This Forum is amazing and I depend on it. I'm interested in others who may have had something similar with auto-immune issues on Besremi. Apologies for the saga.
Diagnosed with PV August 2021, AB 22%, put on Hydroxy for a year, then Besremi for the past 20 months, gradually increased from 50 to 450 mcg and on that dose for the past several months. No serious side effects (other than itching), good platelet control, less HCT, no venesection until summer when had to have 2 partial to keep HCT below 42 (I'm female). I also have been hypothyroid for over a decade and well controlled on fairly low dose Levothyroxine.
Then in September during a trip for my son's wedding, I skipped 1 Besremi injection (with MPN specialist's approval) - a week after the missed injection I developed a terrible case of Hives (first in my life). My MPN specialist suspended the Besremi pending hives evaluation. Zyrtec is managing it and they went away but then came back with a vengeance and are now chronic. I also discovered subsequently that my thyroid went from years of controlled to elevated, and then elevated again. Increased the Levothyroxine. Referred to an allergist/immunologist this week and she diagnosed the Hives as auto immune and potentially influenced by thyroid. Will be on Zyrtec indefinitely. Thankfully it is controlling the intolerable hives.
I have been concerned about being off of Besremi and my MPN specialist (who I value greatly) agreed I could re-start at 200 mcg and see how it goes, however, she also started the process to get approval for Jakafi. I have been so hopeful on Besremi and waiting to get to the end of this year for VAF testing and I am not enthusiastic about starting or combining another heavy-duty solution.
I'm not sure where this road leads next but my question is: Is it realistic to think that the auto-immune issues are not a reason to discontinue interferon and/or can be resolved, or does this need to be the end of the line for Besremi? Thanks for your patience in getting this far.
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C_Anne_Orange
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Sorry to hear about this dilemma. It sounds like you have had an autoimmune response to the Besremi, which unfortunately can happen. Switching to Jakafi would make sense at this point. The good news is that there is recent evidence that Jakafi may also reduce VAF. Hopefully you will find this to be the case.
Thank you Hunter, I guess the good news is that there is a workable alternative. Still hoping I can get stabilized and continue on Besremi - but you are right that we are lucky to have options! Appreciate your insights and support as always! Thank you!
Autoimmune (A-I) issue are among the worse case events with IFN and as you likely have seen are part of the black box warning on the label. So far yours are in the more common and treatable Thyroid category. But your expanding A-I conditions are concerning. One of the worst case outcomes is Sjogren's. See my post below for my experience. IFN has a propensity to this A-I when the worst uncommon reaction occurs and you absolutely don't want to catch it. A final dose of 100 did me in.
I am on Rux and it's a boring ride compared to Bes. As hunter says, it is recently shown to reduce VAF quite well for some, and we see that here. I've posted on that. Rux is not known for catastrophic surprises as IFN can rarely cause. But has its sides:
-Weight gain: It solved my underweight problem too well. Reduced food intake is often indicated.
-Shingles: Be sure you're up to date on Signgrix vax. Shingles risk is higher on Rux
-Skin cancer: if you're prone to this risk, extra precautions are a good idea as they are for any of us older ones. Have dermatological checks regularly as Rux may increase the risk.
Thank you very much EPguy - so sorry you got caught in the A-I trap. Frightening what can happen. Has the Sjogren’s improved for you or resolved on Rux, is that a possibility? Once A-I issues surface do you think they are reversible? These are conversations I will have with my MPN specialist but I am interested in your and other’s actual experience.
Luckily I had the shingles vaccine quite a while ago so that’s not an issue. However on Hydroxy I had 2 squamous cell skin cancers removed in a short period, but have had no additional ones on Besremi (also have family history of melanoma). I have lost weight on Bes and I’m in a good place - don’t like the idea of fighting weight gain but if it means HCT control AND reduced VAF and I have to give up on INF then so be it. I am still hopeful that better thyroid control will mitigate the chronic hives and allow me to stabilize on Bes. Time and continued monitoring will tell. Your experience and advice are very helpful - thank you for taking the time to respond. Wishing you good luck on your journey and continued news on your progress. Much appreciated.
Weight gain is not a given with Rux as I have posted many times, substantial reduction in allele burden is also possible with some , there are minimal if any sides in most cases.
