TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
This week's topics include falls and mortality, orphan drug profits, peanut allergy treatment in young children, and does 24-hour blood pressure measurement reveal more than office-based measurement.
0:42 Blood pressure in the office or ambulatory, and mortality
1:42 Almost 60,000 patients
2:42 Even if not 100% its beneficial
3:42 Involve patient in care
4:00 Treating peanut allergy in very young children
5:02 67% of treatment group reached endpoint
6:05 Amount of peanut on skin 1/1,000 of a peanut
7:01 Orphan drug profits
8:01 Through December 2016 initially
9:03 Gene therapies are orphan
9:20 Trends in deaths from falls in those 65 plus
10:20 Age adjusted mortality rate
11:20 More falls recorded recently
Elizabeth: Treating peanut allergy in very young children.
Rick: Are orphan drugs lucrative for pharmaceutical companies?
Elizabeth: Falls among older people and mortality.
Rick: And does 24-hour blood pressure measurements tell you more about mortality than clinic blood pressure measurements?
Elizabeth: That's what we're talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I'm also the dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, how about if we turn right to The Lancet? This is really a big study and this issue of, gosh, what does your blood pressure tell us about your risk of dying?
Rick: It's clear to everybody that elevated blood pressure puts you at risk for things like cardiac disease, stroke, kidney disease, and increased mortality. But there are different ways of measuring blood pressure, one of which is just to take a blood pressure in the clinic. We know that if done properly, that some people have what's called white coat hypertension. Their blood pressure is elevated in the clinic, but throughout the day it's normal.
Conversely, there are some people whose blood pressure may be normal in the clinic. But if you measured it throughout the day -- that is, doing a 24-hour ambulatory blood pressure where your blood pressure is measured every 20 minutes while you're awake and every 30 minutes while you're asleep, you get many more measurements. The question is, does that ambulatory blood pressure measurement tell you more about mortality than clinic blood pressure measurements?
These investigators did an observational cohort study over a 10-year period called the Spanish Ambulatory Blood Pressure Registry. Almost 60,000 patients now had clinic blood pressure measurements and ambulatory measurements.
What they discovered was about 12% of the patients died and about a third of those from cardiovascular disease. The ambulatory blood pressure measurement was much better at predicting who would die. In fact, when they compared it to the clinic, it was about 5 times better at informing who was more likely to die. When they looked at daytime ambulatory versus nighttime, the nighttime was about 6 times more effective in informing who might die over that 10-year period. What about white coat hypertension? It wasn't associated with an increased risk of mortality at all.
Elizabeth: I'm wondering about the practical aspects of trying to measure somebody's blood pressure at night, even the 24-hour notion.
Rick: Not everybody had 100% of the measurements, but they had enough of the measurements where you could ascertain whether the blood pressure was elevated or not during daytime or nighttime. We know that it cycles throughout the day. The blood pressure is highest between 6:00 and 10:00 in the morning. It goes down its highest between 4:00 and 6:00. This is a diurnal variation. Do most people tolerate the blood pressure measurements? Most do fairly well. Even if you can't do it 100% of the time, any of the incremental information is beneficial.
Elizabeth: As you're aware, there is a lot of resistance to the idea that patients themselves should be able to add information to their medical record, especially actionable information like blood pressure measurements. I'm wondering about how we might integrate patients themselves into this effort because this sounds like this is a really important measurement.
Rick: Yes. First of all, even though this shows that the ambulatory blood pressure does a better job of predicting mortality, this study doesn't address whether treating based upon ambulatory blood pressure measurements is any better.
Apropos to the question you asked, all my patients now with hypertension have a home blood pressure monitoring device and they always bring that information to me. They collect it for 2 to 3 months, and we always enter it into the medical record. I really do think that that will free up the physician and healthcare providers to do what they are uniquely able to do, and also help the patient be involved in their healthcare.
Elizabeth: Maybe reduce some of the recidivism that's apparent with blood pressure medicines.
Rick: Certainly, if a person has to report blood pressure measurements to their doctor all the time and they're interested in getting good results, they are more likely to take their blood pressure.
Elizabeth: Let's move on to the New England Journal of Medicine, this ongoing issue of peanut allergy. Two percent of children in the United States and Canada have peanut allergies, and the prevalence has risen rapidly over the past 20 years. Previous therapies -- including feeding little, minute amounts of peanuts to kids who have this allergy over time -- are pretty good at helping to ameliorate this. They have also looked at this therapy in older children.
This is a study looking at toddlers 1 to 3 years of age with peanut allergy confirmed before entering this study. This is a phase III, multicenter, double-blind, randomized, placebo-controlled trial.
They randomized these kids 2:1 to receive this epicutaneous immunotherapy -- so a patch that allows them to be exposed to this peanut allergy through their skin, versus placebo. This was administered daily for 12 months. They had 362 patients who underwent randomization and just about 85% of them completed the trial.
They saw that 67% of the children in the intervention group -- as compared to 33.5% of those in the placebo group -- reached their primary efficacy endpoint. More about that in just a second.
There was a high rate of adverse events and adverse events were writ large. Those included just skin kinds of reactions, but also some more severe reactions. They occurred in 100% of the patients in the intervention group and 99.2% of the patients in the placebo group. They also did note that treatment-related anaphylaxis occurred in 1.6% of those in the intervention group and none in the placebo group.
