Assessing the Treatment Options for Growth Hormone Deficiency: How to Make a Selection That Is Best for Your Patient

Dennis Chia, MD, pediatric endocrinologist who works at UCLA and program director for the facility’s fellowship program, discusses the different treatment options available for pediatric growth hormone deficiency and how to select the best option for each patient.

Question:

Can you discuss the treatment options for pediatric growth hormone deficiency?

Dennis. J. Chia, MD:

Growth hormone is something that is a natural hormone that we all make; it’s made by the pituitary gland. Then usually I’ll describe a little bit about, some patients don’t make it as well. Classically it’s in the order of 1 in 5,000 people have growth hormone deficiency. Although admittedly, how the testing for growth hormone deficiency and if somebody makes less than they should is a little bit hard. It’s very gray about that. We’re really good about defining those who have really quite severe deficiencies who’ve fallen off, or really very short of falling further over time. For individuals who have milder but still clinically significant in a way, growth issues, whether they have a mild defect’s a little bit hard. Regardless, our treatment then is essentially replacing the growth hormone that they should be making. We have, as a product, something that’s essentially identical to what the body makes.

A long time ago in the pre-1980s, let’s say, it was in limited quantity, and now that’s no longer the case. It’s a recombinant protein. We can make as much as we want for lots of different reasons. Some economics, societal that balance a lot of different things. It’s still very expensive and there’s nuance about how we prescribe it.

Our treatment option for growth hormone deficiency, again, for the past 40 years has been growth hormone replacement with daily growth hormone shots. In the past 3 to 4 years, there have been new preparations with different pharmacokinetics that essentially have that same growth hormone action, that they work identical to what growth hormone would be doing. But the release pattern is such that it allows us to take advantage of instead of doing a daily injection, we can do weekly injections. The idea being beyond that is, one of the issues in terms of getting the optimal result from somebody that we treat is compliance.

We all know that for the things that we might have to do, but it’s hard to remember every day that it’s an injection. For a child, it’s a thing about getting past that, so it might be an extra barrier even. Remembering and that it’s injection, that’s sort of a combination of things. The weekly preparation, a look to address that, then we’re more likely to get a regular. If we do just once a week, then we’re covered. Instead of doing this daily thing that causes us some pain and a stress and things we’re getting away from that. That’s sort of the newer ideas.

Question:

What are the different delivery methods through which growth hormone therapy can be administered to pediatric patients, and what are your thoughts on the options?

Dennis. J. Chia, MD:

In terms of efficacy about how well the growth hormone works, as long as it gets to where it’s supposed to go, my general feeling is that they’re all essentially identical. It gets into the system. It’s like hormones do, travel through the bloodstream. They act on receptors, they elicit their biological effects from you. There are several companies that make growth hormone. Again, up until recently, they were all daily preparations that were available. What’s different about the companies was a little bit about the marketing and what the device administration was. Eventually, like I said, it needs to get into the system, whether that’s by a traditional syringe that you kind of draw up or that it’s by a pen device. Whether the pen device injects through a needle versus [we] used to have one that didn’t have a needle, but it had a burst of air that kind of pierced the skin. Eventually, if it gets in, it’s all the same.

There’s a little bit of patient and family preference with respect to that, but for the most part, I don’t have strong preferences for any of those sort of options. I think that they all work. For each individual, if they experience that, the one that has been prescribed is very difficult for them, I think to kind of talk through, there’s another thing that might be an alternative, certainly makes sense.

Then that’s where the longer acting ones have come in, and how do we balance that whenever we have something new in medicine that’s replacing something that’s still working very well? For the most part, replacing means we’re not looking for it to be superior per se than the daily. We’re looking for it to be equivalent and to be as safe. The studies have been done and they’re FDA-approved about like this, but it’s still new. There’s someone who’s more conservative could be like, “I’ve been using this sort of daily product for the past 20 or 30 years. Now you say you have this one. I feel like this one people have done really well with, and if it were my child, I would just stick with this one.”

There’s not really a right answer to how we balance introducing something that’s new into that versus if we totally felt comfortable with, we knew what the safety profile was, we’ve been doing it now for 30 years and it’s identical. We don’t see any difference in that. Then yeah, obviously there are advantages to doing a weekly versus to doing a daily. How that balances through and what individuals feel comfortable with.

Regarding an oral, currently there’s not one available. The way I usually describe this growth hormone is a protein. In a simplistic way, to me, if you took a protein that’s relatively large orally and it went through your digestive system, it’s going to get broken down into amino acid, and not look different than a protein shake that you had, than a hamburger that you had. It’s going to lose its biological activity. We escape that by giving it as an injection.

There are some things that are coming out that are, I think, not actually growth hormone, but are different preparations which would help induce growth hormone production that might have the same effect. I think it’s going to be similar to what I mentioned about long-acting growth hormone. What’s the data about efficacy? How good do we feel about safety? If those are all non-issues, then yeah, certainly in oral we could see advantages to that to doing, whether it’s a weekly or certainly daily administration.