Autoimmune and Inf is a risky path to continue on but as always get a second opinion from an expert Haem.
Thank you ainslie for your response. It is encouraging to hear that weight gain is not necessarily universal, and that Rux can result in VAF reduction. I have seen a number of posts and read the great links provided on this research. It is fortunate to have not one but two potential avenues. I think I need to get over that Rux is often talked about as a "second line" treatment, aka failure of the first and most preferred treatment, when it is simply another alternative with pros and cons associated with all medications. It reinforces that we are dealing with a very complex set of factors, and that all of our bodies are unique and different in their responses. I will definitely be doing more reading and discussions with my Care Team and strive for an open mind. Thank you!
As KLCTJC also notes, thyroid troubles in their various forms are usually quite treatable and not a show stopper for IFN.
Of more concern is if you get any new or worsened neurological symptoms while on IFN. These can be signs of serious A-I reactions. Separately any new or obviously worsened dryness in any part of the body that should have wetness.
With your risk history for skin cancer and previous reaction to HU, Rux would need particular care and derm checkups. You should discuss with both MPN and derm Drs whether it is advisable to try. But you say you lost best HCT control at 450mcg. So adding a low dose of Rux is worth discussing. A recent thread has one member who had good HCT results switching to Rux. The combo of low dose Rux and Bes at 200 might hold the HCT and reduce the A-I risk.
On Shingles, if you had it "quite a while ago" it might be the older vax, Zostavax. It was a single dose, vs two for the newer one, so you can know which one you had that way. Zostavax is obsolete and getting the new Shingrix is advised for most seniors Rux or not.
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For my Sjo, the MPN Dr said Rux might help. Rux targets Jak1 as well as Jak2. I think its benefits for A-I would be the Jak1 part, while MPN is more the Jak2 part. There are A-I meds that target just Jak1. At ~18 months I can't say it has helped. There is a med that KLCTJC will know about, Sotyktu. It targets Jak4 (Tyk2) and is in phase 3 for Sjo.
I suspect many of the sides on Rux are from the Jak1 targeting.
Sjo currently has no good treatments and is usually irreversible and progressive. Most of the bad A-Is are not reversible. With IFN, when this rare worst case happens, there is usually a tipping point where you either get better or fall in. Immediate stop of the IFN is in order at the first sign, as noted in some reports. Hence my post title "Last Dose".
My Sjo goes up and down, I'm in a not horrible place right now, I can leave the house without fear. One Sjo specialist (there are only a handful worldwide) said mine might get better bec of the unusual way I got it. Unfortunately other members here have also acquired it. "remission" is not normally part of the Sjo experience unlike RA for example.
Hi EpGuy - Thanks for your response, always helpful! I keep thinking about your posts and all of the embedded information. It takes iterations for me to digest, a little more each time. Your advice on neurological and dryness symptoms are insightful. So far I don't think these are current issues for me, but it is important to have these potential markers to identify danger zones. Hopefully as you point out - thyroid and hives are likely to be more manageable. Rux certainly seems to have similar benefits to IFN but also different potential strengths. A potential combo may be an option, and I do regularly see a Dermatologist and need to keep an eye on that front.
I hope for you that Rux truly might not only work well for your MPN but also might help with Sjo. Hopefully treatment breakthroughs will come soon! I'm glad to hear that you're not in a horrible place and hope the you are heading to a good place. It's encouraging to hear that your unusual Sjo onset might open you to getting "better".
As for shingles, I did get the original vaccine (which I heard was only about 50% effective in any event), but then several years later got the 2 dose more effective version. It is confusing to have had two different iterations.
Thank you again for taking the time to share your valuable thoughts and perspectives.
Thanks for the support. Sjo has zero good treatments now but a whole line are in phase 3 trials and finally there is likely to be some. One catch is Rux is can be an issue for some.
It seems your A-I risk is ok, that test KLCTJC is suggesting we hope can put it all in a good place.
