Abstract
Background:
Systematically documented data on real-world use of emicizumab, a bispecific antibody factor (F)VIII mimetic, are still lacking in people with severe haemophilia A (PwSHA). Smart medication, a real-time, online platform, monitors treatment administration and outcomes for people with haemophilia A in Germany.
Objective:
To evaluate annualised bleeding rates (ABRs) and annualised joint bleeding rates (AJBRs), using data documented in the smart medication eDiary, for PwSHA receiving emicizumab.
Design:
Data for 97 PwSHA without FVIII inhibitors who started emicizumab treatment between 1 January 2018 and 31 March 2023, with >24 weeks of documentation after switching from FVIII replacement, were collected in the smart medication eDiary. Those with ⩾24 weeks of pre-emicizumab data were included for analysis 24 weeks before and after switching.
Methods:
The primary objective was to evaluate ABR and AJBR for treated bleeds. The proportion of bleed-free participants was calculated and administration frequency for FVIII and emicizumab were collected. The mean dosing frequencies for FVIII replacement and emicizumab were also evaluated.
Results:
The mean calculated ABR and AJBR were 0.64 and 0.39, respectively, after initiating emicizumab. For those with documentation before starting emicizumab (n = 58), ABR decreased by 79.6% and AJBR decreased by 90.8%. The proportion of bleed-free participants increased by 21.3%, and joint bleed-free participants increased by 18.2%. The median FVIII dosing frequency was every 3.5 days (n = 54; range: 1.0–20.8); median emicizumab dosing frequency was every 11.2 days (N = 97; range: 6.6–29.4).
Conclusion:
Real-world data collected using the smart medication eDiary provide insights into efficacy outcomes after switching from FVIII replacement to emicizumab prophylaxis. Bleeds, including joint bleeds, decreased after switching.
Introduction
The congenital form of haemophilia A (HA) is characterised by a lack of factor (F)VIII. In people with severe HA (PwSHA; FVIII levels <1% of normal), the deficiency of FVIII can cause indiscriminate and spontaneous bleeding, predominantly into joints and muscles. This risks the development of chronic joint arthropathy 1 and, consequently, negatively impacts health-related quality of life and work productivity. 2
Until recently, the standard of care for PwSHA or a severe bleeding phenotype was regular prophylaxis with FVIII replacement. 3 A key limitation of standard half-life (SHL) FVIII replacement prophylaxis is the requirement for administration of intravenous infusions 3–4 times per week, 3 which carries a high treatment burden that can cause issues with adherence. 4 The development of extended half-life (EHL) FVIII therapies allows administration 1–3 times per week,5–7 which can help to reduce the treatment burden. However, all FVIII therapies are associated with the development of inhibitors against FVIII, which occurs in approximately 30% of previously untreated people with HA (PwHA).8,9
Emicizumab, a recombinant, bispecific monoclonal antibody, mimics the functionality of activated FVIII by bridging activated FIX and FX10,11. Numerous clinical trials reported that it was well tolerated and improved haemostasis in adults and children with HA with or without FVIII inhibitors.12–19 These trials demonstrated that emicizumab is effective when administered subcutaneously every 7, 14 or 28 days, which has the potential to reduce the burden of treatment for PwHA.
Several real-world studies evaluating the safety and effectiveness of emicizumab prophylaxis present comparable outcomes to those reported in the phase III clinical trials.20–23 However, systematically documented, detailed data on the real-world use of emicizumab prophylaxis in PwSHA, particularly bleeding outcomes, dosing and administration frequency, are lacking in Germany. There are also limitations with regard to how real-world data can be collected; for instance, data from PwHA are often recorded retrospectively using information from patient files or paper-based diaries, which can result in variable accuracy. 24 Additionally, healthcare professionals may find it difficult to analyse handwritten entries during or following clinical visits, meaning information about the treatment regimen, duration of treatment and outcomes of self-treatment is often delayed or missing.
