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 treating young children for peanut allergy, myocarditis after COVID vaccination, Janus kinase (JAK) inhibitors and rheumatoid arthritis, and screening for atrial fibrillation.
Program notes:
0:40 Myocarditis after COVID vaccination
1:40 Outcome overall fairly good
2:40 With a virus, symptoms weeks or months later
3:34 Treating very young children for peanut allergy
4:35 146 kids, 96 in treatment group
5:38 Started under age 2, most had remission
6:43 How can you tell you should treat?
7:05 Screening for atrial fibrillation
8:08 Used implantable loop recorder to detect
9:08 Controversy in populations at risk
9:40 Tofacitinib and rheumatoid arthritis
10:42 Followed for 4 years
11:42 Doesn’t decrease as much as TNF inhibitor?
12:30 5 years of treatment
13:15 End
Transcript:
Elizabeth Tracey: Efficacy and safety of treating very young children with peanut allergy.
Rick Lange, MD: Should we be screening for atrial fibrillation — abnormal heart rhythm?
Elizabeth: What about Janus kinase inhibitors in rheumatoid arthritis?
Rick: And myocarditis after COVID vaccination.
Elizabeth: That’s what we’re talking about this week on TT HealthWatch, 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 dean of the Paul L. Foster School of Medicine.
Elizabeth: Let’s turn right to JAMA and this is a look at, gosh, what are the impacts on the heart of vaccination against COVID-19?
Rick: There has been a lot of talk about myocarditis — that is, inflammation of the heart after a COVID vaccination. In this particular case, they have results from over 192 million people that have received a total of 354 million COVID vaccines. We are talking specifically about the mRNA vaccines. It identified only 1,626 reported cases of myocarditis that they could confirm.
The median age was 21 years. The median time from when they got the vaccine to myocarditis was about 2 days. By the way, it happened much more commonly after the second dose than after the first dose. Primarily males, about 83%.
For individuals 12 to 15 years of age, for every million doses, there were about 70 cases of myocarditis reported. From 16 to 17 years of age, about 100 cases per million doses given. Then for individuals 18 to 24, 50 to 55 cases per million.
Now, the outcome was actually overall fairly good. They couldn’t document any reported cases of deaths due just to myocarditis. Now, there are still two under investigation. But even if those two proved to be true, that would be two out of 354 million doses. These individuals recover, although the vast majority were hospitalized. Ninety percent of them, their symptoms went away before they were discharged home. At this particular point, we don’t have any evidence of any long-term lingering effects.
Elizabeth: I’m really interested in your hypothesis on why this particular cohort of young people would be very slightly predisposed toward the development of myocarditis following vaccination.
Rick: When you just look at myocarditis by itself — and by the way, most commonly it’s caused by a virus — there is a bimodal peak that occurs during infancy and adolescence or young adulthood. That’s due to viral infections.
This seems to have the same predilection. It’s a little bit different because with viral myocarditis, the symptoms usually appear weeks to months afterwards, not a couple of days, and about 6% of individuals with viral myocarditis end up going to heart transplantation. This isn’t true for vaccination.
The interesting thing is, the only other vaccine that we know of that definitively can cause myocarditis is the smallpox vaccination. I’m not surprised at the young age. I’m not surprised that they do well, and I’m not surprised that it’s a rare event. By the way, for all of our listeners, the benefits of COVID vaccination clearly outweigh the small risk of myocarditis.
Elizabeth: Unquestionably. A couple things that also occur to me. One is that now that we’re looking at rolling out vaccination among very young children — those younger than 5 years of age — I’m wondering if we’re going to see the same phenomenon in that cohort.
Rick: That’s a great question. I would suspect so. Really, what we’re going to be wondering is, does the benefit of vaccinating that younger age group outweigh any risks?
Elizabeth: I guess this remains to be seen. Since we’re talking about young people then, let’s turn to The Lancet. This is a look at administering oral immunotherapy in children aged 1 to 3 years with peanut allergy.
