*Factor-replacement therapy is one class of treatment option for hemophilia patients. This article does not examine factor mimetic, gene therapy, or investigational treatments.
<h2 style="margin-bottom: 11px;">Hemophilia A Treatments: Prophylaxis vs On-Demand </h2>
Prophylaxis treatment is recognized by the World Federation of Hemophilia (WFH) Guidelines for the Management of Hemophilia as the standard of care for individuals with severe hemophilia, and for some with moderate hemophilia. The WFH Guidelines recommend starting prophylaxis before the age of 3 years to help prevent musculoskeletal complications due to recurrent joint and muscle bleeds. 
 Individualized dosing regimens are tailored to a patient's lifestyle, physical activity level, and pharmacokinetics, ensuring that each patient receives the correct dose to <a name="_Int_qo2vpFqm">maintain</a> their target factor VIII level while minimizing the risk of bleeds. On-demand treatment is useful for managing acute bleeds, but doesn’t offer the same level of protection as prophylaxis and may lead to more frequent and severe bleeding episodes in the long run. The WFH Guidelines advise that on-demand factor replacement should no longer be considered a long-term treatment option since it’s only a response to a bleed—prevention of bleeds and long-term joint damage should be the priority for patients and their doctors. 
Types of Factor VIII Replacement Therapies, Infusion Rates, and Dosing Frequency Maintaining adequate factor VIII trough levels is crucial in hemophilia A management to ensure continuous protection against spontaneous bleeding, especially for patients on prophylactic treatment. Previously, experts considered a trough factor level of 1 IU/dL (1%) adequate, but current standards recommend significantly higher levels (&gt;3%-5% or higher). 
 &nbsp;

Standard half-life (SHL) factor VIII infusions have a half-life of approximately 12 hours in adults. The short half-life of SHLs results in the need for frequent infusions. On average, this is 3 infusions per week for patients to maintain minimal trough levels (&gt;1%). Because of higher clearance rates, half-life is shorter in individuals younger than 18 years, which may result in requiring more frequent infusions that many patients are unwilling or unable to do. Conventional factor prophylaxis with SHLs is classified by intensity: high-dose (25-40 IU/kg every 2 days), intermediate-dose (15-25 IU/kg 3 days per week), and low-dose (10-15 IU/kg 2-3 days per week).

Extended half-life (EHL) factor VIII infusions have a half-life that is 1.4-1.6–fold longer than SHL products. However, the half-life of EHLs is still limited to up to 19 hours. 
 While EHLs require less frequent administration than SHL therapy, patients may still require 2 or more infusions per week to maintain desired trough levels. The criteria for high-, intermediate-, and low-dose prophylaxis with EHLs are not yet established, and these definitions may require revision due to the differing pharmacokinetic profiles of SHLs and EHLs.

High-sustained factor (HSF) therapy was designed to extend half-life longer than EHLs (~19 hours) and SHLs (~12 hours), allowing for less-frequent administration.

Hemophilia home-infusion therapy allows people to self-infuse from the comfort of home. The WFH recommends providing adequate education to the person with hemophilia, as well as a family member or caregiver. This includes learning the factor VIII replacement calculation, understanding the factor VIII replacement formula so they are using an accurate and safe dose every time, and learning to recognize potential complications.
The rate of infusion and frequency of dosing are dependent on an individual’s specific needs. Several factors can impact these, including the patient’s weight, severity of bleeding, and level of comfort with treatment. These decisions are made at the discretion of the healthcare provider, who will consider all relevant factors to ensure optimal treatment that is tailored to the lifestyle and goals of each patient.
The frequency of dosing depends on whether a patient is using a prophylaxis treatment or on-demand therapy and whether the factor VIII replacement therapy is a standard half-life, extended half-life, or high-sustained factor therapy.

<h3 style="margin-bottom: 11px;">Switching Treatments for Hemophilia A Patients</h3>
With newer treatments, it is now possible to aim for higher factor VIII levels. Doctors should ensure patients understand that achieving higher trough levels may require higher doses or more frequent infusions with SHL and EHL therapies. &nbsp;
<h2 style="margin-bottom: 11px;">Potential Complications of Factor VIII Infusion</h2>
<h3 style="margin-bottom: 11px;">For Hemophilia Patients With Inhibitors</h3>
One of the most significant complications that should be considered with factor VIII replacement therapies is the development of inhibitors—antibodies that neutralize the effectiveness of the replacement clotting factor. According to WFH Guidelines, patients who develop inhibitors should have access to appropriate hemostatic agents for bleeding control and surgical interventions, if needed, at experienced centers.&nbsp;
Bypassing agents and other non-factor treatment products may be an option for patients with inhibitors. These treatments can provide effective hemostasis and help manage bleeding episodes effectively.

