Lifelong prophylaxis requires pharmacokinetic profiling, monitoring of factor VIII levels, and adjustments at different stages of life.
Jonathan Roberts, MD: Determining a particular therapy dosing administration frequency requires some investment by the patient, the center, and the patient’s care team to tailor the therapy to their needs. So if, for example, I have an adolescent who’s all of a sudden going to start playing basketball and they’re starting to get some breakthrough bleeds, it does sometimes require some extra laboratory visits to measure their factor level at different times after their infusion, to know when they’re safe for participation so that can be some extra burden of help to the health care system, and to the patient, coming to the clinic or going to their local lab. If they live farther away from our center we coordinate with regional labs as well for patients that live too far to drive to us regularly. So really, it depends on the clinical scenario for patients that are more sedentary. Sometimes, we have done a historical PK [pyruvate kinase] for them, but we don’t need to continually update that because they’re not bleeding. Especially someone that has nonsevere hemophilia, like mild or moderate hemophilia. They may not bleed as often. We may have determined their half-life or whatever factor product they’re on or have put them on a nonfactor product and they’re doing well and not having breakthrough bleeds. And then they don’t necessarily need, in my opinion, to go to the extent to do that formal PK study. But if they’re experiencing any breakthrough bleed, if we’re having any therapy change, it’s a good idea to frequently check and see what the individual’s pharmacokinetic profile is and how we can optimize therapy for that patient.
Pharmacokinetic profiling for patients, when they’re on a factor VIII product, is really to look at the baseline level, the peak, the trough, and the area under the curve, really to look at how factor exposure is in the body. So in hemophilia A with factor VIII deficiency, the bleeding phenotype is very tightly correlated with whatever the factor level is. So we talk about peaks and troughs, an area under the curve. Peak typically is 30 minutes to an hour after a factor product is infused and then the trough is really whatever interval we’ve chosen in that treatment and how low we let the factor level get before there’s going to be another factor bolus basically. And then the area under the curve is obviously how high and for how long does the factor level stay? And with different products that are currently available on the market, all of those parameters can be different in the patient. I’ve had patients try multiple different products and we can look at different software available. There are different clinical tools that we can use that will help us to look at what’s their pharmacokinetic profile of a particular medication. We can look at the interval, we can look and see the dose, you know, Monday morning here, your factor VIII level is this until Tuesday afternoon depending on your activity, and do we need to dose you again, etc. It really depends on whatever product they’re on. Again, some population-based pharmacokinetic tools are available, but they usually require at least a few blood samples from the patient at different time points to help us develop that pharmacokinetic curve.
Patient dosing adjustment for factor VIII therapies usually when patients are adults doesn’t need to happen as often unless, as I mentioned, they’re going to be trying a different factor product for whatever the clinical reason is, However, in children, as I mentioned early on, especially in infancy toddlers school age, it the factor VIII level and their pharmacokinetic profile may change. It’s hard to say how often is really the needed and necessary time to do these PK checks. Usually, we’ll do them when it’s an infant that’s starting we’ll at least get what their peak factor level is so we know how high they’re going on, whatever their dosing regimen is. As I mentioned, their metabolism is faster, so we want to make sure we’re getting them high enough and then usually want to get a level at very various few times after that injection to see how long that factor level is staying in the appropriate therapeutic range. But certainly, once they move from infancy to being a toddler, then school age is another opportune time to look at their PK changing. And then really, once they get to be adolescent young adults, it can change as they move farther into adulthood. But it doesn’t tend to, in my clinical experience, change as much. Usually, by that time patients are more attuned to their home therapy, and so they may even be making minor adjustments without talking to us all the time, speaking from personal and professional experience.
Transcript edited for clarity.