Many consider the new year to be a great time to make life changes. With new factor products in the marketplace we thought this article on the pros and cons of switching products would be helpful to our readers. Enjoy!
by Cazandra Campos-MacDonald
originally published in PEN, November 2018
A few myths about hemophilia linger in the community: “Only men can have hemophilia.” “A person with hemophilia will bleed faster than someone without hemophilia.” “People with hemophilia can’t play sports.” “You will outgrow hemophilia.” Belief in these myths can spread fear, and can lead to harmful biases or behaviors: for example, prohibiting a child from playing sports, or not believing women who claim to have bleeding issues.
One fear that is still felt by many people with hemophilia, particularly those who’ve had an inhibitor, is the development or recurrence of an inhibitor as a result of switching factor products. Though there is some evidence to support this,1 we also know that the risk of developing an inhibitor as a result of switching products is very small—too small to accurately measure. Yet many parents give this risk more weight than it deserves. Fear clouds their judgment when weighing the benefits of finding a better product and treatment regimen with the risk of contracting an inhibitor.
The fear of switching products became ingrained in my mind when my oldest son, Julian, was diagnosed in 1996 with a low-titer inhibitor at age one. I learned to infuse Julian with a first-generation factor VIII product (from which he developed the inhibitor), and after two and a half years of daily infusions, his inhibitor tolerized. My husband and I kept Julian on his treatment regimen while also gathering information about new factor products entering the marketplace. First-generation recombinant factor products reconstituted into 10 cc volumes, while some second-generation products reconstituted into only 2.5 cc. Yet our fear of triggering an inhibitor by switching products outweighed the promise of quicker infusions.
My second son, Caeleb, developed a high-titer inhibitor at age 11 months. He eventually began immune tolerance therapy (ITT) on a recombinant factor product, and after a couple of years of daily infusions, we moved him to a plasma-derived factor, hoping to lower his inhibitor level. Given the many complications Caeleb endured over the years, I feared that switching to a different factor product would cause his titer to spike. And daily infusions meant accessing his port every morning and pushing 30 cc of product from four vials of factor concentrate. This was not conducive to self-infusing, although he stopped experiencing episodic bleeds. Not having bleeds regularly was a great trade-off.
Whenever Caeleb visited the hemophilia treatment center (HTC) to have labs drawn, I brought along an extra-large plastic bag of his factor and supplies. Recently, Caeleb’s hematologist, Dr. Shirley Abraham, suggested, “I think it’s time to switch Caeleb to Hemlibra.”2 I was stunned. Another switch? I honestly couldn’t understand why Caeleb needed to switch. Even though Hemlibra® is not a factor product, I realized that the fear of switching was alive and well in my mind. Caeleb still had an inhibitor, and not knowing how a new treatment would affect him was nerve-wracking. Dr. Abraham pointed to the extra-large bag and said, “That is why it’s time to switch.” Over the years, I had grown accustomed to carrying all those supplies for an infusion, and to accessing his port daily. With Hemlibra, a month of product and supplies fit into a small container, and Caeleb receives one subcutaneous injection weekly into his thigh—no more infusions into his port. In that moment, speaking to Dr. Abraham, I understood. Caeleb’s quality of life could be even better if I trusted medical advice and didn’t give in to old fears.
Products are chosen—and kept—for many reasons. For example, in families where more than one person has hemophilia, the choice may be based on another family member’s experience. And if a treatment regimen or product is working well, change may not be needed. But what if you can do better? A common response to changing products came from one mother on social media. “Same manufacturer for 18 years because [the product] works. No reason to change.” Claudia Mackaron, a retired HTC nurse coordinator in Albuquerque, New Mexico, says, “Even though a new product could be more beneficial, the old saying ‘if it ain’t broke, don’t fix it’ creeps in. It’s very frustrating as a clinician to fight with patients in switching, knowing [a new product] could help them.” Fear of the unknown may stop a patient from changing products even if the data shows that a specific product could be a better fit. “Psychologically, the fear of the unknown, and a potentially harmful and difficult unknown, can shape bias tremendously,” says Dr. Mike Wang, associate professor of pediatrics at University of Colorado’s School of Medicine. Inhibitors are frightening, and it’s possible someone could develop an inhibitor after switching products. The fear lives on, even with no clinical evidence that the inhibitor resulted from a new product.
Why do some people embrace change without fear? Debbie Porter has an adult son with hemophilia and inhibitors who always “thought the idea of staying with the same product forever was counterproductive to advancing new and better treatments.” Debbie wanted more for her son Matt, who suffered for years from inhibitor complications. Matt infused recombinant products, plasma-derived products, and bypassing agents over the years, so switching wasn’t a fear. The day Hemlibra became available, Debbie immediately requested it for Matt. He has been bleed-free for seven months now, and his veins get the rest they desperately need. And of course, because Hemlibra isn’t factor, it can’t cause an inhibitor to factor VIII. Yet some people may be reluctant to switch, because they experience few complications with their inhibitors and their current treatment works. But for people like Matt and Caeleb, the severity of complications pushes them to anxiously wait for new products that promise better results.
We are learning more about why inhibitors form, and who is most likely to develop one. Physicians can identify patients who are more susceptible to inhibitor development based on genetics, environmental factors, race, and family history. But people seemingly not at high risk may still develop an inhibitor, and this has continued to feed fears about treatments and products. One HTC provider admitted that for years, he and his colleagues encouraged patients without inhibitors not to switch factor brands because they might get an inhibitor. While there is a risk of inhibitor development when switching products, “current evidence does not suggest that switching products significantly influences inhibitor development,” declared a finding in the Eleventh Zürich Haemophilia Forum.3 Yet fears persist, even in the face of scientific evidence.
Letting go of old beliefs isn’t easy. Once a myth has taken root in your belief system, it takes a lot of effort to remove it. We remain captive to treatments, protocols, and products that may not be the most effective. Staying where we are now—based on assumptions not rooted in the facts—prevents us from embracing the many possibilities that exist today.
Have the courage to overcome fear and seek out what’s in the best interest of your loved ones. Gather the facts, and communicate your treatment needs and concerns to your physician. Trying a different regimen or product may change your life.
F. R. Rosendaal, et al., “A Sudden Increase in Factor VIII Inhibitor Development in Multitransfused
Hemophilia A Patients in the Netherlands: Dutch Hemophilia Study Group,” Blood 81, no. 8 (1993): 2180–86, available at www.bloodjournal.org. Thierry Calvez, et al., “Recombinant Factor VIII Products and Inhibitor Development in Previously Untreated Boys with Severe Hemophilia A,” Blood 124, no. 23 (2014): 3398-3408, available at www.bloodjournal.org.
For more on Hemlibra, see Paul Clement, “ACE910: The First Disruptor,” PEN, February 2018, 4.
Elena Santagostino, et. al., “Switching Treatments in Haemophilia: Is There a Risk of Inhibitor Development?” European Journal of Haematology 94 (2014): 284–89.