<h2 style="margin-bottom: 11px;">Conclusion</h2>
Involving patients in developing personalized treatment plans for hemophilia A is essential. By educating patients on their factor VIII activity and different treatment options, healthcare providers can set individualized and achievable goals. This collaborative approach may enhance adherence to treatment, reduce bleeding episodes, and improve overall quality of life. Engaging patients in their care not only fosters better health outcomes, but also strengthens the patient–provider relationship, ultimately leading to more effective hemophilia A management.
<a href="https://pro.campus.sanofi/us/products/altuviiio" style="color:blue; text-decoration:underline">Learn more about a potential treatment option for your patients.</a>

Ensuring optimal care for patients with hemophilia A requires a thorough understanding of available treatment options, prioritization of bleed prevention and long-term joint health, and comprehensive patient education. This article will cover different types of factor VIII replacement therapies* and will compare an on-demand versus prophylactic treatment approach with the goal of helping tailor treatment plans effectively, which can help enhance quality of life.

HEMOPHILIA-A

RARE-BLOOD-DISORDERS

Exploring Factor VIII Replacement Therapies: A Guide to Choosing the Right Treatment for Patients With Hemophilia A

<h3>We chase the miracles of science to improve people's lives, and transform scientific innovation into healthcare solutions for people nationwide and across the globe.</h3>
Campus Sanofi has been developed to provide a single place to find information relating to our disease and therapeutic areas, product information&nbsp;and other educational materials.
By bringing our digital websites into one place, our aim is to provide an experience which allows you to find information you're looking for more easily and quickly, freeing up your valuable time to support your patients.&nbsp;

A hub for healthcare professionals to discover and find information on our medicines and therapies

GENERAL-TOPICS

OUT-OF-TAXONOMY

Welcome to Sanofi Campus US

Explore the differences between factor VIII and 
 factor IX

Learn more about evaluating multiple pharmacokinetic (PK) parameters

See the additional considerations for the management of hemophilia B

Due to the distinct behavior of factor IX, multiple PK parameters should be considered when assessing bleed prevention. Learn how a broader view of PK may influence evaluation of treatment and management for patients with hemophilia B.1,2

HEMOPHILIA-B

Learn More About a Treatment Option

<h2>Hemophilia A and hemophilia B are different bleeding disorders&nbsp;with unique pathologies and clinical features3</h2>

<table>
 <tbody>
 <tr>
 <td colspan="2" style="white-space: nowrap;">Hemophilia A3,4</td>
 </tr>
 <tr>
 <td>Prevalence</td>
 <td>1:5,000 males</td>
 </tr>
 <tr>
 <td>Clinical symptoms</td>
 <td>Joint bleeding, muscle hematoma, soft tissue bleeding</td>
 </tr>
 <tr>
 <td>Coagulation factor deficiency</td>
 <td>Factor VIII</td>
 </tr>
 <tr>
 <td>Patients with severe factor VIII deficiency</td>
 <td>~50%</td>
 </tr>
 <tr>
 <td>Annual bleed rate in moderate to severe patients</td>
 <td>14-16</td>
 </tr>
 </tbody>
</table>

<table>
 <tbody>
 <tr>
 <td colspan="2">Hemophilia B3,4</td>
 </tr>
 <tr>
 <td>Prevalence</td>
 <td>1:30,000 males</td>
 </tr>
 <tr>
 <td>Clinical symptoms</td>
 <td>Joint bleeding, muscle hematoma, soft tissue bleeding</td>
 </tr>
 <tr>
 <td>Coagulation factor deficiency</td>
 <td>Factor IX</td>
 </tr>
 <tr>
 <td>Patients with severe factor IX deficiency</td>
 <td>~30%</td>
 </tr>
 <tr>
 <td>Annual bleed rate in moderate to severe patients</td>
 <td>9-11</td>
 </tr>
 </tbody>
</table>

<ul>
 <li>Since bleeding phenotype may differ between severe hemophilia A and B,&nbsp;management strategies should be individualized1</li>
</ul>

<h2>Factor VIII and factor IX have unique pharmacokinetic profiles and behave differently in the body1,2,5-7</h2>

