It is a reality familiar to most adults with hemophilia of a certain age:  repeated joint bleeds which subsequently causes joint deterioration, affecting everyday quality of life. But the story does not have to end there. Learn how prophylactic therapy can be used to halt the momentum of degenerative joint damage, decrease pain and help you regain mobility.

Transcription of "The Advantage of Prophylaxis for Adults with Joint Issues"

KELLEY POLLARD (Moderator):  Good evening, everyone, and welcome to The Advantage of Prophylaxis for Adults with Joint Issues, part of the National Hemophilia Foundation’s Hemophilia Webinar series.  This series is supported by an educational grant from Novo Nordisk. 

Our presenters this evening are Dr. Christine Kempton and Jim Munn.  Jim is the Nurse Coordinator at the Hemophilia and Coagulation Disorders Program at Michigan Medicine in Ann Arbor.  Michigan Medicine located at the University of Michigan supports both patient care and research in a broad range of specialties, including hemophilia. 

Dr. Kempton is an Associate Professor of Hematology and Medical Oncology at the Emory University School of Medicine, and holds the Director’s Chair in Hemostasis at Hemophilia of Georgia.  She is also Director at Emory University and Children’s Healthcare of Atlanta Comprehensive Bleeding Disorders Center.

Welcome, Dr. Kempton and Jim.


JIM MUNN: Thanks so much, Kelley.

KELLEY POLLARD: You’re welcome.  Our program will conclude with a question and answer segment.  To ask a question, go to the area in the far lower left of your webinar screen and type your question into the field just to the left of the Send button, which is located in the pod or area labeled Chat.  Click the Send button when you have finished typing your question.  However, please note that your question will be addressed during the question and answer session at the end of the presentation.  There are no handouts for this presentation, however, a recording of this webinar will be available shortly on the National Hemophilia Foundation website 

And now I would like to turn things over to you, Jim.  Please go ahead.

JIM MUNN: Thanks, again, Kelley.  And thanks, everyone, for joining us this evening about the Advantage of Prophylaxis for Adults with Joint Issues. 

Before we get started on that topic in general, let’s take a look at the risks and consequences of having factor VIII or factor IX deficiency.  And we know that the biggest risk of hemophilia is of course bleeding, which occurs primarily in joints, muscles and soft tissue.  And the consequences happen as a result of the bleeding into those areas.  We will have deterioration of the joint over time.  You can be missing school or work days.  And then of course you become physically inactive during the acute bleeding episode, which over time can take a toll on an individual’s psychosocial and emotional wellbeing.  And lastly, of course, the insurance issues always can rear their ugly head. 

Let’s take a look at what happens from X-ray images that we see when bleeding occurs into joints.  As you can see here, this is a nice, smooth, contoured knee joint in which both the femur up here and the tibia down here have beautiful, smooth lines, and there is a wonderful joint space.  Essentially this is the representation of a normal knee. Once bleeding occurs, however, you will see if a joint space narrows we start to get these irregular lines—a little bit of a lytic lesion here, some thinning of the bone.  As that occurs more and more, the end result you see here is essentially bone on bone, which is exhibited with extreme pain and often requires knee replacement at that point.

So, the long-term effects of multiple bleeds are listed here.  You can see them in the pictures.  For instance, this gentleman has a loss of range of motion in his elbow. That’s the extent to which he can extend it fully, similar to this guy’s knee here on the right.  And unfortunately that range of motion will lead to weakness and then atrophy of the muscle.  You’ll see that the calf is smaller here and that the upper arm of this individual has lost some of its muscle tone too.  So, the atrophy occurs.  We also then can have some impaired sensation of the joints, which makes it difficult sometimes for you to recognize proprioception, which is your ability to identify your body and space as a result of the continued bleeding that can occur into the joints.  Stiffness, pain of course will occur.  And then you have difficulty with function, such as walking, standing up, sometimes climbing stairs can be difficult, and even to the point in a joint—elbow bleeding where eating or using your arms can be difficult. 

