My Last (IFN) Dose, my Fateful Decision One Year Ago

[EPguy]

This is a long and not cheerful post, I understand if you don’t wish to wade fully or at all thru it. Sections are marked for easy reference. The thoughts are my opinions only.

--

I wrote a few months ago on my botched flu vax anniversary. Today is the one year mark for my Last Dose of Besremi, step 2 into the abyss. Some thoughts, regrets, and I hope some lessons.

A summary: I was on Bes for 11 months. Great therapy. A flu vax went bad ~month 9. Continuing on Bes I got some new warnings. I opted to take a last dose, and immediately it blew up. One simple life changing choice. I now have aggressive onset Sjogren’s.

Details preceding Last Dose (this is mostly in prior posts

I switched from HU to Bes Feb ’22. I felt ok at the start, up to ~70mcg and held CHR. But Dr wanted to hit 200 in hopes to get best VAF reductions. We topped out at 140 for low WBC.

The post here had some real time thoughts on my dosing. My Dr scolded me for not asking permission to reduce it before this trip (this is relevant later). Throughout my Bes journey past 100mcg I had malaise etc. We resumed afterward at 140 till ~the end but I always felt ~50-70 was where I would feel better.

healthunlocked.com/mpnvoice...

In Nov ’22 I rushed to get the Covid and Flu vaxes after another trip as they predicted a bad season. I opted for the Moderna covid as it is a larger dose than Pfizer, and more seemed better. One week later I got a flu vax, Flublok brand at the same pharmacy, also higher potency. (I have old posts on this)

Immediately after the flu vax I sensed wrong. A whole body weirdness and never before but brief pain in right knee joint. I wish it had been just an allergic reaction. Over next days shoulder pain at the vax site which grew to 8/10. A neurologist Dx Brachial neuritis, a known rare vax risk. Most neuro vax events improve over months or years, but can precede other things.

By new year ’23 neuro was less severe. But on Sunday Jan 15 I was at parents’ new retirement home helping assemble furniture. During dinner I felt a sudden fatigue and malaise of a new sort and had trouble with the further work. Bad vibes continued the next days. The plot here shows my HCT, PLT were reacting too well just prior to the Last Dose. My next Bes dose was due Wed.

My Last Dose, Wed Jan 18

I sent Dr my concerns and asked about reducing or pausing the IFN. This is advised in the FDA label but the urgency part is not clear. Dr got back to me Thurs. Meantime (see “scolding” note above) I didn’t want to change the schedule without confirmation. In fact it was an emergency but I had no clue (do “bad vibes” meet the criteria?). I took a reduced dose of 100mcg late Wed. Within minutes I couldn’t sit up so I went to bed. I stood up ~ an hour later and totally passed out. I hit my eye socket on a low table and twisted my neck which I knew only days later from the bruise.

Aftermath of Last Dose

A few days after the pass out I got eye flashes, eye Dr checked retina, ok so far. For the next couple months I deteriorated. ER visit was not useful. Short episodes of paralysis, twitching on the floor, passing out after eating, leg collapse, general neuro trouble. I needed a walker occasionally. Several episodes felt like a stroke and imminent demise. Thru the summer it developed into obvious Sjogren’s including unprompted disabling anxiety. I had two periods of feeling ok but now all social activities are out. I’m currently in a fairly stable level of misery.

Why worry about Sjogren’s?

A simple internet search will bring up a mild autoimmune disorder that just causes nuisance dryness.

- In fact it is for many victims an (emotional) Death Sentence - . One Voice member with reason to know agrees with that description. I asked my Rheum Dr which rheum disease is the worst with regard to treatments vs symptoms, his answer “Sjogren’s”. You don’t want to catch it. It’s too often a whole body wrecker. I won’t go in to the details. This site has a good reality for understanding the affliction:

sjogrensadvocate.com/

--

Here is a sample from our own HealthUnlocked. this is our reality of this whole body disease and maybe my destiny:

healthunlocked.com/lupusuk/...

"I experienced a dramatic deterioration with teeth and gums 2 years ago, dentist advised I would lose all my teeth within 6 months and because of the lack of saliva..."

"Sjogrens as you know is a nasty illness which is now brutaly attacking my joints, the pain is excuciating !"...

"Your rheumy is very ignorant of how much damage sjogrens can do and i'm afraid needs to be educated. I would be batting him some information."

--

Why should MPN pts worry about Sjogren’s?

No special attention is required except when on IFN therapy. A botched vax is not required. A surprising number of members have been affected to some extent. Sjo is the Auto-Immune (A-I) for which IFN is most specific (other than thyroid issues). I know of no studies checking why this is so, but Medicine's poor grasp of Sjo is one likely reason for its low visibility.

In the Euro label Sjo is the only (non-thyroid) A-I listed as “common” (1-10% pts) on page 9 here:

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

At least Sjo is at the lower end of common. I’ve seen it up to ~4%, but can’t find that reference right now. But in any case a disease this dire rated as “common” needs our attention. Also listed as common is antinuclear antibody (ANA) positive. This is a broad warning of potential A-I events and should be part of monitoring, see “what to do about it" below.

The US FDA in fact gives A-I worthy attention, this is the Black Box warning that I didn’t give a thought to while on Bes:

“Interferon alfa products 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”. The unsolved question is what actual events meet the “withdraw" guidance?

