On-demand Research Articles

Cost-effectiveness Analysis of Prophylaxis Versus On-demand Treatment for Children With Moderate or Severe Hemophilia A in China

BackgroundIt is still being determined if prophylaxis (PR) has superior cost effectiveness compared with on-demand (OD) treatment for moderate or severe hemophilia A (HA) children in China. Objective/PurposeTo evaluate the cost-effectiveness of PR and OD treatment for children with moderate or severe HA without inhibitors in China. MethodsA retrospective cost-effectiveness study was conducted on 640 HA children (373 and 267 children were on the PR and OD treatment, respectively) from January 2021 to November 2022. The Markov model was used to estimate the economic and clinical outcomes and would run for 17 yearly cycles with the initial age at 2 years. The transfer probabilities were extracted from the data of “Hemophilia Home Care Center” and the literature published. All patients’ drug costs were collected from the data of “Hemophilia Home Care Center”. One-way and probabilistic sensitivity analyses were conducted on the data to evaluate the robustness of the results. Results/FindingsPR was consistently associated with higher overall quality-adjusted life years (QALYs) compared with OD treatment (9.59 QALYs vs. 6.85 QALYs). The incremental cost-effectiveness ratio (ICER) of PR compared with the OD treatment was calculated to be approximately US$12,151.35 (RMB¥81,778.55) per QALY gained. This amount was lower than the willingness-to-pay (WTP) threshold of US$38,212.74 (RMB¥257,171.71). One-way sensitivity analysis found that the results were sensitive to the cost of OD and PR treatments. Conclusions/ImplicationsThis study indicated that PR is cost-effective compared with OD treatment for children with moderate or severe HA without inhibitors in China.

THINKING THROUGH THE DEBATE ABOUT CAESAREAN SECTION “ON DEMAND” PART I: THINKING ABOUT CHOICE PART II: THINKING ABOUT RISK

The debate about choosing Caesarean section when there is no medical indication raises many questions for midwives and other maternity care providers about choice, risk, normal birth and our role in a society where attitudes towards technology are changing. Both the popular and professional literature about this debate and the claims of benefit to fetus and mother need to be examined in a social and political context. Midwives have an important role to play in emphasizing that the safest system of care would support low intervention approaches to vaginal birth for the majority of women. The overwhelming reason women choose Caesarean section is fear and anxiety about birth. The request for Caesarean surgery “on demand” can be seen, in part, as a call to improve care for pregnant women and vaginal birth.

Efficacy and Safety of the Anti-Tissue Factor Pathway Inhibitor Marstacimab in Participants with Severe Hemophilia without Inhibitors: Results from the Phase 3 Basis Trial

