Published: Lifelines for Health Fall 2019

With so many changes and advances in the bleeding disorders community, it can leave many of us confused
and uncertain about some of our treatment choices. You may have even asked yourself or your medical care team, "what products can I try?", or "which ones will even work for me?". Most healthcare professionals agree that inhibitor eradication/tolerization is still the preferred choice of care over bypassing agents, new or old. We've hand-picked two of our dearest friends (and their families) to share with you their experiences in inhibitor tolerization (IT.)

Taha Amir

Janet: What was your historic inhibitor B/U?

Taha: From about the age of 7 or 8 to until the age of 33 I had inhibitors. I believe my highest inhibitor BU was when I was a teen, which was about 1,000 BU.

Janet: How many times have you tried IT and with what? Units per kilo/frequency?

Taha: Ever since I was a kid, my hematologist always wanted me to try Immune Tolerance. In the early 1990’s, there was not enough data and research about IT treatments and my parents were a little scared and nervous, so they decided not to go forward.. The first time I tried IT was when I was 33 years old. My BU had been under 5.0 for a couple of years, so my hematologist thought it would be a good idea for me to try IT. However, this came with several disclaimers. The first disclaimer was that I had a very slim chance of eradicating or getting rid of the inhibitor because of how long I have had them and my age. The second disclaimer was that I had to be 100% compliant with the treatment. However, he said that if I did not try, then I would not know the outcome.

Janet: What choices for IT were presented to you by your care team?

Taha: My hematologist first suggested I try a plasma-derived FVIII with vWF complex product, because it had good success with other patients. He made me an appointment for the following month, so I could come into his office and get baseline bloodwork done.

When I had the second visit, he suggested using a recombinant FC Fusion extended half-life product. My partner and I were confused as
to why, because the previous few times, he recommended for me to be on a plasma-derived FVIII with vWD complex product.

Janet: How else did you educate yourself about inhibitor treatment choices?

Taha: Fortunately, we knew of a few people who guided us in our decision making, and we were able to talk to people who were using the product successfully.

Janet: Ultimately, why did you make your current product choice?

Taha: In the end, I chose the plasma derived, FVIII product because it seemed to work for the people I trusted, and I had to start somewhere.

Janet: How is your current regiment working for you?

Taha: So far, this is definitely my “go to” factor for IT. I started off with 100 IU per kilo, every day, for about six months. Then my hematologist lowered the dose to 75 IU per kilo, every day, for about 3 months. I was still being monitored very closely to make sure that my inhibitor did not come back. Currently I am on 25 IU per kilo, every other day and it is working great! I have been able to do more activities that I was not able to do before. If it continues

to go well, my hematologist will consider lowering the frequency to three times a week.

Janet: Would you consider participating in a clinical trial for emerging products?

Taha: I know there are many emerging trials coming out or in trials, but personally I would not consider them at this point. I am grateful to the people who do get on the trials, because without them there would not be better treatments or cures.

The Walker Family

Janet: What was your child’s historic inhibitor B/U?

The Walker's: Our son’s highest titer was 120 BU. Most of the time while on ITT his titer has been under 10 BU. However, each time he failed IT, his titer went historically higher.

Janet: How many times have you tried IT and with what? Units per kilo/frequency?

The Walker's: Our son, J, has tried IT many times with various different products. We initially started out with 100U/kg of the recombinant product he developed his inhibitor on when he was 2.5 years old. We tried a couple rounds of IT with that for 4-5 years, then moved to a plasma derived FVIII- vWF complex at 100 U/kg based on the Factor VIII. His titer was measuring 0 BU for several years on that, but during a growth spurt at age 9, his high titer came back. He began bleeding almost continually, and we took a break n IT by treating prophylactically with a bypassing agent.

After his titer slowly came back down below 10 BU close to a year later, we restarted IT with the PD FVIII- vWF complex again. It came down but spiked back up again around age 12 during puberty. After age 12, he was on a constant inhibitor titer roller coaster ride. Although we consistently infused daily, his titer was continually changing. We went through different periods of doing prophy with two bypassing agents to attempt to control bleeding while still doing IT. Based on other patients’ experiences we heard at the summits, we decided to try a combination of our previous FVIII-vWF complex and rFVIII together in the same syringe.