Of all these FDA severe outcomes, only A-I in the form of Sjo is “common” per Euro. So in effect FDA black box is warning us of a "common" outcome. Importantly Sjo is rarely fatal, designed best for lifetime suffering.

--

There are other Voice members on IFN affected by Sjo, in my rough guess from the forum at about the range above 1-4%. Some of the Voice members affected with Sjo quit IFN in time. There are more than one for whom it is likely too late. Sjo is prone to a point of no return.

The pegylated IFNs (PEG/BES) have improved tolerability, but there is a flip side to this I now appreciate. The advantage of long duration becomes a hazard when there is an urgent need to get the IFN out of the system. It’s likely one reason my Last Dose did such damage over the next month. Support for acting quickly when warranted.

--

The report below discusses IFN being a contributor to Sjo:

“In (Sjogren's) disease, a large number of studies have shown that an overexpression of type I IFN (the type we use)… is present …this finding is associated with the development of systemic extra-glandular manifestations (this is the extra nasties in Sjo) … inhibition or modulation of IFN signaling has been regarded as a potential target for the therapeutic approach”

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

Hence some emerging therapies seek to reduce active IFN. When Sjo is brewing adding more IFN should be contra indicated as it clearly was for me. (There was a time ~1999 where IFN was explored as a therapy for Sjo, but this idea is not current) Clearly this is a problem only when Sjo is present or imminent and most MPN pts are not at risk.

What to do about it? (My opinion)

IFN is an amazing therapy. But it is twitchy. My Dr called it tough medicine and preferred I select Rux. IFN seems unique in our meds in its widely varying effective doses and surprise and suddenness of some its effects. FDA says “withdraw therapy with persistently severe or worsening signs…” My blood count plot here shows something was brewing, the IFN was suddenly working too well just prior to the Last Dose. A sudden increase in general fatigue/malaise without a dose change was my main but too vague indicator.

I suggest if you get new dryness in mouth, eyes, or women’s private parts, and meds haven’t changed, this is time to stop IFN asap and then discuss with your trusted expert. But dryness is optional and if present often starts after the disease is well underway. My case is an example of pre-Sjo hiding as other things. Neuro for example preceded overt Sjo so a dryness indicator would not have helped. Another stop sign is upon an adverse vax reaction (esp neuro issues, not the typical aches and fevers) stop therapy asap and then discuss with your trusted expert. One member saw my posts on this vax angle too late.

--

This old post may have a relevant item. I had plenty of fatigue/malaise on IFN, maybe it suggests extra care required:

“Patients who develop persistent fatigue experience greater increases in IL-6 and 10 in response to IFN-α …(IFN-a, the old non-peg) induces a persistent fatigue in some individuals, which does not abate post-treatment”

healthunlocked.com/mpnvoice...

I recommend IFN pts get regularly monitored for at least the basic set of A-I (autoimmune) indicators. including rheumatoid factor, (RH) c-reactive protein (CRP), erythrocyte sedimentation rate,( ESR), and (ANA). ANA positive is “common" in the Euro label. A full list of all tests I got is in another post today. But these can sometimes all be negative even with severe Sjo, I had only a single positive among all these.

I wish I or anyone could advise more solid ways to know how to predict IFN black box AEs. I also wish someone had posted this before Nov 2022, I would have stayed safe.

IFN Dosing

My opinion: The idea PharmaEssentia is promoting of aggressive dosing (ie starting at arbitrary 250) vs dosing for response is malpractice. The added risk is not rational even if it might (unproven) get a few more VAF points. If it’s that urgent to cut HCT asap get a phleb or take temporary HU if tolerant. I made a plot a while ago of members’ early dose and CHR response, link below. Not a scientific study at all but it showed most those with good CHR response got there on doses way under 250. Low and slow is a theme we’re seeing here, my experience supports and helps inspire this policy.

healthunlocked.com/mpnvoice...

I tried repeating this survey more recently but the response was too sparse to make a plot.

Is there any hope if one has Sjo?

The bad place is moderate to severe disease. I have moderate and aggressive onset. But it can be and stay mild for a long time. Re IFN - timely withdrawal makes mild more likely. For women (9/10 cases) on avg it is less severe. There are finally effective agents post phase 2 or starting phase 3. One problem in trials has been how to even measure the disease, it affects something and/or everything. One theory I've seen on A-I is being a software bug in liver signaling. So acting there might be the cure way in the future

Any other serious IFN effects among members?

I’m aware of a couple: One had deafness, reversed after stop of therapy (“uncommon” in Euro label.) Another had kidney failure ("uncommon to rare”), shortly after starting and then quitting Bes, preceded by mild A-I issues, slowly recovered.

Vaccine strategy

More may not be better. The Moderna shot is 50mcg, Pfizer is 30. Some early evidence showed the Mod was more effective, I’ve posted on that. But for those on IFN, Pfz may be the more conservative choice. On timing, please never get any shot one week after a prior one unless it’s actual protocol. I believe this is one source of my wreck. Two weeks minimum is safer. For me I won’t get an in-arm flu shot again, I’m high risk, it is not that effective (~50% best case when well matched) and the risk is every year. For Covid and maybe flu, I plan to await the next gen nasal vaxes, these should be lower risk and more effective. For those without a history of adverse reactions, these worries are minimal but the 1week contra indication stands in my opinion.

