Besremi side-effects, reverting to Peg

[jon1972]

I've been on Besremi for over 6 months and have been on 400mcg for 10+ weeks. I can see now that I'd need the full 500mcg to control my counts, but have been struggling with side-effects throughout the range of doses, even at my starting point of 150. I have on and off flare ups of swelling of my gums, my tongue is constantly pitted and sensitive, I have severe sore throat and hurts to cough/sneeze, intermittent pleurisy type symptoms in my chest, dehydration issues and these side effects typically all ebb and flow at the same time. I never did get my counts completely under control but my phlebotomy interval dropped from once every 3 weeks to once every 6 weeks once I got to 400mcg. I was reluctant to go back to Peg because it did have some side effects as well and I was of the impression that Bes was superior in some way, but my specialist doesn't think one IFN formulation is better than the other, and that it just boils down to what works best for the individual. So I finally made the call to switch back to Peg.

I'm only the 2nd person I recall on this site who's thrown in the towel and switched back. It seems like most folks are doing pretty well with Besremi and I hope I'm blaming the right thing for all the problems I've been having, but I'll be sure and follow up on my experiences after I've been back on Peg for a while.

[ggrana]

I am up to 450 mcg and my main issue is stomach pain and diarrhea for a few days which begins about four days after my injection. I also feel like it’s affected my eyesight, since I started I’m having trouble seeing in the evening when I drive. My platelet count is still not in the normal range it’s getting close, and my specialist said that I will be doing 500 mcg soon. on top of this I am still taking four hydroxyurea pills a day . I would stop also if I was having all the side effects you are having, good luck to you and hope you feel better soon

[EPguy in reply to ggrana]

Are you seeing an eye specialist? Your night effect is very worth getting checked. INF has rare but serious risks with retina issues.

I've posted about my eye issues on Bes, I've had regular eye Dr appts to keep checking.

[ggrana in reply to EPguy]

I went to the eye doctor before I started Besremi in December but have not been been back since then, thank you I will have them check it out

[Cja1956 in reply to ggrana]

Four hydroxyurea/ day seems highly excessive to me, especially on top of the Besremi. Why does the doctor think you need so much?

[ggrana in reply to Cja1956]

He is trying to get my platele count in the normal range. He feels they were dangerously high with all the medication I am taking.

[Barbiebreath]

I’m no expert but if the peg worked better for you with less side effects- sounds like the right answer to me. Wishing for the best outcome for you.

[EPguy]

Sorry to hear of your trouble.

There is in fact a difference in the INF used for PEG vs Bes. PEG is INFα-2a while Bes is INFα-2b. I've not been able to find actual effects of this difference, or why Bes chose the other one, but it could be you are experiencing the difference.

Look fwd to hear your better results on PEG.

[Hopetohelp]

Thank you for updating us. Hope all goes well when you are back on peg. Always a bit unsettling when making big changes but you just know when things aren’t right. These drugs with our condition seem to affect us all so differently and personally. Look forward to hearing how you get on and the best of luck.

[hunter5582]

I think your specialist is on target regarding how we are each different in how we respond to the meds. Just because it is theoretically easier to tolerate the monoPEGylated formulation in Besremi, that does not mean it will be so fo everyone. We are all learning about Besremi and how people we react. Doubtless some will do better on Pegasys. It isd a good thing that out options are expanding.

All the best moving forward.

[monarch5000]

I was miserable on Besremi (INFα-2b) at biweekly doses of only 125-175 mcg. So I went back to weekly 90 mcg doses of Pegasys (INFα-2a_and all is well again. On the MPN-NET forum, some of the long time interferon users there remember that back in the 1990's and 2000's there was a general consensus that INFα-2b formulations were slightly less tolerable than the INFα-2a formulations.

[EPguy in reply to monarch5000]

do you have any details on that discussion? (2a vs 2b) I've been looking for any background available on this mystery of INF types.