The reasoning behind this combination was to get more FVIII into the bloodstream than vWF, as the vWF would bind to multiple FVIII molecules and protect it. We used 200U/kg FVIII at this time. It was much less fluid volume but still did not tolerize the inhibitor. After his titer went up again and discontinuing FVIII to allow his titer to drop, we restarted IT when he was 14 with a recombinant PEGylated (extended half-life)product at 200U/kg, but his peak titer was not much higher than the rFVIII product we were using before, so we quickly switched for the final IT try to a Fc fusion extended half-life product at 200u/kg. He was using this for IT for a year and it did work in bringing his titer down.

Janet: What choices for IT were presented to you by your care team?

The Walker's: Our care team wanted us to return to his original recombinant VIII product when he was age 2.5. We were offered to be on a randomized IT study where inductees were given either daily treatment or 3 times a week treatment. Ultimately, we chose not to go on it, because we felt strongly that J should be on daily treatment.

After not making progress with that we and our care team easily concluded that we needed to switch to a plasma derived product. We let them choose for us because we did not have any strong opinions about one being better than the other after much research. When it stopped working for him, we were given more freedom to choose the next product. Multiple times we were pushed to try rituximab as an immunosuppressant however, we declined due to low long-term success rates and the high risk of side effects.

We also developed an individualized, independent care plan of how to treat bleeds with our care team, so that when J started a bleed, we knew the procedure. If after treating for the first couple of days we were not seeing improvement, we would contact them for further help.

Janet: How else did you educate yourself about inhibitor treatment choices?

The Walker's: We researched by reading the latest studies via medical journals and talked to pharmaceutical manufacturing representatives and as many medical professionals as we could. The most helpful way we educated ourselves was by going to the Inhibitor Summits and Inhibitor Family Camps, where we could talk to other families and hear what was working for them.

It's important to know that each individual reacts differently to medications, and results can vary; especially when it comes to IT since it’s an attempt to manipulate the immune system. CHES reminds you to speak with your medical care team before changing, discontinuing, or beginning a new regimen. If your doctor isn’t open to discussing or considering certain treatment options, it may be helpful to refer them to another treatment center or doctor who has experience with that specific product or treatment method. And remember, CHES makes no claims nor prescribes any medical advice, as we are strictly an education company. It is our intention to inform others of all options so they can make the best decisions for themselves.

Janet: Ultimately, why did you make your current product choice?

The Walker's: We could see that J’s quality of life was deeply affected being tied to lengthy, daily bypassing agent infusions that were not preventing bleeds and joint damage. Although his titer had historically gotten to a manageable level where we could treat with Factor VIII, his titer was never completely gone and his half-life never went over 6 hours to indicate complete tolerance. So, for us, although IT helped us manage the inhibitor for many years, it wasn’t the ultimate end to his battle with inhibitors.

We felt that trying the bi-specific, antibody product would give him the best chance to experience fewer bleeds, less joint damage throughout his life span and improve his quality of life. We were not able to access the Phase 3 trials, but switched shortly after it was approved for inhibitor patients.

Janet: How is your current regiment working for you?

The Walker's: Our current weekly injection regimen works amazingly. He has had approximately 3 bleeds in the past year and a half, where previously he had bleeding issues 2-4 times a month and now he rarely bleeds. Overall, he has spent much less time on crutches and using his wheelchair. Technically his inhibitor titer has increased in numbers now that we stopped IT, but we are better able to manage the bleeding and daily life issues. We feel he has progressed immensely in regards to his quality of life and ability to be an independent, fully functioning, young man.

Janet: Would you consider participating in a clinical trial for emerging products?

The Walker's: Yes, we would consider it and make the best choice for our individual situation based on the current information available.

It's important to know that each individual reacts differently to medications, and results can vary; especially when it comes to IT since it’s an attempt to manipulate the immune system. CHES reminds you to speak with your medical care team before changing, discontinuing, or beginning a new regimen. If your doctor isn’t open to discussing or considering certain treatment options, it may be helpful to refer them to another treatment center or doctor who has experience with that specific product or treatment method. And remember, CHES makes no claims nor prescribes any medical advice, as we are strictly an education company. It is our intention to inform others of all options so they can make the best decisions for themselves.