Haemophilia A management with emicizumab: A survey of haematologists in the United States
, , , , , , e | 02 mar 2022
Article Category: Clinical Practice
Pubblicato online: 02 mar 2022
Pagine: 155 - 182
DOI: https://doi.org/10.2478/jhp-2021-0017
Parole chiave
© 2021 Anisha M. Patel et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
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![Surgical management strategies adopted by haematologists (n=11) treating PwHA who have had surgery while receiving emicizumab treatment* Due to the long half-life of emicizumab (approximately 30 days), effects of emicizumab can remain for at least 6 months after discontinuation [19]† Other haemostatic treatments include FVIII and BPAsBPA: bypassing agents; FVIII: factor VIII; PwHA: person/people with haemophilia A](https://sciendo-parsed.s3.eu-central-1.amazonaws.com/647217e9215d2f6c89dbbb4c/j_jhp-2021-0017_fig_011.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20240707T161758Z&X-Amz-SignedHeaders=host&X-Amz-Expires=18000&X-Amz-Credential=AKIA6AP2G7AKP25APDM2%2F20240707%2Feu-central-1%2Fs3%2Faws4_request&X-Amz-Signature=728249078200061d67619005d3a3645485f8adeffeeb04a5a15ac9dcda775659)
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Haematologist survey questions
| 1. PwHArE age (%) |
Infants (0–12 months) Children (1–11 years) Adolescents (12–17 years) Adults (18–65 years) Older adults (66+ years) |
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| 2. Previously untreated PwHA (PUPs; not previously treated with FVIII) (%) |
Percentage untreated before emicizumab |
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| 3. Severity of disease (based on FVIII genotype) (%) |
Mild Moderate Severe |
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| 4. Frequency of bleeds for PwHA with mild and moderate disease severity (based on FVIII genotype) while treated with emicizumab |
Percentage of those with ≤2 bleeds per year and >2 bleeds per year for:
Mild Moderate |
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| 5. Currently have FVIII inhibitors or had FVIII inhibitors that resolved (%) | Percentage of PwHArE that have/or had low-titer inhibitors and that have/or had high-titer inhibitors for:
PwHA who currently have FVIII inhibitors PwHA who had FVIII inhibitors that resolved |
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| 6. PwHArE physical activity level (%) |
Low impact activities Moderate impact activities High impact activities Typically fit into >1 category of physical activity |
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| 7. What are the five most important PwHA characteristics that you considered when initiating treatment with emicizumab? Please rank the most important characteristic from the list as number one and the least important as number five |
Age Factor level / disease severity Frequency of bleeds Newly diagnosed Previously untreated Safety or efficacy issues with current product Frequency of hospitalisations / emergency room visits Treats prophylactically or not Physical activity level Participation in physically demanding work / school activities PwHA has inhibitors PwHA has high treatment burden (e.g., venous access, frequency of administration) PwHA's distance from emergency treatment PwHA's distance from routine treatment Type of insurance coverage Others (existing health conditions, patient behaviours, caregiver's ability to administer treatment, etc.) |
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| 8. For PwHArE, in most cases who initiated the discussion about starting treatment with or switching to emicizumab? |
I did PwHA (or caregiver) did Other |
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| 9. What are the top five reasons that you advised the PwHArE (or caregiver) or agreed that they switch to / initiate treatment with emicizumab? Please rank the most important reason from the list as number one and the least important as number five |
PwHA does not adhere to current treatment regimen Venous access issues Efficacy issues with current product Safety issues with current product Need to improve bleed management Cost of treatment to PwHA More effective product available Current treatment product is discontinued Insurance coverage issues PwHA is no longer confident in their treatment PwHA requests emicizumab with no definitive reason Inhibitor development To lower treatment burden (e.g., ease of administration, lower frequency) To improve PwHA quality of life Other |