My benefits on Bes

I did have some of the best benefits of IFN. Blood counts were perfect, even CMPs were flawless, so the black box wasn’t predicted by CMPs in my case. VAF declined well, but seemed to be heading to a lowest limit. Widely spaced dosing was very convenient. My eyesight focus improved and this has persisted.

How about Rux and HU?

These do not share the FDA black box. I’m not aware of severe irreversible adverse events caused by these meds, doesn't mean it hasn’t happened. Rux does have a high risk if quitting cold turkey. Any members with more info to help guide us on signs and prevention of severe outcomes for these is most welcome.

This is an old thread on AEs for Rux and IFN. My take, while I was on Bes, was Rux had fewer high risk events.

healthunlocked.com/mpnvoice...

Conclusion

I’ve put two days into this heartfelt post. I hope it can help protect even just one more member. Researchers should look deeper into the IFN A-I markers and give us something to monitor. Best conclusion I can offer is “Low and slow” and be ready to act on any A-I like emergent.

[Wewo01]

This is great information that you have shared and could definitely help someone else. I know you have been down a really rough road. I hope, with all my heart and strength, that your health stabilizes and you have many more good days.

I admire your persistence and your thoughtfulness towards others in posting the information!

Your friend, Kim

[EPguy in reply to Wewo01]

I'm glad to help. Thanks for the kind thoughts. My road was uniquely bad and incredibly fast even by Sjo standards. Unfortunately if one is in the Sjogren's forum (on a different service) my endpoint is all too familiar. Hoping to keep the intersection of these two forums "rare".

[Wewo01 in reply to EPguy]

I feel like I dodged a big bullet and am glad I stopped IFN when I did. My heme/onc wanted me to continue it. 😳

[EPguy in reply to Wewo01]

I do recall our real time posts, agree it may have been a close one.

[Ovidess]

Thank you for sharing this vital information. None of us knows just how much of it will apply to us, but I at least will proceed with caution and try not to play down the degree or source of ailments that come my way on Besremi. I wish you a reversal of luck, that is, that you get a dose of good luck comparable to the bad luck you've seen.

[EPguy in reply to Ovidess]

Thanks for the kind thoughts.

"None of us knows just how much of it will apply to us" is a perfect summary of all this. The surprising "common" designation was one prompt for my effort.

[hunter5582]

Thanks for sharing the detailed post. It is thorough and well thought out. It is most unfortunate that you learned these lessons the hard way.

I most certainly agree that the Low & Slow approach is better for the IFNs and other drugs. I started at 100mcg and increased in 25mcg increments. i am now at 175mcg, which appears to be my max dose due to neutropenia. I did just get some good news in that I am back at target, HCT = 44.9 and NEUT = 1.60 at my 1/17 CBC. I would not want to push my Besremi dosage any higher. While I am very pleased with my Besremi response, it successful because of the Low & Slow approach. If I had started at 250mcg, I would have been in trouble.

I also agree about not doubling up on vaccines. I had an unpleasant response when I doubled up on flu and pneumonia. I will not make that mistake again. All vaccines will be spaced at least 2 weeks apart.

I believe that there are intrinsic risks with all of the choices we have for MPNs. In order to treat the disease, we have to make some fundamental changes to how our body is working. The kinase pathways have wide reaching effects well beyond blood cell production. We cannot make the alterations we need to treat the disease without also assuming inherent risks. We currently have no way to predict how any one of us will respond. Perhaps one day we will be able to match genotype to the phenotypic response to the treatments, but we are not there yet. Until that time, I feel strongly that proceeding cautiously with dosing is simply prudent. We need to pay attention to what our bodies are telling us without succumbing to fear over every minor event that occurs. We also need an MPN care team that understands the treatment outcomes and listens to their patients.

Wishing you all the best moving forward my friend.

[Pounds11 in reply to hunter5582]

“We need to pay attention to what our bodies are telling us without succumbing to fear over every minor event. “. Wisdom of Hunter and also EP guy who are so kind and so valuable to all of us. You both have helped me tremendously with my personal journey. My heartfelt gratitude.

[EPguy in reply to hunter5582]

Good results on your CBC. I recall your HCT goes a bit over occasionally is that right?

Agree in my case on a 250 start, it probably would have been a permanent cure for every ailment I have.

A we've discussed, the lack of guidance on vax spacing is a scandal. There is plenty of "same day" suggestions and even plans to put 3+ respiratory vaxes into a single shot for a "same minute" series. But I think one week is a worst case to over stimulating the immune system.

[Lillysue19850705 in reply to hunter5582]

Thank you hunter and EPguy for sharing your own experience. You two are awesome and I wish you two all the best.

[mhos61]

This is such a well thought out, heartfelt and articulate post; it’s clearly obvious how much time and effort you have put into this.

You highlight some great points in relation to vaccine dose/timing and interferon therapy.

I agree with your thoughts on the monitoring of A-I markers in interferon therapy (before and during), although in some cases A-I symptoms can present years before a marker proves positive. This was the case for my husband. I would add remain on high alert to common symptoms of autoimmune disease, which leads onto your most significant comment to “Act on any A-I like emergent”.