Smart medication, a real-time, web-based online platform, was developed and set up in 2011 to help monitor treatment administration and outcomes for PwHA. In February 2012, smart medication was launched as part of a pilot study in cooperation with the Association for the Promotion of Telemedicine in Haemostaseology (‘VFTH e.V.’). 25 The decision to offer an electronic platform, as well as selecting which platform to provide, is made at the discretion of the Haemophilia Treatment Centre (HTC). Not all people with haemophilia at a HTC offering the platform are registered; use of the platform is optional, with participants able to opt in and withdraw their consent at any time.
Real-time data were collected via self-reported participant documentation in the eDiary within the smart medication platform. The key objective of this retrospective analysis is to report any observable changes in the annualised bleeding rate (ABR) or annualised joint bleeding rate (AJBR) following the switch from a FVIII concentrate to emicizumab in PwSHA in Germany. Real-world data on the usage of emicizumab prophylaxis are also presented.
Materials and methods
Study design and participants
People of all age groups with severe HA (defined as FVIII at <1% of normal levels) without current FVIII inhibitors, who were switched to or started emicizumab in the evaluation period between 1 January 2018 and 31 March 2023, and with >24 weeks of electronic documentation in the smart medication eDiary after starting emicizumab, were eligible for inclusion in the study. For participants who had ⩾24 weeks of pre-emicizumab treatment documentation prior to study enrolment, analyses of data from 24 weeks before and 24 weeks after the switch to emicizumab were performed. Individuals with a positive inhibitor titre (>0.6 Bethesda units/mL) and those receiving immune tolerance induction (ITI) therapy during the evaluation period were excluded.
Objectives and outcome parameters
The primary objective of this study was to evaluate the ABR and AJBR using real-world data collected via the smart medication eDiary after participants switched from FVIII replacement to emicizumab. ABR and AJBR were calculated based on the number of treated bleeds reported.
The secondary objective was to evaluate the medication frequency and dosing for FVIII concentrate use and emicizumab prophylaxis. Further analyses included participant compliance with eDiary documentation; dose and frequency of FVIII per joint bleed, per follow-up treatment for bleeding events, and for life-threatening bleeds before and after switching to emicizumab; FVIII usage and occurrence of bleeds during the emicizumab loading phase; recurrence of FVIII inhibitors in participants who had previously received successful ITI therapy after the switch to emicizumab.
Data collection
The smart medication platform was developed, classified and registered as a class I medical device according to the Medical Devices Directive of the European Union (Directive 93/42/EEC). 25 PwHA or their carers provided consent to both use the platform and allow anonymous data evaluation.
Treated bleeds were defined manually by identifying bleeds that coincided with FVIII replacement administration, in addition to bleeds documented in the eDiary. Treated bleeds were further stratified according to bleed type: joint bleeds and non-joint bleeds (non-joint bleeds included muscle bleeds). Descriptive analyses of bleeding rates and the proportion of bleed-free participants before and after the switch to emicizumab, differentiated by non-joint ABR and AJBR, were performed.
A number of treatment and bleeding factors could be documented via the smart medication eDiary in real time, including treatment reason; delay between bleed and treatment, details of surgery if responsible for bleed, bleed location and type (muscle, joint or other), bleeding reason and physical activity leading to bleed, bleeding severity, presence of pain or swelling, mobility limitation, resolution of bleeding and symptoms, pain development, and days absent from school/work. All administrations of FVIII, including initial and follow-up treatments, were evaluated. None of the fields concerning participants’ demographic data were mandatory in the platform, to ensure that they would be more likely to provide key data on bleeds and treatment; for this reason, there are few participant demographic data available. Date of birth could also be documented on the eDiary, but this was not mandatory. Weight was only documented if a bleed was reported. A tick box on the platform could be used to define whether treatment was administered to treat a new bleed or as a follow-up treatment for an existing bleed. Data from an additional retrospective questionnaire were also collected (Supplemental Methods).