<h3>The 4 key PK differences between factor VIII and factor IX are</h3>
<ul>
 <li>half-life:&nbsp;The time it takes for the concentration of the drug in the plasma to be half of the initial concentration,&nbsp;</li>
 <li>clearance:&nbsp;The ratio of administered dose and area under the curve, showing the amount of plasma free of drug in a given period of time,&nbsp;</li>
 <li>recovery:&nbsp;The increase of coagulation factor activity in the plasma after dose administration</li>
 <li>and volume of distribution:&nbsp;The relationship between the amount of drug in the body and the plasma drug concentration. Drugs with a high volume of distribution will tend to have lower trough levels.</li>
</ul>

<ul>
 <li>Factor VIII and factor IX are unique blood-clotting proteins with distinct functions in the coagulation cascade5-7</li>
</ul>
<h3>See a broader view of PK</h3>

It's time to&nbsp;look at the bigger picture&nbsp;in hemophilia B

Hemophilia B is different. Let’s manage it that way

<h2>The unique pharmacokinetic profile of factor IX is explained by its widespread distribution in the extravascular space5,8-10</h2>

<ul>
 <li>Factor VIII:&nbsp;largely influenced by its association with von Willebrand factor (vWF), which restricts factor VIII circulation to the bloodstream and limits its extravascular distribution5,12,14</li>
</ul>

<ul>
 <li>Factor IX:&nbsp;greatly influenced by its extravascular distribution and type IV collagen binding. The unique distribution behavior of factor IX allows for its longer half-life5,10,15*</li>
</ul>
*As shown from research of factor IX binding to type IV collagen in human arterial tissue in vitro.

<h2>Compartment models are commonly used to describe the PK of therapies such as factor VIII and factor IX5,14</h2>
<h3>The PK of infused factor VIII may be described by a 2-compartment model5</h3>

<ul>
 <li>After infusion of factor VIII, there is a rapid distribution phase (binding to vWF), followed by elimination. Therefore, its PK may be described by the 2-compartment model5</li>
 <li>However, this early, rapid phase of distribution to vWF rarely contributes to a noticeable difference in the area under the curve (AUC), allowing for an easier PK analysis16</li>
</ul>

<h3>The PK of factor IX can be described by the 3-compartment model, so accurate measurement of its activity is more complex than that of factor VIII5</h3>
Due to the distribution of factor IX outside of the plasma and into the extravascular space, the PK behavior is more complex than that of factor VIII5,13

Adapted from Iorio, et al.&nbsp;Thromb Haemost.&nbsp;2017.

<ul>
 <li>After factor IX enters the plasma, it rapidly distributes into peripheral compartments and eventually redistributes into the central compartment for elimination5</li>
</ul>

<h3>Because factor IX may reside in 3 different compartments, and trough only accounts for one compartment (plasma), trough may not account for all the factor IX activity in the body.5,13</h3>

Clinical studies have shown that factor IX spends more than half of its total time in the body outside the plasma3,5

<h2>Factor IX binds to type IV collagen, which may play a key role in coagulation15,18</h2>

&nbsp;
<ul>
 <li>A study in mice demonstrated that factor IX binds to type IV collagen in the extravascular space15</li>
 <li>A higher affinity to type IV collagen is associated with a significant reduction in bleeding time8</li>
</ul>
Adapted from Gui et al.&nbsp;J Thromb Haemost.&nbsp;2009.

Learn more about this study

<h3>Additional research in humans is needed to confirm these findings.8</h3>
Purple dots represent the length of bleeding time from time of tail clip to bleeding cessation for each mouse. After 10 minutes, bleeding was terminated by firm pressure. Solid purple bars indicate mean bleeding times for the groups.

<h2>Due to the complexity of factor IX, evaluation of factor IX replacement therapies should look at multiple PK indicators5</h2>
<h3>Parameters</h3>

<h3>Peak 
 &nbsp;</h3>
Maximum concentration observed after infusion13
Because other PK parameters may not provide the full picture of factor activity when considered alone, peak should be considered as part of a more comprehensive evaluation19

<h3>Volume of distribution</h3>
Drug distribution in the plasma and rest of the body2,13
Additional research is needed to understand the clinical implications of volume of distribution

<h3>AUC 
 &nbsp;</h3>
Total concentration in the body in a given period of time13
AUC should be considered as part of a more comprehensive evaluation because other PK parameters may not provide the full picture of factor activity when considered alone19