So, is there a way to prevent these risks and consequences?  We do know that prophylaxis can prevent long-term consequences in hemophilia, and that’s been identified in the Joint Outcome Study that was done by Dr. Manco-Johnson and her colleagues.  Total bleeds and joint bleeds increase as time increases with factor levels below 1%.  So, you can see in this picture here—the graph to the left shows essentially those patients who are less than six years of age, and you’ll notice that bleeds increase as the factor level stays below 1% over time.  When you’re ten to 65 years of age, which is this graph here, you’ll notice that that’s even more enhanced.  In the middle what we have now is the probability of having no bleeds if your factor level is kept at less than 1%.  So, over time in children you’ll see that the probability of no joint bleeds really decreases demonstrably, and in the adults it’s even worse.  It starts at a lower probability and continues downward from there.

So, what are the types of hemophilia treatment that are available for patients with hemophilia A and hemophilia B?  Episodic treatment, which is on-demand treatment, is treatment that is given any time you have a joint bleed or any type of bleeding that occurs.  And then we fall into prophylaxis.  Continuous prophylaxis, or sometimes called primary prophylaxis, occurs as a regular treatment that is often started before the age of three, and certainly before a second large joint bleed occurs.  Secondary prophylaxis is a regular, continuous treatment that started when there has been two or more large joint bleeds, but before you have any disease that has occurred.  Tertiary prophylaxis is when you had some joint disease over time and you do continuous treatment to prevent further damage.  And, lastly, we can have periodic prophylaxis, sometimes called targeted prophylaxis, and that’s done just before certain periods of time, such as during and after surgery or before a specific sporting event, season or activity.

So, what’s included in the prophylaxis consideration?  This is something that the patient and the hemophilia treatment center should decide together.  And it’s not just for kids.  So, the first thing we always want to do is take a look at what the bleeding triggers are that are going on in the individual.  What’s their physical activity level like?  Do they already have some established joint damage or an inflamed synovium that may be something that is considered in the process of deciding on prophylaxis for the individual?  What’s the number of acceptable joint bleeds that the two—the individual and the HTC—have decided would be beneficial for the individual over the course of a year, for instance?  And, lastly, what’s the trough level that we want to keep this individual at in order to manage all of the concerns associated with the other points of the triangle?  And, of course, the frequency of treatment is the biggest concern related to cost with prophylaxis.

So, what are the benefits of continuous prophylaxis?  We know that prophylaxis results in a number of things.  Certainly less chronic pain over time, the need for orthopedic surgeries drops off, patients report an increased health-related quality of life and they also report less joint bleeds as a result of being on prophylaxis.  We know from studies that patients miss fewer school and work days.  And then in pediatric patients they have higher physical health status scores.

As far as improved joint health, this was a study called the SPINART study that was done using prophylaxis in patients after joint disease were present in adults.  What they found was that after a three-year period of time the joint health score was improved in the prophylaxis group, but worse in the on-demand group, and that there was a correlation that fewer bleeds led to a greater improvement in the individual.

We also have a study that was done recently by Dr. Manco-Johnson looking at some retrospective data over ten years utilizing the surveillance project UBC data.  She looked at the years 1999 to 2010 and she found that prophylaxis increased during that period of time from 31% to 59% overall, and that bleeding rates were dramatically reduced for all of the patients who were taking prophylaxis.  What we found was that target joint bleeding decreased more with prophylaxis than in those patients who were taking on-demand therapy.

Who should receive continuous prophylaxis?  That’s where I’m going to turn this over to Dr. Kempton so that she can work on her portion of the talk.

DR. CHRISTINE KEMPTON: Thanks, Jim.  That’s a great introduction.  So, we have talked a lot about what the benefits are of prophylaxis.  And when I say continuous prophylaxis here for the adult population, we’re often talking about that secondary or tertiary prophylaxis—often tertiary where there is already joint disease.

