dealing with my haematology team.

Apologies if this comes out as a rant - it seems people with conditions that are not as well known are fobbed off endlessly by medics who should either know better or be willing to listen a bit harder.

I hope you are getting on okay and had a good Christmas.

All the best

Gill

[EPguy in reply to Jellybean129]

If defined by getting Sjo my reaction to IFN is actually "common". But the severity and speed were extra rare. You're right about the misunderstanding that it's just a "nuisance" disease, getting informed care is far harder than for MPNs. Everyone recognizes Lupus, but its evil relative Sjo is in the dark. It's a big problem with trial sponsors.

Great bloods were also my path, in fact it was too good as seen in my 1st "Last Dose" post. If your Dr insists on a confirmed Sjo Dx that can take years for some. Drs with deep IFN experience understand the risk. I am very glad to have helped you recognize its emergence. Maybe if my Last Dose post or something similar were required reading for all IFN pts, including me back in time, we would see fewer Sjo cases from IFN.

If you found a real Sjo expert that is fabulous. They are signif more rare than MPN experts. I saw one who still focused on just dryness, her multi-page to do list was all sicca. My big issues are like yours, other things. But I have experienced dry episodes and the thought of losing those glands is scary. I think the new treatments should come in time for us before we risk being too far gone. The Sx change or rotate as you likely have found. Mental health is a biggie with Sjo and your supportive family is lovely and essential.

[Jellybean129 in reply to EPguy]

Thanks for your reply EPguy and I hope the latest fire in LA is nowhere near you.

I honestly hadn’t realise how system-wide Sjögrens can be, falling initially into the sicca trap. The Doctor I have found runs Sjögrens clinics and her special interests and research are in extraglandular manifestations of the disease. People from all over the country choose to see her if they suspect Sjögrens. The patient stories I’ve read about how it has taken years to diagnose their Sjögrens and the attitude from medical staff along the way are truly awful - ignorance of the disease’s true colours being the main problem.

My latest hurdle is trying to get past my GP receptionist to get the referral letter - all those on this forum from the UK know what a hard task that is 😂

Thank you for your kind comments - I am very lucky and truly grateful for a supportive and loving family. Having never really had mental ‘blips’ before now and being the sort of person who normally takes myself off on my own to work through my feelings I now realise how important it is to have that safety net behind you.

All the best

Gill

[EPguy in reply to Jellybean129]

I suspect the Bes trial evaluators, like most the professional field, were not aware of Sjo's reality since it's "common' but buried in the arcane document I linked. One needs to "catch" Sjo to know. We can consider it no longer buried with regular posts here.

[Bluetop]

Thanks for this informative breakdown, only sorry for you experience. I wish you well in continuing to deal with this

[Smithjoa]

Sorry this is a bit late, but I wanted to respond late or not. Thanks for your help on this, EPguy. Your posts are very helpful, and I wish I had heeded them. My experience is somewhat similar to yours but I did have warnings of the danger, and nevertheless took the final dose that caused a host of problems.

Despite the black box warnings I believe most hematologists know little about the risks of Pegasys or any interferon. My hematologist said the warnings were just to avoid liability. I took Pegasys for just over a year at low doses and at usually 2 week intervals. It gave me warnings of migraines and eventually caused migraines, even at very low doses. I stopped it a little while after a larger dose resulted in an 8 day migraine, erythromelalgia and then a splenic infarct. I can't know for sure if the infarct had anything to do with the Pegasys. I asked my hematologist for a referral to a rheumatologist, but he said it would take too long.

Eight months after stopping Pegasys, I tried it again in two 22.5 mcg doses one week apart along with daily Jakavi because Jakavi was supposed to make the Pegasys less toxic for the patient. I immediately got a splenic infarct, and right after the second dose, migraines which turned into daily nightmares that were almost untreatable (got IV pain meds and steroids and finally NSAIDS with hydromorphone). This lasted for a month and was followed by other symptoms, including a long-term cough, yet another splenic infarct (while still on anti-coagulants for the earlier one) and now chest pain, dizziness and shortness of breath, and what looks like a clot in my aorta. This clot apparently doesn't impede blood flow and so doesn't explain the chest pains, etc.

I did see a rheumatologist after the headaches who said although I had a high ANA titre, the other blood tests were inconclusive. The coagulant tests were either not resulted or not particularly useful since I was already on anticoagulants at the time of the blood tests. The rheumatologist said it could be drug-induced lupus, notwithstanding any blood test results. He couldn't comment on whether this might resolve itself because he had no experience with interferon, which is known to cause auto-immune disease. Most of the above problems have arisen since I saw him, and I hope to be referred back to his clinic. I also have to get back to trying to get my PV under control.

I would suggest at a minimum that anyone who has had an autoimmune disease (I had psoriasis when I was younger), should not take interferon. I should not have proceeded without good expert advice in any event. My hematologist has no real knowledge of this drug and he does not purport to be an MPN expert, although he is on some MPN expert lists.

[EPguy in reply to Smithjoa]

This is the now too familiar black box for PEG with the relevant ones for you bolded. Your spleen trouble fits ischemic event so assuming this serious event is related is reasonable. Nightmares could fit the neuropsychiatric. Migraine is not in the box and "headache" is a "less serious side effects of PEGASYS ..." But an 8 day migraine is probably not what they had in mind.

"May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders "

Your Dr's mention of liability matches Jellybean's Dr “well they always have to put these statements in to avoid lawsuits”.

I've not heard of an actual category of "drug induced Lupus" as a specific Dx , but Dr must have a reason to call it that. If Lupus is suspected you should also carefully rule out Sjo, they are closely related and Sjo has ~30-40% pts are SS-a negative, but most are ANA+ (all except me in a little survey I did on that forum).

I know my Sjo would have reversed before the Last Dose, but it's clearly not going to happen for me.

You were doing the low dose IFN/Rux combo, which as you say is supposed to take the edges off IFN. Apparently IFN for the unfortunate few is very toxic, "harsh medicine" is my MPN Dr's description.

I also had psoriasis before taking Bes, but it was mild, intermittent, localized and fully controlled by OTC hydrocortisone. So I actually did have A-I history, I never thought of psoriasis in the same area as Lupus etc. Maybe psoriasis of any sort is a bigger risk predictor than we thought. I will post this question.

Are you now on Rux alone? It may help with certain A-I disease also.

[Smithjoa in reply to EPguy]

Thanks for this. My psoriasis was also very mild. I had chest pains when I took Rux, so now I’m on anagrelide and just started HU.