TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, 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 treatment of spinal muscular atrophy in infants, treatment of cytomegalovirus (CMV) infection in pregnancy and infant outcomes, complications of type 2 diabetes in youth, and the optimal time span for aromatase inhibitor treatment in postmenopausal women with breast cancer.
1:02 Complications of type 2 diabetes in youth
2:05 Many complications, at least one in 60%
3:05 Medications, a third one now
4:05 Noncompliance increased to 80%
4:15 How long should aromatase inhibitors be used?
5:15 Five years no better than 2 years
6:15 Treatment of type 1 spinal muscular atrophy
7:15 Increases a protein in the blood
8:17 $340,000 per year for treatment
9:18 Trial of hyperimmune globulin to prevent congenital CMV infection
10:18 Did not result in lower incidence of infection
11:30 Preterm births increased in treatment group
13:00 End
Transcript:
Elizabeth Tracey: Can treating cytomegalovirus infection during pregnancy protect infants?
Rick Lange, MD: A new treatment for progressive neuromuscular disorder in infants.
Elizabeth: What is the optimal amount of time to take an aromatase inhibitor for women who are being treated for breast cancer?
Rick: Is type 2 diabetes in youth really a big problem?
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: I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, I think for the first time in these 18 years that we've been recording we are going to cover only papers that are in the New England Journal today. I'm going to say that once and I won't say it again, as we move from study to study. Because you started with type 2 diabetes in youth, is it a big problem? I'm going to suggest we go to that study right now.
Rick: Now when I say it's a big problem, we know that the incidence of type 2 diabetes is increasing in the United States. For example, from 2002 to 2012, the incidence increased about 5% per year. That's due to a couple things. One is obesity in youth, but pathologically it's due to the development of insulin resistance and deterioration of the cells in the pancreas that actually make insulin. OK, so what? We have more kids that have diabetes, but what are the long-term complications associated with it? That's what this study attempted to address.
It was a multicenter clinical trial from 2004 to 2011 that actually evaluated three different types of treatment. After the completion of that study, they decided to follow these youth from 2011 to 2020.
They assessed the incidence of diabetic kidney disease and hypertension dyslipidemia. Here is what they found out. There were about 500 participants aged about 26. They were young, but they've had diabetes for about 13 years. Again, this is type 2 diabetes.
Cumulative incidence of hypertension was 68%, about 52% had dyslipidemia, 55% had diabetic kidney disease, and 32% had nerve disease. About 51% actually had eye disease as well. At least one complication occurred in 60% of these individuals and at least 28% had two complications. This is more than the complications associated with type 1 diabetes in the same age population.
Elizabeth: I was absolutely horrified by this study in just looking at all of that in people who aren't even 30 years old yet. Clearly, they established in this study also the relationship with BMI, but they also showed that varying ethnicities were also impacted disproportionately.
Rick: Right. Elizabeth, I agree with you. They were more common among participants of minority race and specific ethnic groups. This tells me we really have to get this under control.
Elizabeth: We absolutely have to get it under control. It's daunting to consider what those outcomes might be for these folks. Additionally, they describe the polypharmacy that a lot of them were on.
Rick: Here is the unusual thing. In youth, there were only two medications approved to treat type 2 diabetes, metformin and insulin. I said two. There is actually a third one, the GLP-1 agonist. But we probably need to be very aggressive in terms of managing the risk factors because these contribute to the complications that I mentioned.
Elizabeth: No question about that. But I guess what my point is that, gosh, at the ripe old age of 27 you're going to end up on an oral med plus insulin to manage your diabetes. I mean, I think we really need to go back to weight loss, exercise, diet control, and all the other things that we know help.
Rick: Elizabeth, your point is well taken. The other thing we didn't mention is this is a group that compliance is a real difficult problem. Because when you're 26, you feel like you're immortal, or less likely to be adherent. They showed this, because when they looked at the individuals that had poorly control diabetes, looking at hemoglobin A1C, this increased over the 15-year follow-up. It increased from about 25% with poorly controlled sugar to 80%.
Elizabeth: Let's pay attention, I hope. Turning to another study that also affects quite a large number of people, this is the question of how long should a woman who has been treated for breast cancer, postmenopausal breast cancer, remain on an aromatase inhibitor. It's been a place of active investigation.
These were women who, as I mentioned already, were postmenopausal and had hormone receptor-positive breast cancer. This is a phase III trial where they assigned women who had received already 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor, anastrozole, for an additional 2 years or an additional 5 years.
They had 3,208 participants and they looked at, of course, disease progression or death. They also looked at the other really clinically important outcome, which was bone fracture.
Well, all right, what about aromatase inhibitors? What happens to people when they're on them? It's also not insignificant. They have hot flashes, arthralgias, and bone pain are more frequently reported by people who are taking these drugs.
Basically, the upshot was that 5 years was no better than 2 years. But those women who were taking the aromatase inhibitor for 5 years did experience a higher rate of bone fracture. It suggests at least to me that 2 years is just fine thank you very much, if you want to extend it.
Rick: These women had already received 5 years of treatment with either tamoxifen or aromatase inhibitor therapy. That's in addition to either they had neoadjuvant chemotherapy or they had radiation therapy, or they had the breast cancer removed. Elizabeth, I would have thought that the additional 5 years would have been beneficial, but it wasn't.
Here is why this study is particularly important. It's because many of the cancers that recur, recur 5 or more years after the initial therapy. That's why extending it for another 2 or 5 years had potential upside. It's nice to report that 80% of these women that were in the study did not have progression, that is they did not have recurrence of their breast cancer or did not have death due to it. It highlights the fact that the women need to be continued to be followed. We need to find additional therapies for those 20% who have recurrence.
