Interferon and risk of rheumatoid arthritis

[JHigelin]

Hi everyoneNeed to decide which new treatment to go on after HU has stopped working for me after 10 years. Consultant has suggested Jakavi or Interferon. They both have pros and cons and 2 months down the road I'm none the wiser which one would be best for me. However I've found a few comments about interferon triggering rheumatoid arthritis. As my mum developed this a few years ago and suffers badly from it, should I mention this to my consultant? Anyone has experienced this side effect and if so did it get better after switching to a different treatment? Thanks.

[EPguy]

You are right to consider the options carefully and you should absolutely discuss your family history with DR. RA is not explicitly listed on the IFN labels but autoimmune (A-I) in general is a known risk with IFN including RA. Sjogren's specifically is listed as "common" in the Bes Euro label, page 9 and others here:

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

Sjo is a horrific disease in its moderate to severe forms, but any A-I is a bad thing.

The US label covers A-I broadly in the black box warning in this image. We have seen most or all of the conditions among members here.

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As a minimum you should get tests for A-I markers. I have a post "Tests I got" with a long but not complete list. Some basics are RF, ANA, CRP, ESR, SS-a. But your Dr can give you suggestions. However all these can be negative and A-I can still emerge, this is my case.

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On your last question "did it get better after switching to a different treatment? " A-I often but not always will "self limit" (get better) after stopping IFN. But prompt cessation is essential if these risks present. I failed to heed warnings.

Surprisingly pre existing psoriasis is a signif risk also.

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In spite of all that worst case stuff, IFN is excellent medicine for the majority who tolerate and respond to IFN, it is very effective. And like Rux both can reduce the mutation.

BBox

[JHigelin in reply to EPguy]

Thanks for that. I do find the whole thing a bit confusing as I have found articles claiming IFN could trigger RA and others saying it can be used to treat RA??? I will discuss this with my consultant at our next meeting. Looks like Pegasys is out of stuck anyway and Besremy is not prescribed in Scotland so I might have to use RUX.

[EPguy in reply to JHigelin]

I have seen some reports on IFN therapy for autoimmune also, but I recall most were ~20 years ago + or -. Do you have some recent reports? Most of the recent reports look like the trigger you note:

"Our data suggest that, in eRA, IFN-α can cause a sustained, epigenetically mediated, pathogenic increase in lymphocyte activation and proliferation, and that the IGS is, therefore, a robust prognostic biomarker"

and "An interferon (IFN) gene signature (IGS) is present in approximately 50% of early, treatment naive rheumatoid arthritis "

This suggests the best test could be for the IGS. But it doubt it's available clinically.

ard.bmj.com/content/81/9/1214

Sjogren's has the same. IFN type 1 is the general culprit, of which IFN-a is one. For the unlucky few, maybe with that IGS, PEG or Bes may be triggering this reaction. There is a therapy in trials specifically to inhibit the IFN-1 signature.

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But there is a much more recent IFN therapy, "VELDONA" which is an oral very low dose IFN-a

"...clinical trial of VELDONA® in treating Sjögren's syndrome. "

ainos.com/news_view/64

Maybe this will expand to other A-I indications.

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I recall the Scottish rejection of Bes, the authorities deemed it not enough of an improvement vs price. But that was when PEG was available.

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One Rux side that is near 100% is weight gain. In my case no change in hunger or habits, but it fixed my underweight problem too well. Other not common sides can be non melanoma skin cancer and shingles. Also monitor your cholesterol. It's worth getting the Shingles vaccine before starting or near. But Rux is not prone to sudden surprises, most sides can be tracked and treated.

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In my case IFN worked flawlessly on all my counts and mutation, but I experienced the sudden effect. Rux has been boring but effective.

[hunter5582]

All the options for treating MPNs come with a risk/benefit profile. The next step with being refractory to Hu is to consider both Besremi/Pegasys or Jakavi. Compare the risk/benefit for each choice, consider your treeam,ent goals and risk tolerance, then you can make the choice that is in your best interests. Both are viable choices. You can work with a MPN Specialist to make the best decision.

[JHigelin in reply to hunter5582]

That's why it's so difficult to decide why one to go for. What about Anagrelide? I don't suffer from itching, no enlarged spleen. HU still working at controlling white and red cells but not platelets.

[hunter5582 in reply to JHigelin]

Anagrelide is considered a second-line treatment option due to the increased risk of adverse effects. While it can control thrombocytosis, it would not help with the erythrocytosis or leukocytosis. I would be very reluctant to consider combining it with HU. It is likely that either Jakafi or Besremi would be safer and potentially more effective. Note that Pegasys should also be available again soon.

It is also an option to review your target for platelets. Not everyone needs PLT to be less than 450. You could compare the risk of higher PLT to the change in medications if that is your preference. I suspect that changing your medication is likely the best choice as your care team has suggested. You can always try one of the other choices and see how it goes. You can always change again if it does not suit you.

