Science & Medicine

Special Report: Interferon vs. Hydroxyurea


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The moment of truth

  • – Zhenya Senyak

Some decisions are too important be made based on posts, tweets or sound bites.  With our quality of life, longevity and survival in the balance it makes sense to review the evidence.  This Special Report contains testimony of MPN patients and some of the world’s leading MPN specialists on the risk/benefits of hydroxyurea and interferon.

In the first week of December, the results of three large clinical trials comparing the impact of hydroxyurea (HU) and interferon (INF) on our health and quality of life will be presented at ASH.  For ET and PV as well as MF, these are our workhorse drugs. There is no event more relevant to the actual therapeutic choices we face as MPN patients.  

Despite real innovations in development – notably gene therapy and immunotherapy – right now and in the near-term future we have no radical alternatives to HU and INF for treatment of polycythemia vera and essential thrombocythemia. These two drugs, neither of which is FDA approved for use in MPN therapy, are prescribed at one time or another, alone or in combination,  for the great majority of MPN patients. (The myelofibrosis drug Jakafi, recently FDA approved for PV patients, remains a controversial  expensive alternative, alone or in combination with other drugs.)

This Special Report on HU vs INF brings fresh input from patients and physicians to help inform a potentially life-altering decision in advance of the ASH meeting at which some hard data should emerge.  For the significance of these clinical trials, see the video of  Dr. Claire Harrison and Dr. Ronald Hoffman talking about their importance.

You can access each patient experience and expert specialist opinion in this Special Report right here:

ET patient Elizabeth Goldstein reports on how Pegasys both failed and sickened her.

ET patient Barbara Kurtz writes about her 30 year control of ET with hydroxyurea.

Jeremy Smith, an MF post polycythemia vera patient  makes a passionate plea for mindfulness that can save your life.

In the MPN Specialists’ view, Drs. Ruben Mesa, John Mascarenhas, Jerry Spivak and Brady Stein join the discussion with with their combined heavy MPN experience from the clinics of the Mayo Clinic, Mt. Sinai, Johns Hopkins, and Northwestern . (Dr. Hans Hasselbalch comments on Elizabeth Goldstein’s report. )

Beyond direct testimony from patients and specialists, in this Special Report we present pricing and selected published resources to help us determine which of these two frontline drugs for high risk ET/PV might be most effective for each of us.

How to use this Special Report:  We urge you to actively review this Special Report, so you can advocate for yourself. Take notes on the professional opinions expressed here that apply to you. And take patient stories to heart. Share relevant material with your friends, family, and physician. As Jeremy Smith puts it, “This may save your life.”

Context and trials

The Lone Ranger and the Silver Buckshot

Our two main drugs, hydroxyurea and interferon, work more like a load of buckshot than a silver bullet for our MPNs. But for now and in the immediate feature they are the best we have.  At best either of these drugs can help us. At their worst, hurt us. We need to know the real risk/benefits of each.

MPNs are a genetic disease.  The various MPNs all start with a mutation in a gene coding for our blood producing stem or precursor cell.  This leads to a cascade of events including — but not limited to — downstream mutations, shifts in cytokine signalling, proliferating cell production. Even if our physicians knew our complete genotype, every gene, our completely sequenced DNA,  applying a med based on our genotype to block the impact of the initial mutation is not likely to effect a cure.  Although INF can lay claim to restructuring of the marrow and complete remission in some cases, so far only a stem cell transplant can do that, and that’s not an option for all of us.

Like every other drug on the market, neither HU nor INF deals with the cause of our MPN. Each – alone or in combination with other drugs — effectively alleviates some of the effects, in radically different ways. For a time

And there are complicating factors that limit the predicted effectiveness of HU and INF. Epigenetics. the genetic distortions caused by stress, disease or chance can determine which genes are expressed or shut down. Another complication is our microbiome.

While the traffic and commotion generated by our own trillions of cells is beyond our current understanding or control, we are host to an equal number – some say a far greater number  – of other life forms in our microbiome. Not just the foreign inhabitants of our gut, but all those life forms in us and on us, viruses, bacteria, fungi and archaea. These hangers-on, these passengers and microbic workers,  some good, some evil, some neutral have no interest in us beyond their own life support…and yet they affect the way we think, age, dream, respond to food and meds, sicken and die.

To treat essential thrombocythemia or polycythemia vera, our physicans have to largely ignore all this and focus on the  physical signs of our disease using a gigantic sledge hammer to go after an invisible molecular process unfolding in the darkest recesses of the hematopoietic stem cell’s nucleus.   The process is going to smash up a lot of innocent bystanders and interrupt other cellular business whizzing around our bodies. But we can within limits, stop DNA repair, support the immune system,  block the JAK-STAT pathway and throw a wet blanket on blood cell reproduction… for awhile.

And that’s where we are when we’re offered hydroxyurea or interferon. One or the other will likely work for some of us, some of the time. Our age and risk status will certainly be taken into account but our choice boils down to determining which is likely most effective for us while posing the lowest short and-long term risk. Another non-medical factor is relative cost and the frequent need to battle for insurance approval of interferon — at the cost of several thousand dollars per months vs, hydroxyurea’s under $100 monthly tab.