We can all learn from each other, and I for one would like to thank you for your most valuable contribution. Wishing you the best of luck for a breakthrough in the treatment for sjogrens sooner rather than later. X

[EPguy in reply to mhos61]

Same here on the A-I measurables. My initial symptoms were all neuro, and new neuro could be a special warning.

Best case on the therapies will be some flavor accelerated approval. With no viable treatments, one that actually works can even get there after phase 2. I also am seeking trials. MPNs are less likely to see or need this since there are already various decent options.

Is your husband ok with his A-I?

[mhos61 in reply to EPguy]

He’s not doing too bad at the moment🤞Thanks for asking!

The Methotrexate and prednisone offer some level of control over symptoms and lessen the ‘flare ups’. He does have joint damage which wouldn’t have been as severe if he was able to tolerate the Anti TNF/Jak inhibitors/biological therapies, but unfortunately he wasn’t.

There are so many diverse treatments for RA. The disparity is so unfair against sjogrens. It must be as disheartening for the Rheumatologists as it is for the patients.

I do hope you manage to get on a successful trial. Equally, I hope that the sjogrens forum you participate in is as supportive and helpful to you as this forum is for all of us.

[EPguy in reply to mhos61]

Interesting mention of Jak-i's. I was hoping the Rux would help, maybe it would be worse without, or maybe a higher dose (I'm 20BID) would work more.

The Sjo forum is different. For one, the interface in host the service is more cold and clinical, fitting for such an ailment. There is a lot of misery sharing but as here, polite and good support. The RA like symptom subsets are capable of improvements by meds. I contribute analysis of studies etc like here, but there's much less to analyze there.

[Spanelmad]

Thank you for your timely post.I'm on Peg have zero neg rheumatoid arthritis, I've developed a dry ,gritty left eye (currently using drops) will discuss with Jean urgently next week.

[EPguy in reply to Spanelmad]

Do let us know how the eye checks out. Did you have RA before PEG? Any changes in the RA?

[Spanelmad in reply to EPguy]

I was diagnosed with RA 30 years ago ( it's been many different types of arthritis over those years).Started on sulphasalsazine and had a very similar allergic reaction as I did to HU.I now take methotrexate and hydroxychloroquine and it's been well under control.The eye is a new symptom.The optician has given me drops and thought age related macular degeneration.But I'm not so sure has appeared since starting peg(45 mg fortnightly) .I'm 3 injections in and luckily will see Heam just before next jab is due.

As for the hands the cold chill claim look is also new.As is the pain when puting any sort of cream/balm on.The Rheumatologist is not particularly helpful at the moment as nose is out of joint regarding the ET jak2 diagnosis.But will definitely contact the nurse specialist as a go.between them she might take interest.

[EPguy in reply to Spanelmad]

Today's posts in the Sjo forum happen to mention Rheum dissing Raynaud's. So you have company.

If your Haem is well knowledgeable on A-I's that will be very helpful. Wishing you a productive visit. That is a lot of A-I like stuff since starting PEG.

You should see an ophthalmologist vs optician. This comes up in the Sjo forum also, it's too complex to leave to an optician. Get a Schirmer's test or equiv suggested by the ophthalmologist to check tear production.

And *important* while at the ophthalmologist you need to get a retina exam. HCQ long term can lead to permanent retinal damage. You need a baseline early in HCQ therapy and 6-12 month exams. There is also a color perception test my Dr gave me. Usually the risk starts increasing after 5- 10+ years, and like IFN, prompt discontinue is required (it's usually not as time sensitive as IFN) It brings up a question, whether the rare IFN and less rare long term HCQ retinal risk add to each other. HCQ risk is cumulative, so a 400mg dose will start the risk earlier. Not all pts require the full 400.

I couldn't tolerate HCQ, a rare reaction of tinnitus at two weeks and hearing loss if I had continued. So I didn't need those eye tests.

[Spanelmad in reply to EPguy]

Had the tear test done this time and have had the colour perception test since I started the hydroxychloroquine.

[EPguy in reply to Spanelmad]

Did your Dr not suggest the retina exam? I got that too but maybe it's not required.

[mhos61 in reply to Spanelmad]

Sulphasalizine….that was the first med my hubby was put on for RA+, had forgotten about that one. Hubby also diagnosed over thirty years ago. Presume you’ve been through the different biological therapies?

Sorry to hear that your Rheumatologist is being awkward, you can certainly do without that attitude. My husband has a fantastic Rheumatologist and has built up a trusting relationship with him over the years, we are so grateful. Why has your Rheumatologist had ‘his nose put out of joint’ if you don’t mind me asking?

[Spanelmad in reply to mhos61]

Ask away!I had a fantastic rheumatologist for 20 years until he retired.He believed in intergrated care and treated you as a whole not just joints!!!

Now it's a a revolving roundabout of docs.

Current rheum s nose is out of joint as survived I was making a lot of fuss about nothing.She thought the raised platelets were due to 💊meds.Plus I don't think she has a clue regarding mpns .

[mhos61 in reply to Spanelmad]

That’s such a shame, I feel for you. No doubt your Rheumatologist apologised to you for not acting on what happened to be your correct suspicions…

It was the other way around for my husband initially he had a Rheumatologist who was pretty useless then we found his current one who he has been with for around 20+ years. I do worry about my husband’s Rheumatologist moving/retiring. We’ve already followed/stalked him from one hospital😂.