Data analysis
Data from PwSHA before and after switching from FVIII replacement concentrates to emicizumab were evaluated retrospectively. Information collected via the smart medication eDiary included the age at which participants switched to emicizumab, the prophylaxis treatment plan, frequency of prophylaxis administration, and prophylaxis dosing before and after switching. From data collected, ABR and AJBR, proportion of bleed-free PwSHA, FVIII consumption (per kg of body weight) per joint bleed and per infusion, and the initial treatment plus follow-up administrations for FVIII consumption per joint bleed were calculated. Any bleeds that occurred during the emicizumab loading period after switching were attributed to FVIII use, as therapeutic plasma concentrations of emicizumab were not yet reached. The treatment regimen for emicizumab was calculated based on the number of treatments and number of reported documentation days.
Compliance to documentation entry and/or the treatment regimen was calculated by determining the median number of days between the time of receipt of documentation to the eDiary backend versus the date when the participant entered their administered prophylaxis. A median of ⩽3 days was classed as documentation compliant (⩾50% of eDiary entries are made within 3 days). Additionally, any participants recording fewer than five injections of emicizumab were excluded from the analysis, due to the likelihood of poor documentation compliance, or an indication of an observation period that is too short to make meaningful conclusions.
Results
Participant characteristics
As of March 2023, approximately 1600 PwHA and 40 HTCs in Germany had utilised the platform. Approximately 800 PwHA of any severity were actively using the platform in 2023. Data for 109 PwSHA using emicizumab prophylaxis were available at the data cut-off date (31 March 2023; Figure 1). Eleven PwSHA had documented fewer than five injections (including loading doses) with emicizumab on the smart medication platform and were not included in the main analysis. These participants were excluded due to poor documentation compliance; nine participants ceased documentation following the switch to emicizumab, one participant stopped documentation before resuming towards the end of the observation period (one documentation entry at switch and three weekly documentations towards the end of the period) and the remaining participant switched back to SHL prophylaxis following three injections (the reason for this was unknown). None of these participants developed a bleed following the switch to emicizumab.
Participant disposition.
One participant with chronic synovitis and severe joint pain, who switched to emicizumab therapy in October 2020, discontinued emicizumab prophylaxis and switched back to FVIII replacement prophylaxis in June 2021. At their physician’s discretion, they were also excluded from the main analysis due to a high number of documented bleeds and a concern that the severe pain could have been erroneously interpreted as bleeding events by the participant.
A subtotal of 97 PwSHA were included in the main analysis, 39 of whom only started documentation following the switch to emicizumab and 58 of whom had a recorded treatment history before switching. Twelve of these 58 recorded an average FVIII infusion frequency of more than 5 days. Our analyses indicated that these five participants were using FVIII replacement on demand before the switch to emicizumab prophylaxis. The seven additional participants were not included as on-demand participants because they had periods of documentation where FVIII infusions were equivalent to that expected during prophylaxis, but other periods where there was no documentation.
ITI therapy had previously been used in five participants. One of these participants switched to emicizumab in January 2019 after several ITI attempts without achieving complete success. Six months after the switch, a low inhibitor titre was detected, which increased to a high inhibitor titre following plasma-derived FVIII treatment for a psoas bleed. As the participant was unable to exhibit sustained successful ITI, he was not included in the main analysis of this study. One of the other four participants who had previously received successful ITI therapy switched to emicizumab in June 2018, before emicizumab was approved for PwHA without inhibitors in March 2019. This participant had received on-demand FVIII replacement before switching.
Of the PwSHA who had provided their date of birth via the eDiary (n = 80), the mean (median, range) age at which participants switched to emicizumab was 34.6 years (38.3, 0.3–71.2 years). The proportion of the participants who switched before the age of 12 years was 20.0% (16/80); 8.8% (7/80) switched between the ages of 12 and 18 years, and 71.3% (57/80) switched after the age of 18 years. Eighteen participants over 50 years of age switched to emicizumab. The age at switch was not available for 17 participants.