Previous work in this arena has been in older kids and so this is the first time that they have taken a look very rigorously at this very young age group. Administer this peanut protein to these kids — can we desensitize them?
This is a randomized, double-blind, placebo-controlled trial in five U.S. academic medical centers. They had these young children who were reactive to 500 mg or less of peanut protein who could be eligible for this, and they were randomly assigned to receive either the peanut oral immunotherapy or placebo for 134 weeks. They gave them 2,000 mg of peanut protein per day, followed by 26 weeks of avoidance. They wanted to see, well, what happens with these people?
They had 146 kids, 96 participants to the treatment group and 50 to the placebo group. Some of these kids actually who received the peanut oral immunotherapy did become tolerant and it was durable. One of them in the placebo group actually sort of grew out of this peanut allergy, if you will. It’s okay. You can probably use this in very young kids and there is some efficacy. I’m a little interested in why it wasn’t better than it was.
Rick: The earlier they started, the more likely they were to have complete remission. During the 134 weeks that they received it, about 70% of the kids showed that they could eat up to 5,000 mg — that’s 16 peanuts. These were all kids that were allergic to less than 2 peanuts. Then they stopped it and then they tested them again a half a year later. Unfortunately, only about a third of the kids still had that ability to tolerate that many peanuts.
Now, by the way, there was a significant number that were able to tolerate somewhere between 2 to 16 peanuts before they had an allergic reaction. But the interesting thing is if they started under the age of 2, 80% of those kids had remission. Earlier immunization is safe and it can protect them during that entire time.
Elizabeth: I think it’s worth noting also that — they gave us background — 2% of the U.S. pediatric population does have peanut allergy. That is a very large number of kids. If you look at their annualized allergic reaction rate, even when people are trying really hard to practice this strict allergen avoidance, they have got a very good chance of having an exposure that’s going to result in a reaction. This, I think, is a strategy that’s well worth considering.
Rick: Absolutely.
Elizabeth: I’m wondering about just continuing to administer peanut protein because they stopped to see whether or not they ended up having their allergies come back, if you will. So if we continued to administer it, maybe that would make it a lot more durable even if we did it at a much lower level.
Then the other thing is, how do you know when a kid who is only 2 months old? I know there is some family history and all of that, but sometimes it’s sporadic and we don’t know that this is a kid we should institute this therapy in.
Rick: Yeah. You’re right, Elizabeth. I mean, you’d like to detect it as early as possible. And the only way you do that is by observing an allergic reaction in a child that somehow you know has been exposed. Once that’s been identified, it’s in the child’s best interest to begin immunotherapy.
Elizabeth: Exactly. All right, let’s turn to your second one, back to JAMA. The USPSTF is up to their antics again.
Rick: Elizabeth, we’re talking about atrial fibrillation — that’s the irregular heart rhythm that’s fairly common. Once you get to be 80, it occurs in about 10% of individuals that predisposes individuals to having strokes.
In fact, 20% of patients who have a stroke associated with atrial fibrillation (AF) are first diagnosed with AF at the time of the stroke. There has been some thought that maybe we ought to be screening individuals, especially those at risk, who may not have symptoms.
Now, the United States Preventive Services Task Force (USPSTF) examined this in 2018. They said, “Gosh, we just don’t know whether screening is beneficial or not, so let’s get more data.” Well, this is the update.
Primarily, they looked at two additional studies — one that did intermittent EKG twice daily for 14 days of screening and they were able to detect individuals that had asymptomatic atrial fibrillation, in which case it would put them on anticoagulant, a blood thinner, to try to prevent stroke. When they followed them up, it looked like that in fact it wasn’t beneficial, although it was fairly modest and there were a lot of troubles with this particular study.
A second one is more robust ways of looking for atrial fibrillation, what’s called an implantable loop recorder. This is in older individuals, and they were able to detect atrial fibrillation in asymptomatic individuals and put them on blood thinner, but it didn’t show that it reduced the risk of stroke. What the USPSTF says is, “OK, we still don’t know.”
