Episode 31: Is Dupixent forever? Is tapering Dupixent desirable or even possible?
Dupixent (also known as dupilumab) has transformed the lives of people with moderate to severe eczema, but will patients need to use it indefinitely? Many parents ask: When can my child stop taking Dupixent? Or: How can I wean my child off Dupixent?
In this episode we explore tapering and stopping Dupixent with two researchers from University Medical Center Utrecht in the Netherlands that have created a patient-led roadmap for successful tapering. They are: Pediatric Dermatologist Dr. Marlies de Graaf, Head of the National Expertise Center of Atopic Dermatitis in Children; and Dr. Celeste Boesjes, who is a PhD candidate and Medical Doctor. (If you like our podcast consider supporting it with a tax deductible donation.) Check out the transcript here.
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Lynita: Hello and welcome to the podcast. My name is Lynita and I'm here with Korey Capozza, founder of GPER. Dupixent has been a game changer for kids with severe eczema.
But is Dupixent forever? Until now, the question has remained unanswered in scientific literature.
With us today are two researchers from the Netherlands that have just published a paper about successfully tapering dupilumab. Also referred to by its trade name Dupixent.
Their names are Dr. Marlies de Graaf. She is a dermatologist and allergist at the University Medical Center Utrecht in the Netherlands, where her focus is evaluating the care of children with eczema.
And also joining us is Dr. Celeste Boesjes. She's a PhD candidate in the Department of Dermatology and Allergogy, also at University Medical Center Utrecht. Welcome to the podcast.
Celeste: Thank you.
Lynita: I'm really curious about what [00:01:00] motivated you to do this study?
Marlies: Yeah. Uh,
In 2017 when Dupilumab became available for the treatment of eczema patients, We found that dupilumab was very effective in most patients, so we had the idea, maybe we can reduce the dose by prolonging the interval of dupilumab as this might be beneficial for the patients because they need less injections and they may experience less side effects when you're using less medication.
And as well, it might be of benefit for the budget for the whole society. Of course one of those requirements for prolonging the interval was that patients still need to benefit from dupilumab treatment without experiencing eczema flares. So therefore, we implemented a standardized and patient-centered
Dupilumab dosing protocol in which patients were able to prolong the interval from every two weeks to every three or four weeks and so on. [00:02:00] So we started this protocol in 2019, and after a few years, we wanted to evaluate our protocol in order to assess, for example, how many patients can actually take dupilumab how many patients is this successful? And that became the focus of this study in our adult population.
Lynita: Okay.
Marlies: in 2017 in several hospitals in the Netherlands. We initiated the Bio Day Registry. And this registry follows patients of all ages with moderate to severe eczema who are treated with biologicals, such as Dupilumab, it's an injection that is prescribed every two weeks and also JAK inhibitors, which are pills so the main goal of our registry is to evaluate the effectiveness and safety of these treatments.
Lynita: So you just had a look at all the data that had been meticulously gathered and were able to see the results of people trying to taper?
Marlies: Exactly, if the eczema was in control, [00:03:00] patients were asked to prolong the, interval fall and sometimes there were reasons for patients or for me as a doctor, not to prolong the, interval. But when they fulfilled the criteria, we tried to do it and then we afterwards we evaluated the effectiveness of this.
Korey: Just before we get to what you found. , who is a candidate for this prolongation of dose or maybe tapering off of Dupixent altogether?
Marlies: In this study easy score below seven and NRIs each below four, we started to prolong the interval.
Korey: And just for regular folks, do those equate to mild eczema or is that clear?
Marlies: Yeah, that's a good question. Easy score of below seven is mild eczema and N R s h below four reflects mild H
Korey: and if someone is sort of in that range of having now mild eczema and manageable itch. What's the [00:04:00] timeframe that they need to sustain that type of control in order to be eligible?
Marlies: In this study the patient was on dupilumab treatment for at least one year and that there was controlled disease for at least six months.
We are now doing a study in which we're already prolonging the interval of dupilumab after four months of treatments.
These results are not there yet. We need to analyze those data and collect more data.