As most of the people on this forum know I work in dermatology. And hives can be in response to an environmental cause or autoimmune or really a thousand other things! If the hives persisted after being off of Besremi and controlled with Zyrtec that is a good sign if you want to restart Besremi. Most autoimmune hives typically need something else, I have had patients on MTX, xolair, dupixent, etc. if they think it is from your thyroid then you just need to adjust it and see if it improves. Besremi pushed my thyroid over the edge! And it has taken over a year to get it straight but now I am on medicine and just now got controlled. Thyroid fluctuates, luckily can be managed. I think it seems reasonable to try the Besremi again, stay on the Zyrtec and get thyroid back under control and see what happens. If truly autoimmune they could always calm it with steroids if it got really bad. But I love Besremi I would be devastated if they told me to stop it so I get it. I think they all just need to work together. Did they draw a CU index?
Hi KLCTJC - what an interesting post. Yes, the hives persisted after being off of Besremi AND have been controlled with Zyrtec twice a day. Hives came out of nowhere, a week after I skipped my routine Besremi injection because of travel (will never do that again). I had a tick bite a couple of months before all of this and so was tested for Lyme, Rocky Mountain Spotted Fever / Alpha Gal. Results were positive for Alpha Gal but at the lowest level. The subsequent meat allergy tests were all negative and my meat/dairy abstinence during the interim made no difference.... so that was all ruled out. I am unfamiliar with CU Index but it sounds like an important bit of information. I will have to do some investigation and get more educated, this stuff is SO complicated! I will have an Allergy follow up in 3 months. Would CU Index test need to be done after discontinuing anti-histamines for several days? I tried to stop the Zyrtec before the Allergy visit but within one day it was intolerable and they said I could resume, so no further lab tests were done. In the meantime, my MPN specialist approved the Besremi 200 mcg injection last week and my next labs will be in about 2 weeks to check on HCT and TSH. Surprised to hear that it has taken you a year to get your thyroid straight, that is concerning! So glad to hear that the solution was found! I guess I should not be surprised if it's not a quick fix. We shall see. Thank you so much for adding additional insights .... very helpful! Appreciate your time and perspectives very much! Thank you.
I would ask them about the CU index lab. If it is high it will indicate autoimmune cause which would be important to know. However I bet yours is normal which is good because you are responding to Zyrtec which is such a safe and easy way to manage them. When it doesn’t work it becomes tricky, but the information would be important in your case. Sometimes things just happen and may just a new separate issue. Sometimes we get in the habit of blaming our current issues for everything new when as the old going says crap just happens! But glad it is controlled with Zyrtec.
Good points - all. Stuff does just happen. Agree that so far I’m fortunate to have a working solution for now and sounds like overall positive signs. Will check out the CU Index lab.? Appreciate your very helpful comments. Best of luck on your continued path. Thank you!
A bit off topic, have you Rx Sotyktu much so far? If so how is that working out? It's considered a promising agent for Sjo and is in ph 3. There are no ph1 or 2 to compare. Might work well for me since my Sjo is IFN induced. But I might need to quit the Rux.
More on topic, Sotyktu is a type 1 IFN inhibitor and a novel thought I had was using it to rescue a bad reaction on IFN. I suspect if I had taken it just after my Last Dose I might have prevented Sjo. Instead the long action of IFN pegylation did me in. Stretching it further, taking it prophylactically to moderate IFN's harsh edges or for those who don't tolerate IFN. I don't expect there to be any trials of this but just a thought.
I was unaware that sotyktu did anything with INF, but it kind of makes sense by the way that it works. I do have one or two patients with psoriasis on it and it is tolerated well. Best way we understand it to work in dermatology is mostly by turning down IL23 which is a big player in most autoimmune diseases like sjo, psoriasis, Crohn’s, UC, etc. The IL23 drugs that are out are super appealing because they work so well and are very safe. No lab monitoring other than a TB prior to starting. The drugs I have seen come out in the last few years for psoriasis have been incredible on how well they work and the safety is amazing! As far as you having to stop the Rux, when looking it up it just say caution advised. So, you may not have to stop the Rux, you obviously need to talk to your doctor, but it is a good drug. I hope it works out for you.
