Corticosteroids as the Mainstay of First-line Treatment in Immune Thrombocytopenia
Corticosteroids currently remain the mainstay of initial management of immune thrombocytopenia (ITP) for patients unless there is a contraindication to corticosteroids or a need for a more rapid response due to life-threatening bleeding. For those patients, intravenous immunoglobulin (IVIg) and anti-D immunoglobulin are recommended as first-line treatment options, but these emergent treatments are not used long term due to toxicity and limited duration of response. A recent meta-analysis assessed shorter courses of high-dose dexamethasone compared with prednisone and reported that there was a small (11%) difference in overall platelet count response at 6 months. At 2 weeks, overall platelet count response remained 20% higher for dexamethasone, with fewer reported toxicities with treatment. Although treatment with corticosteroids is associated with a high initial response rate, these agents are also associated with low rates of long-term remission. The addition of thrombopoietin receptor agonists (TPO-RAs) to the available treatment options for ITP has greatly changed ITP treatment and patient outcomes. TPO-RAs have been extensively studied as second-line treatment in ITP, but their use in newly diagnosed patients as first-line therapy remains unclear. While the role of TPO-RAs is likely to evolve with the continued development of clinical safety and efficacy data, research and clinical use to date have shown encouraging results. Our featured experts in the field discuss the use of corticosteroids as first-line therapy in patients with ITP.
Q: Given newly developed treatment options, should corticosteroids remain the mainstay of first-line treatment of patients with ITP?
Director of the University of Washington
“The question to me is related more to how long you should continue with first-line treatment, and I think that the answer to this is that you very rapidly move away from first-line treatment with a corticosteroid.”
I will almost always start with a corticosteroid because there are still patients who can be given 1 blast of steroids and the whole episode is over. The episode was something that set them off, and you can give them a blast of steroids and then taper, or you can give them some dexamethasone, and they respond and can walk away from it. You follow them for a while, and it is obvious that itis over. The question to me is related more to how long you should continue with first-line treatment, and I think that the answer to this is that you very rapidly move away from first-line treatment with a corticosteroid. Corticosteroids and IVIg are the most commonly used first-line therapies, but they should be used for very short treatment durations. It is no longer the practice, when you start to taper them off the prednisone, if they relapse and then go back to the effective dose and taper more slowly, you know, I do not think that people who understand the way that they should be used are really doing it anymore. I think that people are very rapidly moving on to a second-line therapy.
Donald I Feinstein Chair in Medicine
“I think that we all consider corticosteroids as agents that we apply, but we do not do the long-term extended courses that were recommended in the 1960s to 1980s. And so, we move off the drugs very rapidly to a second-line treatment because there is no advantage in doing a long course of corticosteroids, even if they work.”
I think that we all consider corticosteroids as agents that we apply, but we do not do the long-term extended courses that were recommended in the 1960s to 1980s. And so, we move off the drugs very rapidly to a second-line treatment because there is no advantage in doing a long course of corticosteroids, even if they work. What is very important, in my mind, is to see a response to corticosteroids and plus other agents such as IVIg because it really defines, in my mind, the diagnosis of ITP. I begin to worry if a patient does not respond at all to corticosteroids and to IVIg and, while TPO-RAs are fine, they also work in a number of patients, including patients who do not have ITP. For example, they may be myelodysplastic patients or patients with liver disease. I saw a patient who was refractory to corticosteroids and the patient had hypoplastic myelodysplasia with paroxysmal nocturnal hemoglobinuria and was on a TPO-RA. I donot think that patients should be treated corticosteroids long term, even if an initial response is seen. But initial treatment with corticosteroids is useful because it does signal to me that this is an immune-mediated process.
Assistant Professor of Medicine
“Should we be giving steroids with something else as combination therapy up front,such as rituximab or a TPO-RA, with the goal of improving long-term response rates? More data are needed with long-term follow-up to know whether those strategies truly have the potential to cure patients versus postponing relapse.”
There are many parts to this question. It is true that steroids are the preferred first-line treatment for now, but how should we give them? The 2 major choices we have at this
point for first-line treatment with corticosteroids are standard dosing of prednisone or high-dose dexamethasone, and I do think that the updated treatment guidelines will make a recommendation regarding the choice between those regimens. I remain relatively unimpressed by the high-dose dexamethasone data. I think that it is clear that, compared with standard-dose prednisone, high-dose dexamethasone reduces the time to response. And it may improve response rates over the short term (at 30 days), but the data are also fairly clear that over longer periods of time, high-dose dexamethasone does not seem to produce longer-term responses than prednisone, and it does not seem to reduce bleeding. In terms of what would be considered to be patient-important outcomes, I do not think high-dose dexamethasone is a significant improvement over standard-dose prednisone. In addition, as a clinician who takes care of these patients, I dislike high-dose dexamethasone because I find it very hard to decide what to do if the patient does not respond. With prednisone, we follow the patient, we taper the dose after the patient responds, but what happens if we give high-dose dexamethasone and the patient does not respond, or what happens if he or she responds but the response wanes? This is another question. Do we give the patient more cycles of high-dose dexamethasone, or should we switch the patient to prednisone? I find that prednisone is much easier to use, and I like that it gives me more control as a clinician in my ability to adjust and taper the dose. The first part of the question about first-line corticosteroid treatment is as follows: if we are going to use corticosteroids for front-line therapy, what do we use? So, the second part of the question is, should we be thinking about doing something else first line? These are 2 ideas that require further study. Should we be giving steroids with something else as combination therapy up front, such as rituximab or a TPO-RA, with the goal of improving long-term response rates? More data are needed with long-term follow-up to know whether those strategies truly have the potential to cure patients versus postponing relapse. Another question is whether we should just be leaving corticosteroids out of first-line therapy altogether because of all the nasty side effects they cause patients and because we know that, in general, when corticosteroids are given by themselves, they do not tend to produce lasting responses. And so, should we just cut the steroids out altogether and go, for example, to something like a TPO-RA, which is, in all likelihood, going to produce similar response rates to or better response rates than corticosteroids with a better safety and toxicity profile?
Khan AM, Mydra H, Nevarez A. Clinical practice updates in the management of immune thrombocytopenia. P T. 2017;42(12):756-763.
Mithoowani S, Gergory-Miller K, Goy J, et al. High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2016;3(10):e489-e496.
Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.
Neunert CE. Management of newly diagnosed immune thrombocytopenia: can we change outcomes? Blood Adv. 2017;1(24):2295-2301.
Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168-186.