The MASAC committee with NHC has recommended the benefits of prophylaxis when prophylaxis has begun at a young age in persons with hemophilia A and B.  They recommend that prophylaxis be considered as optimal therapy for all individuals with severe hemophilia A and B. 

With that in mind, who will benefit?  In my practice it’s not just patients with severe hemophilia; I try to look more at the degree of bleeding.  Some patients with moderate hemophilia have sufficient bleeding that prophylaxis is warranted to improve their joint health and function.  I start to think about it when patients have had more than two or three joints bleeds per year.  This may seem like a low number, but even this number is going to be contributing to joint damage and dysfunction over time.  You definitely want to be thinking about it when there is a target joint, which we define as three joint bleeds in the same joint, so three bleeds in that same joint in a six-month period.  That’s really a bad sign that that joint is going to be damaged significantly and have problems in the future.  Additionally, if a patient has had a limb or life-threatening bleed, even in the absence of significant joint bleeding, I think about wanting to prevent that from happening again, and prophylaxis is the way to do that.

Thinking now on the flipside, who could pass on it?  Who doesn’t need it?  Even a patient with sever hemophilia may do okay without prophylaxis.  There are patients that do have infrequent bleeding despite having severe hemophilia and don’t need prophylaxis.  Additionally, those who maybe only are having their joint bleeding or muscle bleeding with clearly identifiable trauma or activity in which case we can take a strategy of targeted prophylaxis or intermittent prophylaxis where you treat before that event or activity where you know every time I go out and I play soccer, I get a bleed.  Well, if we just treat it before soccer and avoid those bleeds, then we would not have problems with joint bleeding and we would be able to preserve joint function that way.  Those are the kinds of situations where a targeted strategy may be adequate and continuous prophylaxis is not needed.

Once we decide to do prophylaxis, it’s often a decision between the patient and the provider.  But how is it done?  The first choice is often the product to be used.  Once you’re starting to use prophylaxis, we start to think more about the extended half-life products.  I highlight the factor VIII product here a little bit more just because I think there is a lot more confusion around exactly what is considered an extended half-life product or not.  A lot of products are starting to say that they have a longer half-life, but they weren’t really designed that way.  In comparison to a standard product, their half-life or pharmacokinetics is not particularly different.  So, I’m going to consider that the extended half-life products for factor VIII are Eloctate and Adynovate.  These have been studied and have been demonstrated to have sufficient efficacy with a twice-weekly dosing strategy, which for a lot of patients is ideal or is a nice benefit to be able to decrease dosing from three times to two times a week.

In factor IX in hemophilia B, Idelvion and Alprolix are also long-acting options that are available, and those can allow once-weekly.  With Alprolix some patients may even be able to get to every ten days, or with Idelvion it could be up to every two weeks.  Those are the long-acting factor IX products that are ideal for prophylaxis. 

Although the factor VIII Eloctate and Adynovate were targeted for twice a week or every four-day dosing, there are some patients that can use standard factor products with a twice-weekly dosing strategy.  It really depends on the pharmacokinetics, which we’re going to be talking about more in just a little bit.  A lot of this is an individualization, and it takes conversations between the patient and the treatment team.  Additionally, even with the use of products that are truly designed as extended half-life products, not everybody is going to have a meaningful prolongation with the extended half-life products.  Even with factor VIII Eloctate or Adynovate, not everybody is going to be a good candidate to be dosing twice a week.

So, what are the goals of therapy?  The primary goal is really the prevention of bleeding.  All else is going to stream down from that.  I really want to see an improvement in the number of joint bleeds per year.  Like Jim said, this is a conversation between the patient and the treatment team as well.  I’m counseling folks that we want to see definitely less than four joint bleeds per year.  And if we’re seeing more than that, I want to start working on some strategies to get as close as I can to a no-joint-bleed state.  I also want to see resolution of those target joints.  If there is a single joint that’s having three or more bleeds over a six-month time period, I am really going to pay attention to that joint and see if I can get it to a zero-bleed state.