Lynita: What was the first thing that you would say to someone, you're a candidate for extending your, interval and then they would start using it every three weeks and monitor their symptoms? Is that how it worked?
Celeste: Yeah. So we started prolonging the interval to once every three weeks from the standard dose and then after three months, if the disease was still in control, we prolonged again to every four weeks. And if that went well after three months again then we prolong to every six weeks or every eight weeks.
But of course, [00:05:00] when. There was flaring of the eczema and the flaring state for like several weeks, for example. And then we went back and shortened the interval.
Lynita: And I noticed from your study if people weren't successful the first time they extended it, they did have another opportunity to try again. And did that work for some people?
Celeste: Yeah, Maybe a second attempt or third attempt that's worked actually for several patients.
Korey: And were you able to publish your data on the much longer intervals that you just talked about.
Celeste: Yeah, we have that data also available in this study and also in a previous study with a smaller cohort of patients. We also uh, published a study and that also includes biomarkers, that measure uh, disease. And also the dupilumab levels in the bloods.
And we know from that study that it was also safe to prolong the interval
Korey: Could you just sort of like directly summarize the results and what you found?
Marlies: Okay, so we we found [00:06:00] that prolongation of the interval in 400 eczema patients was successful in 83% of these patients. And which
successful we mean that the eczema is still in control, so without flaring of symptoms.
Lynita: Which is great. It's such a high percentage. It's really positive news.
Marlies: Yeah, it is. And we also recently analyzed data of all our bio day patients treated with Dupilumab, which are almost 1300 eczema patients from 14 different Dutch hospitals. And this study is not published yet, but we can give a sneak peek and in this study we found. Approximately 70% of all patients were able to uh, tap dupilumab.
And most patients were able to taper to an end of fall of every three to four weeks. But some patients even taper to every six or eight weeks. And in addition to that, we are also collecting data of tapering of the PM up in children. [00:07:00] But dupilumab is not registered for a long time already for our children, so we need more time to collect more data,
Korey: That's great. Certainly. The parents in our network will be very interested to see those findings when you publish them.
Bio day registry success
Lynita: The 70% that are tapering, on the bio day registry is that just people who are well controlled, or is that the whole registry?
Celeste: That's just everyone. Yeah.
Lynita: So you're saying about 70% of people should be, if we can take your data able to taper Dupixent at some point.
That's really great news.
Celeste: According to our data. Yes, that's correct. Yeah. Yeah. And it also included some children already,
Korey: thank you for taking this on. You know, it's a question that I think parents and patients have had since the introduction of Dupilumab onto the market for atopic dermatitis.
I mean, it's been. A game changer for so many people and [00:08:00] has resolved their eczema in a way that didn't seem possible but the question that we
hear from parents all the time is, is this something that my child needs to be on for life? At what point could we explore getting the child off of it and how, when, who is a candidate, these are all questions that we need to understand in order to do that safely. So I think this study in adults is the first step to getting us there. Especially when we look at children's whose immune systems are evolving all the time, so really understanding this is super important. I wanted to ask you didn't taper folks off completely, you just increased the interval and I wondered if your future studies might look at those type of questions of. Who would be a candidate for tapering off completely or if it's something that you're looking at in the future through the registry?
Celeste: Yeah, it was not part of this study. But in one of our more recent studies, we looked at that [00:09:00] and in that study, as Marlies already said, we included almost 1300 eczema patients. And 10 of those patients stopped the dupilumab treatment due to controlled disease. So that's only a small, number of patients.
But yes, it's possible to stop the treatment in some of the patients. We know that using dip up every eight weeks, you can probably stop. The treatments as the eczema is probably in remission because after approximately 10 weeks, the Dupilumab is out of the blood.
So extending longer than eight weeks is probably not effective.
Korey: I see. And so, , part of what you did was this very Careful approach of extending bit by bit and seeing how that goes, and so that may be a roadmap for how people could do this. You know, start it every two weeks, see if you can get to every month, see if you can get every six weeks.
