Sequencing Therapy in Patients With Chronic Immune Thrombocytopenia
In the sequencing of therapy for chronic immune thrombocytopenia (ITP), multiple factors should be considered when choosing first- as well as when proceeding to second- and third-line therapies, such as cost, convenience, lifestyle, and comorbidities. First-line emergent treatments include corticosteroids, intravenous immunoglobulin G (IVIgG), and anti-D immunoglobulin. Second- and third-line treatment options for chronic ITP, which were once limited to splenectomy or rituximab, now include thrombopoietin receptor agonists (TPO-RAs) as an additional treatment option. The risk-benefit profile of medications should be weighed in treatment choice. Our featured experts in the field discuss the factors that should be considered when sequencing therapy in patients with chronic ITP.
Q: In the sequencing of therapy for chronic ITP, what factors should be considered when choosing first-line therapy, as well as when proceeding to second- and third-line treatment options?
Assistant Professor of Medicine
We traditionally think about what we estimate to be the patient’s bleeding risk based on his or her platelet count, his or her age, whether he or she has had bleeding before, and his or her lifestyle. If a determination is made that treatment is appropriate, we think about the efficacy and safety profiles of the treatments that are available. We are also thinking about how those treatments might interact with the patient’s comorbidities or concomitant medications, the patient’s lifestyle, the patient’s own personal values and preferences, and cost of treatment. This is the list of things that I think about when I am making treatment decisions with my patients, but notably absent from that list are any sort of biomarkers that reflect the pathophysiology of ITP in the individual patient. I believe that, in the future, we will have tests that will help us to understand the pathophysiology of ITP in the individual patient and will allow us to match treatment with pathophysiology, which will, in turn, improve response rates.
Director of the University of Washington
“We are recognizing that ITP is mostly a chronic disease, particularly in adults. If the patient relapses after first-line therapy, you should not necessarily try a second course of steroids, which is what people used to do in the past, but instead move on to either an anti-CD20 or a TPO-RA.”
One of the things that physicians are clearly doing is moving very rapidly away from corticosteroid after first-line therapy. The whole idea of treatment is to keep patients safe until they go into remission on their own or remission is induced with some kind of immune modulation. We are recognizing that ITP is mostly a chronic disease, particularly in adults. If the patient relapses after first-line therapy, you should not necessarily try a second course of steroids, which is what people used to do in the past, but instead move on to either an anti-CD20 or a TPO-RA. A TPO-RA might be a better choice. The way I interpret the data, you would be better off going immediately to a TPO-RA because you have a better chance of response overall and because, from what we’ve seen long term, you are more likely to come off the drug and have a longer-term remission than with the anti-CD20, for which the data, after 5 years, are not looking very promising. In patients for whom steroids may be a poor choice (eg, patients who are older, who have diabetes, who have hypertension, who have obesity), you should move very rapidly away from steroids or perhaps even start by giving IVIgG and putting them on a TPO-RA. In addition, you should move more rapidly to giving effective therapy in an older age group who appears to be more at risk of bleeding. I have concerns about splenectomy, and there are still places where people do not go to the TPO-RAs for whatever reason. Some do not believe in TPO-RAs, or they think that patients are going to be on them for the rest of their lives. Since they believe that TPO-RAs are too difficult to work with, they wind up going to a splenectomy too early.
Donald I Feinstein Chair in Medicine
“Most physicians who treat a lot of patients with chronic ITP have moved away from long-term corticosteroid use. The TPO-RAs have changed the whole treatment story because they allow patients to move off corticosteroids and maintain a safe platelet count.”
From the 1960s to the 1980s, long 12- to 14-week courses of corticosteroids were reported in the literature, with 13% or 17% of patients not requiring additional therapy when they weaned off the steroids. This shows that only around 15% of patients treated with first-line therapy with corticosteroids had a long-term remission unmaintained, meaning that 85% of patients are going to need some additional intervention. Therefore, why put a patient through 3 months or more of corticosteroids? Most physicians who treat a lot of patients with chronic ITP have moved away from long-term corticosteroid use. The TPO-RAs have changed the whole treatment story because they allow patients to move off corticosteroids and maintain a safe platelet count. I am willing to leave patients on TPO-RAs for long periods of time, and I have patients who have been on a TPO-RA for many years. I do prefer to try some immune modulation, and I think that is reasonable. The advantage of TPO-RAs is that they allow patients to maintain a safe platelet count off of corticosteroids and their side effects and they allow us to do immune modulation. There are a number of agents, like azathioprine or mycophenolate, that are very effective in modulating the patients, and you can take them off the TPO-RA. Some of those patients, after a period of time, can come off those drugs and have very long-term remissions. It surely is a better strategy for older patients, where splenectomy is less effective. I am not willing to give up on splenectomy totally yet because there are data that suggest that there are patients who are going to respond to splenectomy within the first 2 years and have long-term remissions. Given the issues of needing immunization and the long-term potential risk of thrombosis, I think that splenectomy is a reasonable choice. I am less enthusiastic about rituximab, but I think that there are certain patients, particularly young women, who are more likely to have a reasonable long-term, unmaintained remission. I don’t believe that the data really support the use of rituximab in older patients.
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