Background:Marstacimab (PF-06741086) is a monoclonal antibody targeted to the tissue factor pathway inhibitor protein to improve hemostasis via the extrinsic pathway of blood coagulation. Previous phase 1/2 studies demonstrated the efficacy and safety of long-term administration of marstacimab up to 450 mg weekly for reducing bleeding episodes in adults with severe hemophilia A (HA) or hemophilia B (HB), with or without inhibitors, compared with on-demand (OD) therapy. We evaluated the efficacy and safety of marstacimab in participants with severe HA or moderately severe to severe HB without inhibitors compared with previous factor replacement therapy. Methods: BASIS (NCT03938792) is an open-label, multicenter, pivotal phase 3 study that enrolled male participants aged ≥12 to ˂75 y with severe HA (factor [F] VIII ˂1%) or moderately severe to severe (FIX ≤2%) HB, with or without inhibitors. Following screening, participants entered a 6-month observational phase (OP) and were categorized by factor replacement treatment: (1) OD or (2) routine prophylaxis (RP). Participants who completed the OP crossed over to 12-month active treatment phase (ATP) and received a single subcutaneous loading dose of 300 mg followed by once weekly 150 mg marstacimab. Primary endpoints were annualized bleeding rate (ABR) for treated bleeds and safety outcomes. Secondary endpoints included incidence of various types of breakthrough bleeds and health-related quality of life (HRQoL) measures. Participants who completed the ATP were eligible to enroll in the long-term extension (LTE) study. Informed consent/ethics committee approvals were obtained. Results for participants without inhibitors are presented. Results: Participants (N=128; 108 adults, 20 adolescents) with HA or HB without inhibitors entered the OP (OD: HA n=29, HB n=8; RP: n=72, HB n=19); of these, 116 entered the ATP. The median age was 30 [range, 13-66] y, most participants were White (50.8%) or Asian (47.7%) and predominately from Europe and India (51.6%). At baseline, 89 participants (69.5%; OD: n=36; RP: n=53) had ≥1 target joint. Mean (range) duration of marstacimab treatment was 12.1 (11.5-13.1) months for OD and 11.6 (0.9-12.8) months for RP. Eighty-eight participants entered the LTE (OD: HA n=22, HB n=7; RP: HA n=45; HB n=13). Data were not available by the cutoff date for 1 RP participant and was not included in the LTE safety analysis set. The mean (range) treatment duration in the LTE was 8.0 (1.2-14.5) months for OD and 6.5 (1.1-16.1) months for RP. In the phase 3 study, the OD group reported 12 (36.4%) adverse events (AEs) during ATP vs 9 (24.3%) in OP whereas the RP group reported 62 (74.7%) AEs in ATP vs 20 (22.0%) in OP. Both groups reported more treatment-related AEs during ATP ( Table 1). ADAs developed in 23/112 participants (20.5% incidence), of which titers were low and resolved in 22 participants by end of study. One RP participant discontinued due to a non-treatment-related SAE, and no deaths or thromboembolic events were recorded in the phase 3 study or the LTE. Mean (95% CI) ABR for treated bleeds was reduced for OD (91.6% [88.1-94.1%]) and RP (35.2% [5.6-55.6%]) participants over the 12-month ATP and marstacimab demonstrated superiority vs OD (P<0.001) and non-inferiority and superiority vs RP (P=0.0376) therapy. Marstacimab was also associated with significant reductions in ABR across all breakthrough bleed categories vs OD, and numerical reductions vs RP (non-inferiority). Overall, mean ABR declined over the first 6 months of ATP, which continued to Month 12 (data not shown). Bleed rates for an additional 16 months of follow-up in the LTE were consistent with those observed during the first 12 months of treatment in the phase 3 study ( Table 2). The ABR reductions observed with marstacimab during ATP were consistent across hemophilia types and age groups for OD and were generally consistent across hemophilia types and age groups for RP, with all point estimates for a difference <2.5 (non-inferiority margin for the ABR of treated bleeds). HRQoL parameters demonstrated non-significant improvements vs OD therapy and non-inferiority vs RP therapy. Conclusion: Compared with previous OD or RP therapy, once weekly subcutaneous marstacimab was safe and effective for reducing bleeding events in participants with severe HA or moderately severe to severe HB without inhibitors beyond 12 months in the phase 3 study and up to an additional 16 months in the LTE study.

Estimating the impact of improved management of haemophilia a on clinical outcomes and healthcare utilisation and costs

