Ahmar U. Zaidi, MD: As far as preventive therapies go, hydroxyurea is the mainstay of therapy in sickle cell disease. And hydroxyurea is quite an interesting drug that has been studied very extensively for quite some time. It’s a medication that we suggest using in individuals who are 9 months and older with either sickle cell hemoglobin SS type or sickle cell S/beta-zero thalassemia. The data surrounding hydroxyurea in the pediatric population come from a study called BABY HUG, which has followed individuals for quite some time showing the reduction in the majority of complications associated with sickle cell disease. The MSH study, which was the multisite hydroxyurea study, published in the mid-’90s, gave us the same data in adults. And that was a game-changer for us. So we try to initiate hydroxyurea therapy in our children at the youngest age possible.
Neil B. Minkoff, MD: Which is?
Ahmar U. Zaidi, MD: Nine months. So 9 months old is the bare minimum that they have to be. Hydroxyurea is a medication that works by providing a little bit of toxicity to the bone marrow. It’s what we call a ribonucleotide reductase inhibitor, and that causes a little bit of marrow stress and marrow toxicity. So the adverse effect profile of hydroxyurea is something that is discussed very prolifically with patients. We spend a lot of time discussing the adverse events and possible bad outcomes with hydroxyurea. And unfortunately, that’s resulted in some issues with adherence and patient comfortability, the patient’s comfort with hydroxyurea. We do struggle a little bit as the provider to keep patients on hydroxyurea. It requires pretty intense monitoring, requiring the patient to come to clinic about every 6 weeks.
Neil B. Minkoff, MD: What are your expected outcomes if you get them?
Ahmar U. Zaidi, MD: The expected outcomes are increased survival as an overarching principle, decreased pain, and a reduction in stroke incidence. Really the benefits of hydroxyurea cannot be overstated. It is definitely a medication that will keep patients out of the hospital. The most recent trial in hydroxyurea was actually the REACH trial, which happened in sub-Saharan Africa. And it showed a tremendous level of adherence in the 90% range, and the patients in that cohort did tremendously well. It was a very eye-opening study that was recently published and really shows that if you take your hydroxyurea and you stay consistent with it, you really can have good outcomes.
Neil B. Minkoff, MD: And you mentioned starting at 9 months. But there’s Siklos for children 2 and older. What’s the advantage of that?
Ahmar U. Zaidi, MD: It’s a formulation difference between what we typically use in pediatric populations, which is the compounded solution, which is sometimes difficult to access because it requires a compounding pharmacy. It requires a lot of work behind the scenes, and patients may not have access to that compounding pharmacy able to deliver that solution. Siklos has been interesting in providing a low-dose capsule that allows us to start minimizing the necessity of a compounded approach.
Neil B. Minkoff, MD: Could you tell us how you would define a patient who failed hydroxyurea?
Ahmar U. Zaidi, MD: For me a patient who has failed hydroxyurea would be categorized as somebody who has had hematologic toxicity at doses that are known to be safe that are very difficult to manage, number 1. Number 2 would be people who have had other adverse effects like abdominal discomfort, nausea, or vomiting, which seem to be the most common ones that limit our ability to use hydroxyurea. I would say it’s really between those 2 complications, the bodily adverse effects like gastrointestinal distress in combination with the hematologic toxicity that hydroxyurea is known to cause, sometimes disproportionately in certain patients.