One of the challenges with this, though, when we’re dealing with tertiary prophylaxis is that typically these joints already have a lot of arthritic changes and pain as a result, so it may be difficult to distinguish what is a bleed from what is arthritis pain.  Both patients and healthcare staff can get it wrong.  We sometimes think there are certain characteristics that may be more likely to be associated with arthritis versus a bleed.  These can be guides, but it is a challenge.  Sorting it out, one requires an open mind to the fact that pain may be more arthritis than a bleed.  I think this is particularly difficult for our young adult patients where they maybe aren’t really aware yet that they have arthritis and pain in the past has always been a bleed.  So, this is a shift for them to recognize that their pain is now as a result of arthritis. 

Imaging, particularly ultrasound, may be useful, or MRI may be useful to help identify a joint as to whether there is active bleeding or arthritis as the culprit for their pain and their symptoms.  Additionally, trial and error.  It may take a little bit of time with changes to the prophylaxis regimen to see if bleeding can be suppressed or not.  And pharmacokinetic testing can help guide as to whether we’re on the right track with our dosing strategy.

Another concept to think about is we’re really focused, as our primary goal, on the annual joint bleeding rates, which I kind of think of as the tip of the iceberg.  So, it’s what we see out here, but there is growing concern that there may be some of the iceberg that’s submerged under the water that we don’t see as much.  This is what we call subclinical joint bleeding.  I still put a question mark here, because I don’t think this is very well characterized to know just how big this iceberg is under here.  Maybe this line really should be down here rather than up here, and that it’s not as big of a problem.  We’ve been suspicious of this based on the joint outcome study that Jim mentioned that Marilyn Manco-Johnson did where a number of the young kids, who never reported a joint bleed, did have changes on their MRI that suggested that they had bleeding that they did not recognize.  So, this is kind of where the concept of subclinical bleeding came from.  It’s going to take a lot more work to understand how frequently we see this.  How do we identify it?  What are the consequences?  As we get better with our imaging—with ultrasound or MRI—I think we’ll be having more discussions on this.

This is something just to keep in mind that when your physical therapist or your treatment teams want to be evaluating your joints, they’re going to be considering if they’re seeing joint changes progressing despite maybe good suppression of bleeding on prophylaxis. 

Some of the other goals of therapy that we look at and want to consider when using prophylaxis and maybe making adjustments to achieve them, even if we’re having good bleed suppression, or maybe we’re not having as great bleed suppression, but maybe getting some of these other important goals, and that’s increasing the capacity for activity without bleeding.  We all want to be out being active.  It’s good for our muscles.  It’s good for our brains to be out in the community.  So, we want to do that without inducing bleeding.

Additionally, folks with pain from their arthritis, it may reduce chronic pain.  As there is less acute bleeding, there will be less-frequent acute pain that comes in the setting of bleeding.  So, prophylaxis is really an integral part of a pain treatment strategy.

It’s going to lead to fewer missed days of school and work, if those are occurring because of bleeding.  Over the long terms it’s going to be preserving joint function.  These are all the reasons to be considering prophylaxis and potentially making adjustments if we’re not reaching these goals.

How do we make those adjustments and think about what we are doing to get to where we want to go with our prophylaxis?  This is a little similar to the other triangle and the three points that Jim showed you earlier.  But in the center is our primary goal, which is to keep our annual joint bleeding rate low.  The thing that is going to be contributing to this rate is activity level.  The higher the activity, the more likelihood of trauma on the joints and the more likely we’re going to be potentially having a joint bleed.  That doesn’t mean we don’t want to be active.  It means we need to take that into consideration as to how we’re going to be tailoring our prophylaxis.

The pharmacokinetics is another aspect here.  It’s not only the pharmacokinetics of the factor product that is prescribed, but also the individual’s pharmacokinetics.  As I’ll show you in a minute, there is a lot of variation between individuals. 