Elizabeth: Indeed. Let's turn to your next one, which actually affects a very small number of people worldwide, infants, but it's received a lot of attention because of the cost of these treatments. This is a treatment for type 1 spinal muscular atrophy.
Rick: This is, as you mentioned, a pretty rare disease, but it's pretty devastating. It's a progressive neuromuscular disease. It's evident at a very young age. Kids 6 months of age or younger have the inability to even sit up without support. It's due to deficient levels of a particular protein called survival of motor neuron protein.
As you mentioned, we've had two recent therapies that have been approved by the FDA. One type of therapy actually has to be put inside the spinal fluid, that's intrathecal administration, and we have another type, an intravenously administered. Again, it's a gene replacement therapy.
The study is about medicine called risdiplam [Evrysdi]. It's an oral medication that actually modifies the pre-messenger RNA splicing that increases the levels of this protein in the blood. It took infants that had type 1 SMA (spinal muscular atrophy), and gave them the oral medication. The endpoint was a very simple one. At the end of 12 months, were they able to sit up without support for at least 5 seconds?
What they've found after 12 months of therapy is that as opposed to the historical controls in which it was expected about 5% of the kids would be able to sit up on their own, about 30% of the 41 infants that received this oral medication were able to sit up on their own. Somewhere between about 60% to 85% of these kids had an improvement of neuromuscular function. Whereas in the historical controls, that would only be about 12% or 15%. So a new medication, a new target.
Elizabeth: As I suggested, this issue of the treatment of spinal muscular atrophy has been in the news because the things that have been approved by the FDA are breathtakingly expensive. I looked up the annual cost of this particular medicine, just to see what it would be, about $340,000 annually to treat an infant with this. A couple of the other ones are actually more expensive than that. The question I think, for me is, "Hmm, what about the long-term impact of this?" Clearly, an oral med is better than an intrathecal med.
Rick: You're right. It's much easier to administer an oral medication than it is to put something in the spinal fluid or even to give something intravenously in a youngster. As you noted, these drugs are new in class and so they're prohibitively expensive. As we develop new medications, the price of these should go down and especially if we have competing companies.
This is very akin to what happens in many of our new cancer therapies too, Elizabeth, where the cost is almost prohibitive. We're seeing a backlash about this. We're also seeing the cost come down as a result of having, again, different medications, different pharmaceutical companies manufacturing them. But it's still a big issue.
Elizabeth: I'm hoping some CRISPR-based technology will step into this space and cure this particular disorder.
Rick: The therapies I have mentioned are things that weren't available 3 or 4 years ago. The fact that we're even talking about this now despite the prohibitive cost, I think, is an advancement.
Elizabeth: Finally, since we're talking about infants, let's look at a trial of hyperimmune globulin to prevent congenital CMV or cytomegalovirus infection.
CMV turns out to be a much bigger problem than many of us, I think, realize. In this study, they took a look at pregnant women with primary CMV infection that was diagnosed before 24 weeks of gestation. They were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin or a matching placebo until delivery. Their outcomes were a composite of congenital CMV infection or fetal or neonatal death.
It took them a while to accumulate all these folks into this study. They ended up with 399 women who underwent randomization -- 4.9% of fetuses or neonates in the hyperimmune globulin group and 2.6% in the placebo group died.
They also found that this administration of the hyperimmune globulin did not result in lower incidence of a composite of the congenital CMV infection or perinatal death than the placebo did, and was associated with a bunch of side effects that were really pretty troubling. This is very disappointing.
Rick: As you mentioned, it took a while to do this study. This was conducted at 16 different centers. When they were looking for active CMV infection in pregnant women, they were only able to find in about three to four out of 1,000.
But the reason why this is a problem is because congenital cytomegalovirus affects about 40,000 infants in the U.S. every year and is associated with stillbirth, neonatal death, deafness, and also cognitive and motor delay. If the mother has primary CMV infection, the chance that the fetus will have it is estimated to be somewhere between 35% to 40%. About 20% of these kids don't have evidence of the CMV infection at birth, but they develop deafness later. That's why trying to identify mothers that have active CMV infection and give them effective treatment is desirable. I was disappointed to find out that the hyperimmune globulin did not prevent congenital CMV infection.
Elizabeth: The other thing that they note is that preterm births of less than 37 weeks of gestation was 12.3% in the immune globulin group and 8.4% in the placebo group. To me, that sounds like that's reaching significance. I'm disappointed because the consequences of CMV infection in the infant are pretty dire. They also suggest in their discussion, should we be doing universal CMV screening in the United States?
Rick: You should be doing it if, in fact, there's a treatment available. But you can make the case that without any treatments available that we're better off identifying infants that have had symptomatic CMV infection. I'd feel differently if we had some effective treatment, but unfortunately this isn't one of them.
Elizabeth: I would just note that in the wake of the relaxation of mask restrictions and other things nationally, we're seeing a really big uptick in CMV infection.
Rick: Elizabeth, I wasn't aware of that. Obviously, we had talked about the fact that use of mask in the COVID era decreased flu spreading by about 99.7%. What you're saying is taking the mask off now we're seeing a recrudescence of these viral illnesses.
Elizabeth: Absolutely. Maybe one more reason to put those masks back on, which, of course, we are continuing in healthcare settings. On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.
Rick: I'm Rick Lange. Y'all listen up and make healthy choices.