HiSome good news to share when I was diagnosed with PV in May 22 my jak2 result was 44.65 I was just having venesections and had 16 from diagnosis till Aug 23
In March 23 Jak2 had slightly increased to 55.44 so we had discussions re starting Pegasus
I started Pegasus 45mcg fortnightly in Aug 23 then in April 24 this dose was increased to 45mcg weekly as I had another 4 venesections during that 8 month period
I had a repeat Jak2 in June 24 which was slightly lower 44.07 then I had repeat Jak2 in December 24 (prior to start of Besremi) and was 21.59 with no venesections in this period so I was really pleased with the result
Fingers crossed improvements will continue with Besremi
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That's wonderful to hear and inspiring to me who has just started my own interferon journey some 3 months ago - so far the counts are coming down nicely with a slow steady approach and after a year or so the AB will be revised so fingers crossed and thank you for sharing your pos news! X
I am surprised more people haven't tried Peg or Besremi or Jakafi earlier. I know they are more expensive solutions, but they have the ability to alter the disease progression most effectively. Congrats on the reduced Jak2 burden, that's a very good drop.
Hi there, Absolutely.... although in fairness it's only in recent times that the effectiveness of disease progression is fully coming to light, as we learn more and more about these curious diseases we have - and for this I am most grateful. Had I had the opportunity of a BMB sooner, and therefore realised how high my AB was, I would have certainly started the medications sooner. But better late than never I guess - if anyone reading this is in doubt about starting the meds for the same reasons I was ie short and long term side effects, I would advocate that they go for it and start the meds to see how you get on (or at least push hard for a BMB so that you have the full picture, I was lulled into a false sense of security for many years!!) Thank you Luthorville for bring up this valid and helpful observation. All best wishes Sarah
I completely agree—this makes perfect sense. We're still in the early stages of integrating these drugs into PV treatment, especially for earlier use. Besremi was only approved in the U.S. in 2022, and when I started it in 2023, my hematologist thought I was crazy. That experience was an eye-opener, making me realize just how uninformed some physicians can be about emerging treatments.
Yes that's correct, I recall watching the trails with interest for Bes but only dreaming that I would ever be able to get it (as it was only due to medication shortages, that I managed to jump the system due to Peg shortages ) I always felt that when I was able to, I would use this drug as my preferred option, so it worked well in a way although the AB% of 77 was def the decision maker in the end. I am sure people being diagnosed more recently, will be given BMB earlier. Let's hope so. Again if anyone is putting it off for fear of pain, I didn't find it 'too' bad and am so pleased that I found out about my high level of mutation - had it not been for the test I would have been ignorantly waiting in the sidelines, with the watch and see approach, whilst the mutation (I imagine) gradually took a hold!
I am confident that progress now will soon unfold with the medical research and treatment avenues, so that in time, progression will be extremely rare and management optimised. We have come a long way - I am a 2017 "initiate".
Have you considered combining Jakafi with Besremi? I just started Jakafi (and finally updated my profile to include my journey). There is some indication that the combination is more effective than either individually. This isn't conclusion, far from it, but here's the idea...I think...
Potential Rationale for Combination Therapy
Besremi is an interferon that works by targeting the diseased hematopoietic stem cells, potentially leading to long-term disease modification and even molecular remissions.
Jakafi is a JAK1/JAK2 inhibitor that primarily controls symptoms and reduces spleen size by suppressing JAK-STAT signaling, though I think some of the more recent research has shown it can also help with disease modification as well. I think this point is still contested, however, even if Jakafi is taken earlier in diagnosis. I'm more in the camp right now that it can cause disease modification.
Interferon (Besremi) may be more effective when JAK2 signaling is suppressed. Since most PV patients have a JAK2 mutation, Jakafi could help limit excessive JAK-STAT activation while Besremi promotes normal hematopoiesis.
Jakafi might reduce inflammation and cytokine-related side effects of interferon therapy, potentially improving tolerance. Since PV is also an inflammatory issue, I think the theory is that the Besremi could then be more effective.
Both drugs could lower hematocrit, but Jakafi does so through inhibition of erythropoiesis, while Besremi gradually reduces the disease burden. I'm not entirely sure if this is correct for Jakafi...
Using them together might provide faster hematocrit control while waiting for interferon to exert its full effects.
Following up on this further...The RESPONSE trial and other studies do show that Jakafi can lead to some reduction in JAK2 p.V617F allele burden over time. However, the reductions are typically modest (ranging from -12% to -40% in some cases), and not all patients achieve meaningful molecular responses.
In contrast, interferon-based therapies (e.g., Besremi, Pegasys) have been shown to induce much deeper and more consistent reductions.
ps hello again, I note that you take (or did take) 500 mcg Bes, I am only on 50 mcg once per fortnight atm, but considering an increase to 100 mcg soon, so will perhaps go to this increased dose before introducing another drug (i.e. the Jakafi) if this is considered a good route for me to have this double action approach. I am with you on the itch thing, did you find that this was alleviated when you introduced the Jakafi at all, many have cited this to be the case - sorry more questions........ we all help one another so much don't we, it's FAB! Like you I am/was a youngish member to the gang, diagnosed at 49 yo and until then was super fit and healthy never seeing a doctor hardly ever.
HiI am only on 60mcg Besremi fortnightly too started end of December, can I ask why they may increase yours to 100 is it because your bloods are out of sorts still or another reason, I am under Guys too and on last visit all bloods in order and as previous post AB reduced although that was prior to start of Besremi reduction was from Peg, but there was talk of if I am tolerating well maybe increase to 100 soon, I will question when asked why increase if all well, as I Iike to take smaller doses as not to increase any side effects just curious if raising yours and all bloods in range or not
Wow 50 mcg is only the starting dose. Typically people start at that and then increase by 50 mcg for some time, every dose. Jakafi completely eliminated the itch issue. If you need another itch solution, because you aren't on Jakafi then Cetirizine did 80-90% of the trick for me and most others. I would still occasionally get an itch monster break out, but it was much more rare.
With Jakafi, the itch issue has been 100% gone almost as soon as I took it. But if you are only on 50 mcg Besremi, that would be unusual to add Jakafi too until they see how you respond to the Besremi. I guess my thought is that if your AB was 77, that's quite high and you clearly clearly want to bring it down. That's considered high risk and I would personally want to bring that down as quickly as possible. Given the impact from Jakafi, and again this is just a personal opinion, I'd probably want to consider both to bring it down sooner rather than later. Jakafi also seems to get HCT under control a bit faster too, in my opinion. I guess the negative of taking both is you are unsure which is working the most effectively. But it does seem that people start on these drugs too late. I could imagine starting both very soon after initial diagnosis with PV. Dose could likely start small to see if it prevents AB increase.
I've seen enough right now that I pushed for Jakafi even when I only had an AB of 15%. To be fair the drugs are not devoid of risks, either.
I posted on the VAF reductions via Rux. My impression is IFN was better for the higher starting mutations, over 60% in one example. But Rux looked quite good in the newer Majic PV trial as in this plot that I've frequently posted. They went to three years, this waterfall plot looks similar to those for IFN. We're seeing early signs of this effect on the forum.
Importantly all the long term studies of Rux in PV have required HU intol/resistance, a tougher audience.
They claim a deep effect in Majic-PV trial:
"Upon evaluating molecular responses at a stem/progenitor cell level, a substantial reduction in the clonal burden of JAK2V617F HSPCs in ruxolitinib-treated patients achieving a molecular response was demonstrated, consistent with ruxolitinib-induced clearance of JAK2V617F stem cells"
I think this benefit was not expected by the designers of Rux.
Very interesting. I guess the next question is whether my dose of only 5 mg twice daily is really meaningful enough to do anything. I suppose I could give it 3 months and see if I have a phlebotomy need with HCT of 45 and if none is needed then I don't need to go up. If one is needed I can go up to 10 mg twice daily. I won't have another AB measure for at least 6 months, I'd think so I'll have to depend on HCT impact.
There are other members on 5mg BID. In the trials I may recall they claimed 5 would not be therapeutic. But in the combo, a low dose of one or both is a key point. I agree giving it some time makes sense. Controlling HCT is the top near term goal for reduced MPN events, and once that happens reduced mutation is more likely via the typical correlation between them.
I asked my Dr, if I get lucky and VAF goes under 1%, could we pause the Rux, he's never tried, but agreed it's reasonable. More likely we'd try a reduced dose. It would be an experiment, I'm not aware of any study that looked into this for very low VAFs on Rux since the whole idea of low VAFs on Rux is new. My guess is a VAF fraction of 1% may be needed. I think this also depends on having no other mutations.
I agree with experimenting if you fall below 1%. Rux is not the best drug to be on indefinitely. Even reducing the dose seems beneficial. It seems highly unlikely there is any study for this also because so few fall below 1%. The sample size on these studies is already so low. I’m doubtful they would have enough enrollees.
One hope is the latest set of Jak inhibitors in trials or pre-clinical may improve upon all the treatments we have now. Better targeting, less risk if all goes well.
Thank you - it is actually on my mind to discuss this with Guys, esp as the AB was so high (need all the help I can get!) and also that I suffer now that I am on Bes with increased itch (post shower, bathing) so the Jakafi I think may help with this too. The only thing that puts me off this route (combined meds) is the risk of skin cancer as I am of the fair freckled type of English complexion, but as with all things its getting the balance right. Thank you for your suggestion. It's so positive knowing that these meds are working so brilliantly for many of us now.
I'm a fairly skinned person as well. The normal starting Jakafi dose is 10 mg twice daily. I'm at 5 mg twice daily, so I'm hoping I can have less risk for the skin issues.
I'm also hoping that I can get off of the Jakafi once I reduce things enough. Perhaps I could lower Besremi to 200 mcg monthly and/or 5 mg of Jakafi daily or reduce it to zero. If my numbers don't climb, I'd try cutting back further. So I'm hoping this is more temporary to simply get my numbers down to CHR and then will adjust accordingly.
very good news! So glad IFN is working well for you. My goal is to get to ET steady state in a few more months and then cruise on maintenance dose. IFN has been good for me, too. Stay safe!
In June 2016 I was diagnosed with PRV and tested + for Jak2 V617F with an AB of 59% I have been taking 11/500mg Hydroxycabamide weekly for over eight years.In December 2024 my AB for Jak2 V617F was down to 46%.
I have never taken hydroxy myself. I have only ever taken interferons, pegasus then besremi due to shortage of pegasus, from what people say here the interferons do work on reducing the AB, maybe speak with your team if it's possible for a change to interferon if that's an option for you,Any AB reduction is good though and wishing you well going forward
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ET, JAK2, ASXL1 and Besremi
Pegasys Journey
Itching on pegasus.
Splitting Pegasus vials