Lastly, the joint status itself is something that we need to take into consideration with respect to how we’re going to approach our prophylaxis.

I’m going to talk first in more detail about pharmacokinetics.  This is probably the more difficult of the concepts.  So, pharmacokinetics is the study of how a drug is distributed and eliminated from the body.  This is a curve here of factor VIII that you get a rise pretty immediately after the end of the infusion.  Within fifteen minutes you’ll have reached your peak.  There is a rapid redistribution, so a sharper slope and then a slow decay over time, which is the second phase in the terminal elimination.  It comes down here to a trough.  If you were to give another infusion, if you are doing every-other-day prophylaxis, this is the day you would do your infusion, and this level here would be called your trough.  We start here with our peak, our decay to our terminal half-life and then our trough. 

The whole area under here in blue is called the AUC, the area under the curve, which is the total exposure to the factor.  A lot of these things are linked.  If you have a higher peak, you’re going to have a higher AUC.  A longer half-life would be a longer time before you get to a set trough.  These are the parameters that are typically measured with the peak, the trough and the half-life. 

As Jim had mentioned before, shown in this graph here on the right is a tight link between the number of bleeds that occur and the factor VIII that is in circulation.  The graph here on the left is actually not patients that are on prophylaxis, but patients from severe hemophilia with a factor VIII level less than 1%.  In between these bars of 1 to 5 would be those with moderate hemophilia, those above 5 with mild hemophilia.  This was a cohort in Sweden.  As you can see, as the factor VIII level moves from 1 to 5 and higher, the number of joint bleeds decreases.  And so for some patients 1% may be sufficient.  For others it may be closer to 5% factor VIII activity to lead to an adequate reduction in joint bleeding.

This graph here on the right, showing the time the factor level is below 1%, increases as associated with an increase in the joint bleed rate.  This is where the idea of your trough level being 1%, the more time you spend past that 1% line, the more likely you’re going to have a bleed. 

In order to estimate how frequently you need to dose your factor is going to depend on your half-life.  The longer the half-life, the more time before you get to whatever trough it is that you need and your strategy is going to stem a lot about your half-life.  And even for a single product, there can be a big variation in half-life.  This is one example here of a standard factor VIII product that had a median half-life of 11.1 hours.  That means that half of the cohort had a half-life that was longer than 11.1 hours, and half of the cohort had a half-life that was shorter than 11.1 hours.  Ten percent of folks had a half-life that was as long as 15.4 hours or longer, and 10% had one that was shorter than 8.8 hours.  So, you can see there is even a twofold difference here in just individuals with a standard product. 

As a comparison and as a reference point, the extended half-life products have about a 40% to 50% longer half-life in comparison.  So, we see even greater inter-individual variation than we see inter-product variation.  That’s why your treatment team, when they’re working to get you to a set goal, may need to take into account your own half-life in order to get to where you want to be with your prophylaxis. 

Knowing your personal pharmacokinetics may help your doctor to tailor your factor regimen.  Identifying your half-life will require multiple measurements over a several-day period.  Then from those measurements some calculations are done and the half-life is determined.

A little more straightforward and sort of a down-and-dirty approach would just be measuring the trough level with the idea that if you’re above a trough level—if you never go below that set level, then you should be safe whether your trough level is 1%, or if you’re a more active person you may need to be up at 5% or 10% accordingly.  The trough level would be done just once prior to your planned infusion time, whatever your standard interval is, whether it’s three, four or five days between your factor infusion product.

The activity level may influence what trough you need.  How high does the factor VIII level or IX level need to be for you to be able to go out and do your activities?  Or it may also influence the timing.  One strategy would be to do your most intense activities at the times that you do your infusions.  You do your infusion, you get your peak and that’s when you’re going to be doing your most intense activities.  And you avoid those intense activities during those trough periods.  This will work if one’s activities are pretty intermittent.  If one is doing more intense activity daily, then that’s where you may need to consider having a trough level that’s high enough that supports the activity that you want to do.