Good luck with Rheumatology and haematology going forward in your care. It’s good you have an appointment with Guys coming up.

[Spanelmad in reply to mhos61]

I even asked if he was going go to do some private work still ,as I would have paid .In fact now the whole rheumatology department has fallen apart as the original nurse specialist retired as well.Hoping it will get back on track now as we have a new senior nurse.

[mhos61 in reply to Spanelmad]

Fingers crossed for you. X

[EPguy in reply to Spanelmad]

I see in your prior post you have RA as well as cold white hands. Has your Dr mentioned Raynaud's? It is often in the A-I mix.

[saltmarsh]

I would like to add my thanks to you for your post. For me, with interferons being a possibility going forward, this was incredibly helpful. Your effort in putting together such a comprehensive post is very much appreciated. Good luck as you move forward. You will be in my thoughts as well as those of the other forum members.

[Cityreach]

Wishing you the very best in your journey going forward I really hope things improve for you, thankyou also for your wealth of knowledge and your willingness to always help others despite the hard time you are going through personally xx

[Anouchka in reply to Cityreach]

Hear hear!

[S031251]

Hi EPguy - I am glad I’m on Rux!!

I hope your health improves soon and I thank you for providing such insight to help others

Anna

[EPguy in reply to S031251]

Is the Rux keeping your itch down? Did you get the Shingles vax?

[S031251 in reply to EPguy]

Yes it certainly has - it’s over 5 years since I started it on 35mgs a day now. I did have the shingles vax with no problems

[EPguy in reply to S031251]

Good to have that done, I got it a couple years ago. The post from Walshman below is a good reminder to keep the dermatology appts up to date to avoid any surprises.

[Scaredy_cat]

I'm so sorry for your problems but really impressed with your posts. I had a sct last year and have recently started a long period of revaccination. I decided to leave at least 10 days between each in case I got a reaction and then would be able to tell which one was the problem. I think I'll extend that to 2 weeks. I'd not heard of sjogrens until your earlier posts but I do have it in my mind now. I too have a dry mouth but have attributed it possibly to medication. I will be stopping Acyclovir soon as I've now had the shingles vaccine and am hoping my mouth will improve. I've never been on interferon

[EPguy in reply to Scaredy_cat]

Most likely your dry mouth is just the meds. So many have that side effect. That all by itself can be innocent.

I chose not-same-day vax precisely to know which made trouble if any. I got my answer. But with longer spacing that answer is knowable more safely.

[ciye]

Thank you for sharing this really valuable information, it makes me glad I stopped interferon. Wishing you well.

[EPguy in reply to ciye]

I see your prior posts on various troubles. Did you have a specific A-I that emerged or worsened while on IFN?

[Anouchka]

So sorry EPguy to hear you had to go through this. I just want to thank you as well for being so informative and helpful with your invaluable insights et al, and so encouraging, to all of us on this forum.

Wishing you all the very best moving forward.

[DiveGoddess]

Dear EPGuy, First, thank you for the detailed post. Secondly, wishing you strength and healing. I follow your posts, and always wonder how the people who post are doing. So, not just for the information but the connection, I thank you.

ET in 2022, Besremi started 2023, now going from 150 every 2 weeks to monthly. I inquired about going back to 100 when my WBC dropped out but Specialist said no, stay 150. I will see how my labs fare, but you are arming me with compelling information.

My Specialist stated most of his people stay at 150.

I am very happy to see your list of recommended labs. My PCP doesn’t feel comfortable ordering anything not standard. My Specialist has been honest and stated insurance doesn’t like to pay.

Specialist also said, don’t read on the Internet. But, I will continue to value the information this group shares, as it helps me to find peace. No 2 experiences are the same, but knowledge is very powerful and truly helps to center me.

Please know your Journey is important to me, take care my friend.

Christy

[hunter5582 in reply to DiveGoddess]

Hello my friend. I hope all is going well and you are enjoying your diving activities.

It is quite common to experience some leukopenia when using Besremi or other cytoreductive medication. It is a balancing act to achieve the desired reductions without off-target effects. Each type of leukocyte has a purpose. Lymphocytes fight viruses. Neutrophils fight bacterias. Lymphopenia is quite common on Besremi. Neutropenia can also occur. Your immune system can still respond when the leukocytes are low, providing they are not too low. My MPN care team has set the criteria for acceptable levels of leukopenia at LYMPH>0.50 , NEUT>1.00. Levels above target are considered acceptable even though they are technically low.

Glad to hear that you doc is honest about the challenges of authorization for labs. Negaoting healthcare is one of the biggest challenges we face in managing a MPN or other conditions. The good news is that NO does not mean NO in many denials for services. NO mean that you have to know how to file an appeal and work the system to get the approval.

Wishing you all the best.

[DiveGoddess in reply to hunter5582]

Hello Dear Hunter 😊,

Thank you for your post! I have been your #1 since I have found this site! I stay at the minimum in WBC and neutrophils, but never seem to dip beyond what is allowed, which has allowed me to continue Besremi. Happy to be allowed to space dosing to once monthly. I have read studies, but seem to learn more about this from these posts; reminds me of test taking in college, where I learned so much more with the end of chapter questions, just a whole new level for my understanding.