ObjectiveHaemophilia A (HA) is associated with high clinical and healthcare burden. We developed an Excel-based model comparing current practice to improved management in severe HA patients currently managed on demand (OD). Outcomes included short- and long-term bleed events. Expected annual bleeds were estimated based on locally-derived OD annualised bleed rate (ABR), adjusted by relative prophylaxis-related ABRs (published literature). The objective of our study was to explore the impact of improving HA prophylaxis in target countries with limited published data (Algeria, Argentina, Chile, India, Malaysia, Mexico, Taiwan and Thailand). Bleed-related healthcare resource use (HCRU) and costs were estimated as a function of bleed type, with inputs obtained from local expert estimates. Clotting factor concentrates (CFC) consumption related to treatment and prophylaxis was estimated based on locally relevant dosing. CFC costs were not included.ResultsWhen 20% of OD patients were switched to prophylaxis, projected reduction in bleeds was estimated between 3% (Taiwan) through 14% (Algeria and India); projected reductions in hospitalisations ranged from 3% (Taiwan) through 15% (India). Projected HCRU-related annual cost savings were estimated at USD 0.45 m (Algeria), 0.77 m (Argentina), 0.28 m (Chile), 0.13 m (India), 0.29 m (Malaysia), 2.79 m (Mexico), 0.15 m (Taiwan) and 0.78 m (Thailand). Net change in annual CFC consumption ranged from a 0.05% reduction (Thailand) to an overall 5.4% increase (Algeria). Our model provides a flexible framework to estimate the clinical and cost offsets of improved prophylaxis. Modest increase in CFC consumption may be an acceptable offset for improvements in health and healthcare capacity in resource constrained economies.

On the modelling chain for production loss assessment for wind turbines in cold climates

This paper presents results from a validation study of the EMD-WRF On Demand (OD) ICING modelling chain for production loss assessment for wind turbines in cold climates. The emphasis has been on validating the modelled seasonal instrumental icing using 29 meteorological masts and 49 seasons. The observed instrumental icing was extracted from wind data from meteorological masts using windPRO. The modelled results were compared to the observed instrumental icing and the sensitivity of the industry threshold limit of 10 g (for a 1-m-high standard cylinder) was evaluated. The study showed very good performance of the modelling chain and confirmed the industry threshold limit of 10 g (for a 1-m-high standard cylinder) to be the best match. Furthermore, the IEA Task 19 Ice Class system for translating modelling icing into a production loss was evaluated, and it was found that using meteorological icing is the desired and recommended solution.

Integrating Autonomous Busses as Door-to-Door and First-/Last-Mile Service into Public Transport: Findings from a Stated Choice Experiment

Autonomous busses and on-demand (OD) services have the potential to improve the public transport system. However, research on potential traffic impacts is still ongoing, mainly because of a lack of existing use cases of autonomous driving as part of public transport. The availability of revealed preference data for mode choice decisions is thus very limited. Therefore, we conducted a stated choice experiment to assess mode choice preferences with regard to use cases as the main mode of transport and as the solution for the first and last mile. We also distinguished between OD and schedule-based (sched.) services. The target population of the survey is the population of Baden-Württemberg, a state in southwestern Germany. The responses of 1,434 people were analyzed using a nested logit approach. On this basis, we established exemplary utility functions and descriptively derived recommendations for efficient forms of deploying autonomous busses in addition to already existing well-developed public transport systems. It was found that, under the given conditions, public transport pass owners without a car in their household would be the most interested in using autonomous busses. Car owners without a smartphone see less benefit. It was also shown that the recruiting method of the respondents is crucial. Those reached via social media were significantly more positive than those contacted via an online panel. Further evaluations show that autonomous busses are rated similarly to existing public transport and consequently have particularly high potential on medium distances, especially if their deployment leads to shorter access routes.

#4183 A PHENOTYPIC DRIVEN RITUXIMAB MAINTENANCE APPROACH IS EFFECTIVE AND SAFE IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS

Abstract Background and Aims Rituximab (RTX) has emerged as the first-line treatment to maintain remission in ANCA-Associated Vasculitis (AAV). However, the ideal strategy to RTX re-dosing is still unclear [1]. Method In this monocentric and retrospective study we evaluated the efficacy and safety of two RTX-based maintenance regimens in patients with AAV. Fixed-dose (FD) RTX dosing, consisting of at least 3 pre-emptive RTX administrations every 6 months, was preferred in patients judged to be at high relapse risk. Instead, a biomarker-guided on-demand (OD) RTX dosing strategy was preferred for patients deemed at lower risk of relapse; this consisted in RTX re-treatment only in case of B-cell repopulation or rise in ANCA titer. The single patient relapse risk was assessed according to the disease phenotype (granulomatous vs vasculitic), the ANCA specificity and the disease status (onset vs relapse). Relapses were defined as increase of disease activity requiring escalation of immunosuppression; major relapses were defined in case of life/organ-threatening manifestations. Results The study included 100 patients followed for a median of 24 months (IQR 20-30), 51% treated with an OD and 49% with a FD strategy. The main baseline characteristics of our cohort are shown in the Table; patients treated with a FD strategy were more often GPA, PR3-ANCA positive, with relapsing disease and ENT involvement and less frequent renal involvement. The FD group received a median of 4 (IQR 4-4) administrations of RTX for a median cumulative dose of 2 g (IQR 2-2). Only 6 (11.8%) patients in the OD group received RTX as maintenance therapy with a median of 1 (IQR 1-3) administration of RTX for a median cumulative dose of 0.75 g (IQR 0.5-1.75). Thirteen relapses occurred, 6 in the FD group and 7 in the OD one. Remission rates were comparable in the two cohorts, with respectively 87.6% and 85.9% of the patients in remission at 24 months (Figure 1 - panel A). No significant differences in remission rates across the 2 groups were observed after considering only major flares or after stratification according to clinical diagnosis (MPA/GPA) and ANCA specificity (Figure 1 - panel B to F). Ten and 20 severe infections (p = 0.383) and 3 and 1 cancer (p = 0.581) occurred respectively in the FD and OD group. Conclusion In our case series, a phenotypic-driven approach to RTX maintenance showed comparable efficacy and safety between fixed and on-demand dosing, despite different baseline characteristics between the two groups. These results suggest that personalizing RTX maintenance may be a feasible and safe strategy.

SamurAI: A Versatile IoT Node With Event-Driven Wake-Up and Embedded ML Acceleration

Increased capabilities such as recognition and self-adaptability are now required from IoT applications. While IoT node power consumption is a major concern for these applications, cloud-based processing is becoming unsustainable due to continuous sensor or image data transmission over the wireless network. Thus optimized ML capabilities and data transfers should be integrated in the IoT node. Moreover, IoT applications are torn between sporadic data-logging and energy-hungry data processing (e.g. image classification). Thus, the versatility of the node is key in addressing this wide diversity of energy and processing needs. This paper presents SamurAI, a versatile IoT node bridging this gap in processing and in energy by leveraging two on-chip sub-systems: a low power, clock-less, event-driven Always-Responsive (AR) part and an energy-efficient On-Demand (OD) part. AR contains a 1.7MOPS event-driven, asynchronous Wake-up Controller (WuC) with a 207ns wake-up time optimized for sporadic computing, while OD combines a deep-sleep RISC-V CPU and 1.3TOPS/W Machine Learning (ML) for more complex tasks up to 36GOPS. This architecture partitioning achieves best in class versatility metrics such as peak performance to idle power ratio. On an applicative classification scenario, it demonstrates system power gains, up to 3.5x compared to cloud-based processing, and thus extended battery lifetime.

EE203 The Impact of Varying the Target Population on the Outcome of a Cost-Effectiveness Analysis: Hemophilia B As an Exemplary Disease

AAV-mediated gene therapy (GT) is a promising new treatment for hemophilia B patients. In contrast with the standard treatments that rely on replacing the missing clotting factor, either on-demand (OD) or by regular prophylactic infusions (Pro), GT provides endogenous factor production long-term after a single infusion. Patients who have factor inhibitors or neutralizing AAV-antibodies are mostly not eligible to receive GT and are thus often excluded from cost-effectiveness analyses. Our study examined the cost-effectiveness of GT compared to alternative treatments in two target populations, the GT-eligible cohort versus the total hemophilia B population.

Prophylaxis with recombinant von Willebrand factor in patients with type 3 von Willebrand disease: Results of a post hoc analysis from a phase 3 trial.

