Q: What efficacy and safety data should be considered when choosing between the TPO-RAs as second-line therapy for patients with chronic ITP?

When I talk to patients about the 2 TPO-RA treatment options, eltrombopag and romiplostim, the main differentiator that we discuss is the route of administration. Romiplostim is a once-weekly subcutaneous injection that, for most patients, needs to be given in a doctor’s office. So, that can impose a certain level of inconvenience for some patients, although we have had success getting home administration for some of our patients. Eltrombopag is a once-daily pill, but it, too, has inconveniences because the pill has to be timed appropriately so that it is not taken in proximity to other polyvalent cations, such as magnesium or calcium. It has to be taken apart from dairy because that will interfere with absorption of the drug. It has to be taken apart from iron because that will also interfere with absorption of the drug. So, we discuss the issues related to the route of administration with patients, and very often, in my experience, patients will develop a preference for 1 based on that discussion.

There are other things that also play a role for me in choosing between the TPO-RAs. Comorbidities can play a role. One example would be that, in a minority of patients, eltrombopag is associated with hepatobiliary laboratory abnormalities and hepatotoxicity. If I have a patient with liver disease, I would probably be more inclined to choose romiplostim over eltrombopag. In addition, it is my sense that there is greater platelet count fluctuation with romiplostim than with eltrombopag, but that is not in every patient. We have some patients on romiplostim who have very steady platelet counts, but we have others who have major swings in their platelet counts. Because eltrombopag is taken once a day rather than given once a week, it has been my experience that we do not tend to see such large platelet count fluctuations with eltrombopag. For some patients, that might be a relevant differentiator.

Lastly, there is published literature—and I have personal experience with this as well—where there is a fairly high rate of patients who, when they switch from 1 TPO-RA to another, respond to the second agent even when the reason for switching was lack of response to the first agent. This might be because they have somewhat different mechanisms of action. The 2 drugs bind to different parts of the thrombopoietin receptor. It might also have to do with potency. It is my sense that the highest doses of romiplostim are more potent than that highest approved doses of eltrombopag. These are some of the differentiators that I think about when choosing, but I would say that, when we are making that initial treatment decision for a patient who has not previously been on a TPO-RA, route of administration is the major differentiator.

The efficacy and safety data are similar for these 2 drugs, and I think that these 2 drugs are neck and neck. There are data from meta-analyses suggesting that eltrombopag may reduce the risk of bleeding more than romiplostim, but I certainly do not think that that is actually accurate. Due to similar efficacy and safety, the choice between eltrombopag and romiplostim frequently comes down to what the patient wants concerning the route of administration. For example, with romiplostim you must consider whether the patient wants to come in weekly to get an injection, but, hopefully, we are going to see the ability to do self-injection in the near future. I have a few insurance companies here that are now allowing that, but, for now, most patients who are on romiplostim have to come in weekly, and that could be a real disadvantage for some people. Interestingly, I have some patients who like coming in—they prefer to do that versus oral therapy with eltrombopag.

The other consideration is whether the patient can take an agent such as eltrombopag, which has dietary restrictions. Some patients cannot have that period, which is going to be a good 3 to 4 hours of fasting when they take the drug, and this fasting can be difficult for patients. There are some drugs that are coming down the pike that are similar to eltrombopag but without the dietary restrictions. That will change the algorithm. For now, I think that is what we have in terms of choosing between those 2 drugs.