On Drugs.com the interaction lists Major, but not contraindicated. I know sotyktu is very well targeted to a precise part of Jak4(Tyk2) unlike Rux (both Jak1 and 2) so that should limit interactions. I'm also on a fairly low dose. But for sure I'm disqualified from that trial (I've applied to several diff ones)
IFN type 1 (alpha and/or beta) is a very active target for A-I drugs now. Certain Sjo pts express excess IFN type 1, which connects for me at least to the medicinal IFN-1's going haywire when things line up.
I'm not aware of drug work re il17/il23 for Sjo. A lot of the reports are early 2010's. But it's quietly brewing. Sjo shares mostly with SLE, while drugs for other A-I's have all failed in Sjo. Sotyktu could a be 1st exception. I think psoriasis, Crohn’s, UC are more related to each other.
An active target for Sjo/SLE is CD40-CD40L. Several are in late trials. For SLE there are cell trials right now that point to a cure, Sjo is following with some prospects. This is a distant relative to the potential curatives for CALR MPN. The latest in cell therapy is allogenic NK, a safer successor to the better known CAR-T. A sample for hematology:
"Allogeneic NK cell therapies have multiple advantages over existing CAR T-cell therapies. Allogeneic T-cell–based therapies cause graft-versus-host disease (GVHD), whereas NK cells do not. Compared with T cells, NK cells have remarkably reduced cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome toxicity"
I think it wouldn’t hurt to try. Like I said from a dermatology prospective we look at the IL23 reduction which from the reps and meetings I have been to is the largest target for that drug. But as you know drugs come out and get new indications all the time because they find out it works for something else too. But IL23 is such a common marker in autoimmune diseases. I know they have looked at drugs for MS like this too, but they don’t seem to be affective. And I would have thought there would have been a major interaction, but I use epocrates and it said caution advised. The only reason I could think is because sotyktu isn’t a heavy immunosuppressant like others. At least this is what they say, they say it “turns things down, not off”. I just hope it helps you! It is worth a try!
The sales info you got has a basis, I found sotyktu uses the path I went to detail here for the new Jak2 mutant killer. But my take is it does turn off something, but it is specific enough to leave everything else alone:
which pointed to the new Jak2 drug being not completely original theory as I had thought. But sotyktu success ups the odds that the idea behind incb160058 works out
It seems IL-23 is not a hot area for B-cell A-I, not sure why. But it is for non-B-cell.
Sometimes things just happen! It just so happened that the dermatology liaison for sotyktu came in today! I asked her a few more in depth questions about it. The way she explained it to me is that this is a small molecule drug that’s goal is to bring the immune system down to homeostasis. So, it reduces IL23 and in turn IL17, currently in phase 3 for SLE and in phase 2 for sjo, which you mentioned. And it does have some TNF inhibition as well. And makes sense to bring the immune system down to a more normal level, but not completely suppress it which makes it very appealing and safe for multiple autoimmune conditions. It does bypass the Jak/stat pathway which again contributes to its safety. I really think it is a great drug, and makes perfect sense with the way it works and the safety profile is good. I really hope you at least get to try it
Deucravacitinib (sotyktu) shares the small molecule category with Rux. I like the wording "bypass Jak/Stat." Its target, tyk2, has also been called Jak4, and likely would have been called Jak1 since it is the earliest Jak studied, before they called them Jaks.
This report before its approval discusses it "Deucravacitinib has a differentiated safety profile that has shown it doesn’t have the downstream effects of JAK1/2/3, which are targeted by existing JAK inhibitors" in context of: "TYK2, also colloquially known as JAK4, is part of the JAK family. Amid the FDA’s classwide safety scrutiny on oral JAK inhibitors’ heart risks, some industry watchers have raised concerns that the agency might treat TYK2 drugs with the same brush."
TNFs have not worked out for Sjo. So I think it's the IFN inhibition part. With your insight, I understand now there is an IL-23 drug for Sjo. It's in Phase 3 actually. There never was a Ph2, so no public info whether it works.
But the concept that SLE has priority is broadly accurate. Many SLEs are likely to have a long term cure option as an alternative.
It was just so funny that the liaison came in today. But you brought up things that made me ask better questions to truly understand how the drug works so I can explain it better to my patients. Always good to learn more from each other! And it is good to hear that these drugs are being looked at for other autoimmune diseases. I wish you the best of luck and hope you get an opportunity to try it. I think it is a great drug with lots of promise.
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