As data were provided via the eDiary and the additional questionnaire by PwSHA and their healthcare teams, not all information was provided for all participants. As such, there are differences in the number of participants analysed for each endpoint.
Bleeding outcomes 24 weeks before and 24 weeks after the switch to emicizumab prophylaxis
For all participants included in this analysis (N = 97), following initiation of emicizumab, the mean calculated ABR was 0.64 for all bleeds, 0.25 for non-joint bleeds and 0.39 for joint bleeds. Three joint bleeds occurred in three separate participants during the loading dose phase of emicizumab prophylaxis, two of which were reported on the first day of the switch. The other reported joint bleed occurred after one administration of emicizumab, 21 days after the switch.
A total of two non-joint bleeds occurred during the loading dose phase in two separate participants, and these were both classed as single events that were treated with a single dose of FVIII replacement. During the maintenance dosing period, two participants each had a joint bleed; they then received three and ten doses of FVIII replacement, respectively.
For the cohort of participants who provided data before switching (n = 58), there was a 79.6% reduction in mean ABR (3.51 before vs 0.72 after switching), a 63.3% reduction in the mean ABR for non-joint bleeds (1.44 vs 0.53) and a 90.8% reduction in the mean AJBR (2.07 vs 0.19) following the switch to emicizumab (Table 1). Three participants reported a total of five muscle bleeds during FVIII replacement prophylaxis, before the switch to emicizumab. During emicizumab prophylaxis, no muscle bleeds were reported (Table 2). Following the switch to emicizumab, there was a 21.3% increase in the number of PwSHA who were free from all bleeds (n = 37 [62.7%] before switch vs n = 47 [79.7%] after switch) and an 18.2% increase in the number who were free from joint bleeds (n = 45 [76.3%] before switch vs n = 55 [93.2%] after switch; Table 1). No life-threatening bleeds were recorded via the eDiary or the questionnaire during the observation period.
Bleeding outcomes before and after the switch to emicizumab prophylaxis (n = 58).
ABR, annualised bleed rate; AJBR, annualised joint bleed rate.
Summary of bleed locations before and after the switch to emicizumab prophylaxis (n = 58).
Prophylaxis dosing and administration frequency 24 weeks before and 24 weeks after switching to emicizumab
In the participants who had treatment documentation before the switch to emicizumab (n = 58), 32.8% were treated with a plasma-derived SHL FVIII product, 36.2% were treated with a recombinant SHL FVIII product and 31.0% were treated with a recombinant EHL FVIII product. The median FVIII replacement dosing frequency was every 2.4 days (interquartile range [IQR]: 1.8) for participants who received a plasma-derived SHL FVIII product (n = 17), 3.4 days (IQR: 1.7) for participants who had received a recombinant SHL FVIII product (n = 19) and every 3.7 days (IQR: 1.1) for participants who had received an EHL FVIII product (n = 18). For the cohort of participants who were treated with FVIII replacement only prior to switching to emicizumab, and including participants for whom documentation was incomplete, the median FVIII replacement dosing frequency was every 3.5 days (n = 54; IQR: 1.9; Table 3). The FVIII replacement dosing frequency excluding those with poor documentation is outlined in the Supplemental Results.
Frequency of prophylaxis treatments 24 weeks before and 24 weeks after switching to emicizumab.
EHL, extended half-life; F, factor; IQR, interquartile range; PD, plasma-derived; r, recombinant; SD, standard deviation; SHL, standard half-life.
In the full cohort (N = 97), the median dosing frequency of emicizumab was every 11.2 days (range: 6.6–29.4 days). Of these 97 participants, 41.2%, 49.5%, 5.2% and 4.1% were on once weekly (QW), every 2 weeks (Q2W), every 3 weeks (Q3W) and every 4 weeks (Q4W) treatment plans, respectively. Emicizumab prophylaxis dosing information was provided for 31 participants; the mean weekly dose was 1.55 mg/kg (range: 0.66–2.96; Table 4). As weight was not collected for all participants, FVIII replacement dosing information before the switch to emicizumab was available for 27 participants only. In this group, the mean weekly dose was 58.86 IU/kg (range: 9.66–154.3; Table 4).
