Neil B. Minkoff, MD: There are nonpharmacologic treatments as well, where you can move into things like blood transfusion or even stem cell transplant. Can you talk about where those fit into your practice?
Ahmar U. Zaidi, MD: Absolutely. Blood transfusion is something that we use primarily in children who are deemed at high risk for stroke, for a primary stroke as gauged by the velocity on their transcranial Doppler. Children who have elevated velocities on their transcranial Doppler are deemed high risk for a stroke, and those children at this point are placed on chronic transfusion therapy. There has been a recent adjustment in our management approach with a study that came out of Cincinnati Children’s Hospital called TWiTCH, which looked at our ability to take patients who were getting chronic transfusions in the setting of an elevated transcranial Doppler and switch them to hydroxyurea as an alternate. And that study was basically terminated early because it was very clear that hydroxyurea was not inferior to transfusions in that setting. So we do now have this shift where we’re starting to move patients who are on chronic transfusions toward hydroxyurea.
The other setting in which transfusions are a must is in somebody who has had a stroke. Children and even really any patient with sickle cell disease who has had a stroke is high risk for a second stroke. And time and time again, it has been shown in a variety of settings, in a variety of studies, that taking patients off of transfusions in that setting results in bad outcomes. Those are really the 2 major areas where we use transfusion. The third area is in the preoperative setting to prepare patients for a procedure.
Neil B. Minkoff, MD: Are there any downside effects or adverse effects that worry you about putting patients on this therapy?
Ahmar U. Zaidi, MD: The biggest one we struggle with is iron overload, and that mandates then the initiation of chelation therapy. And we get into that same song and dance of adherence where when you have poor adherence with chelation therapy, then you have organ failure, liver issues, cardiac issues, and that becomes quite a problem. The second issue that we see come up with transfusions is the development of alloantibodies. And that becomes a little bit of a challenge in some patients.
John C. Stancil, RPh: Do you think some providers see a patient who has had an ischemic event and moved to transfusions as a treatment failure to hydroxyurea, where that’s no longer considered as an option or they don’t use it any longer?
Ahmar U. Zaidi, MD: That’s interesting. There was a trial called SWiTCH, which looked at changing those patients who had had a stroke to hydroxyurea, and it showed that you really couldn’t without having bad outcomes. So I don’t know if we can say that it was necessarily a treatment failure, but I think we’ve shown that it doesn’t work as well as reducing that hemoglobin S level to almost undetectable levels.
Neil B. Minkoff, MD: Who moves on to stem cell transplant? Who do you consider for that and what are the ups and downs?
Ahmar U. Zaidi, MD: A lot of that decision making is actually driven by the families. A lot of families would rather seek out a cure than deal with therapy that reduces the severity of their disease. But in short, the candidates for transplant first and foremost require a suitable donor. And most often that suitable donor is a matched sibling. And that seems to be the biggest barrier in having kids go to bone marrow transplant, the lack of a suitable donor.
There has been a push to expand the donor pool with things like haploidentical protocols that allow for parents, for example, to be used as potential donors and cord blood, which we discussed earlier. These issues have allowed us to expand the donor pool. But the biggest issue with bone marrow transplant is, even though we reserve it for often the most severe patients—patients who are repeatedly in the hospital with pain, patients who have had stroke, things of that nature, patients with severe antibodies, alloantibodies, those patients who are most severe—the issue with transplant becomes graft-versus-host disease after the transplant. You always struggle with trading one bad disease for another bad disease.
Neil B. Minkoff, MD: Maria, you manage both sides of the house, the pharmacy side and the medical side. As we talk about the pharmacological therapies and now these medical benefit therapies including stem cell, how do you envision those being managed and integrated together?
Maria Lopes, MD, MS: Yes, that’s a great question, how do you integrate not only medical pharmacy but also the behavioral health component? But as I think as John alluded to before, hydroxyurea nobody manages. It’s a pharmacy benefit. It’s underutilized. If anything, we want it used more, so it’s usually sitting in the lowest tier. In Medicaid it’s usually irrelevant what tier you’re talking about with very little patient cost share. When you get into the higher cost therapies, L-glutamine is a pharmacy benefit as well.
Some controversy on the payer side, one of the challenges you may be faced with, is the compliance on hydroxyurea or intolerance, but also this issue of it is a medical food or is it not a medical food? And as you probably know, Neil, from your past history, if it’s a medical food from a certificate of benefit coverage, payers are usually reluctant to pay for medical foods unless you have an inborn error of metabolism. I would say that some payers still block access based on if it is a medical food, can you get it in a health food store, etcetera, which is perhaps more inconvenience in terms of the amount. But if it’s covered it’s usually pharmacy benefit as well or specialty pharmacy because of the cost.
And then you get into the stem cell transplants, as well as transfusions, which are typically medical benefit. With a stem cell transplant, most payers will have a center of excellence or several centers of excellence where they’re directing the patients to for evaluation. And then, the decision is to proceed if there’s a suitable donor, covered under the medical benefit.
Neil B. Minkoff, MD: But is that usually considered after failure of traditional medications?
Maria Lopes, MD, MS: Yes. I totally agree with Ahmar that usually these are the more chronic longstanding patients for which you’re running out of options at that point.
Ahmar U. Zaidi, MD: That’s right.
Maria Lopes, MD, MS: But there’s a supply issue.
Ahmar U. Zaidi, MD: Absolutely.
Maria Lopes, MD, MS: You’re still limited in terms of what that’s looking like.