To describe efficacy/safety of recombinant von Willebrand factor (rVWF) prophylaxis in patients with type 3 von Willebrand disease (VWD). This post hoc analysis of a phase 3 open-label trial provides a more detailed analysis of adults with type 3 VWD, categorized based on prior treatment at screening: "Prior On-Demand (OD)" (OD VWF; ≥3 documented spontaneous bleeding events [BEs] requiring VWF in previous 12 months) or "Switch" (plasma-derived [pd] VWF prophylaxis for ≥12 months). Annualized bleeding rates (ABRs) were evaluated during 12 months of rVWF prophylaxis versus historical data from medical records. In the Prior OD group (n = 10), mean spontaneous ABR (sABR) for treated BEs was reduced by 91.6% (ratio, 0.08; 95% CI, 0.02-0.45) versus mean historical sABR. In the Switch group (n = 8), mean sABR for treated BEs was reduced by 47% (ratio, 0.53; 95% CI, 0.08-3.62). One non-serious adverse event (AE) was considered possibly related to rVWF. No treatment-related, fatal, or life-threatening serious AEs were reported, and no patient developed VWF inhibitors. rVWF prophylaxis reduced sABR in type 3 VWD patients previously treated with OD VWF therapy, and maintained a similar level of hemostatic control in those switching from pdVWF prophylaxis to rVWF prophylaxis.

Assessing the value of bypassing agent therapy used prophylactic versus on-demand, during immune tolerance induction for treatment of inhibitors: a retrospective chart review

BackgroundHaemophilia A is a bleeding disorder caused by deficiency of coagulation factor VIII (FVIII) which leads to severe and repeated bleedings. There is a need to understand the optimal treatment pathway for FVIII inhibitors with the use of immune tolerance induction (ITI) and the role of haemostatic ‘bypassing’ agents (BPA) on-demand (OD) or prophylactically (Px). The aim of this study was to gain a better understanding of the real-world use of BPA therapy administered prophylactically or on-demand concomitant with ITI, for the treatment of an inhibitor to FVIII replacement therapy in patients with severe haemophilia A.MethodsRetrospective observational data were used to capture disease management information for patients who were aged 16 or under and had received ITI and BPA treatment for their most recent inhibitor from Jan-2015 to Jan-2019, for 47 patients in the UK and Germany. Descriptive comparisons of the clinical effectiveness and resource utilisation of Px and OD BPA therapy during ITI were conducted.ResultsDuring ITI and BPA treatment, for an inhibitor, bleeding events averaged 1.5 and 1.2 for Px and OD treatment respectively. Compared to only BPA therapy we see 3.4 and 1.4 bleeding events for Px and OD respectively during an inhibitor.ConclusionBaseline disease characteristics differed between BPA therapy cohorts and this resulted in higher clinical effectiveness of ITI treatment alongside BPA Px than BPA OD during an inhibitor.

An optimization approach for hybrid workflows in platform-enabled private service marketplaces

The future of work is likely to include private platform-enabled marketplaces which remain a new, fertile ground for research. This paper focuses on hybrid workflows which utilize the expertise of in-house (IH) and on-demand (OD) workers to perform complex knowledge intensive tasks under service constraints. Our primary contributions are in identifying and modeling an innovative application of OR in the new economy, proving its complexity and proposing a high-quality heuristic. We formulate a scenario-based mathematical programming model of a private talent marketplace for Knowledge Intensive Business Services (KIBS). This model considers uncertainty in task, worker, and OD marketplace characteristics. Problem complexity is illustrated. We develop a simplified queuing theory-based model of PKIBS to characterize the structure of the OD marketplace. Propositions from the queueing model inform IH workforce size, IH and OD workforce composition, and OD pricing decisions. A Tabu-based One Period Look Ahead heuristic based on propositions from the simplified queuing theory-based model is proposed. Heuristic performance is evaluated using a problem upper bound and MIP solution for small problems, and experiments based on a cyber security use case. Results illustrate the mix of OD and IH workforce and sophisticated hybrid workflows for different market conditions.