Prophylaxis dosing before and after switching to emicizumab.
F, factor; IQR, interquartile range.
During the 4-week loading phase of emicizumab dosing, 69.1% (67/97) of participants were not treated with FVIII replacement therapy. Of the 30 participants who were treated with FVIII replacement during the loading phase, 70.0% (21/30) recorded receiving >1 dose of FVIII, and 33.3% (10/30) received ⩾4 doses of FVIII. As weight was not provided for all participants, the average dosage per kg per infusion was available for 14 of these participants. For these participants, the mean (range) dosage per infusion was 32.1 (12.2–64.9) IU/kg.
Treatment and interventions for joint bleeds 24 weeks before and 24 weeks after switching to emicizumab
Before the switch to emicizumab (n = 58), the mean (median, range) consumption of FVIII used to treat a joint bleed was 30.7 IU/kg (n = 17; 25.3, 12.4–63.8); however, following the switch, the mean (median, range) consumption was 40.8 IU/kg (n = 7; 46.7, 13.2–64.9; Table 5). For the same cohort, the mean (median, range) FVIII consumption used per follow-up treatment per joint bleed was 92.2 IU/kg (n = 7; 56.7, 28.6–222) before the switch to emicizumab versus 41.3 IU/kg (n = 2; 41.32, 30.0–52.6) after the switch (Table 5).
Treatment and interventions for joint bleeds 24 weeks before and 24 weeks after switching to emicizumab.
F, factor; IQR, interquartile range.
Participants with a history of FVIII inhibitors
A total of 26 participants had a history of FVIII inhibitors. Two participants received FVIII replacement therapy whilst undergoing emicizumab prophylaxis: one received two FVIII administrations to treat one joint bleed and one non-joint bleed, and the remaining participant received one infusion (reason for infusion not reported). Neither of these participants developed inhibitors during emicizumab prophylaxis.
The participant who experienced inhibitor recurrence and was subsequently not included in the analysis, was treated with plasma-derived FVIII replacement during the 24-week observation period before the switch to emicizumab, and for 7 days during the loading dose period. One non-joint bleed occurred during emicizumab prophylaxis, which was treated with one infusion of recombinant FVIII replacement. Following the development of a positive inhibitor titre, this participant was switched to weekly administration of emicizumab. No bleeds were documented following this switch.
Based on the eDiary data, there were no cases of de novo FVIII inhibitor development during the observation period within the complete cohort.
Documentation compliance
Participants were classed as documentation compliant if there were ⩽3 days (median) between their treatment administration and documentation in the eDiary. For the participants who provided data before switching (n = 58), there was a 62% compliance rate for FVIII replacement, which increased to 70% for emicizumab prophylaxis.
Discussion
This retrospective analysis of real-world data collected via the smart medication eDiary provides additional information on bleeding outcomes for PwSHA of all ages following the switch from FVIII replacement to emicizumab prophylaxis. The data collected via the eDiary also provide real-time insights into treatment patterns and adherence to prescribed medication regimens. These findings provide further evidence for the effectiveness of emicizumab prophylaxis over FVIII replacement in PwSHA.
Data from the smart medication eDiary indicate that there was a 79.6% reduction in the mean ABR and a 90.8% reduction in the mean AJBR following the switch from FVIII replacement to emicizumab. A 21.3% increase in the number of PwSHA who were bleed free and an 18.2% increase in the number of participants who were free from joint bleeds was also observed after switching to emicizumab.