If you get there, test every eight weeks. And then if you're controlled at eight weeks, then you may be in remission and you could possibly stop altogether. So, [00:10:00] I think that's really helpful information about the, how to go about this. I wondered though, after you finished the study. Was there anything you could say in the analysis about those who did do well on tapering versus those who did not, that might guide people in sort of deciding if they wanna go this route?
Celeste: Yeah, so we do know from clinical practice, that all patients can actually try it when the disease is in control. We know, that tapering of dupilumab is probably not successful in patient that still experience a lot of itch or that have a moderate.
To high disease activity
Korey: thank you.
Marlies: Maybe in addition to that, what we do when we start. We already discuss when the effectiveness of the Dupilumab is good to prolong the interval. So it's really interesting because what you already mentioned is that many of our patients are really happy when [00:11:00] they finally get their eczema in control and experience. Very much improvement of their quality of life. And therefore they might be a little bit reluctant to taper because it's so effective and they are really afraid of getting their active eczema back again.
So by already introducing at the start of the treatment that you might want to prolong the interval. Patients are really motivated to try to do it
Korey: right. This idea of, the minimal effective dose, I think is something that patients care a lot about. It may be that, patients get to six weeks and it comes back a little bit. But that may be something they're okay to live with. So some of it has to be probably preferences of the patients too.
Celeste: Yes, it, of course it differ per patients. And we did saw sometimes a little flaring in patients when prolonging the interval. [00:12:00] But we know also from clinical practice. That mostly, that was only for short periods of time. And when patient increased the use of topical steroids it was also better to get the disease in control again.
And mostly only needed for short periods of time. And only a low amount that they needed to apply. But that's something to discuss with the patients.
Marlies: I think it has a lot to do with active, management counselling by the doctor informing the patient that it is possible to taper. And also to reassure them if it's getting worse, we can always go back to the usual interval. And we also see that it is effective again.
Celeste: Yes. And also to manage expecta.
Marlies: it's all about expectations.
Lynita: So what you're saying is a lot of the success that you're seeing is probably because you've set that expectation that we're going to try this and if, you can handle a little bit less control of [00:13:00] eczema, you may actually be able to increase the time between your doses.
Marlies: Yeah, that's right. What we've seen, because we have 14 hospitals participating in our registry. That the doctors in the hospitals which are informed by us well enough that they really need to do it and how to do it have better success in taping their patients.
Lynita: I think that's really interesting.
Korey: And I will say, I know our systems are very different in the US compared to the Netherlands. But there's a very considerable cost consideration here in the US for patients because they pay out of pocket a lot of times for these medicines, and they're not cheap.
So being able to extend that dose, you know, takes that burden off of patients and the healthcare system. So I think it's important.
Marlies: In the Netherlands we are very lucky that all patients are insured and that because it's registered medication it's paid for them, but [00:14:00] still yeah, but yet can be also reason to take, but not for the individual patient, but from a broader perspective.
Lynita: It's a reason to fund the study though, so that's great that there is some financial motivation to look at this process of tapering Dupixent.
Marlies: Yeah. Yeah.
Taper dose not time
Lynita: I did wanna ask a question. We are talking here about tapering Dupixent, when I think of tapering things, I always think of tapering the dose rather than the time between doses. And I do understand it makes sense because it's an injection, and particularly with children, these can be unpleasant associations.
But is there any value in reducing the amount of Dupixent rather than increasing the length of time between doses.
Marlies: Yeah, you already mentioned that less injections is beneficial for most patients, especially children. But in our experience adult patients also like to have less frequently injections and the other [00:15:00] reason for us, for choosing prolongation of the interval is that we only have injections of two dosage, one of 300 milligram and one of 200 milligram. So we cannot fine tune
this dosage that much. So that's also one of the reasons we have chosen for prolongation of the.
Lynita: Do we give. Six months old, the same 200 milligram dose it seems, if that would be okay for an adult.
That seems like a lot, but it’s okay?
Marlies: Yeah. Yeah. They have been done studies. And children, depending on their age and weight, are getting dupilumab once every month. So actually in children, the interval is already prolonged. Like Celeste already mentioned we have looked at dupilumab levels, in the blood and we've seen that Dupilumab level is varying between patients a lot.
