The Significance of Patient Age in Treatment and Management of ITP

A commentary on the significance of the patient’s age in treating and managing ITP.

Transcript:

Howard Liebman, MD: We now have 4 population-based studies, beginning from the United Kingdom, from Korea, from Japan, from Denmark, Sweden, and Norway, that say that, in fact, there's an early disease—which is Cindy's realm—which is the pediatric population, slightly male dominant. Most of the cases, maybe 75%—at least what I read in the literature, since I'm an adult hematologist—go into remission. Starting around puberty, we see a shift and a period of what I was once told is this disease of young women. In reality, yes, they are predominantly women in the childbearing years, but beginning about the age of 50, the actual incidence rises and the total population—because this is a chronic disease in many cases—the prevalence is predominant in a population of older individuals.

Age is a very important aspect in thinking about how I'm going to manage [disease in] patients. First of all, there are 2 real choices in steroids nowadays, and they've been studied in randomized trials and there have been many analyses as well. That is dexamethasone—high-dose dexamethasone, 40 mg a day for 4 days, and there is prednisone. When you really look at the data, there's no difference in the outcome at 6 months. The only difference—which may be important—is within the first 14 days of the midanalysis, you're more likely to get a response with a platelet count above 50,000 as defined by a good response, or literally a doubling if we use the ITP [immune thrombocytopenia] International Working Group criteria, which is doubling of the platelet count above 30,000. That's significant if the patient presents with bleeding manifestations and very low platelets. If you use dexamethasone but have additional problems, If your patient is an elderly patient who has diabetes type 2, he's going to have hyperglycemia; they get a lot more sleep disturbances. There can be frank psychosis in older patients receiving high-dose dexamethasone. I've seen that.

Altogether, I think you have to look at the patient, but on the other hand, remember, the data is pretty clear now that older patients have more bleeding manifestations and are at a higher risk of bleeding. They're the ones to more likely have the rare complication. I emphasize the rare complications or episodes of bleeding. I'm going to have to balance all those factors when I choose whether I'm going to just do prednisone a milligram per kilogram to dexamethasone, or maybe, in fact, use IVIG [intravenous immunoglobulin]. The issue there is that there's data that's saying that in fact, the 1 gram per kilogram dosing, now this comes from actually the neurologic data, is associated with increased vascular events, particularly in older patients. There are arterial vascular events. I don't want to give my patients a stroke, yet the response rates can be just as good if we use the historical control by Paul Limbach, which is 40 mg per kilogram a day with less of the vascular events. Again, for older patients, I tend to use the lower intravenous hemoglobin combined with steroids, and for healthy, younger patients with very low platelets, I may want to use the gram-per-kilogram dosing. You have to look at the patient totally. Age, bleeding manifestations as Danny mentioned, and you have to talk to them about the tolerance. No matter how you treat them with steroids, the low dose or the high dose is going to have psychological and sleep disturbances and other factors that are important, but we don't want to go long term on steroids because then you add on the problems of diabetes, hyperglycemia, increased risk of infection, obesity, and other problems.

Morey Blinder, MD: I think those are all good points. I think the age-related issues and the nuances of initial therapy are important and something to consider even for first-line therapy where we think we have a pretty good answer with some combination of steroids and/or IVIG.

Cindy Neunert, MD: I would love to come back to Howard's point about age because it really is, as we're talking, clear we have other ITP, kind of the classic presentation where it comes on very quickly. It's very likely to resolve. Bleeding rates are very, very low in that population and that's the population in which our guidelines really suggest that our goal of treatment is to let the child kind of naturally resolve unless we have very acute bleeding that we need to be treating. We don't even really take the platelet count into consideration there. In the adult guidelines, we do have some kind of goals and criteria for our platelet counts surrounding this 20,000 [or] 30,000 as initiating treatment. To Howard's point, maybe that number is more appropriate for the elderly patient or patients with lots of comorbidities or other risk factors for bleeding. What we really don't know about is sort of the AYA [adolescents and young adults] population, and where they cross over. I always say if an 18-year-old walks into the ED [emergency department], they're going to get admitted to my service, and I’m going to treat them a certain way. If they go to the hospital down the street, that same patient would end up in the adult ED and may likely get very different treatment. I think a population that really merits some investigating is this adolescent and young adult population where they may be treated as an adult, but perhaps not all adults need the same degree of treatment needed by that other group of elderly patients or patients with comorbidities and other medication risks or fall risks for bleeding. I think there's still a lot that we don't know about age stratification and how to think about our initial therapies when there's overlap.

Morey Blinder, MD: That crosses my mind as well from the adult side of the street where I see an 18-year-old and I hope they have the pediatric form of ITP that'll get better, but in my experience, most of them do tend to behave a little bit more like an adult ITP.

Cindy Neunert, MD: Absolutely.

Morey Blinder, MD: In that same sort of vein, are there patients where you would defer therapy? Is it related just to the platelet count, or are there any other issues where you might qualify for observations rather than an initial treatment? Cindy, do you want to start, since it might affect you most?

Cindy Neunert, MD: Yes, I was going to say that I think for us, this is actually a very common treatment approach, but again, it comes back to the fact that in pediatric patients, we know that the risk of bleeding is very, very low. We have a very good kind of natural history data there to let us know that even at a very low platelet count, even less than 10,000, the majority of children will do fine. We also know that the course is going to be very short. Basically, 50% of the children will even have a normal platelet count within 6 weeks. It's very, very different than dealing with a chronic condition, one in which you're trying to do things up front that might also alter remission rates, although I'm not quite sure we have successful therapy yet in the adult realm even for that. We do observation quite frequently. It is the recommendation in children with no or minor bleeding that you can feel comfortable just doing observation and letting them try to recover on their own.

Transcript edited for clarity.

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