Lastly, as I mentioned, joint status can influence how you’re going to deliver the prophylaxis.  Some of this is related to those target joints or joints that have had a fair amount of bleeding, even if they’re not technically a target joint.  But there may be synovial hypertrophy within the joint space, and this joint may be sort of boggy or kind of squishy.  In the squishy synovium there are blood vessels that are more prone to bleeding, so it may take more factor, a higher trough level and more intense treatment in order to get those blood vessels to not bleed.  Over time likely the synovium will recede, and then you may be able to back off on the prophylaxis at that time.  

So, with that, I’ll turn it back over to Jim, who is going to talk more about the barriers and things to consider when doing prophylaxis.

JIM MUNN: Thanks, Dr. Kempton.  At this point we are going to go into some of the barriers and challenges associated with prophylaxis.  When you think about the whole concept of prophylaxis, one of the things that patients are most concerned about is when they have poor venous access how will they be able to do it.  Some patients accomplish that by using central venous access devices.  Those patients really need to be aware of subtle changes in their clinical status that might be a sign of sepsis that’s occurring.  So, for instance, if patients have fevers, if, when they go to infuse their product, they get either chills or have some shaking that’s associated with the infusion, those are signs that sepsis might occur.  And at the site itself, you really need to make sure that you’re paying attention to make sure that the port area, or if it’s Broviac, that the site itself doesn’t have any redness, any swelling or any kind of drainage associated with it.  Again, signs that infection might be occurring.

This can be a demanding regimen for some families, and especially if you’re having to do it frequently throughout the week depending on if you stay with a traditional half-life product versus an extended half-life product. 

We know that adherence challenges occur, and we’ll talk about those in greater detail in a little bit.  Cost of course increases.  As patients get more and more in tune with their prophylaxis, what happens is you may have this decreased ability to understand or recognize that you’re having a joint bleed.  Some of the information that Dr. Kempton was saying about pain, patients are having to determine, “Is this arthritis because I had joint damage to begin with, or am I really having a bleed?”  And depending on whether or not the individual makes the correct decision, there may a delay in appropriate treatment if bleeding is actually present.

So, as far as adherence in prophylaxis, we know that adherence itself is the extent to which patients take their medications as prescribed by healthcare providers, but the caveat here is that this is a plan that has developed in correlation with the patient and the physician, so they both have input into the actual plan.  So, it makes a little bit more understanding when an individual has had the opportunity to be a part of the plan decided upon as to whether or not they’re adhering to their regimen.

We know that the World Health Organization has said that rates of nonadherence with medications can vary anywhere from 15% to 93%, and the average estimate is around 50%. 

Adherence to prophylaxis is great for individuals at making sure that success is maintained.  It’s most effective if your factor levels are continuously above the target trough level that Dr. Kempton mentioned.  And we know that once you start missing or skipping the doses and you spend time at that less-than-1% range, the graphs have already shown you that bleeding risk increases.  A previous study by Dr. Thornburg and others showed that physicians were reluctant if they felt that the patient might be non-adherent to the regimen that’s prescribed.

There are other barriers and motivators to adherence.  It’s interesting that for both the motivators and the barriers, age falls into that scenario.  We’ll see that in a little bit.  But essentially the motivator, as far as age, it’s the very young and those who start to become 30-ish years of age or older.  And under the barriers we see that adherence tends to drop off in teens and young adults. 

Some of the other motivators to adherence would be the ability to recognize symptoms, a belief that the prophylaxis is necessary and is going to work, and also, interestingly enough, Dr. Tran has shown that the relationship with the healthcare provider, whether it’s a positive, trusting relationship, would increase adherence as well.  