No diving recently, but did go to Yellowstone early fall and highly recommend it. So much beauty and animals. Literally you never have to leave your car and can see so much! Hopefully diving in this New Year! Here’s to our Health and Happiness in 2024!

Christy

[hunter5582 in reply to DiveGoddess]

This is a great place to learn and find support. I feel truly blessed to have this valuable resource as I travel on this journey.

Glad to hear that you are finding the right balance with Besremi. While it is a very big step forward in our treatment options, Besremi is not a panacea without potential downfalls. We each need to proceed cautiously to find our optimal dose in order to accrue the potential benefits.

Yellowstone is amazing! One of the true natural wonders. There is so much to see beyond the geysers and mineral pools. Lots to see from the car but if you want to get out of the vehicle, the backcountry is incredible. I would love to go back there again.

All the best my friend.

[EPguy in reply to DiveGoddess]

What dose others are on should not bias what any one else is on, esp with IFN. Same here, my Dr wanted to get to that arbitrary 200.

Agree some specialists don't like our browsing. Details matter, what is being browsed and who is doing the browsing. It takes great patience to put the endless info into context.

[Mishie14]

I so admire your courage and tenacity. What a challenging time you have had, praying that relief is going to come your way. Your thoughtfulness and determination to share the journey and bring very relevant information to the forefront to help others is deeply appreciated. I have copied your post and several of the link content to ensure they are available for my continued reference and to share with my care team. Bless you, EPguy.

[EPguy in reply to Mishie14]

Thanks for the thoughts. I'm currently taking TCM herbs (chinese medicine) from a skilled specialist. It seems to help some. I will post more on it (and another exotic FDA approved therapy) if I get a enough info over time.

[George1976]

Sorry you’re having such a rough time since that last dose. I too had a rough last dose of peg and have been to many docs trying to figure out how to get back to my baseline of manageable symptoms.

Have you considered the possibility your gut is off? It may sound overly simplistic but ever since I started treating my ET almost 10 years ago I’ve had often intense pain in my upper abdomen that was ultimately classified as IBS. Colonoscopy’s and endoscopy’s, imaging and blood tests have never figured out what is going on until a SIBO test was positive for methane.

I’m on an anti-candida diet now and within a week the pain was 90% better and I lost 7 pounds. My reflux was gone too. Candida overgrowth can cause leaky gut and possibly autoimmune issues. It starts often due to high levels of stress and excessive consumption of high carb foods.

Treatments for microbiome imbalances appear to help with many other types of diseases. Might be worth a try if you have not already considered what if any role your digestive health is playing here.

[EPguy in reply to George1976]

I recall you had increasing neuro symptoms on PEG. That is one the the stop signs.

I've been mostly ok on GI. It was more messed up there on Bes, but not a controlling issue. But Sjo can trash the gut, and I appreciate the info. I do take a probiotic, not sure if it makes a diff.

I got a certain poop test, (calprotectin and elastase) but SIBO is more than that, right?

[George1976 in reply to EPguy]

Not sure about the test you refer to.

My understanding of SIBO is limited to diet and pain and dysfunction that I suspect comes from eating certain foods. The general theory as I understand it is that the pain and dysfunction that can come from eating the wrong things damages the lining of the intestinal tract which then allow toxins into the blood where they can cause various types of health problems. It can start with antibiotics and other meds that alter the balance of intestinal microbiome. And blood too has a microbiome that is probably heavily influenced by those toxins as well.

[Walshman]

Unfortunately, I think all meds can have adverse side effects. I agree that interferon dosage should be low and slow. I cannot understand why some docs now think it’s a good idea to ramp the dosage up so quickly. Sorry to hear about your experience with interferon and appreciate you sharing your experiences.

I attached recent research on Rux and skin cancer. I’m also not sure about the safety of HU. All of these drugs can cause serious side effects unfortunately. I wish you the best moving forward and hopefully you have now found the best therapy for you.

ashpublications.org/blood/a...

[EPguy in reply to Walshman]

Thanks for the link. I did ask for info on Rux/HU. I think the full report is the link here. Skin cancers are a known Rux effect, while death by SCC (squamous cell carcinoma) qualifies as a "severe irreversible adverse event" noted in my post. Good reminder that "non-melanoma" doesn't mean "non-hazardous".

ashpublications.org/blood/a...

9 of the 71 (13%) of skin cancer pts died of SCC, while 6/71 (9%) died of MPN. It would be good to know the total number of Rux users in this study group to see the total risk.

Interestingly in Fig. 1 only ~20% of pts with the skin cancer Dx fully discontinued Rux. They may have more details on this in their data.

--

This study shows more broadly the increased risk of squamous cell carcinoma at (IC025=3.92). This is a signif increased risk. This is known from prior info, but the death rate is new info.

pubmed.ncbi.nlm.nih.gov/357...

--

It's good support for recommended dermatology checkups while on Rux.

Hoping we can identify similar prognostic markers for the occasionally acute A-I risks of IFN we've seen here

My preferred therapy is or would have been the low dose Rux/IFN combo. But it is not normally available.