Question:

How do you talk to families and patients about these treatment options and guide them in the selection process?

Dennis. J. Chia, MD:

I do think it’s the provider. How you frame things can certainly make a difference. Again, I think some of us are probably more conservative than others. Prior to the long-acting growth hormones that were available, what I usually tell families is that there are, whatever the number is at that time, 5 different companies that make growth hormone. In terms of which of those I choose, and some of this frankly is just to make it easier on me and feel like I don’t push out biases, and even ones that are unconscious in terms of how I prescribe. But my usual thing is, I feel like in terms of efficacy, if they get in, they all work the same. What do I make my decision on? Typically, the logistics are, what is your insurance, and is there a preferred drug for your insurance? What is your out-of-pocket cost?

Beyond that, if you express to me that, “I really prefer this brand. Oh, I’ve had the success with that brand with other things. I think their social mission is really great.” I’m happy to write for anything. I think that, again, they’re equivalent. It’s really just the issue of what’s the coverage, what’s the out-of-pocket for you, and how does that balance with things?

Beyond that, I really, for the different daily preparation, I sort of consciously don’t go into details about any preferences consciously, to avoid the unconscious bias that I introduced. Now if you look at my thing that somebody has access to, I prescribed 80% this versus 10% this or something like that. I haven’t actually ever seen those numbers, but I wouldn’t like that reflected on me, I guess I would say.

In terms of the long-acting preparations, the way I usually frame it is, it’s similar to what I just told you. I should tell you the truth, probably I’m a little bit on the conservative side with this. Actually, a little bit has to do with my own background with I’ve done some growth hormone research in the past. I know maybe a little bit more than the most pediatric endocrinologist about or think a little bit more about replacement and what normal profiles of growth hormone are. I present it as if it’s FDA-approved, it means that there are studies that have shown efficacy and safety through that, but it is new, and it’s not like people don’t continue to follow things after they’ve been released. It’s not like they’ve ever been medicines that have been FDA-approved, but once they’ve been released we start seeing things and then come off the market. That sort of idea.

I do have some of my own biases about that dailies work well. I’m comfortable with that. I’m shifting a little bit, and I think this is probably similar to lot of people. The longer they’re out, the more we’re doing. What becomes the norm, what’s the community norm, that there’s more data that we sort of shift. Again, it’s hard not to appreciate that if they’re equivalent, like we really know that they’re equivalent in terms of safety and things, that a weekly is going to be easier.

The dosing options, there are some that are logistical, in that, I think, one of the companies makes, their product come in set doses. It’s sort of like a quantum, you have to choose between. It goes up, and then 20% more. Rather than you can dial to smaller amounts. There’s a little bit of that.

In terms of dosing consideration, I think it’s really just experience. Usually, when I talk with my families that I’m following with growth hormone deficiency that I’m treating is, for the most part, as you’re following up, what am I doing? I’m looking at your growth. I’m making sure there’s no side effects. What’s the main medical decision I’m making is like, should we adjust your dose at all?

How do we decide on dose adjustments? I go over and I actually, not everybody does it the same, I probably use all 3. I say it’s some combination of, in pediatric medicine in general, most things are weight-based. Looking at what’s your dose for weight, and then looking at outcome. If we’re looking at high data as an outcome, how are you growing? That one is a little bit tricky, because you could be growing well, could you be growing more? Are you growing okay, but if you did more, would you be growing more? That sort of thing. It’s a little bit harder now.

Then the last is laboratory based studies to kind of influence things. That’s looking at the markers for growth hormone. The main one we look at is IGF-1. I would say the last one is the one that with the newer medicine, it’s not as automatic about how to do that, because they’re new. We used to check, and again, some providers more than others would use that as quite religiously about, “Oh, here’s where we’re targeting. If you’re not at that target, even if you’re growing really well, we’re going to try to push it. If you are above where I feel comfortable, we’re definitely going to cut it down” etc.

With the kinetics of the new one, when to check that, and how we were relate it to what we’re more accustomed to looking at isn’t automatic for people. There are certainly algorithms that are out there that we can use. I’ve used them a little bit. Is it a factor? I mean it’s a little bit, but for the most part, at least for myself, I don’t use that as the main factor, or the sole factor, I should say. It doesn’t really make that much a difference. If a patient is on a smallish dose, and if they’re not growing as well as I think that they might be, it would be a relatively uncommon occurrence that their lab testing would say to me we shouldn’t be on a bigger dose.

I think for the different injection devices, I probably don’t have as much of a preference. I guess it’s again, more the logistics of what a family can have available to them or valuable retention is lost. I really try to present the long acting data to families as well, because I put it out there, and I also don’t want to minimize what they go through. I think for them, if it’s much better, I think I’m going to weigh that. It’s not like I’m uncomfortable with it. It’s just like kind of put that out there. What are you interested in?