The bleed rate reductions reported by a non-interventional study (NIS) correlate with the values reported in our analysis. The NIS was carried out prior to the HAVEN 1–3 trials12–14 and collected data on FVIII prophylaxis before the initiation of emicizumab prophylaxis. 26 Adult participants with inhibitors from the NIS then transferred to HAVEN 1, children with inhibitors transferred to HAVEN 2 and adults without inhibitors were transferred to the HAVEN 3 trial, which enabled a comparison of bleeding rates before and after switching to emicizumab. Of the participants without inhibitors who transferred to HAVEN 3, bleeding rates were significantly reduced (68% lower) following the switch from FVIII replacement prophylaxis. 14 Although similar bleed rate reductions were observed, it should be noted that the data collected following the switch to emicizumab were calculated in a clinical trial rather than in the real-world setting.
Previously, real-world studies have used a range of methods, including health insurance and claims data,27,28 and hospital records, 29 to collect data on the bleeding outcomes for PwHA treated with emicizumab. In contrast with our study, Escobar et al. reported no differences in ABR following the switch to emicizumab; however, as that study used claims data to analyse bleeding outcomes, only bleeds that resulted in a claim could be included. 28 In another real-world study by Ramanan et al., bleeding rates from a claims database in PwHA before and after initiating emicizumab treatment were compared. Significant increases in zero-bleed prevalence were observed in those on prior on-demand FVIII treatment and in paediatric PwHA, but not in adult PwHA or in those who were on prior SHL or EHL prophylaxis. 30
The information regarding the real-world usage of emicizumab presented in this analysis provides a greater understanding of the dosage and administration frequency of prophylaxis using a real-time documentation app. The finding of Q3W emicizumab use indicates that it may have been used off-label in some cases, as the label indicates that dosing should be either 1.5 mg/kg QW, 3 mg/kg Q2W or 6 mg/kg Q4W. 31 Reasons for this may include adaptation of the dosing amount based on the vial size to reduce emicizumab wastage, or an attempt to provide the longest administration period for the benefit of participants. It is also plausible that some PwHA skip some administration days in the real-world setting.
During the emicizumab loading dose period, our analysis indicated that, although only five bleeds were reported, a total of 30 participants administered at least one dose of FVIII replacement. The emicizumab label states that FVIII prophylaxis may continue for the first 7 days of emicizumab treatment, since therapeutic concentrations of emicizumab would not be reached during this time; 31 therefore, this observation is reasonable.
Notably, the data indicate that the mean consumption of FVIII to treat a joint bleed was greater following the switch to emicizumab than before the switch (40.8 IU/kg vs 30.7 IU/kg, respectively). It is difficult to evaluate the significance behind this finding due to the small sample size for this part of the analysis. However, it could be explained by inconsistencies in documentation: during FVIII treatment, follow-up infusions may be mistaken for prophylaxis, whereas during treatment with emicizumab prophylaxis, FVIII infusions can clearly be recorded as follow-up treatments. Alternatively, the participants may themselves have chosen to administer FVIII at a higher dose, either due to a lack of familiarity with emicizumab treatment or a belief that if bleeds occurred on emicizumab, that they must be more severe and therefore require a higher dose of FVIII to achieve haemostasis. Additionally, as the dose to treat relevant bleeds is agreed upon by the people receiving FVIII and their physicians, a higher dose may have been chosen following the switch to emicizumab.
Furthermore, a higher dosing frequency was reported when taking EHL FVIII therapy compared with SHL therapy after initiation of emicizumab. Due to potential efficacy concerns regarding emicizumab, these participants may wish to maintain higher FVIII levels in order to have better protection against bleeding events.
Our analysis also found that participants were more compliant with their eDiary documentation after their switch from FVIII replacement to emicizumab. However, it is important to note that a lack of documentation compliance may stem from a lack of treatment adherence.
Here, our study has an advantage in that treatment patterns and outcomes could be recorded in real time through an online platform from the participant’s home, or by their healthcare team. Another advantage of our study is that the majority (58/97 [59.8%]) of PwSHA included in the analyses had at least 24 weeks of data during FVIII replacement and after the switch to emicizumab prophylaxis, which were collected using the same methodology.