2089. Relative patient preferences for starting daily, on-demand, and long-acting injectable HIV pre-exposure prophylaxis among US men who have sex with men, 2021-2022

Abstract Background Daily oral (DO) HIV pre-exposure prophylaxis (PrEP) effectively prevents HIV acquisition, but few men who have sex with men (MSM) currently use it. Newer options, such as on-demand (OD) oral and long-acting injectable (LA) PrEP may improve uptake, but little is understood about relative preferences among these options in practical start scenarios. Preferences for starting various PrEP options were examined among a US nationwide online convenience sample of MSM age 15+ collected September 2021 to February 2022. Methods Participants reporting no prior HIV diagnosis were given brief descripitions of each PrEP option and were asked “If [PrEP option] were available from your local doctor and you could access it for free, would you go to your doctor in the next month to start [PrEP option]?” Those who said yes to multiple options were asked to rank them in order of preference. MSM currently taking DO PrEP were asked whether they would switch to OD or LA. Willingness to start LA was examined by age, race/ethnicity, insurance, and prior awareness of LA. Results Of 5585 MSM not currently using DO PrEP, 50% (n=2805) would start at least one option with greatest preference for OD (Figure 1). Among this group, 73% (n=2060) were willing to start more than one option, with LA the most preferred option. Among the 27% (n=745) who would start only one, OD was the most preferred. Overall, 58% of DO PrEP users (n=1342/2332) would switch to either OD or LA, with LA being most preferred (Figure 2). Hispanic MSM who were not DO PrEP users were more likely to start LA compared to white MSM, and those with other/multiple health insurance were less likely to start LA compared to those on private health insurance (Table 1). Regardless of current DO PrEP use, MSM aware of LA were more likely to start it. Conclusion There is substantial interest in new PrEP options. Current DO PrEP users appear to be more aware of and interested in LA than PrEP naïve. Although OD PrEP may be favored by those who are PrEP-naïve, most selected multiple options and preferred LA PrEP. Increasing awareness of LA PrEP may bolster interest in its use. These findings highlight the potential role that newer PrEP options will play in community uptake of PrEP and can also inform patient-provider decisions about which PrEP options to consider. Disclosures Travis Sanchez, DVM, MPH, ViiV Healthcare: Grant/Research Support S. Wilson Beckham, PhD, MPH, MA, Viiv Healthcare: Advisor/Consultant Keith Rawlings, MD, ViiV Healthcare: Employee Alex R. Rinehart, PhD, ViiV Healthcare: Stocks/Bonds Supriya Sarkar, PhD, MPH, ViiV Healthcare: Salary|ViiV Healthcare: Stocks/Bonds Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds.

MOTIVATORS FOR THE USE OF VEHICLE SHARING SERVICES ON DEMAND IN BRAZIL

The study focused on determining the motivators for the use of means of transport on demand in Brazil. The methodological procedures involved the Exploratory Factor Analysis to validate the variables and the Confirmatory Factor Analysis established the adjusted model and the dimensions in which these elements appeared in the users' perception. It can be observed that the motivators were relevant, however, only three variables of a utilitarian nature are strongly linked to the consumption process, indicating the cost, the moment of use and the technological facilitator as indicators of the use of this type of service in Brazil.

A real-world study comparing pre-post billed annualized bleed rates and total cost of care among non-inhibitor patients with hemophilia A switching from FVIII prophylaxis to emicizumab