In the barriers we know that infrequent or absent symptoms make it difficult for patients to adhere.  So, if I’m not feeling any bleeding or anything, I may say, “I can skip another day here, because I really don’t feel as if anything is going on.”  Depression and other considerations from an emotional standpoint can have a barrier to adherence.  It’s a time-consuming process.  The cost itself—some patients may say that that’s too much for them to consider.  And, of course, venous access, which we talked about earlier.

As far as adherence to therapy is concerned, we know that it decreases during teen and young adult years.  Unfortunately bleeding increases and quality of life decreases when patients opt to drop prophylaxis and move back to an on-demand approach to their treatment.

Several studies looking at nursing perceptions of adherence.  Looking at 147 hemophilia treatment centers around the world, they looked at high or very high adherence to prophylaxis in age groups.  You’ll see that, as I said before, in the younger cohort—the zero to twelve-year-olds.  Adherence was rated as high or very high in 90% of that age group.  We start to see a drop off so that the teen years, between thirteen to eighteen, when teenagers start to take care of themselves.  We see adherence drop to around 54%.  In the young adults who are off to college, on their own, starting their careers we see that drop a little further to 36%.  Then once patients have been established at their jobs and really get an understanding of what’s necessary, we notice that adherence jumps back up once they hit about 28 years of age.

There was another study that also looked at the impact of treatment regimen on adherence. The study looked at patients who were thirteen to 25 years of age.  The patients who fell into the eighteen- to 25-year age group range, they had 6.2 times more likelihood to be non-adherent than the younger cohort did in that study.

Another consideration, when you’re doing prophylaxis, is of course this concept of treatment.  We would tell you that treating in the morning is best for factor coverage, because that’s when you’re going to be awake, and that’s when you have the most coverage for activities.  For any kind of sports that you may be playing, you want to make sure that your coverage is at its best.  So, treating at night before you go to bed, although some patients tend to that, you’ll notice that the coverage is highest when they’re asleep and less active.  And we really want to make sure that their coverage is best during the time when they’re most active.

Keeping track of infusions—any type of infusions—your prophylaxis and your bleeding episode is extremely important.  As HTCs, we’ll take anything that you provide us:  calendars, if you happen to do diaries—either paper or electronic ones.  We would be happy to take those.  And we’re even happy to take factor labels that have been placed onto a plain piece of paper that have dates written on them so that we can decide what has been working, what may not be working, because we try to correlate breakthrough bleeding with prophylaxis regimens to determine if changes need to be made to the therapy.

One of the biggest things to make sure you’re doing is to avoid being without any factor whatsoever.  It’s great if you can develop this inventory process that you keep track of what’s happening at home, and you’re working with your home care provider as well so that they’re calling you on a regular basis to make sure that you have adequate supply at home and you never run out.

Setting up infusion reminders.  You can do those on your mobile devices now.  It’s a great piece of technology that I’m so glad has been helpful in our teenage population.  They have used that in order to say, “If I’m on every ten days, sometimes it’s not easy to remember that.  But if I set that tenth day into my phone, it will send me a reminder to do my infusion.” 

It’s great if you can establish a routine.  Routines are perfect for patients in the sense that you fall into this scenario where when you wake up and it’s your day to do your prophylaxis, you’ve already got stuff set up and you’re ready to go. 

And then, lastly, we want to make sure that if you start to run into any problems that you alert us so that we can decide if there is something going on from an activity level, if there has been further deterioration of joints or any other concerns that we can work with you as an individual in order to make prophylaxis a little bit more seamless for you.

So, in summary, a few things that we should remember is that bleeding and hemophilia obviously has a major impact on joint health.  Dr. Kempton has shown the number of benefits to continuous prophylaxis even in the adult population in patients who have joint problems already.  Several approaches exist in order to do prophylaxis, and a number of products are available to help us accomplish prophylaxis depending on what’s decided between the HTC and the patient.  And, lastly, you may need to work with your treatment team to individualize the regimen to make sure that it’s right for you.  Again, Dr. Kempton showed the triangle of all the things that are taken into consideration, and you should really have that very firm discussion with the treatment center team to make sure that all of those points are covered in order for your trough level to be decided on and what product you’ll be taking.  And then of course be mindful to the barriers of prophylaxis that we just mentioned.  If you’re running into any concerns, always, always call the treatment center. 