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| 10. How do you help PwHArE (or their caregivers) recognise a breakthrough bleed? Please select all that apply. |
We provide educational materials to help PwHA recognise bleeds PwHA (or caregiver) calls the clinic and describes symptoms and we help diagnose the bleed PwHA (or caregiver) has experience with bleeds and knows when they are having one Other (recommend an ultrasound, etc.) |
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| 11. Do you change the guidance that you provide PwHA for treatment of bleeds (with FVIII or BPA) once they start treatment with emicizumab? |
No Yes |
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| 12. How has the guidance that you provide PwHA with and without inhibitors for treatment of bleeds (with FVIII or BPAs) changed once they started treatment with emicizumab? | I am less likely to recommend; I recommend about the same; I am more likely to recommend; or not sure/NA, for PwHA with inhibitors and PwHA without inhibitors, for the following categories:
Treatment as soon as bleed is suspected Waiting until it is clear they are bleeding, then treat PwHA call an HCP and discuss symptoms and seek help on how to treat the bleed Other treatment guidance |
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| 13. What percentage of the time do PwHArE with and without inhibitors typically seek care from you, the haemophilia treatment center or another healthcare facility when they experience a bleed? (%) | Percentage of PwHA with inhibitors and PwHA without inhibitors for:
Minor bleeds (i.e., requiring a single dose of factor or BPAs to resolve) Significant bleeds (i.e., requiring multiple doses of factor or BPA to resolve) |
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| 14. For each of the following types of bleeds, please select the primary methods for treatment and management of bleeds that you most often suggest to PwHA with inhibitors (or their caregivers) treated with emicizumab. Please select all that apply for each bleed type. | For joint bleeds, muscle bleeds, superficial or other soft tissue bleeds, and other internal bleeds:
Wait until it is clear they are bleeding, then treat Treat as soon as they suspect they have a bleed Contact HCP and discuss symptoms and seek help on how to treat the bleed before treatment rFVIIa as first-line treatment of bleeds Treat with a single dose of rFVIIa Treat with single dose of activated prothrombin complex concentrates Treat until bleed has been resolved Other |
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| 15. For each of the following types of bleeds, please select the primary methods for treatment and management of bleeds that you most often suggest to PwHArE without inhibitors (or their caregiver). Please select all that apply for each bleed type. | For joint bleeds, muscle bleeds, superficial or other soft tissue bleeds, and other internal bleeds:
Wait until it is clear they are bleeding, then treat Treat as soon as they suspect they have a bleed Contact HCP and discuss symptoms and seek help on how to treat the bleed before treatment Treat with a single dose of rFVIIa Treat until bleed has been resolved Other |
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| 16. In general, what would you advise PwHA if they miss a dose of their emicizumab treatment? |
No guidance Take the next dose as planned Administer as soon as possible and then resume dosing schedule Administer as soon as possible and then contact your healthcare provider regarding resuming dosing schedule Other |
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| 17. Which of the following factors would contribute to PwHA discontinuing emicizumab treatment? Please select the top three reasons. |
Issues with insurance Cost of emicizumab Tolerability of subcutaneous injections Tolerability of side effects Compliance with the dosing schedule PwHA choice or desire to discontinue Development of anti-drug antibodies Other |
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| 18. For PwHArE, do you measure FVIII activity more or less frequently than you do for PwHA taking other treatments? |
FVIII activity is measured less frequently in PwHArE FVIII activity is measured at about the same rate in PwHArE FVIII activity is measured more frequently in PwHArE Because I only recently started prescribing emicizumab, FVIII activity is temporarily measured more frequently until I build up more experience Not sure |
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| 19. In general, how often do you measure FVIII activity in your PwHArE with and without inhibitors? Are there any other times that you measure FVIII activity? | For PwHArE with inhibitors and PwHArE without inhibitors, select one of the following for each population:
Once per month Once per quarter Once per year Other frequency Not done on a set schedule When I feel it is necessary When the patient/caregiver requests it Other reasons Not done at any other times |
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| 20. For PwHArE, do you test for FVIII inhibitors more or less frequently than you do for PwHA taking other treatments? |
PwHArE are tested less frequently PwHArE are tested about the same PwHArE taking emicizumab are tested more frequently Because I only recently started prescribing emicizumab, PwHA are temporarily tested more frequently until build up more experience Not sure |
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| 21. How often do you test for FVIII inhibitors in PwHArE with and without inhibitors? | For PwHArE with inhibitors and PwHArE without inhibitors, select one of the following for each population:
Once per month Once per quarter Once per year Other frequency Not done on a set schedule When I feel it is necessary When the patient/caregiver requests it Other reasons Not done at any other times |
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| 22. Do you provide any specific guidance for recreational physical activities to PwHArE? |
No Yes |
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| 23. What type of guidance regarding recreational physical activities do you provide PwHArE? Please select all that apply. |
Customised guidance based on their age Customised guidance based on their fitness goals Customised guidance based on severity Avoid activities that have caused bleeds in the past Follow exercise guidelines (e.g., NHF's “Playing it safe”) I provide the same guidance to all PwHA regardless of the treatment product they use No specific guidance |
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| 24. Once a PwHA begins treatment with emicizumab, is there any change in the guidance that you provide to PwHArE regarding recreational physical activities? Please select all that apply. |
No change in specific guidance Yes, to avoid activities that have caused bleeds in the past Yes, to gradually increase their activity level Yes, to immediately increase their activity level Yes, to additionally use FVIII before any major physical activity Other No change in specific guidance Yes, to avoid activities that have caused bleeds in the past Yes, to gradually increase their activity level Yes, to immediately increase their activity level Yes, to additionally use FVIII before any major physical activity Other |
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| 25. In general, how has the physical activity level changed in PwHArE after starting treatment with emicizumab? |
PwHArE are less active PwHArE have similar activity levels PwHArE are more active Not sure |
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| 26. Have any PwHA had surgery since starting emicizumab? |
No Yes |
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| 27A. How would you manage PwHArE under the following surgical scenarios? Please select all that apply for each category. |
For minor surgery, lower and higher risk of bleeding; major surgery, lower and higher risk of bleeding, select all that apply:
Provide close monitoring of bleeding control Manage timing of emicizumab dose Suspend treatment with emicizumab prior to surgery Pre-operative prophylaxis management with other haemostatic treatments (BPA/FVIII) for additional coverage Intra-operative bleed management with other haemostatic treatments (BPA/FVIII) Post-operative bleed management with other haemostatic treatments (BPA/FVIII) |
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| 28. In PwHArE, do you use ITI with FVIII with the goal of resolving inhibitors? |
Yes, I use ITI in PwHArE No, I haven’t used ITI yet, but I probably will in the future No, I haven’t used ITI yet and I am unlikely to do so in the future [ |
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| 29A. Which one of the following best describes how you manage PwHArE during ITI? |
No additional management of PwHArE during ITI Manage timing of emicizumab dose during ITI Suspend treatment with emicizumab during ITI Other Not sure |
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| 30. ITI dose for PwHArE, compared with PwHA taking other treatments. |
No change Treat with lower dose for ITI (e.g., standard half-life or extended half-life FVIII 50–100 IU/kg for 2 or 3 times per week) Treat with higher dose for ITI (e.g., standard half-life or extended half-life FVIII >100 IU/kg for ≥3 times per week) Other Notsure |
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| 31. ITI duration in PwHArE, compared with PwHA taking other treatments. |
No change Attempt ITI for a shorter duration (e.g., ≤12 months) Attempt ITI for a longer duration (e.g., >12 months) Other Notsure |
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| 32. Treatment for ITI in PwHArE. |
Treat with standard half-life FVIII Treat with extended half-life FVIII Treat with plasma-derived FVIII Treat with recombinant FVIII Other Not sure |
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| 33. Treatment for bleeds in PwHArE during ITI. |
Treat with standard half-life FVIII (for low-titer inhibitors) Treat with extended half-life FVIII (for low-titer inhibitors) Treat with plasma-derived FVIII (for low-titer inhibitors) Treat with recombinant FVIII (for low-titer inhibitors) Treat with low-dose activated prothrombin complex concentrate Treat with rFVIIa Other Not sure |
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| 34. In general, since your PwHA have started emicizumab, do they seek care at your clinic, outpatient clinic, or ER more or less frequently than before, for each of the following? | Since starting emicizumab, PwHArE are seen less frequently, about the same, or more frequently; for each of the following:
Routine care (i.e., annual visit, scheduled appointments) Non-routine care (i.e., trauma, major bleed, surgery) Follow-up care (i.e., after a surgery, trauma, etc) Notsure |
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| 35. In general, do your PwHArE seek care at your clinic, outpatient clinic, or ER more or less frequently than your PwHA on other treatments, for each of the following? | Compared with PwHA on other HA treatments PwHArE are seen less frequently, about the same, or more frequently; for each of the following:
Routine care (i.e., annual visit, scheduled appointments) Non-routine care (i.e., trauma, major bleed, surgery) Follow-up care (i.e., after a surgery, trauma, etc) Notsure |
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| 36. What are the top five factors that impact the frequency of non-routine care office visits for PwHArE? Please rank the most important factor from the list as number one and the least important as number five |
Age Factorlevel Breakthrough bleeds (non-trauma) Bleeds caused by trauma Follow-up after hospitalisations / emergency room visits Need to alter treatment regime or change treatment Need guidance on FVIII or BPA use for bleeds Change in physical activity level Participation in physically demanding work / school activities Inhibitorsstatus Training with self-infusion Change in insurance coverage Other (existing health conditions, patient behaviours, etc.) |
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| 37. For PwHArE do you recommend they keep more or less FVIII/BPA doses at hand for the bleed treatment, than you recommend for PwHA on other treatments? Note: Assume everything about PwHA is the same except their treatment. |
Less FVIII/BPA product doses at hand Same FVIII/BPA product doses at hand More FVIII/BPA product doses at hand Specific to each PwHA Not sure |
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| 38. For PwHArE, how many BPA or FVIII doses do you typically advise they keep at hand in case of breakthrough bleeding? |
1–2 doses 3–4 doses >4 doses Specific to each PwHA Notsure |
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| 39. How does PwHA's level of adherence with emicizumab compare with PwHA taking other treatments? |
Adherence with emicizumab is significantly worse than with PwHA taking other treatments Adherence with emicizumab is worse than with PwHA taking other treatments Adherence with emicizumab is about the same than with PwHA taking other treatments Adherence with emicizumab is better than with PwHA taking other treatments Adherence with emicizumab is significantly better than with PwHA taking other treatments Notsure |
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| 40. How do you monitor PwHA's level of adherence with emicizumab? Select all that apply |
Do not monitor adherence Periodic phone calls/texts to the PwHA (or caregiver) Try to assess adherence at each visit Work with multidisciplinary care team to track adherence Review treatment log with PwHA to assess adherence Other |
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| 41. How do you encourage adherence with emicizumab? Select all that apply. |
We are unable to do anything to encourage or maintain adherence with emicizumab Reminder phone calls/texts to the PwHArE (or caregiver) Discuss the importance of adherence at each visit Provide literature (e.g., tips for adherence or importance of adherence) Provide access to online resources (websites, patient portals, etc.) Recommend educational websites Plan and provide interventions by a healthcare provider for PwHArE who you suspect are not adhering Other |
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| 42. How often do PwHA encounter health insurance coverage issues for the following (never, rarely, occasionally, frequently, always, not sure): |
Coverage for emicizumab Coverage for FVIII/BPA for bleed treatment while taking emicizumab Care for HA while taking emicizumab (i.e. office visits, physical therapy, etc.) |
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| 43. How has the level of disease management support that you provide PwHArE changed since they started treatment with emicizumab? |
Less support than PwHA taking other treatments No change, the same support as PwHA taking other treatments More support than PwHA taking other treatments Notsure |
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| 44. Why do you provide less disease management support to PwHArE? |
PwHArE have fewer disease-related issues than PwHA taking other treatments PwHArE have a lower disease burden than PwHA taking other treatments PwHArE have fewer bleeds I am not as concerned about PwHArE having breakthrough bleeds I am not as concerned about PwHArE needing emergency care Other |
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| 45. Why do you provide more disease management support to PwHArE? Please select all that apply. |
PwHArE have more disease-related issues than PwHA taking other treatments PwHArE have a greater disease burden than PwHA taking other treatments PwHArE are engaged in more physically demanding activities I am concerned about PwHArE having breakthrough bleeds I am concerned about PwHArE needing emergency care Emicizumab is a newer agent with limited, long-term safety and efficacy data Other |
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Demographics and clinical characteristics of PwHArE treated by haematologists in this survey, as reported by haematologists.These data are presented as perceived by the haematologists who completed the survey and do not include patient-level data
| Infants (aged 0–12 months) | 1.6 |
| Children (aged 1–11 years) | 16.2 |
| Adolescents (aged 12–17 years) | 16.2 |
| Adults (aged 18–65 years) | 55.3 |
| Older adults (aged >65 years) | 10.6 |
| 10.1 | |
| Mild | 12.8 |
| Moderate | 21.3 |
| Severe | 65.9 |
| ≤2 bleeds/year | 64.3 |
| >2 bleeds/year | 35.7 |
| ≤2 bleeds/year | 54.0 |
| >2 bleeds/year | 46.0 |
| Low titre inhibitors | 35.3 |
| High titre inhibitors | 64.7 |
| Low titre inhibitors | 39.7 |
| High titre inhibitors | 60.3 |
| Low impact activities | 24.0 |
| Moderate impact activities | 34.5 |
| High impact activities | 29.7 |
| Typically fit into >1 category of physical activity |
11.8 |
Screening criteria required for survey participation
| Profession | Medical doctor |
| Primary specialty | Haemophilia A |
| Board-certified in haematology? | Yes |
| Number of years of post-residency experience | ≥2 years |
| Geographical location | US |
| PwHA treated in an HTC | ≥5 PwHA |
| PwHA treated in a non-HTC | ≥3 PwHA |
Geographical location of haematologists
| Arizona | 3 |
| California | 6 |
| Connecticut | 1 |
| Florida | 5 |
| Georgia | 1 |
| Illinois | 3 |
| Iowa | 1 |
| Kentucky | 2 |
| Louisiana | 3 |
| Michigan | 3 |
| Missouri | 1 |
| Nebraska | 1 |
| New Jersey | 1 |
| New York | 4 |
| North Carolina | 1 |
| Ohio | 3 |
| Pennsylvania | 3 |
| Tennessee | 1 |
| Texas | 2 |
| Virginia | 1 |
| Washington | 2 |
| Wisconsin | 2 |
Survey themes
| Professional qualifications, medical specialty, board certification, post-residency experience, practice setting, geographical location, number of PwHA treated, and treatment | 11 | |
| Part 1 | Initiating treatment with emicizumab | 9 |
| Part 2 | Bleed management | 6 |
| Part 3 | Missed dose or discontinuation | 2 |
| Part 4 | Monitoring | 4 |
| Part 5 | Activity guidance | 4 |
| Part 6 | Surgery management | 2 |
| Part 7 | ITI | 6 |
| Part 8 | Resource use and care | 8 |
| Part 9 | Treatment access | 1 |
| Part 10 | Change in overall disease management | 3 |