[KLCTJC]

I am so grateful that I saw Dr V before he left MDA. He said low slow. Otherwise who knows what my local oncologist would have done since he has zero experience with Besremi. And since then we inched up slow. Currently 225mcg and I still hope I can reduce it or will be ready for once a month dosing. Will see I have labs next week. I have dry eyes on this, but just when I wake up or when it is 20 degrees outside! So, not constant and unlikely anything other than dry eyes. But you have opened my eyes to Sjogrens. Even though I test people for this and have patients with this I never realized how severe it could be. Even my husband who worked in rheumatology for 5 years said he has never seen a case like yours. I hate it happened to you! Thank you for all of your posts and great information. You were so nice to me after I found out I had MS too. I appreciate your help. You sent me things that helped me plead my case to try INF. Still always wishing you the best.

[EPguy in reply to KLCTJC]

Thanks for the kind words. I was my MPN specialist's first and maybe last Bes pt. Maybe if he'd had more Bes experience we would have used a safer dose. Being among the 1st users has its downsides.

Dry eyes are a known IFN effect, listed as "common" in the Euro label. With so many other reasons to have it yours does seem no worries at all.

Assuming the Sjo forum is representative as we hope the Voice is, Sjo is every bit as nasty as my Rheum agrees. It's hosted on "SmartPatients" but requires registering to see any posts. I don't like that host service. I wish Unlocked had an active Sjo group.

A difference from MPN is even "moderate" Sjo can be debilitating. One problem is severe Sjo is so often mis or non diagnosed. It takes years to get Dx for many, per info on that forum. So debilitated pts may be hiding in plain sight. Another trouble is bias among some Drs that women's (90% of Sjo) complaints are exaggerated, again from real posts on that forum.

----

Here is a sample from Unlocked, this is our reality of this whole body disease and maybe my destiny:

healthunlocked.com/lupusuk/...

"I experienced a dramatic deterioration with teeth and gums 2 years ago, dentist advised I would lose all my teeth within 6 months and because of the lack of saliva..."

"Sjogrens as you know is a nasty illness which is now brutaly attacking my joints, the pain is excuciating !"...

another post there: "Your rheumy is very ignorant of how much damage sjogrens can do and i'm afraid needs to be educated. I would be batting him some information."

----

- However you're right my crash and burn intro to Sjo is unique, - this was the part so closely tied to IFN. Seeing this week that Sjo is "common" on the Euro label was a surprise motivating this post.

BTW, which test(s) do you use for Sjo?

[KLCTJC in reply to EPguy]

You have always been so helpful and sharing your journey has been so informative. I took the time after reading your post to learn something new. Me and my husband both!

don’t usually do a “ton” of autoimmune labs, really depends on why I am doing them since dermatology and rheumatology cross over so much. But I usually get an ANA with reflex which catches anti SSA/SSB. The most common reason I am doing inflammatory tests is to see potential for autoimmune disease to determine if they need to see rheumatology. We have other reasons to do them in dermatology that are more serious and rare but most of the time I am looking for underlying disease that maybe causing the problem that I am seeing the patient for. So my tests are pretty generic and if positive I send to rheum to be worked up.

[EPguy in reply to KLCTJC]

That's good to have with reflex on the ANA. I had to get Ss-a separately. In your searching you may have found that Sjo is SSa negative for ~30-40% of pts. Full deal cases can be sero negative for everything, hence the tricky Dx. Part of its evil doings. Lip biopsy is a common Dx method if all others are negative.

[KLCTJC in reply to EPguy]

I appreciate you educating me and all of us! Definitely opened my eyes to this sometimes overlooked disease

[Jamesxyz]

Hi,

Very sorry to hear that you have gone thru this.

I was always told that autoimmune problems with IFNs are extremely rare.

I guess it doesn't matter that it's rare if it happens to you.

Best wishes for a recovery.

[EPguy in reply to Jamesxyz]

I agree I figured if it's in the FDA black box it must be very rare as I always posted till this week. But per Euro label, Sjo is "common", an eye opener.

[Jamesxyz in reply to EPguy]

Hi again,

Another thing which is kind of a catch22 with the IFNs.

Usually a higher dose is required to get to the promise land (remission).

And of course that increases the chances of sever side effects.

Just my 2 cents.

[Jamesxyz in reply to Jamesxyz]

Ok here's an interesting tidbit, which I just read on the MPN voice

general info on different treatmesnt, which I believe is checked for accuracy by experts.

Most people tolerate hydroxycarbamide very well because it comes as a capsule and is easy to take. It is also very effective at bringing blood counts down to normal levels, reducing the risk of clots or bleeding in most people with MPNs. There is also evidence to suggest that hydroxycarbamide reduces the long-term risk of bone marrow scaring or myelofibrosis.

The last part is very significant if true, REDUCES long term risk of MF.

I have not heard this talked about much.

[EPguy in reply to Jamesxyz]

IFN seems to have a unique variation in its dose, response and sides. It's part of its magic and its risk. I posted long ago an early survey of members finding the dose for CHR was way lower than used in the trials. I think some of these member doses have gone up but a 2nd try at survey didn't work out.

I've also posted often before on IFN-VAF response being not tied to dose, rather more tied to CHR. This was the conclusion of the Ropeg study which I've looked into deeply. More mysteries of IFN.

healthunlocked.com/mpnvoice...

Rux is boring in comparison.

[Jamesxyz in reply to EPguy]

Ok here's an interesting tidbit, which I just read on the MPN voice

general info on different treatmesnt, which I believe is checked for accuracy by experts.