[JHigelin in reply to hunter5582]

Thanks for that. Platelets are 705000. Used to vary between 400-650 with lots of ups and down but now only going up for the past 10 months des pite increase in HU. Consultant not too worry unless it goes over a million but we need to have a plan in place before it gets to that.

[hunter5582 in reply to JHigelin]

Given what you describe, I would be inclined to consider a switch to Jakavi or an interferon. I have set prevention of progression as a primary treatment goal. Suggest that you may want to have that discussion with your MPN care team if you feel that is an appropriate consideration in your case.

All the best as you move forward.

[Roxanne22]

Hi I wish you well in your search. The truth is that without a thorough genetic profiling which EPGuy touched upon, it is impossible to make the 'right' decision as each of us is so unique in our biochemistry - that we shall interact with drugs so differently. At a v basic level, one person may eat say strawberries and it's a heavenly dose of vit C and phytonutrients, another may come out in hives and never taste the again, so one can only imagine the complexity of introducing a drug to a body which is already in some way 'out of sync' - to encourage you, I would say try it and see - I am on Bes. 6 mnths in now and although my itching has flared up, I am seeing extraordinary pos+ results on cytoreduction and I feel so much more energy. I hope and pray longer term it will red my VAF. I have had no need for vene in this period. Of course the longer term may bring in different aspects who knows, all we can do is make the most informed decision we can, in your case discussing the maternal link to RA, and then monitor our tests and our body sensations and symptoms along the journey, and to switch course if need be....it's true that there is never an absolute 'perfect' meds choice, but there will be a best choice for you if that makes sense. I didn't know Bes was unavail in Scotland....That is interesting - sending you love and well wishes on your journey from down here in sunny Yorkshire X

[JHigelin in reply to Roxanne22]

I haven't asked my consultant about Besremi and she hasn't mentioned it but having checked NHS Scotland website it looks they have turned it down up here even on a short term basis until new batches of Peg become vavailable. But I will ask my consultant at our next meeting.

[Loubprv Volunteer]

Bit of a dilemma for you I was on HU successfully for 16 years but then had skin issues ( actinic keratoses)

Put onto peg interferon which for me had very very serious side effects - multoskeletal issues ( really severe joint and muscle pain) nausea and eventually vomiting.

Also ravaged my autoimmune system so am now coeliac.

Came off Peg that last July and am now on Rux /Jakafi which touch wood, seems to be fine

What can I say?

Each drug affects everyone differently.

However, my haematologist - a Prof - is super and says he doesn't get many complaints about Rux, except a bit of weight gain. ( Rux decreases production of leptin which increases appetite)

All the best

Louise

[ainslie in reply to Loubprv]

Glad to hear Rux is working for you, one small point Rux doesn’t increase appetite for everyone, mine is unchanged , tendancy to put on weight if I allow yes but no change in appetite

[JHigelin in reply to Loubprv]

Thanks Louise. I had managed to lose a few kilos and was hoping that I would only put those back on and no more!!! I must admit that I'm not that keen on self injections. The mood change is also a worry as I'm a teacher and really need to be mentally strong with/for the kids.

[Mieshie]

absolutely mention the family RA. When I was going through diagnosis, the information requested included checking boxes what parents and siblings had experienced. RA was on the list and I checked it as my mother had it but at age 71 I had no signs of it. The genetic test I took then was the most telling. It included confirming RA was negative for me. Tremendous peace of mind. You should consider getting tested.

Update: I checked my earlier genetic test. the marker for RA is the HLA-DRB1 gene. That being negative and no RA proteins found in a blood test are what gave me peace of mind.

[EPguy in reply to Mieshie]

In Sjogren's and likely some other autoimmunes, various marker tests can all be negative in presence of the disease. For those pts getting the Dx can be a long road.

But tests are well worth doing as the values, at least for the non-genetic ones, can change over time.

[Pennypen]

I was on Interferon for eighteen months when I first got diagnosed with MPNs and he took me off it to see what the out come would be but after a while my platelets started rising again didnt have a problems with it. I was off all medications for a while two years ago as my platelets were dropping but I started to feel ill as the platelets got too low. He wanted to give me a blood transfusion but didnt like the idea of having someone else's blood after taking the Covid Jab as I hadn't had any. He put me on Jakavi and noticed a big improvement. It can make you put on weight and hard to lose but maybe that is my age. I started to take iron tablets and eating liver for a while and he is happy now the way I am going if this is any help to you. You have to listen to your body sometimes as I wish I didnt have to take anything at all. I was having sweats at night and Jacavi has stopped that so that is one good thing. Hope this is a help

[eladhil]

hey. I am using peg and it works well. About the triggering rheumatoid arthritis I don’t really know