The current trio of comparative clinical trials comparing the two drugs – AOP Orphan Pharmaceutical, the Danes, and MPD-RC – might help clarify the decision-making process. All  three will report results at ASH and present posters. It’s unlikely anything that comes out at this meeting will be a game-changer. And the results will not be surprising.   AOP didn’t spent millions of dollars to prove its variant of pegylated interferon is not effective.  The Danes have been using interferon successfully for decades. And the ambitious but incompletely enrolled 30 country MPD-RC trial will have only partial, provisional data to report.

See the Addendum to this report for details on relative drug pricing and the specific clinical trials we’ll be focusing on at ASH. 



MPNforum has been a strong supporter of interferon. The editors recognize INF is not the solution for everyone and that there is a place in MPN therapy for hydroxyurea. We have long been a vocal critic of corrupted clinical trials.  And while believing extensive clinical anecdotal clinical evidence collected by reputable MPN specialists —  and replicated in separate clinics — is an equally valid measure of effectiveness, we value the statistical data that can might come from a well-designed randomized clinical trial.
How the two drugs stack up.
Aside from the price gouging difference in cost to patients and the healthcare system — interferon costs over $3000/month vs. under $100 dollars for HU – INF has certain clear advantages.  It is a recombinant form of a naturally occurring substance in the body’s immune system. It is not cytotoxic and has been shown to produce both molecular and hematopoietic responses in a great many cases over many years. HU is cheap, much faster acting in reducing blood counts and, with careful management, can be a tool for longterm control of symptoms.  HU does not affect the underlying disease.


Take me back to the Contents

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Comments on: "Special Report: Interferon vs. Hydroxyurea" (11)

  1. Have been on hydroxycarbomate for over 4 years. With break recently because of leg ulcers on interferon, which I felt fine, but have now been put back on hydroxycarbonate . I have all sorts of side effects really bad heads, stomach pains etc etc all I get told is this is not due to the polycythemia, I keep and busy but feel a bit let down. Sue

  2. Linda frank said:

    I have controled my PV fir 6 years through aspirin and periodic phlebitomy’s. Red counts under control but platelets at 700 an white blood count to high. Doctor has recommended interferon alpha, instead of the cost and sticking myself with a needle once a week, i am trying to determine if hydroxyurea can bring all those numbers to normal. So….interferon/ injection once a week OR hydroxyurea in pill form??? Any help out there??

    • Clearly, Linda, this is a question to take up with your hematologist since beyond economics there are efficacy and toxicity issues to address. HU is an appealing and tested option since it is inexpensive and easy to take. Short term effectiveness vs. interferon is comparable. While waiting for a deeper consultation with your doc to discuss the basis for his recommendations why not post your issue to the MPNforum Facebook page. There are PV patients there on HU both long and short-term as well as patients who transitioned to interferon and their experience might be informative. Good luck.

  3. “Failing” is when a treatment modality does not effectively control blood levels.

  4. Given the overwhelming scientific evidence supporting the use of IFN as first line therapy, what is the plan to implement it?

  5. Why did we have to wait 30 – 40 years for an Interferon Trial ? Now it has proven superior to HU on every metric, Its time to move forwrd with it and develop it further and investigate further improvements, combinatioin therapies basic science . I believe some time ago for example Ann Mulally at Harvard had already proven its benefit at a molecular level for PV. Jakafi need to be trialed against BAT that means IFN now. Any new therapy trialed against BAT must be trialed against IFN otherwise results are meaningless

  6. Arnie McConnell said:

    And, at the risk of being annoying, I’m going to make another point. The body in question is always a wild card. Who is to say categorically that it is impossible for my broken chromosome to repair itself?

    Every time I’m injected (infused, I should say with infusiasm) my stalwart self gets another, not only clear, but assisted, shot at breaking the join, or, reconnecting it in a better way. My blood could possibly be breakthrough blood. Then, it could heal YOU.

    Doctors, allow me to make a point. Most of you already find the practice of medicine in a hyper-capitalistic environment to be somewhat daunting.

    Keep the joy of being respected practitioners.

    Fight the good fights, like we all have to.

  7. Arnie McConnell said:

    OK. My mind is a little blown. And, admittedly, I’ve not read the articles yet. Just the titles got to me. When I come down from the ceiling, I will read the content closely.

    I’ve been among the fortunate minority for whom Interferon has been available. Taking it hasn’t always been a picnic, but I’ve tolerated it well. (How does one know efficacy for sure, except by the way one feels? I look and feel three or four years younger than my sixty-seven years would indicate.)

    What I find much harder to tolerate than my disease is the cost effectiveness argument. Yes, it would be cheaper to treat my illness by poisoning me a little each time I take my med. When you poison my cells, you poison me.

    But, after eight years or so of taking this med, with an almost two-year hiatus, I’ve come to believe that Interferon has been a boon to me. My counts are great; my disease has not advanced to anywhere near myelofibrosis levels.

    Please don’t ask me, in the political and economic context in which we live, to pretend that money isn’t the matter. It’s very much the matter.

  8. Shelley Sonnenberg said:

    In many cases, insurance will pay for INF therapy. In my case it was approved after failing on a course of HU. My cost is $10 per single use vial. Cost should not be a factor in receiving the best treatment available for each individual!

    • Roy V. Randall said:

      Define “failing”?

      • Without putting too fine a point on it, if your blood counts are headed in the wrong direction, if your clinical condition is declining, if you feel rotten, I think it’s fair to say the drug on which you’re relying is failing in efficacy. It’s also the standard used in clinical trials.

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