<h3>Clearance</h3>
Amount of plasma free of drug in a given period of time5,13
The representation of clearance in the multicompartment model may explain why the half-life of factor IX is longer than that of factor VIII, even though factor IX clearance is higher5

<h3>Half-life</h3>
Time to half of initial concentration13
Because half-life may be affected by the extravascular distribution of factor IX, considering it alone may not provide the full picture of factor activity. Extravascular distribution may complicate the PK analysis of terminal half-life because the estimate will be different depending on the compartment model used5,13

<h3>Trough</h3>
Minimum concentration1,2 
 &nbsp;
Evaluating trough alone during a PK assessment may not measure protection due to the complex behavior of infused factor IX20

The ISTH recommends that PK assessments include at least 6 parameters13

<h2>Trough levels, which measure factor in the plasma, may not always correlate with bleed rates1,2</h2>

Although clinical trials have not directly compared extended half-life factor IX replacement drugs, individual trials have shown21,22:

A broad range of trough levels 
1% to 27%

A narrow range of bleed rates 
1.04 to 1.40

Despite a wide range of trough levels, bleed rates have shown a narrow range1,2,23

<h2>Multiple considerations may be needed to help evaluate the treatment and management of hemophilia B5,13</h2>
<ul>
 <li>Due to the distinct behavior and&nbsp;extravascular distribution of factor IX, there is a need to consider hemophilia B as a unique bleeding disorder5,13</li>
 <li>Trough alone may not provide a full picture of factor IX activity and should be&nbsp;one of multiple ways&nbsp;we measure bleed prevention in hemophilia B1,2,19,24,25</li>
 <li>A more&nbsp;complete PK assessment&nbsp;(including half-life, trough, peak, AUC, clearance, and volume of distribution) may provide a different way of thinking about bleed prevention in hemophilia B1,2,5,13,26</li>
 <li>A&nbsp;patient-centered approach&nbsp;that includes evaluation of bleed rates, joint bleed prevention, adherence, and quality of life should be considered when assessing your patients with hemophilia B25,27</li>
</ul>
<h2><a tabindex="0">INFOGRAPHIC:&nbsp;View factor IX differences</a></h2>

It's time to look at the bigger picture in hemophilia B

To read the full content, activate your Sanofi Campus account. Please confirm your email address in the email you received.

If you didn't receive our first email at {email} to confirm your account you can request a new one below. If you don't see it, you may need to check your spam folder.

This information will only be used to validate your account and will not be distributed.

title

Before starting exploring, we can suggest you specific and relevant content

Title

This website is for healthcare professionals only.

Welcome to BP Sanofi Campus

Create new password

To offer you a personalised experience, you must

Your profile is incomplete

The ADCT gives a measure of how controlled the eczema is. Answer these 6 simple questions with your patient to find the ADCT score. It will indicate proper course of action.

Atopic dermatitis, a type of eczema, may be affecting your Patient's life in more ways than you know.

Take the Atopic Dermatitis Control Test (ADCT)

Enjoy more exclusive content{newline}by <a>registering today</a>

Already have an account? <a>Sign in here</a>

Best practices on optimising patient care

Get a customised view of the topics that you're interested in, along with the ability to save content to watch or read at a later date.

Unlimited access to premier content, white papers, case studies, research papers, webinars, training, and up-to-date scientific medical resources.

Personalised content based on your areas of interest

Connect and stay up-to-date with peers in your area of speciality and topics of interest through free events and leadership forums.

Please sign in to continue and read the full article

Please sign up to continue reading the full article.

We respect your privacy and will not share your information with any 3rd parties.

Topical guides written specifically for patients

Unlimited access to the latest patient guide guides and resources. Share content with your patients with easy-to-use online tools.

Please complete your profile to read the content.

Your profile is not validated yet. Please verify your inbox.

Restricted Access

We can't find the page you're looking for

You are going to a website that is not operated by Sanofi. Sanofi has no control over the content or availability of linked sites or resources, and accepts no liability or responsibility for them or for any loss or damage that may arise from your use of them. Please ensure that you read the legal and privacy policy sections of any third-party site to which you link.

You are about to leave Sanofi Campus website.

You are now leaving this site to visit a partner website.

Thank you for visiting COPD Sanofi Campus.

Welcome to COPD Sanofi Campus.

This website is for US healthcare professionals only.