However, the upshot of this is that for these kids 1 to 3 years of age with peanut allergy, this epicutaneous immunotherapy for 12 months absolutely resulted in desensitizing kids to peanuts and increased their peanut dose that would trigger allergic symptoms.
Rick: The amount of peanuts they were putting on the skin was one-one thousandths of a peanut. The first time they did it, they did it under medical observation for 3 hours to make sure that kids didn't have a severe allergic reaction. Then they gradually increased the dose and, as you mentioned, kept it there for a year.
This epicutaneous patch has been proven to be effective in kids between the ages of 4 and 11. In kids younger, the only thing we really have is oral therapy. Two-thirds of the kids were able to tolerate a large dose of peanuts without having a severe reaction.
Elizabeth: This to me sounds like a really practical thing to do. I wonder if it is better. I'd like to see a head-to-head comparison with simply feeding peanut.
Rick: Yep. When you feed them, it's an arduous cycle of getting kids to eat them. It's a little bit easier when you just have to slap a patch on and leave it there for most of the day. It would be interesting to see what the cost is for this, Elizabeth. I agree with you: a head-to-head comparison would be nice at some point.
Elizabeth: Let's move on to JAMA, a research letter taking a look at orphan drugs.
Rick: A little bit of background on this. What was discovered in the '70s and '80s is that even though pharmaceutical advancement, research and development in pharmaceutical agents was developing, there were a lot of people that were being left out, people that have rare diseases. The pharmaceutical companies weren't willing to spend the money to do the research and development for those particular drugs.
In 1983, the Orphan Drug Act was enacted to provide incentives for the pharmaceutical companies to invest in developing prescription drugs that target these rare diseases. Right now we define a rare disease as affecting less than 200,000 individuals. The incentives were, they protected the drug for at least 7 years and then they provided about 50% of the funds for the research and development of the drug. We've had a couple of decades now of orphan drug development.
What's the sales look like? They identified drugs first marketed from January 2008 through December of 2016 with 5 years of follow-up through 2021. They identified 315 newly-marketed prescription drugs. One-fourth of them were orphan.
The sales of the orphan drugs was not any different than the sales of the non-orphan drugs. The revenue for orphan-designated drugs with one indication was $717 million. It ranged from $284 million to $1.7 billion.
For those that had multiple indications, as much as $1.2 billion in sales. For those that weren't orphan drugs, the 5-year net sales was approximately $812 million. It's really very close. Perhaps because they're charging as much as 7 times more than the price for non-orphan drugs, we should require them to repay some of the tax credits.
Elizabeth: Absolutely, particularly since the basic science is funded by public dollars to begin with.
Rick: Well said, Elizabeth.
Elizabeth: Right now, of course, we have a number of gene therapies that are on the threshold of being practical for what are admittedly rare diseases. Do these fall under this designation also?
Rick: They do. Biologics, small molecule, traditional or accelerated approvals, oncology drugs, non-oncology drugs, and even different routes of administration.
Elizabeth: Finally, another research letter from JAMA and this is looking at trends in deaths from falls among adults aged 65 years and older in the U.S. between 1999 and 2020. Falls, hip fracture, a procedure relative to that is often followed by death. That's a trajectory we've noted many times in this podcast.
In 2020, this research letter cites, there were 42,114 deaths in the U.S. that were related to falls, and 86% of those occurred among adults aged 65 and older. Falls are the leading cause of injury and among the leading causes of death among older adults in the U.S.
The really bad news is when you take a look at the trajectory those trends and deaths from falls are increasing. This study then further examines how is it doing relative to sex, race, and ethnicity during those years.
They used the CDC's WONDER platform to take a look at this and they calculated these age-adjusted mortality rates. What they found out is that age-adjusted mortality rate was highest for men across this period. It was highest among white people, followed by American Indians or Alaska Natives. This is one of the few times that we note that the risk is higher for Caucasians than it is for other ethnicities. When we take a look at magnitude of the increase, it was highest among women and white older adults.
Rick: It's clear this is a substantial problem, especially for elderly individuals. Some of the limitations in this particular study is this is all done from coding. They looked at the hospital records and they said, "Here is a record of the person who had a fall. Here is a record that the person died." There is a lot of other information missing. What other comorbid conditions did the patient have? Did they have a stroke? Did they have severe diabetes, or obesity, or a cardiovascular disease? Have they fallen before? Were they on blood thinner medications? Where did they fall, by the way?
There are more falls recorded more recently than previously. It looks like the age adjusted-mortality rate has gone up. We do need to address falls, there's no question about it, but the overall issues are, what are the surrounding circumstances that contributed to that?
Elizabeth: I agree. I mean, I think more specific information relative to all of the things that you've identified would be very helpful. Having said that, I would also say that even among hospitalized patients, this is a huge problem. We have also reported on the benefits of things like tai chi and helping people to maintain their balance and try to avoid falls. I would like to see this translated into more interventions, especially those that we already know are helpful.
Rick: When you say intervention, you're talking about specifically prevention -- that is, things that maintain muscle tone, things that maintain stability, and things that maintain ambulation. It can even be something as simple as having glasses where you can see what's going on and outfitting your home.
I agree with you. We need to look at this holistically. Things that we can do to prevent falls are things that improve overall health as well.
Elizabeth: Excellent public health message. On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.
Rick: And I'm Rick Lange. Y'all listen up and make healthy choices.