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TPO Receptor Agonists in ITP

Panelists: Ivy Altomare, MD, Duke University Medical Center; Terry Gernsheimer, MD, Fred Hutchingson Cancer Research Center; Keith R McCrae, MD, The Cleveland Clinic
Published: Monday, Feb 12, 2018



Transcript: 

Ivy Altomare, MD: Let’s discuss all of the second-line agents that are available for use. I’d like to start with the thrombopoietin mimetics. We were just talking about how thrombopoietin mimetics are not recombinant thrombopoietin. What are these drugs? There are 2 that the FDA approved for use in America: romiplostim and eltrombopag. How do they differ, molecularly, from each other?

Terry Gernsheimer, MD: First of all, eltrombopag is a very tiny molecule, and it inserts itself.

Ivy Altomare, MD: Is that good?

Terry Gernsheimer, MD: Well, it depends on how you look at it, right? There are reasons why you wouldn’t want a tiny molecule, and there are other reasons why it’s really good. It can be absorbed via the gastrointestinal tract, which is great, and it inserts itself into the intramembrane portion of the TPO receptor.

Romiplostim is actually a combined molecule of the Fc portion of IgG, and the piece that’s actually fitting into the receptor. The reason that was done was so that it would have a nice long half-life. It can be given once a week, as opposed to daily with eltrombopag, and that binds exactly at the same spot on the outer portion of the membrane that TPO binds at.

Ivy Altomare, MD: Eltrombopag is oral, and romiplostim is?

Terry Gernsheimer, MD: Subcutaneous.

Ivy Altomare, MD: It’s subcutaneous injection, given weekly?

Terry Gernsheimer, MD: It is given weekly. Because it’s subcutaneous, we know it’s getting into the system. With eltrombopag, there’s going to be some problems with availability because of when a patient eats. I always worry if somebody has chronic diarrhea. There are a lot of gastrointestinal disorders and autoimmune disorders that are associated with idiopathic thrombocytopenia purpura. Then you have to worry, “Is this patient really getting it?” It’s also a matter of convenience for the patient. Some patients really prefer taking a once-a-day oral dose. Some patients tell me, “I’d rather come in once a week and get the injection.” It’s a little bit difficult because the original studies were done with self-injection once the patient was actually on a steady dose. Medicare has not allowed that, so most insurance companies have not allowed that. But there are some insurance companies that do allow self-injections. So, it’s kind of important to check. Patients, after a while, do want to self-inject, especially if they’re coming from far away.

Ivy Altomare, MD: Right. But I would imagine that is once there is a stable dose that achieves the goal platelet account. Often, romiplostim has to be titrated based on the platelet count. So, then you would want patients to still come in and get their complete blood counts.

Terry Gernsheimer, MD: Right. But eventually, when I know what they’re doing, I don’t want to keep checking the platelet count. I like to tell patients, “I want you married to your spouse, not to your platelet counts.” They get very anxious about their platelet count. It’s so much better for them, once I know they’re safe, to not think about it.

The other problem is that the platelet counts tend to rock around a little bit. And so, you don’t want to be reacting to every single platelet count and titrating doses up and down. That’s where I see patients getting into trouble with the drug. They have a low-ish count one week. Somebody increases the dose. They go too high. They hold it. They go too low. So, it’s really good to find a dose and just stick with it. I usually just check my patients every couple of months and leave it at that, unless there are some symptoms or something that make me say, “You know, you better come in and get another count.”

Ivy Altomare, MD: Yes.

Transcript Edited for Clarity 

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Transcript: 

Ivy Altomare, MD: Let’s discuss all of the second-line agents that are available for use. I’d like to start with the thrombopoietin mimetics. We were just talking about how thrombopoietin mimetics are not recombinant thrombopoietin. What are these drugs? There are 2 that the FDA approved for use in America: romiplostim and eltrombopag. How do they differ, molecularly, from each other?

Terry Gernsheimer, MD: First of all, eltrombopag is a very tiny molecule, and it inserts itself.

Ivy Altomare, MD: Is that good?

Terry Gernsheimer, MD: Well, it depends on how you look at it, right? There are reasons why you wouldn’t want a tiny molecule, and there are other reasons why it’s really good. It can be absorbed via the gastrointestinal tract, which is great, and it inserts itself into the intramembrane portion of the TPO receptor.

Romiplostim is actually a combined molecule of the Fc portion of IgG, and the piece that’s actually fitting into the receptor. The reason that was done was so that it would have a nice long half-life. It can be given once a week, as opposed to daily with eltrombopag, and that binds exactly at the same spot on the outer portion of the membrane that TPO binds at.

Ivy Altomare, MD: Eltrombopag is oral, and romiplostim is?

Terry Gernsheimer, MD: Subcutaneous.

Ivy Altomare, MD: It’s subcutaneous injection, given weekly?

Terry Gernsheimer, MD: It is given weekly. Because it’s subcutaneous, we know it’s getting into the system. With eltrombopag, there’s going to be some problems with availability because of when a patient eats. I always worry if somebody has chronic diarrhea. There are a lot of gastrointestinal disorders and autoimmune disorders that are associated with idiopathic thrombocytopenia purpura. Then you have to worry, “Is this patient really getting it?” It’s also a matter of convenience for the patient. Some patients really prefer taking a once-a-day oral dose. Some patients tell me, “I’d rather come in once a week and get the injection.” It’s a little bit difficult because the original studies were done with self-injection once the patient was actually on a steady dose. Medicare has not allowed that, so most insurance companies have not allowed that. But there are some insurance companies that do allow self-injections. So, it’s kind of important to check. Patients, after a while, do want to self-inject, especially if they’re coming from far away.

Ivy Altomare, MD: Right. But I would imagine that is once there is a stable dose that achieves the goal platelet account. Often, romiplostim has to be titrated based on the platelet count. So, then you would want patients to still come in and get their complete blood counts.

Terry Gernsheimer, MD: Right. But eventually, when I know what they’re doing, I don’t want to keep checking the platelet count. I like to tell patients, “I want you married to your spouse, not to your platelet counts.” They get very anxious about their platelet count. It’s so much better for them, once I know they’re safe, to not think about it.

The other problem is that the platelet counts tend to rock around a little bit. And so, you don’t want to be reacting to every single platelet count and titrating doses up and down. That’s where I see patients getting into trouble with the drug. They have a low-ish count one week. Somebody increases the dose. They go too high. They hold it. They go too low. So, it’s really good to find a dose and just stick with it. I usually just check my patients every couple of months and leave it at that, unless there are some symptoms or something that make me say, “You know, you better come in and get another count.”

Ivy Altomare, MD: Yes.

Transcript Edited for Clarity 
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