Objective Factor VIII (FVIII) replacement and emicizumab have demonstrated efficacy for prevention of bleeds among patients with hemophilia A (PwHA) compared to on-demand (OD) use. Evidence investigating clinical outcomes and healthcare costs of non-inhibitor PwHA switching from prophylaxis with FVIII concentrates to emicizumab has not been well-established within large real-world datasets. This study aimed to investigate billed annualized bleed rates (ABRb) and total cost of care (TCC) among non-inhibitor PwHA switching from FVIII-prophylaxis to emicizumab-prophylaxis. Methods This retrospective, observational study was conducted using IQVIA PharMetrics Plus, a US administrative claims database. The date of first claim for emicizumab was defined as the index date. OD patients and inhibitor patients were excluded. Bleeds were identified using a list of 535 diagnosis codes. Bayesian models were developed to estimate the probability ABRb worsens and TCC increases after switching to emicizumab. Wilcoxon rank-sum tests were used to test statistical significance of changes in ABRb and TCC after switch. Results Among the 121 identified patients, the difference in mean ABRb between FVIII-prophylaxis (0.68 [SD = 1.28]) and emicizumab (0.55 [SD = 1.48]) was insignificant (p = .142). The mean annual TCC significantly increased for patients switching from FVIII-prophylaxis ($518,151 [SD = $289,934]) to emicizumab ($652,679 [SD = $340,126]; p < .0001). The Bayesian models estimated a 21.0% probability of the ABRb worsening and a 99.9% probability of increasing TCC after switch. Conclusions This study found that in male non-inhibitor PwHA, switching from FVIII prophylaxis to emicizumab incurs substantial cost increase with no significant benefit in ABRb. This evidence may help guide providers, payers, and patients in shared decision-making conversations around best treatment options.

Effectiveness of long-term prophylaxis using pdFVIII/VWF concentrate in patients with inherited von Willebrand disease.

BackgroundPatients with symptomatic von Willebrand disease (VWD) should be offered long‐term prophylaxis (LTP) to prevent recurrent bleedings. Our objective was to evaluate the effectiveness and safety of Voncento®, a plasma‐derived FVIII/VWF concentrate (ratio 1:2.4), administrated in LTP.MethodsWe included patients from the OPALE study (May 2016 to April 2021), a French multicenter observational study following patients with inherited VWD, who received a Voncento® LTP during the study period.ResultsAmong the 130 OPALE‐study patients, 23 patients (12 women) received a LTP and were therefore included. The median (range) age was 16 (1–85) years; 16 patients were type 3, 1 was type 2A, 6 were type 2B. Before inclusion, 19 (83%) were under LTP and 4 (17%) received on‐demand (OD) treatment. The indications for initiating prophylaxis in the overall population were joint bleeding (43%), ear, nose, and throat (ENT) bleeding including epistaxis or oral bleeding (39%), and recurrent muscle hematoma (22%). The medians (ranges) dose of Voncento® per infusion, frequency, and weekly dose were 45 (33–109) IU/kg, 2 infusions per week, and 96 (44–222) IU/kg/week, respectively. The median (range) annualized bleeding rate (ABR) was 0.8, 0.7 (0–3.5), and 0 (0–2.3) for type 2A, 2B, 3 patients, respectively. There was no difference regarding to the dose, frequency of infusion, or in terms of ABR in 9/19 patients who replaced previous concentrates with Voncento®. During the study period, no adverse event was reported.ConclusionThese results suggest that Voncento® is effective to prevent recurrent bleedings in patients symptomatic VWD.

POSA83 Economic Assessment of Switching Patients with Severe Hemophilia A from On-Demand Treatment to Intermediate Prophylaxis in Thailand

Hemophilia A (HA) is a debilitating disorder associated with high healthcare burden. Prophylaxis (Px) treatment helps reduce these associated costs and healthcare resource utilization (HCRU) by reducing the number of bleed-related outcomes. In Thailand, uptake of Px is low. This study explores the potential health and cost benefits of switching patients with severe HA from on-demand (OD) to Px treatment.

Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia a or B without Inhibitors (ATLAS-A/B)

Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia a or B without Inhibitors (ATLAS-A/B)

Exposure-Response Relationship between Von Willebrand Factor (VWF) Activity and Bleeding Events Following Prophylaxis with Recombinant VWF (rVWF, vonicog alfa) in Patients with Severe Von Willebrand Disease (VWD)

Exposure-Response Relationship between Von Willebrand Factor (VWF) Activity and Bleeding Events Following Prophylaxis with Recombinant VWF (rVWF, vonicog alfa) in Patients with Severe Von Willebrand Disease (VWD)

Bleeding Data across Baseline FIX Expression Levels in People with Hemophilia B: An Analysis Using the 'Factor Expression Study'

▪IntroductionComplications such as spontaneous and trauma-related bleeding events typically experienced by people with hemophilia B (PWHB) are associated with long-term joint damage and chronic pain, and burdensome treatment with intravenous factor IX administration.Gene therapy, designed to enable the endogenous production of the missing clotting factor, has potential for curative benefit in PWHB (Dolan et al, 2018). Due to its link to risk for bleeding episodes, factor expression level (FEL) is commonly used as an endpoint in hemophilia gene therapy trials. However, little data currently exist linking FEL to bleeding risk in PWHB, most notably within the mild range. As such, the aim of this analysis was to examine the relationship between annual bleed rate (ABR) data across baseline FEL in PWHB.MethodsData from adult non-inhibitor PWHB, across Europe and the United States (US) who received clotting factor on-demand (OD), were drawn from the 'Cost of HaEmophilia in adults: a Socioeconomic Survey' (CHESS) studies. The CHESS studies are retrospective, burden-of-illness studies in people with hemophilia A or B, capturing the economic and humanistic burden associated with living with hemophilia. Additional data were collected to supplement the existing CHESS studies, particularly in people with exogenous FEL in the mild and moderate range. ABR was defined as the physician-reported number of bleed events experienced by the patient in the 12 months to study capture. A generalized linear model (GLM) was used to analyze variation in ABR data across FEL, adjusting for covariates age, body mass index (BMI), and blood-borne viruses. Following this, a multivariable restricted cubic spline (RCS) GLM regression was performed to create, model, and test for the potential non-linear relationship between FEL and ABR. The RCS regression employed 3 knots, located at baseline FEL values of 1, 5, and 10, and controlled once again for age, BMI, and blood-borne viruses.ResultsA total of 407 adult non-inhibitor PWHB, receiving an OD therapy regimen and with information on ABR, were profiled. The GLM provided adequate fit for the modeling of bleed data; the average marginal effect at the mean was computed from the GLM regression outputs. After controlling for the effects of all other model covariates, the regression analysis showed a significant association between FEL and ABR; for every 1% increase in FEL, the average ABR decreased by 0.08 units (p<0.001). The results of the RCS regression found a significant non-linear relationship between FEL and ABR, ceteris paribus (p<0.001).ConclusionsThe results of this analysis found baseline FEL to be significantly associated with ABR in PWHB; as baseline FEL increased, ABR reduced. This highlights the clinical importance of new hemophilia gene therapies potentially increasing FEL to that of the mild or non-hemophilic range in terms of reducing patient burden through the better prevention of bleeding events in PWHB. DisclosuresAli: UniQure: Current Employment. Li: UniQure: Current Employment. Konkle: Pfizer, Sangamo, Sanofi, Sigilon, Spark, Takeda and Uniqure: Research Funding; BioMarin, Pfizer and Sigilon: Consultancy. O'Mahony: BioMarin Pharmaceutical Inc.: Consultancy; Freeline: Consultancy; Uniqure: Speakers Bureau. Pipe: Apcintex: Consultancy; ASC Therapeutics: Consultancy; Bayer: Consultancy; Biomarin: Consultancy, Other: Clinical trial investigator; Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; Freeline: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Other; Sangamo Therapeutics: Consultancy; Sanofi: Consultancy, Other; Takeda: Consultancy; Spark Therapeutics: Consultancy; uniQure: Consultancy, Other; Regeneron/ Intellia: Consultancy; Genventiv: Consultancy; Grifols: Consultancy; Octapharma: Consultancy; Shire: Consultancy.