Lynita: Wow.
Marlies: Uh, so because it's a treatment which is blocking the receptor. [00:16:00] We think that may be receptors vary also a lot between eczema patients with. Um, And you're measuring in the blood, the free dupilumab, which is swimming around and not, which is on the receptor. So probably, the dosage of dupilumab needed. Is also varying and that's why it's worth tapering or prolonging the interval because there are probably many patients in which we overdose dupilumab if we start with 300 milligram every two weeks.
Lynita: Right? And of course I didn't even think that we are all individuals and the way we react to a drug is different, so I think it's really great that you are capturing that piece of information of how much is in people's blood as time goes by.
Korey: And I wondered on that note. What is going on? Like is Dupixent modifying the immune system or correcting it to a degree that you know, it's no longer needed? Or sort of like what is the [00:17:00] biology within the body that's allowing someone's eczema to go from moderate to severe their whole life to in remission on Dupixent?
Marlies: That's, it's probably the $1 million question and hard for me to answer, but something we all want to know. I think all doctors and probably also all patients because we want to know if we are suppressing only the disease or are we really modifying the immune system.
And especially in young patients, it'll be very interesting if it's. It's possible to modify the immune system in terms that eczema will go away forever. And
probably also other atopic diseases like asthma because Dupilumab is also effective in cases of severe asthma.
That if you treat it in an early phase then maybe you can. Also prevents the child for getting other atopic diseases. [00:18:00] So it's something we don't know yet, but what we want to know. And yeah, more research is necessary probably, and hopefully in the future we can answer that question.
Korey: Yeah, I think what you said about understanding the age and the time period at which to do it is probably going to be really important because, you know, if you can intervene early when the immune system is still developing it seems like what you're saying could very well be true, but intervening once it's been more cemented and in place, maybe harder. So I think that's a really exciting area of research that I hope researchers are pursuing because, it does seem like intervening early. Can rebalance immune system in such a way that perhaps you're free of the atopic march.
Marlies: yeah, yeah. And on the other hand, we also need to realize that. In children, their immune system, like you said, is developing and [00:19:00] it can also probably have a negative effect to intervene in the development of the immune system. Cause we know that there are some side effects associated with Dupilumab, for example.
Adult patients can develop Conjunctivitis, but I've seen it also in children. Especially in the eczema population, because we don't see it in the patients which are treated for asthma with dupilumab.
Korey: Yeah, and that's super interesting that the conjunctivitis side effect isn't seen in other types of patients
Marlies: that's also one of the focuses of our research group
So yeah. Hopefully it's all good what we do by interfering in the immune system, but we don't know exactly for long term what the effect will be in a positive or maybe in a negative way.
Korey: Maybe as you do that research, you'll shed more light [00:20:00] on what's going on in the body with atopic dermatitis or eczema, because that's a unique, you know, dysfunction or perhaps in the body that's part of this condition.
Closing statement
Korey: Um, I think this has been top of mind for patients and parents for a long time, and also for doctors who know that parents and patients wanna do this, but they've been hesitant to take it on because there's no roadmap.
We, haven't had that information. And so in the absence of it, you know, people don't wanna take that risk cuz they don't know if they're gonna make their eczema worse, like you said.
And for people who have lived with moderate to severe eczema, going back to those days is probably very anxiety producing, I would think. . So I wanted to thank you for taking on this research, which I think will now allow patients, parents, and physicians to explore doing this type of tapering .
And I think the the. Detailed way in which you've kind of created a protocol for that is a huge breakthrough, and we are really [00:21:00] excited. See your research published to feature it on our social channels and then to have you here on the podcast cuz we think it's a great service to our community.
We are very eager to see what you do next, so please do share that with us. And of course, very excited to see your data in children and the future publications that come out. So with that thank you so much for being on the podcast and look forward to staying in communication with you.
Marlies: Thank you. Thank you for inviting us.
Celeste: Yeah. Thank you.
Research discussed in this podcast:
