Haemophilia A management with emicizumab: A survey of haematologists in the United States
, , , , , , and | Mar 02, 2022
Article Category: Clinical Practice
Published Online: Mar 02, 2022
Page range: 155 - 182
DOI: https://doi.org/10.2478/jhp-2021-0017
Keywords
© 2021 Anisha M. Patel et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Haemophilia A is a congenital bleeding disorder associated with spontaneous or traumatic bleeding, most commonly into joints, muscles, and soft tissues [1]. It is caused by a deficiency in coagulation factor VIII (FVIII) [1,2], and can lead to secondary complications such as arthropathy [3] and functional deficits [4,5,6].
The introduction of emicizumab represents a paradigm shift in the treatment landscape for haemophilia A. Against this background, understanding how haematologists are adapting their management of treatment of people with haemophilia A receiving emicizumab is key.
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Prophylaxis with plasma-derived and recombinant factor concentrates has been used for haemophilia A treatment for decades [7]; however, factor replacement therapies require regular intravenous infusions 2–3 times per week [8]. These burdensome treatment regimens can result in reduced adherence [9]. Furthermore, up to 20% of people with haemophilia A (PwHA) develop FVIII inhibitors, making them resistant to factor replacement therapies [10]. PwHA with FVIII inhibitors are typically treated with bypassing agents (BPAs) [11]. Some PwHA with FVIII inhibitors undertake immune tolerance induction (ITI), a costly and demanding process consisting of prolonged daily or alternate day high-dose FVIII intravenous administration with the aim of eradicating FVIII inhibitors [12,13].
Emicizumab, a recombinant, humanised, bispecific monoclonal antibody, is currently the only non-factor therapy approved for routine prophylaxis in PwHA with and without FVIII inhibitors. Emicizumab bridges activated FIX and FX to restore the function of missing activated FVIII in PwHA [14], and is administered subcutaneously either once weekly, every 2 weeks, or every 4 weeks [15,16,17]. The pivotal phase 3 HAVEN clinical trial programme of emicizumab demonstrated its efficacy and safety; marked reductions in annualised bleeding rates of treated bleeds were observed, regardless of FVIII inhibitor status, and a majority of PwHA participating in the trials reported zero treated bleeds [15,16,17,18]. Data from HAVEN 1–4 [15,16,17,18] supported the approval of emicizumab by the US Food and Drug Administration for routine prophylaxis in PwHA of all ages, regardless of inhibitor status [19].
As emicizumab has a different mechanism of action and mode of administration compared with factor replacement therapy or BPAs [20], this raises the question of whether haematologists have adapted their care of PwHA accordingly. Many PwHA receiving emicizumab (PwHArE) experience few bleeds [21], and the sustained therapeutic plasma levels of emicizumab [22] offer different coverage for bleed prevention compared with the peaks and troughs of factor replacement. This may impact management of PwHArE by haematologists, including considerations such as surgery management and physical activity guidance. Use of emicizumab with ITI in the real-world setting has been covered through an increasing number of case reports [23] and a retrospective review study [24] on the concomitant use of emicizumab and ITI. As emicizumab prophylaxis is effective in preventing bleeding, FVIII can be administered solely for the purpose of inducing tolerance, and therefore at a lower dose or lower frequency than is typically used when undertaking ITI [13].
Due to these distinct features and the growing adoption of emicizumab in clinical practice, it is theorised that haematologists may adapt the way they treat PwHArE. The aim of this qualitative survey of haematologists was to understand the disease management practices of haematologists when managing and treating PwHArE, and to examine any changes in such practices.
A multi-level approach was used to develop the survey (Appendix / Supplementary Figure 1). To identify haematologists both to help with development of the survey and participate in the survey, the directory of the Centers for Disease Control and Prevention was used to locate haemophilia treatment centres (HTCs) in the US (
Invites for the survey were sent to haematologists across 140 HTCs as well as those working outside HTCs who were identified by MedPanel. From 8 May 2019 to 20 May 2019, eligible board-certified US paediatric and adolescent/adult haematologists were surveyed to understand their experience treating PwHArE, and to assess any changes in disease management practices in response to emicizumab. The haematologists surveyed during this time did not include any of the haematologists who had participated in the survey development and pilot survey. Participants were screened to determine if they met the inclusion criteria (Appendix / Supplementary Table 1), which included: board certification in haematology, practising in the US, ≥2 years of post-residency experience, currently treating ≥3 PwHArE. The survey topics ranged from emicizumab initiation to monitoring and special circumstances, such as surgery and ITI (Table 1). The final screening and survey questions are provided in the Appendix / Supplementary Table 3. Reported percentages are averaged across all survey responses.
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 |
ITI: immune tolerance induction; PwHA: people with haemophilia A
A total of 208 haematologists responded to the invite. Fifty-one met the screening criteria and completed the survey (n=83 screened out on one or more exclusion criteria; n=74 partially completed the screening or survey but did not finish). One of the completed surveys was excluded, leaving 50 surveys completed by 50 haematologists across 22 states (Appendix / Supplementary Table 2).
Of the 50 haematologists surveyed, more than three quarters (78%) had ≥10 years of post-residency experience and 46% practised at academic/teaching hospitals; of these, 78% (n=18/23) were federally funded. The majority (62%) of haematologists treated ≥25 PwHA per month; approximately 70% of all PwHA treated were adolescents/adults, and roughly one quarter (adult, 24.5%; paediatric, 22.1%) had FVIII inhibitors. All results presented here are as reported by the 50 haematologists who completed the survey, and the patient characteristics, outcomes, and experiences reported reflect the haematologists’ perception of these factors.
Of the PwHArE reported by the haematologists surveyed, 66% were adults (≥18 years old); 13%, 21%, and 66% had mild, moderate, and severe haemophilia A, respectively (Table 2). When starting emicizumab, approximately 10% were previously untreated with FVIII. A majority of the PwHArE (64%) engaged in moderate or high impact physical activities. When asked “What are the five most important patient characteristics that you considered when initiating treatment with emicizumab?”, the most common options chosen by the surveyed haematologists were: presence of FVIII inhibitors (70%), high treatment burden (62%), and frequency of bleeds (60%).
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 |
FVIII: factor VIII; PUP: previously untreated person with haemophilia A; PwHA: people with haemophilia A; PwHArE: people with haemophilia A receiving emicizumab
Not previously treated with FVIII
As determined by FVIII genotype. Frequency of bleeds were reported for people with mild and moderate haemophilia A only
Only haematologists who indicated they treated mild (n=22) or moderate (n=37) PwHArE, respectively, were eligible to respond to this question
PwHA participating in mixed activities
In total, 86% of surveyed haematologists reported that, in most cases, they initiated the discussion concerning emicizumab prophylaxis, with the remaining 14% reporting that, in most cases, the PwHA (or their caregiver) initiated the conversation. When providing reasons for initiating this discussion, haematologists could select multiple answers; lowering treatment burden (64%), improving quality of life (QoL; 64%), FVIII inhibitor development (56%), improving bleed management (56%), and venous access issues (48%) were the top five reasons reported (Figure 1).
Figure 1
Reasons for PwHA starting emicizumab treatment, as perceived by haematologists (N=50)
These reasons are presented as perceived by the haematologists who completed the survey and do not include patient-reported data
PwHA: person/people with haemophilia A; QoL: quality of life
* Examples: ease of administration and lower administration frequency
Haematologists could similarly select multiple answers concerning bleed management. To assist PwHArE (and their caregivers) in recognising breakthrough bleeds, some haematologists provided educational materials (68%) or suggested PwHArE call their healthcare provider (HCP) for diagnosis support and to discuss bleed symptoms (70%), while others reported that their PwHArE and caregivers know how to identify current bleeds (64%). Other means, such as providing an ultrasound scan, were offered infrequently (16%).
About one third (34%) of haematologists surveyed reported that they have changed their guidance on bleed treatment for PwHArE. Changes to guidance stratified by FVIII inhibitor status are shown in Figure 2; haematologists responded that they are more likely to advise PwHArE to call an HCP to discuss symptoms and treatment, regardless of FVIII inhibitor status. When asked what percentage of time PwHArE seek medical care for minor and significant bleeds, haematologists reported that PwHArE with FVIII inhibitors sought slightly more care than those without FVIII inhibitors (minor bleeds: with FVIII inhibitors, 41%; without FVIII inhibitors, 39%; significant bleeds: with FVIII inhibitors, 67%; without FVIII inhibitors, 60%); however, the numerical difference between subgroups was minimal.
Figure 2
Changes to haematologists’ (n=17)* guidance on bleed management in PwHA with FVIII inhibitors (a) and without FVIII inhibitors (b), since starting emicizumab
FVIII: factor VIII; HCP: healthcare professional; NA: not applicable; PwHA: person/people with haemophilia A
* The remainder of the haematologists surveyed (n=33/50) indicated that they did not change their bleed management guidance when their patients began receiving emicizumab
Treatment guidance varied by FVIII inhibitor status and bleed type (Appendix / Supplementary Figure 2), but overall, a large proportion of haematologists recommended a few strategies, including asking PwHArE to treat as soon as a joint, muscle, or other internal bleed is suspected, regardless of FVIII inhibitor status. For superficial/other soft tissue bleeds, 50% of haematologists recommended that PwHArE with FVIII inhibitors call an HCP to discuss symptoms and obtain treatment advice before treating, while 54% recommended that those without FVIII inhibitors take a single dose of FVIII as soon as a bleed is suspected. A majority of haematologists (48%) advised the same number of FVIII/BPA doses should be kept on hand by PwHArE compared with those on other HA treatment (Appendix / Supplementary Figure 3a); for most haematologists (42%), this recommendation was 3–4 FVIII/BPA doses (Appendix / Supplementary Figure 3b).
When asked “How does the patient's level of adherence with emicizumab compare to your HA patients on other treatments?”, 50% of haematologists surveyed perceived that PwHArE have better or significantly better adherence to their prophylactic regimen, while 40% perceived a similar adherence, compared with PwHA taking other prophylaxis. Most haematologists reported monitoring adherence through assessment at each office visit (74%) and working with a multidisciplinary care team to track adherence (44%). To encourage treatment adherence, 86% of haematologists reported discussing its importance with PwHArE at each office visit (Appendix / Supplementary Figure 3c).
Overall, 94% of haematologists reported that they provided guidance to PwHA on a missed emicizumab dose. Administering the missed dose as soon as possible and then resuming the recommended dosing schedule was the most frequently reported advice (44%), followed by administering the next dose as planned (26%) and administering the missed dose as soon as possible before contacting an HCP to discuss resuming the dosing schedule (24%).
When queried about factors contributing to PwHA discontinuing emicizumab, insurance coverage issues (70%), treatment cost (50%), personal choice of the individual (44%), and tolerability of subcutaneous injections (44%) were the most frequently cited reasons.
Some haematologists reported less frequent measuring for FVIII activity (52%) and testing for FVIII inhibitors (28%) in PwHArE compared with PwHA taking other haemophilia A treatments, while 34% and 54% were measuring and testing about the same, respectively.
For PwHA with FVIII inhibitors, haematologists were more likely to report measuring FVIII activity monthly (18%) and at additional times when they thought it was necessary (64%) compared with PwHA without FVIII inhibitors (6% and 58%, respectively). Others reported measuring FVIII activity for PwHA with and without FVIII inhibitors once a quarter (30% and 36%, respectively), once a year (22% and 26%), and upon PwHA/caregiver request (both 30%) (Appendix / Supplementary Figure 4). Most haematologists (76%) also reported testing for FVIII inhibitors when they felt it was necessary. For PwHA without FVIII inhibitors, haematologists reported testing for inhibitors once per quarter or once per year (36% each; Appendix / Supplementary Figure 4); however, the majority (60%) reported that they would also test at additional times when they felt it was necessary.
When asked “In general, how has the physical activity level changed in your patients after starting treatment with emicizumab?”, the majority (84%) of haematologists surveyed perceived that the recreational physical activity levels of PwHA remained the same (52%) or increased (32%) after starting emicizumab treatment (Figure 3a). Among the 27 haematologists who provided specific guidance on recreational physical activities, most developed customised plans for PwHArE based on fitness goals (81%), disease severity (74%), and age (56%; Figure 3b); further, after starting emicizumab, 48% of haematologists who provide activity guidance recommended that PwHArE gradually increase these activities, while 37% also recommended to avoid activities that have caused bleeds in the past (Figure 3c).
Figure 3
Haematologists’ perceptions of (a) how physical activity levels have changed in PwHA since starting emicizumab (N=50), (b) what type of physical activity guidance they provide to PwHArE (n=27)*, and (c) if their guidance changes once PwHA start taking emicizumab (n=27)*
These outcomes are presented as perceived by the haematologists who completed the survey and do not include patient-reported data
Multiple strategies in the surgical management of PwHArE were reported, with 22% (n=11/50) of the haematologists surveyed treating PwHArE who have undergone surgery at the time of the survey. Haematologists reported varying levels of management, from close monitoring of bleed control to pre- or post-operatively using other haemostatic treatments, depending on the type of surgery and risk of bleeding. Overall, the least preferred management option was suspending or stopping emicizumab prior to surgery. For minor and major surgeries with a high risk of bleeding, 91% (n=10/11) of haematologists managed PwHArE pre operatively using other haemostatic treatments (BPAs or FVIII; Appendix / Supplementary Figure 5) for additional coverage.
A minority of haematologists surveyed (22%, n=11) reported that they were carrying out ITI and 38% (n=19) were considering using it in the future. Among those currently carrying out or considering initiating ITI in the future, treatment choice for ITI and bleeds in PwHArE varied (Figure 4a and 4b, respectively).
Figure 4
ITI products and bleed treatments used or considered for use in PwHArE (n=30)
aPCC: activated prothrombin complex concentrate; FVIII: factor VIII; ITI: immune tolerance induction; PwHArE: person/people with haemophilia A receiving emicizumab; rFVIII: recombinant factor VIII; rFVIIa: recombinant factor VIIa
* PwHArE and receiving ITI: n=11
† PwHArE and who may receive ITI in the future: n=19
Of the 11 haematologists currently carrying out ITI in PwHArE, the majority (73%) opted to prescribe a lower dose of FVIII for ITI (e.g. FVIII 50–100 IU/kg 2 or 3 times per week) compared with PwHA taking other haemophilia A treatments. Almost half (45%) opted to shorten the duration of ITI (e.g. ≤12 months), with the next most popular option being no change to duration (36%) (Appendix / Supplementary Figure 6a). Most haematologists (64%) reported managing the timing of emicizumab dosing during ITI, with a minority (27%) stating that no additional management was required.
Among the 19 haematologists who were considering ITI, approximately half (53%) planned to prescribe a lower dose of FVIII for PwHArE compared with those taking other haemophilia A treatments. Around half (47%) planned no change to the duration and about a third (32%) planned to shorten the duration (Supplementary Figure 6b). Responses regarding how they intended to manage this treatment were mixed; 42% indicated that no additional management was planned; an equal amount (16% each) planned to either manage the timing of emicizumab dosing or suspend treatment with emicizumab; 5% indicated other methods; and 21% were unsure.
In this survey, routine care was defined as annual visits and scheduled appointments. Most haematologists surveyed (72%) perceived that PwHA seek the same amount of routine care pre- and post-emicizumab prophylaxis initiation, while 14% perceived that less routine care was sought. The proportion of haematologists who perceived that PwHArE sought less non routine care (trauma, major bleed, and emergency surgery) post-emicizumab initiation was 32%; 46% of the haematologists perceived that non-routine care levels remained the same. Follow-up care was defined as post-surgery and trauma care. Over half (56%) of the haematologists surveyed perceived that PwHArE seek the same amount of follow-up care as they did prior to starting emicizumab prophylaxis (Figure 5a).
Figure 5
Haematologist-reported changes to (a) level of care sought by PwHA since starting emicizumab and (b) level of care sought by PwHArE compared with PwHA taking other haemophilia A treatments (N=50)
These outcomes are presented as perceived by the haematologists who completed the survey and do not include patient-reported data
PwHA: person/people with haemophilia A; PwHArE: person/people with haemophilia A receiving emicizumab
When comparing with PwHA receiving other haemophilia A treatment, 78% of haematologists perceived that PwHArE seek the same amount of routine care, while 14% perceived that they seek less. Regarding non-routine care, a higher proportion of haematologists (36%) perceived that PwHArE sought care less frequently compared with PwHA receiving other haemophilia A treatment; 58% perceived these levels were about the same. The top five reasons PwHArE received non-routine care were: non-trauma-related breakthrough bleeds (76%); trauma-related bleeds (54%); guidance needed on FVIII or BPA use (52%); follow-up care after hospitalisations/emergency room visits (48%); and participation in physically demanding work or school activities (44%). After trauma or a surgery, most haematologists (60%) thought that PwHArE sought similar levels of follow-up care compared with those taking other haemophilia A treatments (Figure 5b).
When surveyed on the frequency of issues encountered with insurance coverage of emicizumab by health insurance providers, at the time of the survey, 46% of haematologists believed that the PwHA in their care frequently/always experience these issues with emicizumab. In addition, 38% of haematologists believed that PwHArE frequently/always experience issues with FVIII/BPA coverage for bleed treatment and 22% found the same for care (e.g. office visits, physical therapy) while on emicizumab (Figure 6).
Figure 6
Proportion of PwHA who experience insurance coverage issues for emicizumab treatment (a), FVIII/BPAs treatment for bleed management while taking emicizumab (b), and care for haemophilia A while taking emicizumab* (c), as reported by haematologists (N=50)
These experiences are presented as perceived by the haematologists who completed the survey and do not include patient-reported data
BPA: bypassing agent; FVIII: factor VIII; HA: haemophilia A; PwHA: people with haemophilia A
*Example: office visits and physical therapy
When asked how the level of disease management support they provided to PwHArE had changed since starting emicizumab, the majority (58%) of haematologists reported no change compared with the support they offered to PwHA taking other haemophilia A treatments (Appendix / Supplementary Figure 7). Of those who reported that they provided less support (n=6), they cited fewer bleeds (100%), fewer disease-related issues versus PwHA taking other haemophilia A treatments (83%), and not being as concerned about breakthrough bleeds for PwHArE (67%) as the most common reasons. For those reporting that more support was required (n=13), limited long-term efficacy and safety data (at the time of survey) was the most frequently cited reason (54%).
A total of 50 haematologists in the US were included in this qualitative survey, most of whom practiced at federally funded haemophilia treatment centres. The majority of PwHA treated by these haematologists were adults aged 18 years or over, with severe haemophilia A. Approximately 10% of PwHA had not received FVIII treatment prior to starting emicizumab.
The most common reasons given for initiating emicizumab prophylaxis in PwHA included: lowering treatment burden, improving QoL, FVIII inhibitor development, improving bleed management, and venous access issues. This may be due to the reported efficacy of emicizumab in PwHA regardless of FVIII inhibitors [15,18], and its subcutaneous administration on a weekly, every 2 weeks, or every 4 weeks basis [17], which are afforded by its mechanism of action [20]. Emicizumab is not structurally analogous to FVIII [14] and therefore can be used in PwHA with and without FVIII inhibitors without causing the development of new FVIII inhibitors [19]. It was anticipated that this would be a strong motivating factor for switching to emicizumab, which is supported by the results of this survey. The reasons for initiating emicizumab chosen by haematologists in this survey are supported by data from the HAVEN clinical trials, including improvements in QoL, as quantified using measures such as the Haemophilia Quality of Life Questionnaire for Adults and the Haemophilia-specific Quality of Life Questionnaire for Children Short Form [25,26,27]; high rates of zero treated bleeds [21]; and the results of the Emicizumab Preference Survey [28]. It was also perceived by the haematologists surveyed that the majority of PwHA maintained or increased their recreational physical activity levels after starting emicizumab, which may play a role in improving their QoL.
Most haematologists surveyed reported no change in the disease management support sought by PwHArE since starting emicizumab, and that they receive a similar level of support compared with PwHA receiving other haemophilia A treatments. Around a quarter of haematologists surveyed reported that PwHArE sought more support; this may be due to the novelty of emicizumab, although this consideration likely only applies to the initial period after treatment switch. The primary reason given for this increased support was limited long-term efficacy and safety data at the time of the survey; however, it should be noted that more long-term data and real-world evidence have since been published [21,29,30,31,32]. Of the haematologists who reported that PwHArE sought less support than previously, and less than PwHA receiving other haemophilia A treatments, most indicated that this was due to fewer bleeds and disease-related issues, and less concern regarding breakthrough bleeding in PwHArE, an opinion supported by data from the HAVEN clinical trial programme [15,16,17,18]. There were some differences in disease management when PwHA began receiving emicizumab, as noted by the haematologists. For example, in the event of a bleed, they were more likely to advise PwHArE to call an HCP to discuss symptoms and treatment for guidance on determining whether a bleeding episode could be confirmed, which may reflect the need to confirm a bleed given how new emicizumab was at the time of the survey. Over half of the haematologists surveyed reported monitoring less frequently for FVIII activity for PwHArE compared with other haemophilia A treatments; this may be due to the difficulty of quantifying FVIII equivalence for a therapy with a fundamentally different mechanism of action [33], or it may reflect the sustained protection afforded [22], in contrast to the peaks and troughs of FVIII replacement therapy.
Although only small numbers of haematologists in the survey had handled more challenging situations such as surgery and ITI, these are important topics in the haemophilia community. As such they were included in the survey to gather information on best practice and haematologists’ experience of how they can be managed in PwHArE. Many haematologists administered FVIII or BPAs pre-, intra-, and postoperatively for PwHArE undergoing major and minor surgeries, more so if there was judged to be a higher bleed risk. These findings were aligned with the HAVEN programme, in which 83% of major surgeries were performed with prophylactic coagulation factor and the majority had no treated post-operative bleeds [34]. Most haematologists used lower doses of FVIII for ITI and would maintain or shorten duration. This is presumably due to the prophylactic bleed protection provided by emicizumab, so FVIII can be dispensed only at the dose needed to induce tolerance [13].
Emicizumab is a bispecific humanised monoclonal antibody in a treatment landscape primarily characterised by iterative improvements on factor replacement. As it becomes more widely prescribed, the experience of haematologists currently using emicizumab to treat PwHA is invaluable. This survey can therefore be used to inform clinical practice and decision making by haematologists when initiating treatment with emicizumab in the PwHA under their care. Moreover, the implications of these findings can be used to guide insurance coverage policies; for example, the recommendation by many of the haematologists surveyed was for PwHA to keep 3–4 doses of FVIII or BPAs on hand to treat any potential breakthrough bleeds. Furthermore, the haematologists consulted in this survey collectively highlighted the treatment access issues encountered by PwHA, which were cited as the most common reason for discontinuing emicizumab. This finding is consistent with data from a survey of people with haemophilia where insurer-restricted access to HTCs was highlighted as an issue of concern [35]. Emicizumab has an established long-term safety profile, proven efficacy in bleed prevention [21], and, as illustrated by better treatment adherence reported in this survey compared with other haemophilia A treatments, a low treatment burden. It has been found that high treatment adherence is vital for achieving optimal clinical outcomes and improvements in haemophilia-A-related QoL [6,36,37]; therefore, it is critical that appropriate PwHA should be able to access this therapy.
Potential economic benefits of emicizumab, particularly in PwHA with FVIII inhibitors [38,39,40], were also expanded upon by the results of this survey. Despite the cost, ITI remains the only proven modality for eradicating FVIII inhibitors [41]. In the current survey, most haematologists indicated that they would treat PwHArE with a lower dose of FVIII for ITI and many also indicated that they would shorten the duration of ITI, representing potential cost savings to the insurance provider and/or PwHA. Two recent Institute of Clinical and Economic Review reports demonstrated cost savings of emicizumab over FVIII and BPA therapies in non-inhibitor and inhibitor populations, respectively [42,41,42,43]. Emicizumab's cost-effectiveness has also been shown in other short- and long-term economic models [38,39,40].
Limitations of the data include those inherent to survey research, such as restrictive wording of the questions and responses, subjective interpretations by respondents, and human errors in memory and reporting [44]. Further limitations are the relatively small sample size of haematologists surveyed (N=50) and limited number of years’ experience managing PwHArE. Additionally, although it was noted that roughly one quarter of the PwHA managed by the haematologists in this survey had FVIII inhibitors (an important factor in the context of disease management), this was not quantified for the PwHArE. However, since 56% of haematologists reported that FVIII inhibitor development was one of the most important reasons for initiating treatment with emicizumab prophylaxis, it is likely that a higher proportion of their PwHArE had FVIII inhibitors compared with the wider population of PwHA that they manage. The proportion of PwHArE with FVIII inhibitors may have impacted many of the survey findings, for example bleed frequency, physical activity, level of routine care, and treatment adherence. Furthermore, the findings reported here represent the haematologists’ own personal experience and opinions and have not been confirmed as best practice in a trial setting; as such, reported changes in disease management practice should be interpreted with caution. Finally, the aspects of patient experience described here (for example, treatment adherence and treatment burden) are according to the surveyed haematologists’ perception and not the patient's own report, and may therefore be subject to the haematologists’ own bias. As the availability and quantity of post-approval emicizumab data and experience increases, new analyses will enable the generalisability of the results presented herein to be analysed and interpreted further.
The advent of emicizumab, a fully prophylactic treatment with subcutaneous administration once weekly, every 2 weeks, or every 4 weeks, represents a paradigm shift in the haemophilia A treatment landscape. Publishing the experience of haematologists using emicizumab in a real-world setting is important to inform clinical practice and disease management in PwHArE as its availability and use increases. The findings of this survey illustrate that some haematologists have adapted their management of haemophilia A in PwHArE, including how they handle bleed management, FVIII monitoring, and situations such as surgery and ITI. As emicizumab is increasingly prescribed and long-term, post-approval data continue to become available, patient characteristics, treatment methods, and disease management practice should continue to be monitored to support haematologists’ treatment and care of PwHA.