Optimizing Iron Chelation in Sickle Cell Disease Management
In this episode, Sherif M. Badawy, MD, MS, speaks about strategies for optimizing iron chelation in sickle cell disease management from pediatric through adult care. Dr Badawy also presented this topic at ASPHO 2022 on May 6 in Pittsburgh, PA.
Sherif M. Badawy, MD, MS, is a pediatric hematologist at Ann & Robert H. Lurie Children’s Hospital of Chicago and an assistant professor of pediatrics at Northwestern University Feinberg School of Medicine (Chicago, IL).
For more information about ASPHO 2022, visit http://aspho.org/meetings/conference/overview
Jessica Bard: Hello everyone. And welcome to another installment of Podcast 360, your go-to resource for medical news and clinical updates. I'm your moderator, Jessica Bard, with Consultant 360 Specialty Network.
Sickle cell disease affects approximately 100,000 Americans and is particularly common among Black, African American, or Hispanic American populations according to the Centers for Disease Control and Prevention. Dr Sherif Badawy is here to speak with us today about his session at ASPO 2022, “Strategies for Optimizing Iron Chelation in Sickle Cell Disease Management From Pediatric Through Adult Care.” He's a pediatric hematologist at Anne and Robert H. Lurie Children's Hospital of Chicago, and an assistant professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Thank you for joining us today. Can you please give us an overview of your session?
Dr Sherif Badawy: Overall, I mean, I think sickle cell disease is really kind of complicated sometimes, and we think about it as a progressive disease where patients have end-organ damage over time, as they grow older from infancy to childhood, to adolescents, into adulthood. A lot of complications start at different ages, but some of the things that are really key to sickle cell disease, regardless even of iron overload include sine and cerebral infarct, which happens in almost 40% of patients. Pulmonary hypertension happens later in life. Sickle cell retinopathy, increased cardiac output, problems related to diastolic dysfunction, and myocardial fibrosis. And then a good number of patients will end up with other complications also related to renal failure or chronic lung disease or cardiovascular disease. And all these comorbidities can also lead to early mortality in some of those patients. And as I said, as they get older, some specific complications can really be more problematic, especially if you take the renal abnormalities and kidney disease.
We see it across age groups, starting with losing albumin in the urine, albuminuria, or start to develop hematuria or chronic kidney disease. And a significant number of patients might end up with chronic kidney disease, up to 60% actually, into adulthood. And about 20% of patients might end up with end-stage renal disease. So, I think what I'm trying to highlight here is the significant comorbidities that a lot of sickle cell disease patients experience, and maybe with a specific emphasis on renal abnormalities, cardiovascular disease, risk of a stroke, and CNS complications.
Jessica Bard: Could you please elaborate on how optimizing iron chelation in sickle cell disease management impacts clinical practice?
Dr Sherif Badawy: That's a great question as well. And, I think when we think about iron overload and how can we optimize managing iron overload, we are really talking about iron chelation, right? We know that having iron overload can contribute to comorbidities even further because we know sickle cell already has at baseline risk of comorbidities, but when you are requiring chronic transfusions for one reason or another, then you develop iron overload, and that will add other cumulative risk factors to your comorbidities and complications. And the best way to deal with that is get rid of the iron, and the way to get rid of the iron is by iron chelation. As many of you know, a lot of patients might need a kind of iron chelation or need chronic transfusion in the first place, if they are at risk of a stroke, if they already developed a stroke, or already had other current complications, and that was deemed to be the best way to prevent that.
However, the problem is with every one unit of blood that we are giving the patient, we are also giving the patient iron, which is usually beyond the patient's physiological capacity to get rid of that iron. So if a blood unit is 300 mL, we're giving the patient also 300 milligrams of iron, and usually an adult patient for example, will get 2 or 3 units. And that means we're giving them a lot of iron. So, what happens is a lot of the iron itself can be toxic to the tissue if it stays in the blood, which we would call the NTBI or non-transfusion bound iron, and that can get deposited specifically in 3 areas in our body. One is the heart, 2 is the liver, and 3 are the endocrine glands, such as the pituitary, the thyroid, the parathyroid, and the pancreas.
And, having iron in all these organs lead to tissue damage, lead to complications related to abnormalities in these organs. And as you can imagine, can be at risk for heart failure, can be at risk for fibrosis and liver failure, later on diabetes, hypothyroidism, hypoparathyroidism, and hypopituitarism. So all of these complications definitely happen. I would note that specifically for sickle cell, we see a little bit less of the cardiac iron overload for reasons sometimes we don't exactly understand. There is more iron deposition in other organs, specifically the liver and the endocrine glands. However, with very high levels of iron, there are some case series and case reports out there suggesting that sickle cell disease patients are still at risk for iron overload in their heart, but it really has to be very, very high levels of iron. So how you address it? It's iron chelation, which we definitely can talk about a little bit more.
Jessica Bard: Did you want to mention some more challenges relating to iron overload in sickle cell disease? I know you touched on several just now.
Dr Sherif Badawy: I feel like the other way to ask that question is “why should we care?” Right? Like why should we actually care about iron overload in sickle cell? And there are really studies out there, one of them just came out maybe 4 years ago looking at iron overload and what is the risk for patients who have iron overload vs not iron overload among sickle cell patients? And what does that mean for the risk of organ failure and mortality, and what the author reported was that when you have iron overload, your risk of having organ failure is almost 71% compared with 19% if you do not have iron overload. So definitely almost 3 and a half times more at risk of organ failure. And when you look at the risk of mortality, the risk was 65% among patients with iron overload compared with 5% among patients without iron overload.