With that, we’re open for any questions that you might have.

KELLEY POLLARD:  All right.  Thank you very much.  And ladies and gentlemen, to a question via the web presentation, select the Chat Pod located in the lower left corner of your screen and then type and send your question.  If you would like to ask a question live via your phone, press star 1 on your telephone key pad.  I will announce each caller prior to bringing you into the conference.  Please remember if you have your phone on mute, take it off mute when you are selected to ask your question.  Once again, to ask a question via the web presentation, select the Chat Pod located in the lower left corner of your screen and then type and send your question.  And to ask a question live, press star 1 on your telephone key pad.

All right.  And the first question we have is:  are there benefits of prophylaxis for adults whose joints are already damaged?

DR. CHRISTINE KEMPTON: I can take that one.  Yes, there are lots of benefits for patients or adults with even very severe, advanced arthropathy.  I think one is pain management as a reduction in chronic pain over time.  There are some reductions with continuous prophylaxis over time.  And also the obliteration or avoidance of some of the acute pain that comes with bleeding.  I think that’s a big impact.  A potential benefit would be a greater capacity to engage in activity and/or physical therapy that may benefit the joints to maybe rebuild some muscle that has atrophied around the joint.  That muscle then may provide some greater stability.  Preventing joint bleeds and improving joint function will over time preserve the joint health.  So, if you’re not having any more bleeds, you’re less likely to have a decline in your joint function.  As Jim mentioned with the SPINART study that was with adult patients with pretty advanced joint disease, they definitely had improvement in their joint health score as a physical exam score.  They demonstrated improvements in that score, which would be greater range of motion, better muscle strength, less atrophy and then less bleeds and an improvement in quality of life.  So, I think the SPINART study is very much targeted and generalizable to patients that are adults with already existing joint disease.

KELLEY POLLARD: Thank you.  The next question we have is:  the new non-factor therapies have a higher consistent peak.  Does this mean there are less subclinical joint bleeds on these products?

DR. CHRISTINE KEMPTON: I think with the non-factor products, what is currently being investigated would be things like Emicizumab, otherwise known as ACE910, and also fitusiran, the antithrombin knockdown.  Those are in development.  The concept of their pharmacokinetics are a little different.  There are not really peaks and troughs, but more stable levels since they have much longer half-lives.  Then you’re not even really reaching a trough level.  I think that’s an open question.  We don’t quite really have a good handle on how to measure subclinical bleeding, so I don’t think we would know whether there is or not.  I think we have to wait to see what the data is as it’s to be fully presented regarding even clinical bleeding.  That is the hope, but I don’t know that we know nor even could evaluate that issue right now.

KELLEY POLLARD: All right.  Our next question:  are you seeing better prophylaxis adherence in adult patients on extended half-life factors?

JIM MUNN: I can tell you from my experience we have seen some increase in adherence in adult patients specifically who have switched over to prophylaxis.  There was a study, or at least an abstract that was presented at ASH last year or the year before that looked at adherence in adults with both factor VIII and factor IX deficiency comparing standard half-life products and extended half-life products.  The initial information, which was over a few months’ time to a year, there was some increase in adherence noted for those patients based on some of the pharmacy records, dispensation and the actual reporting of patients with diaries and things like that. 

KELLEY POLLARD:  Thank you.  It looks like that was our last question.  I would like to thank you both, Dr. Kempton and Jim Munn.  And now for our audience, your feedback is critical to us not only in evaluating this presentation, but in planning of future webinars.  Please complete this five-minute survey appearing on your screen now by clicking on the link.  We would like to thank you for attending.  This will conclude the program.  Have a great evening.