ITP: When to Switch to Second-Line Therapy


James B. Bussel, MD:It’s a very complicated issue about how long to go with first-line treatment. If, for example, you use high-dose dexamethasone, then you can give 4-day cycles 3 or 4 times even. But if that’s not working, then most people would change to something else after that, and depending how long each cycle induces the platelet count to be good, that could be 2 months or 6 months or 12 months. If one is using prednisone, that’s a little more complicated. On the one hand, when you use prednisone, pretty much everybody knows by now that continuing a significant dose of prednisone, which might be considered to be 10 mg a day or more, is not optimal for general health. There are certainly more different side effects of prednisone that are pretty well known than I could name using one of my fingers for each one, and my hands at least in terms of numbers of fingers are anatomically normal.

But if it would turn out that what might happen is prednisone is given at a high dose, as it was in this woman, she takes a milligram per kilogram for 2 to 4 weeks, her platelets hypothetically go up nicely, then she is tapered off and either manages to get off prednisone or gets to a very low dose and her platelets crash. If whoever is managing her does not want to admit her to the hospital and/or wants to admit her to the hospital but only for a day or two and maybe gives her IVIg then, it is very hard to get rapid approval for other agents such as rituximab or a thrombopoietin receptor agonist. So, there’s a certain amount again in the United States of an insurance trap whereby it’s a lot easier to continue the prednisone.

And even if you try to plan ahead and say, “Well, if and when the count falls again, I’ll be set to go with whatever other treatment I want,” that may not work with insurance. If she’s getting a first or second course of prednisone, the count may be good, and then the insurance company may not agree to use rituximab or a TPO receptor agonist because they’ll say, “Well, it’s not justified. The platelets are 60,000,” and then there’s sort of a catch-22 that’s involved. In principle, you wouldn’t give more than 1 course of prednisone, especially since the chances that that will result in a long-term remission are well under 10%, so the side effects seem to outweigh the benefit there given that there are other treatments available. But insurance may make that more difficult than one would anticipate.

Transcript edited for clarity.

Case: A 48-year-old woman presenting with unusual bruising

October 2017

  • A 48-year-old woman presents with complaints of bruising after minor bumps, bleeding gums despite regular tooth cleaning, and a recent spontaneous bloody nose; symptom onset about 1 year ago
  • Physical evaluation reveals a woman of normal weight and average height, afebrile, no splenomegaly
  • No personal or family history of cancer, autoimmune disease; no recent viral illnesses; no bone pain or night sweats
  • Current medications: ibuprofen as needed, generic hydrochlorothiazide (HCTZ)
  • Laboratory findings:
    • CBC reveals platelets 28 X 109/L
    • WBCs within normal
    • Renal and hepatic function within normal
  • Diagnosis: idiopathic thrombocytopenic purpura
  • Patient started on a course of prednisone 1 mg/kg for 21 days, then tapered off
    • Platelets: 29 X 109/L
    • Second course of prednisone 1 mg/kg for 21 days

April 2018

  • After 2 courses of prednisone, patient’s platelets have not recovered
    • CBC shows platelets at 28 X 109/L
  • Symptoms of easy bruising and bleeding from gums continue
  • After discussion with patient, she is started on the thrombopoietin receptor agonist (TPO-RA) eltrombopag (PROMACTA), at a dose of 50 mg/day
    • Dose increased to 75 mg/day; last platelet count, 65 X 109/L
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