Most people tolerate hydroxycarbamide very well because it comes as a capsule and is easy to take. It is also very effective at bringing blood counts down to normal levels, reducing the risk of clots or bleeding in most people with MPNs. There is also evidence to suggest that hydroxycarbamide reduces the long-term risk of bone marrow scaring or myelofibrosis.

The last part is very significant if true, REDUCES long term risk of MF.

I have not heard this talked about much.

[EPguy in reply to Jamesxyz]

You're right on the HU marrow advantage. It comes up in some studies and posts here, and makes one think about combos with low dose HU. One example:

"PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU."

ashpublications.org/blood/a...

This study didn't go past 2 years.

[Jamesxyz in reply to EPguy]

Interesting.

So if Hydrea really reduces the chance of progression to MF,

that's a big plus.

[Janis12]

Hi, so sorry to learn that you have experienced such a traumatic event, the more I read individual stories about our MPN journey the more anxious I become but on the plus side sharing is a way of educating. I have recently changed from hydroxy to Pegasys by my own choice 45 mcg every two weeks but still remain on hydroxy which will be reduced gradually. My platelet levels were increasing and I did not want to increase my hydroxy intake any further. On peg for 12 weeks now and have noticed my existing dry eyes of many years has now got worse and also existing general aches and pains (very long standing, way before ET) has now ramped up. Mentioned to the haematologist who felt it time to increase the Peg dose which I refused then when I got home I started to have second thoughts...maybe I should have gone along with it? After reading your post I am glad I did not, I will re read your post a number of times so that I am able to 'go armed' with knowledge to my next appointment and hopefully as a result make a n informed decision as to how I will move forward with my journey. Thank you so much for committing your time to presenting this information to the forum. I do hope things improve for you in the near future.

[EPguy in reply to Janis12]

Your effects are on the labels so probably no worries, but caution makes sense. As we're learning few Haems are keen on A-Is.

You might want to discuss with your GP or Rheum Dr some of the A-I tests I posted recently.

[Jamesxyz in reply to Janis12]

Hi,

Just curious. I have PV and on Hydroxyurea. I'm thinking of switching to besremi.

To date I've had no problems with the Hydrea (low dose 1 daily). I'm 75.

What was your dose and hw old are you? Thanks

[Janis12 in reply to Jamesxyz]

I have ET and started on hydroxy , one per day. After a while my platelet levels were increasing so increased dose to 10 tablets per week. This had the desired effect but then levels were on the rise again and that is when I decided to try Pegasys, 45 mcg every two weeks and aiming to reduce the hydroxy gradually. I am 65 years old and have had ET for three years. Best wishes.

[TLJ-1]

Thank you for courageously sharing the horrible journey you have endured. It may well save me. While I was piecemeal accessing the lab results for blood and BMB tests resulting in my PMF diagnosis 20 months ago, I self-diagnosed that I likely have Sjogren’s syndrome based on symptoms and positive antinuclear antibody numbers. However, when the full set of results was in, the evident PMF was so much more serious in its deleterious effect upon my life, SJO was just ignored. Your experience indicates that it is important for me to take that into consideration as I switch from HU to something else in the coming months. Again, thank you very much!

I truly hope you will feel better physically and emotionally. At least, you should feel some warm thoughts coming from me!

[Bodensee]

Hello EPguy

You sent me such a comprehensive and helpful reply to my recent question about changing from HU to Rux or IFN. I didn’t know then that you yourself are suffering severely from Sjogren, which makes me appreciate the effort behind your response all the more. And now your warning after your last IFN dose will certainly not go unheeded. I shall also keep the list of AI Tests just in case! While I don’t understand all the details, I‘ll be able to watch out for the warning lights! In very difficult circumstances you have provided this valuable input for the common good: a true hero! Heartfelt thanks and every good wish for your onward journey in the hope there will be an encouraging development soon. Pamela

[Wyebird]

many thanks for all the effort you put into your post. I do hope your health will improve with treatment.

[EPguy in reply to Wyebird]

I share that wish. Unfortunately there are currently no Sjo treatments, other than the Chinese herbs I'm taking. This is unlike many other A-I's. Hence the incentive to "zero" out the chance of "catching" it. We get used to multi good options with MPNs so it is a twist to be without them.

[marlenablue]

Thank you for posting your experience and including all the details with links. It's so I am so sorry to hear about your new condition and wish you all the best.

[Pte82]

Have you researched Leaky Gut Syndrome as possible contributing factor to your immunity issue?

[EPguy in reply to Pte82]

My Dx is 100% Sjogren's. But Sjo can cause near any secondary condition imaginable. GI troubles are one typical such effect and quite common. I'm ok on GI, but not on many of Sjo's other evil doings.

[Pte82 in reply to EPguy]

I was refering to gut permeability. often associated with autoimmune conditions.

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

[EPguy in reply to Pte82]

Thanks for the context. No surprise, Sjo uniquely in A-I's can molest just about any and everything. They indicate Sjo is top of the A-I list in GI effects, matches posts on the Sjo forum.

This report is consistent with GI issues being 2ndary to Sjo vs causing Sjo. Interesting that the GI effect was direct in Sjo while indirect in MS.

So far GI is not a source of misery in my Sjo, but as Sjogies know, it's something new each week.