And I think the comparison here is very clear, right? 19% versus 71% about organ failure and 5% versus 64% risk for mortality related to likely iron overload. So challenges related to that, other than the actual risk that patients have is iron chelation, right? And there are some options that are available out there. Some of them are injection that patients have to take subcutaneous Desferal 5 days a week for 8 to 10 hours every day. On average, people end up doing 8 hours. It went out of favor because of that inconvenience. People don't want to be connected to a pump 5 days a week, and now we have other oral therapies. There is deferasirox available in 2 forms. It is a once-a-day therapy. And then deferiprone, which is available, initially, it was 3 times a day, now it's 2 times a day, at least in the pill form. And they are both really kind of effective and work quite well.
I think the biggest challenge I can tell you is adherence, right? And how often people actually take their medicine and what I always like to say, and I think it was a quote from earlier research, “if you don't take it, it doesn't work.” And, if you're really trying to commit to taking a medication every single day, 1 or 2 times a day or 3 times a day, it really can be burdensome for patients over time. And I think that's one of the biggest challenges, especially, we see as patients move from childhood to adolescence to adulthood. When they are kids, it's really their parents are the ones who are responsible for giving them their medicine. And we even see sometimes the challenges there, but as they become adolescents and young adults, the responsibility shifts from the parents to patients.
And with that transition of responsibility, teenagers are maybe busy with other things and distracted by school work. They move on into young adulthood. And I think that really adds more challenges in this specific age group, which we call AYA, as you may be familiar with it, adolescent and young adults. And I think this is really where it can be a little bit problematic. And I think that's why engaging them in the decision-making process, engaging them and empowering them to take ownership and leadership when managing their own disease, taking their own medications, understand why it is important for them to take it, right? What are the short term gains, what are the long term gains, and what are the tools that can help them with that?
You know, as simple as like a phone reminder, right? Something that can help them because the number 1 reason why people don't take their medicine is forgetfulness. And then some of the common barriers are lack of understanding why they have to take it and how does it work and what are the benefits? In our own research, we also show that stronger habits, when people have a strong habit in taking their medicine, they are more likely to continue to do that. In a way it becomes more of like an automatic process. They really don't think about it a lot. It happened more natural. It becomes part of the routine, and they are more likely to stick to it and be able to take it all the time.
Jessica Bard: I think that's a good segue for our next question. How has iron chelation therapy evolved in recent years?
Dr Sherif Badawy: We might have answered a little bit of that earlier. You know, really kind of the biggest evolution has been when we moved from deferoxamine as the injection formulation in the last decade or 2 to actually become an oral formulation. And that's deferasirox and deferiprone. I think these are the 2 that are orally available. I mean, I don't know what is going to be next yet from the iron chelation standpoint. I think we're still kind of, there have been some other efforts or trials that really try to look into that in more details, but I don't think we have any other iron chelators that are available right now. So I think the biggest really evolution is moving from injection that is subcutaneous and intravenous only to oral therapies that are currently available now, which again, deferasirox and deferiprone.
Jessica Bard: What's next for the study of iron chelation in sickle cell disease management, and are there any gaps in that research?
Dr Sherif Badawy: There are definitely other gaps for sure that exist. And one of them is what is really kind of the ideal strategy to try to help patients engage them in their adherence behavior and really iron chelation taking behavior, and really trying to understand the barriers themselves and address them with the notion that we know that one size fits all doesn't work either because it has to be customized. It has to be tailored based on specific needs and specific barriers that patients have. So digging into that in some more details is going to be very helpful. We're already almost done with a project, looking at barriers to adherence, to iron chelation and using a conceptual model came from University College of London, called COM-B model or behavior to change real and trying to take a holistic approach into the barriers problem and use the information that come from that to tailor some interventions that we have worked on as well, but for adherence to other medications.
And we try to adapt that for iron chelation medications. So using like mobile apps, like we developed a platform called Medguard, and the idea of Medguard is to again, send patients reminders, do some more education, connect patients with their pharmacies, have some behavioral economics actually in the platform itself that patients can be more engaged in taking their iron chelation therapy. And then other tools that we are kind of developing to create positive associations between the iron chelation taking behavior and hopefully that helps to improve their outcomes long term. To summarize, it really is what are the challenges? What are the barriers? How can we address them? And let's take some actions to address them together with patients involved in the entire process.
Jessica Bard: That's a good summary there. Are there any other take-home messages from our conversation today that you'd like to add?
Dr Sherif Badawy: Always involve patients, always talk to them, ask them what are really kind of their challenges and listen to them and try to implement the strategies that involve patients and parents, especially for the younger ones, because this kind of buy-in is always critical for long-term sustainability of behavior change and tailored as much as you can as well. Sometimes motivational interviewing helps. Sometimes, even asking them to set up a reminder on their phone on their own can work. Whatever it is that actually patients think is going to work for them, try to work around it with them and try to make sure that their voice is heard and always engage them in the conversation. I hope that was helpful for you all. And definitely happy to take any questions over email. I'm sure you can find me if you just put me in Google. I'm going to come up with my email and please shoot me an email or a note if you have any questions for me or would love to chat more, but thanks for having me, Jessica.
Jessica Bard: Perfect. Thank you