Did your fatigue diminish when you switched from hydroxyurea to a JAK2 inhibitor such as ruxolitinib?

[TLJ-1]

Did your fatigue diminish when you switched from hydroxyurea to a JAK2 inhibitor such as ruxolitinib? Published studies show that most patients who take JAK2 inhibitors have diminished spleen size, and they also report composite symptom scores, e.g., TSS, improving for the majority of patients. However, since fatigue is a really major problem for my MF (calreticulin mutant), I would like to hear from those of you who have had the experience of taking a JAK2 inhibitor and whether or not that had an impact on your fatigue. Thanks!

[Chicagopv]

Hi--I didn't have fatigue in the first place, so it didn't change. A few years ago I did have fatigue on Jakafi because it gave me anemia. I used to take iron pills but the past few months have been trying to add iron to my often-vegetarian diet instead. I'll see after my next blood test if this worked. I can't tell if I'm fatigued, frankly. I've always needed at least nine hours of sleep, which is very annoying!

[TLJ-1 in reply to Chicagopv]

Many thanks for your reply, Chicagopv. Inducing anemia has been a major reason I have not switched to ruxolitinib so far. My fatigue is not subtle; it hit me a couple years ago and makes me nonfunctional in the middle of the day, every day. Imagine you've been awake for 24 hours and feel you just can't stay awake. A 40-min nap is necessary, but it won't completely alleviate the fatigue; after a nap, I can partially function, but it is a struggle. After about 4-5 hours, i.e., around 4 PM, I can actually start to feel normal again. Pain from MF exists, but I can basically deal with that.

[Chicagopv in reply to TLJ-1]

I'm so sorry. The anemia is worse the higher your dose of Jakafi. I take 5 or 10 mg. a day. You might as well try it. You can always go back to HU.

[Sivasi]

HiI changed from Pegasys to Ruxolitinib and the effect was miraculous! No more fatigue. I feel entirely normal .

[JP1952]

My experience is lack of energy and everything being a tremendous struggle, ie legs of lead and breathlessness from walking up our garden steps or light housework rather than the need to sleep. First noticeable even before diagnosis in 2019 and steadily progressed through 2 years taking hydroxy and 3 years on Rux, ramped up significantly when haemoglobin level very low. I am now on 20/25 mgs Rux on alternate days and bloods slowly risen but still well below normal except platelets.Should add I am undergoing tests for heart failure which came to light several months ago so that probably adds to the battle.

[gjh8733]

Like Sivadi I changed from interferon (for me it was Besremi)to Jakafi and my energy levels and endurance have gone way up. I have been able to build back some muscle mass so now can ride for 3-4 hours without fatiguing whereas before I would be hurting after an hour

[ainslie]

generally speaking those with MF going on Rux feel a lot better , IF and that’s IF a patient becomes anaemic that will take away from feeling a lot better depending on the degree of anemia. You could of course try it to see how you feel, if it doesn’t suit you can always go back to current meds (check that with a expert first if you can), I don’t think many go back though, another consideration is Rux for MF (not PV) can for some but not all lose effectiveness around 3.5 years although I know one patient on it over 10 years and it helped him hugely.

[Endlesssunsets]

hello there! Yes although it took awhile. For me I switched from HU to Jakafi Had been on HU for over 5 years. It took just about a year for me to get some energy. I am on 10mg twice a day. The only issue I have is my platelets keep going up. I am due for BW soon everything else very stable and my RBC in normal range now. I lost about 41 lbs so trying to stay active and I need to lose another 20 lbs. I started swimming it really helped me!! Good luck give it some time hope you get some energy soon wishing you the best

[TLJ-1]

I really appreciate all of your responses. Chicagopv and JP1952, I'm sorry to hear of your continuing issues and certainly wish you well. The positive experiences of some of you is encouraging me to try the switch from HU to ruxolitinib. My hematologist is in no hurry as he correctly notes that HU is maintaining my platelets quite well (~550) with RBC at the low limit of "normal". As JP1952 suffers from low energy levels, I too feel much less energy than 3 years ago as well as the overwhelming midday fatigue. I think I can convince the hematologist to permit me to switch, however. Then I'll find out if I move from one type of fatigue to another due to anemia. Unfortunately, momelotinib appears to have more side effects, and reports show it did not improve symptoms as much as ruxolitinib while it did inhibit anemia. I would appreciate hearing from anyone else who has had the experience of making the switch to use of ruxolitinib or other JAK2 inhibitors.

[EPguy in reply to TLJ-1]

I've been on HU-IFN-Rux. Rux has been the least eventful of the three, IFN worked well but malaise was a regular problem and you can read my bad ending.

I have had some weight gain on Rux, but not a biggie for a skinny guy and a small change in intake is fixing it. I've had increased hair growth, a known Rux association. My Jak2 allele has continued down on Rux as of early this year.

Unfortunately I can't judge how I would feel overall since my rare IFN induced evil condition overwhelms all.

[MWxxxx]

Hi. I have moved from hydroxy to rux. The main good thing I have found is that rux allows me to have a good night's sleep. I didn't realise how badly I slept on hydroxy as I think it increased over the 5 years I was on it. I am finding it difficult to say whether rux has improved or worsened my fatigue overall though. It is different. I am more anaemic on rux and this still needs to be sorted out and clearly has an effect. However, I am less breathless and feel healthier on rux. Sorry that probably doesn't help very much.

[TLJ-1]

Thank you, EPGuy and MWxxxx for your input. Honestly, it is good to hear your experience. I have previously seen posts from EPGuy listing the many terrible travails of their journey with the disease. MWxxxx, I wonder if the “different” fatigue you experience was previously from the disease when you were on HU but with rux perhaps the fatigue is due to anemia. It occurs to me that maybe using less HU than I currently do (500 rather than 1000 mg) to help keep platelets down might enable a lower dose of ruxolitinib, which could help to minimize anemia. My hemotologist does not think mechanistically but would probably accept a protocol if there was a report citing the beneficial use of HU+rux. EPGuy, you have been a cornucopia of info for many people. Do you have at hand any published work (or other) on such a combination? Thanks!

[EPguy in reply to TLJ-1]

To confirm, the evil disease I got is Sjogrens, as detailed in my post Last Dose. My MPN symptoms have been generally mild, while I had plenty of malaise on IFN.

--

There is one study of the HU/Rux combo:

They added HU "when Ruxo proved to be unable to reduce WBC and/or platelet count."

ashpublications.org/blood/a...

The part that may be relevant for you is they were able to increase the Rux dose without toxicity via too low of certain counts. These seem to be PLT in particular, they don't describe explicitly an anemia benefit. But there is an implication of better Rux tolerance in general in the combo.

I recall there may be members using this combo. Better known is the IFN/Rux combo.

[TLJ-1 in reply to EPguy]

Thank you very much for the link and your comments! I'll check it out.

[Exeter21]

I can definitely state fatigue went once I changed from Hydroxy to Peg Interferon so I know it was the drug g causing fatigue for me. I would almost sleep anywhere at anytime because I had lost all energy.

Totally caused for me by Hydroxy. Once I stopped it my energy returned hair grew & life was normal again. I was glad I contacted MPN to get advice & changed to Peg Interferon which for me is brilliant drug .

Julia . U K

[Cja1956]

I definitely feel an improvement in my fatigue symptoms now that I switched from hydroxyurea to jakafi. My appetite is better and other symptoms improved like night sweats, shortness of breath, and mouth sores. It also reduced my spleen. I do get EPO injections if my hemoglobin goes below 10. I have MF.

[Standard_Error]

My situation may be different from yours, so take from this what you will. In short, Ruxolitinib has improved my fatigue. I am on 10mg twice a day.

I am 65, recently diagnosed with Primary Myleofibrosis (PMF) and also recently started on Ruxolitinib.

Before diagnosis, but when I was fairly sure what was going on I found a Myeloproliferative Neoplasm Symptom Assessment Form online and started tracking my symptoms daily. I have 33 days of observations and 12 since I started Ruxolitinib (so 21 days before treatment). I have not found out how the composite symptom scores, e.g., TSS used in the medical papers are calculated so I have my own method of averaging the results.

There are a couple of questions on the form I consider related to fatigue. One direct question: “Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your WORST level of fatigue during the past 24 hours”. There is also a question related in inactivity that I broke into two separate measures: “Inactivity - Ability to Walk (Low Aerobic Activity)” and “Inactivity - Ability to Ride (Zone 2+ Aerobic Activity)”.

The reason I am going to include my inactivity scores with my fatigue scores below may be idiosyncratic. I found that when fatigued I had trouble a) getting up off the couch; and b) walking; but not cycling. My regular, pre-PMF exercise routine was a morning walk (stroll) and 5 or 6 days a week an afternoon bike ride that was more vigourous (1 1/2 hr). The fatigue interfered with walking but less so with cycling. As long as I could get off the couch the cycling was fine whereas with walking would be tough. I have read that exercise is good for fatigue but as everyone who has it knows saying you should exercise is easier said than done. Nonetheless, I had this paradox and so I tracked walking and cycling as separate “Inactivity” scores.

Now on to your question and my results to date. In short, Ruxolitinib has improved my fatigue. In the past 12 days I have rarely noted any interference with walking or cycling. The scores before and after Ruxolitinib - (Absent) 0-10 (Worst Imaginable):

For fatigue: before – 3.7; after - 0.3.

For walk inactivity: before – 3.8; after – 0.8.

For bike inactivity: before – 2.3; after – 0.6.

Some cautions and caveats:

1) The scores were coming down before starting the drug. The scores may have been, and may continue to decline because I am able to tolerate them more or I have developed coping or avoidance strategies.

2) I have bone pain but have tried to separate that from the inactivity scores even though it may interfere with activity by making it unpleasant. I take pain killers for the bone pain and track bone by the number I take each day.

Good luck TLJ-1 and I hope this helps.

[TLJ-1]

Thanks very much, Exeter21, Cja1956, and Standard_Error. Your experiences are definitely good to know (hopefully, for others as well as me). Standard_Error, your noting that part of the fatigue problem relates to “getting up off the couch” hits home. I used to look forward to bike rides, but now I have to kick myself in the butt to do so; once out, I’m quite happy and feel better.