[monarch5000 in reply to EPguy]

"Peginterferon-alfa-2a and -2b are the two types of pegylated interferons widely available for the treatment of chronic hepatitis C (HCV) infection. However, peginterferon-alpha-2a has a very restricted volume of distribution, longer half-life, and reduced clearance, and hence, it can be given once weekly, independent of the body weight. But, peginterferon-alpha-2b has a shorter half-life in serum and hence, it requires body weight-based dosing. Furthermore, peginterferon-alfa-2a has a relatively constant absorption and is mostly distributed in the blood and organs, while peginterferon-alfa-2b has both a rapid absorption and a wider distribution in the body." pediaa.com/what-is-the-diff...

[EPguy in reply to monarch5000]

Thanks. It seems to focus on how the PEG part is attached, which might relate to the details below:

Looking deeper than most here may want to know, I finally found a clear answer, there is an acid substitution at "position 23". Many of us have MPN because of a single DNA substitution at Jak2617, so maybe this matters in INF. (I know DNA and INF are not really comparable, but interesting)

originalText

<<IFN-alpha 2 has three acid stable forms (a,b,c) ... IFN-alpha 2a shares 99.4% , 98.8% aa sequence identity with IFN-alpha 2b and 2c respectively>>

So α-2a is 0.6% different from 2b, this could be significant, and here seems to be the 0.6%:

originalText

<<The difference between IFNA2A and IFNA2B is in the amino acid present at position 23. IFN-alpha 2a has a lysine at that position 23 while IFN-alpha 2b has arginine.>>

I think the different ways each peg-INF combo works may matter more, but what the INF contains at "23" could matter too.

[Lin_Hsu in reply to EPguy]

Perhaps this document can also help.

Impact of Interferon Alpha/Beta in the Management of Chronic Myeloproliferative Disorders

intechopen.com/online-first...

[EPguy in reply to Lin_Hsu]

Thanks for the reference summary. One item on the point of dose was from a large but short Italian study <<Ropeginterferon (Besremi) was administered every 2 weeks at a constant dose of 100 μg.>>

This dose is closer to what we often see here but not what they used in the main trials.

[ciye]

Really sorry it's not working for you and I hope you get things sorted so you are feeling better soon.

[Wyebird]

Hi it awful that you are struggling with your medication For future reference if Peg is too much did you know you could combine a reduced Peg with other with Hydroxicarbomide?

Good luck

[jon1972]

Well I still have to go through the whole insurance thing, but hopefully we don't run into any obstacles there. Based on the number of people I've seen that have also been struggling with getting their counts under control with Bes I get the impression Pharmaessentia made some sort of trade off between potency and the half-life the drug has in the body. It may not be a problem for most folks, but I've seen quite a few that are having to double up with other drugs or they're maxed out at 500 and still waiting for something to happen. I only needed around 135mcg of Pegasys to achieve CHR (180 is the max). I was in CHR for 1 year at that dose before switching to Bes. I'm going to roll the dice that it doesn't matter which one you use as long as you achieve CHR. In the back of my mind my only concern is that I'm wrong about these issues being caused by the Besremi and that it's something environmental in this new place I'm living or that I have some other health condition, but the doctors, including my specialist are baffled at my symptoms and I've run out of things to rule out.

[EPguy in reply to jon1972]

Thanks for the clear info. How quickly did you get to CHR on PEG?

You may have seen the plot here:

healthunlocked.com/mpnvoice...

Your result is the red circle. From this early feedback, it seems we may know quickly how we will respond to Bes.

Your note on trade off is a good point, there must have been something about the a formulation that wasn't a fit for their goal.

BesDoseVoiceSurvey

[PhysAssist in reply to EPguy]

I'm at 100 mcg every 2-weeks, but we're going slow to see where my sweet spot is.

The good news is that I feel somewhat better [which I tend to think is all the HU effects resolving] and my Hct is trending downward from 46 3-wks ago, on Hu 500mg/day and Besremi 50 mcg every 2 wks- to 45 after one dose of 100 mcg of Besremi.

When I get to the CHR stage, I'll message you.

Best,

PA

[Solyesh]

Hope things get better back on Peg. The good news is that these days we have options and our response to the various options can be as individual/different as we are. Best of luck!

[jon1972]

I probably have not given it long enough. I actually think somewhere between 450 and 500 may have worked, but I made the decision the side effects of this formulation are not worth it. I do appreciate the work you're doing with keeping a log of results on this site EPguy.