Welcome to COPD Sanofi Campus

Welcome to CSU Sanofi Campus

Please refresh the page to access the content

Sorry, something went wrong

We're usually a treasure chest of knowledge, but we couldn't find what you're looking for.

We were unable to find what you're searching for

Sanofi does not review or control the content of non-Sanofi websites. 
MAT-US-2405606-v1.0-06/2024

You are about to leave Campus.sanofi/uk.

Images from <a>iStockphoto.com</a>, Fotolia.de, <c>gettyimages.de</c>, <d>pexels.com</d> and <e>photocase.de</e> were used for our websites.

Thank you for registering. Before we get started, we need to confirm your email address to ensure that we have the correct information.

Please follow these steps to complete your registration:

Would you like to receive future text messages about Beyfortus updates?

Sanofi is here to help support your patients, their families, and caregivers. For more information regarding Beyfortus®, call <a.callPhoneNumberBeyfortus>1-855-BEYFORTUS (1-855-239-3678)</a.callPhoneNumberBeyfortus> or sign up below to receive the latest updates via email or text. All fields are required.

Would you like to learn more about Beyfortus® (nirsevimab-alip) 50 mg and 100 mg injection? Leave us your contact details, and a Sanofi representative will be in touch.

Would you also like to receive future messages and updates about Beyfortus?

Do you want to participate in the Beyfortus Reservation Program?

What information are you interested in learning more about? (Optional)

Request a visit from your local ALPROLIX representative to learn more. Call <a.callPhoneNumberAltuviiio>1-800-745-4447</a.callPhoneNumberAltuviiio>, Option 5, or complete the form below. The information you provide will be maintained in accordance with our <a.usPrivacyPolicy>Privacy Policy</a.usPrivacyPolicy>. All fields are required.

Request a visit from your local ALTUVIIIO representative to learn more. Call <a.callPhoneNumberAltuviiio>1-800-745-4447</a.callPhoneNumberAltuviiio>, Option 5, or complete the form below. The information you provide will be maintained in accordance with our <a.usPrivacyPolicy>Privacy Policy</a.usPrivacyPolicy>. All fields are required.

Request a visit from your local QFITLIA representative to learn more. Call <a.callPhoneNumberAltuviiio>1-800-745-4447</a.callPhoneNumberAltuviiio>, Option 5, or complete the form below. The information you provide will be maintained in accordance with our <a.usPrivacyPolicy>Privacy Policy</a.usPrivacyPolicy>. All fields are required.

Sign up to schedule an office visit with your ALPROLIX® Representative or receive updates about ALPROLIX. Please complete the form below. The information you provide will be maintained in accordance with our <a.usPrivacyPolicy>Privacy Policy</a.usPrivacyPolicy>. All fields are required.

Sign up to schedule an office visit with your QFITLIA Representative or receive updates about QFITLIA. Please complete the form below. The information you provide will be maintained in accordance with our <a.usPrivacyPolicy>Privacy Policy</a.usPrivacyPolicy>. All fields are required.

This site is intended for healthcare professionals and relevant for HCPs.  It contains information on Sanofi medicines, educational resources, and promotional contents.  By entering this site, you are confirming that you are a healthcare professional.  

MAT-US-2405606-v1.0-06/2024

This content is only available to registered users. Please sign in or register to view this content.

Please Sign In

Email verification

You're seeing a preview of the portal. Clear your cookies (by closing your browser window for example) to go back to public mode.

We've updated our privacy notice to better protect your data and enhance your experience. Please take a moment to review the changes by <privacyNewTab>clicking here</privacyNewTab>. Your privary matters for us. Please click on continue to confirm you have read the new privacy notice.

Privacy Notice Update

Communication consent

My consents

Password

Confirm password

{resultsCount, plural, one {result} other {results}}

Please log in to access to the results

You need to sign-in to your account in order to access medical content.

Please Log In

To access the results, please register in under 1 minute

You are now leaving the Sanofi content section of our site and entering the external medical bibliographic search content section.

You are entering to the External Scientific Content Site

You are now leaving the external medical bibliographic search section of our site and entering the Sanofi content section.

You are entering to Sanofi Content Site

You are about to leave the T1D website

Welcome to the T1D Step Ahead Sanofi website

Enjoy more exclusive content by registering today

Welcome to Sanofi Campus US

Scientific News

Exploring Factor VIII Replacement Therapies: A Guide to Choosing the Right Treatment for Patients With Hemophilia A

Welcome to Sanofi Campus US

Hemophilia B is different. Let’s manage it that way