The real-time entry of data is an important feature of smart medication, as this process is also likely to result in the collection of high-quality data; 25 for instance, the patient is able to select medication from their pre-filled stock. Data reports are also sent via a software interface that does not require the manual post-processing procedures needed for registry data. 25 Registries, such as the German National Haemophilia Registry, distinguish between collective reports (pooling of all patient data in one report) and individual reports (individual patient data); however, many centres only release collective reports. Reports are generally not developed until the middle of the year following the reporting year, meaning the registry may receive data with a delay of up to 1.5 years. Furthermore, most data are collected manually, so the data entry process may be prone to error.
Study limitations
There were no data before switching for a large proportion of the cohort; as such, there are limited data to support the comparison between outcomes before and after switching to emicizumab. As our analysis depended on complete and correct input from PwSHA and their healthcare teams, the study was limited by some missing data; for instance, demographic data including date of birth was not recorded for some participants, which hindered the analysis regarding the age at which the switch to emicizumab occurred. Smart medication was not designed to capture a wide range of demographic characteristics, to minimise the volume of personal data being collected, as it was not the key focus of this analysis. Missing data may have also been a contributor to our finding that a shorter dosing frequency for EHL FVIII therapy than SHL therapy was observed. Lack of documentation compliance may have also resulted in greater inaccuracy when reporting treatment administration; for example, the eleven PwSHA who documented fewer than five injections and were subsequently excluded, and the participant who documented one emicizumab administration in 21 days after the switch. This may have been a result of a lack of compliance to either emicizumab prophylaxis or documentation and could have impacted the results. The data reported by some participants were also not monitored by their treating physician, so the correct input of treatment or bleeding episodes was not reviewed by a healthcare professional in these cases. Furthermore, as previously mentioned, the sample sizes for some of the analyses were relatively small, so it was not possible to evaluate the statistical significance of these observations.
Conclusion
Real-world data collected using the smart medication eDiary adds to the current literature on bleeding rates in PwSHA of all ages after switching from FVIII replacement to emicizumab prophylaxis. Electronic devices could be included in the standard treatment protocol for haemophilia care, providing information rapidly for healthcare teams and ensuring an early response in the outpatient setting. This study indicates that convincing PwHA and HTCs who are still reluctant to implement electronic documentation may be a key issue for understanding current and future treatment modifications. In agreement with clinical trials and in the real-world setting, smart medication has further captured a 79.6% reduction in ABR and a 90.8% reduction in AJBR, with a 21.3% increase in PwSHA who were free from all bleeds following the switch to emicizumab prophylaxis when compared with prior FVIII replacement.
Supplemental Material
sj-docx-1-tah-10.1177_20406207241295653 – Supplemental material for Efficacy of emicizumab in patients with severe haemophilia A without factor VIII inhibitors in Germany: evaluation of real-life data documented by the smart medication eDiary
Supplemental material, sj-docx-1-tah-10.1177_20406207241295653 for Efficacy of emicizumab in patients with severe haemophilia A without factor VIII inhibitors in Germany: evaluation of real-life data documented by the smart medication eDiary by Carmen Escuriola Ettingshausen, Wolfgang Eberl, Hermann Eichler, Ronald Fischer, Christina Hart, Katharina Holstein, Ralf Knöfler, Jürgen Kreutz, Caspar David Kühnöl, Wolfgang A. Miesbach, Christian Pfrepper, Andreas Rösch, Ulrich J. Sachs, Karolin Trautmann-Grill and Wolfgang Mondorf in Therapeutic Advances in Hematology
Footnotes
Acknowledgements
This analysis was sponsored by Chugai Pharma Germany GmbH and Roche Pharma AG. The authors thank the study participants and their families, as well as the study investigators, research coordinators and nurses. Third-party medical writing assistance, under the direction of the authors, was provided by Jake Hunter, MSc, and Hope Roberts-Dalton, MSc, PhD, of Ashfield MedComms, an Inizio company, and was funded by Chugai Pharma Germany GmbH.
Declarations
Supplemental material
Supplemental material for this article is available online.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