Elizabeth: Of course, you Sir, cardiologist, I’m going to back you into a corner here and say, what are your thoughts? What are you going to do with your patients who have, and many do, what amounts to undiagnosed or atrial fibrillation?
Rick: You don’t go looking for something if you don’t know what to do about it. Now, it’s a very different situation when someone has symptomatic atrial fibrillation for a long period of time. Especially if they have risk factors for stroke like diabetes, or hypertension, or older age, or female gender.
Elizabeth: I would just note for you this study that we talked about recently, within the last year I believe, that was looking at these implantable loop recorders in people who were at risk, who had already had a stroke, just to see what’s going on with the A-fib. I think there is still a lot of controversy even in that population about these things. Frankly, I have to say that as an older person I probably would be resistant to having one of those things implanted in me.
Rick: It’s easy to implant. That’s the easy part. The hardest part is knowing what to do with the information. If you don’t need to be on a blood thinner and you’re put on one, it puts you at risk. Conversely, if you’re at very high risk and you would benefit from it, you’d want to know about it. We don’t have good enough studies in large enough populations looking at outcomes to say whether screening of atrial fibrillation is beneficial. At this particular time, I don’t do it and I wouldn’t recommend it.
Elizabeth: We’re going to stick with that. Finally, let’s turn to the New England Journal of Medicine, “Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis.” Folks with rheumatoid arthritis are treated with a number of different things. Of course, they start with methotrexate and frequently people do not respond as well as we would like clinically to that, and so there are the addition of these other agents. One of them, of course, is this Janus kinase inhibitor, tofacitinib. Then there are some other ones, TNF inhibitors — tissue necrosis factor inhibitors — that are also employed.
In this study, they took a look at 1,455 patients who received tofacitinib at a dose of 5 mg twice daily, just less than 1,500 who received it at a dose of 10 mg twice daily, and, again, just under 1,500 who received a TNF inhibitor, and this was in addition to their methotrexate. These were folks who were 50 years of age or older and had at least one additional cardiovascular risk factor in addition to their rheumatoid arthritis.
They followed these folks for a median of 4 years and they looked at the incidence of what they abbreviate MACE — which is major adverse cardiovascular events — and cancers, eliminating non-melanoma skin cancers. The tofacitinib was associated with both higher risks of MACE and cancer. It also had a number of other negative impacts on people’s lives in comparison with the TNF inhibitor.
Rick: Both of these agents fall in the category of what’s called disease-modifying anti-rheumatic drugs. Rheumatoid arthritis in and of itself is associated with the increased risk of cardiac events and an increased risk of cancer, just because of the chronic inflammation. These disease-modifying drugs reduce the inflammation and they may actually reduce the risk of cancer and major adverse cardiovascular events as well. Is this JAK inhibitor, tofacitinib, actually increasing the risk? Or is it not decreasing it as much as the TNF inhibitor?
I would first of all agree with you that given the choice, if someone doesn’t respond to methotrexate, the next step shouldn’t be going to tofacitinib, the JAK inhibitor. It ought to be going to the TNF inhibitor. But there will be some individuals that don’t respond to that. In that particular case, this ought to be at least available as a treatment option.
Elizabeth: I get that if the person doesn’t respond to the TNF inhibitor that there ought to be another option. It’s just that it seems to me like, wow, there are some factors relative to the use of the tofacitinib that really are not very good.
Rick: We are just saying it’s not quite as good as a TNF inhibitor. It would be very different if it increased the risk of cancer or major cardiovascular events compared to just methotrexate alone. We have no evidence that it does that.
Elizabeth: Researchers estimate that during 5 years of treatment, 113 and 55 patients would need respectively to be treated with tofacitinib at a dose of 5 mg twice daily, rather than with a TNF inhibitor, to result in one additional cardiovascular event and a cancer case. That’s not huge. I agree.
Rick: Yeah. Again, it’s not as good as the other available agent, and that’s why we do comparative studies. But there is no indication that it’s worse than just the underlying disease — that is, rheumatoid arthritis.
Elizabeth: On that note, 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.