Best Practices for the Treatment of Hemophilia - Episode 5
Practice Pearl 2: Determining the Role of Factor VIII
With a review of the available treatment options, the panel moves into practice pearl #2, specifically factor VIII.
Luigi Brunetti, PharmD, MPH: The next clinical pearl that I'd like us to cover today is identifying the different treatment options available for prophylaxis. When is it that you choose factor VIII concentrate for prophylaxis?
Robert F. Sidonio, Jr, MD: We're all going through this shift right now in therapy, and it's interesting. We were at a meeting not that long ago, and I've only been doing this for about 10 years, but it was interesting, the question that came up, do we even need factor VIII anymore for hemophilia A, which seemed like an insane question. Ten years ago nobody would have said that. But now you're seeing people feel comfortable with the idea that maybe we don't need a factor VIII product to replace the deficiency, which is factor VIII deficiency.
And so, the majority of our patients are still on standard half-life, or extended half-life, factor VIII products. The patients who are on there are the ones who are doing relatively well. And some patients have this mentality, "I've been on this product for 10 years, I've had very limited joint bleeds. I'm locked into my rotation. I know what to do. I get up in the morning, do the infusions." They feel very comfortable and safe. And so obviously if they're doing well, they're not having lots of emergency department visits or having issues or having joint problems, we don't feel the need to push them into any new therapies.
We obviously discuss all the emerging therapies, and there are so many of them that are coming in the next few years, including gene therapy. But the standard is still for us to strongly consider factor VIII replacement in these patients. We do have a clinical trial that we're opening soon looking at Hemlibra [emicizumab-kwah] for infants as prophylaxis. The label does have it available for newborns as well. And I know my colleagues have started some patients on that early in their life. But we're trying to collect some of those data uniformly so we can show that it's a pretty reasonable option.
Luigi Brunetti, PharmD, MPH: Factor VIII concentrates will still have role regardless in the management of acute disease.
Robert F. Sidonio, Jr, MD: Of course.
Luigi Brunetti, PharmD, MPH: And I'm sure, Dr Slocum, that's probably what you encounter in the emergency department.
Giles Slocum, PharmD: Exactly. I completely agree. The factor VIII products are used for acute bleeds, where we need to be able to get levels up relatively quickly, levels that we know we have these pharmacokinetic responses to and recoveries. That's primarily where we see the use, whether it's in the emergency department or in our short-stay units in the operating room [OR] pre-operation, post-operation. So we haven't really tiptoed into that world of extended half-life or these longer agents quite yet in this patient popullation with acute bleeds.
Luigi Brunetti, PharmD, MPH: And some of the adverse events that you encounter with factor VIII products, what have you encountered, or what have you see?
Giles Slocum, PharmD: Realistically, there is a relatively minimal adverse effect profile with it. It’s up to the patient preference and the rate of infusion of these intravenous [IV] pushes that we use. But again, 1 to 2 minutes for most of these products is fine, so that typically is the big thing. Inhibitor production is something I’m sure we’ll address a little bit as well, but that would be an adverse effect potentially of some of these products that we’re infusing. I don’t know if you have others.
Robert F. Sidonio, Jr, MD: Inhibitor development is the main thing that still remains a challenge. Like you said, there are relatively minimal blood clotting complications. There are some issues in the people with central lines. But usually if you have a relatively good center, they’re managing the dose, and that’s where you work with a pharmacist to make sure you’re following these levels closely and you don’t let the levels get astronomically high.
In children, with the dosing, we don’t worry as much if you’re overshooting a little bit or undershooting. But in adults, if you have an obese patient who is a smoker with heart disease, you’ve got to be a little tighter on the management of the factor VIII levels. So having a good laboratory, working all together to take care of the patient, and making sure you’re giving just enough factor VIII and not more, is important.
We were talking about how using continuous infusions can be helpful because you can dial in to the level that you want. But outside of that, things like anaphylaxis are relatively rare. You see those in some of the newer products. But again, that’s a pretty rare complication. The biggest thing that we see now is inhibitor development, which nobody has seemed to be able to develop a factor VIII product to closely eliminate the risk. They’ve been able to reduce it slightly but not enough to the satisfaction of patients.
Luigi Brunetti, PharmD, MPH: And you know, we already spoke about the administration. And correct, it is intravenous, but it still requires IV access, so that’s something to consider. And from what I understand, the adverse effect profile is relatively benign, right?
Robert F. Sidonio, Jr, MD: Yes.
Luigi Brunetti, PharmD, MPH: You can have infusion-related type reactions, maybe fever, chills, that sort of thing. But generally, those are pretty easily supported and rare; again, anaphylaxis is rare.