Development of Women, Girls, and People Who Have or Had the Potential to Menstruate (WGPPM) questionnaire for PROBE study

Kucher A, Skinner M. W., Clearfield E., Brennan F., Rotellini D., Colle Y., Wilton P. A. Development of Women, Girls, and People Who Have or Had the Potential to Menstruate (WGPPM) questionnaire for PROBE study. (2025), Book of Abstracts. Haemophilia, 31: 21-109. https://doi.org/10.1111/hae.70032

Objective

The Patient Reported Outcomes, Burdens, and Experiences (PROBE) survey was first developed in 2012. PROBE currently collects data from people with hemophilia A or B, including carriers, and people without a bleeding disorder (NoBD) who serve as a control group. To date, there has been limited global comparative patient reported data on health outcomes and quality of life (HRQoL) about WGPPM.

Methods

A targeted PubMed literature review was conducted to identify concepts impacting WGPPM quality-of-life. The study team also provided additional examples of past surveys for review. Novel topics and items were mapped to a conceptual framework. The resulting framework was compared to the PROBE questionnaire and subsequently PROBE was updated to include missing concepts. It is anticipated that this exploratory questionnaire will lead to an expanded PROBE to more comprehensively include WGPPM. The questionnaire was developed in consultation with the World Federation of Hemophilia, Coalition of the Americas, European Haemophilia Consortium and National Bleeding Disorders Foundation who constituted the project working group. The new WGPPM questionnaire will be initiated as an on-line survey.

Results

The group identified von Willebrand Disease (VWD), platelet disorders, rare factor deficiencies, and other rare bleeding disorders for inclusion. New concepts include access to healthcare (including specialties); visits to emergency room; bleeding episodes unique to WGPPM (e.g., menstrual bleeding; gynecological problems), decision-making around having children, and impact on social and leisure life.

Conclusions

To advance management and treatment for this underserved population it is crucial to collect and report comprehensive data on WGPPM health outcomes and quality of life.  The WGPPM PROBE exploratory pilot was launched in early 2025. Through this pilot we anticipate more accurate and comprehensive data will be available to support future advocacy, research, management and treatment.  Insights from the pilot will be applied to future PROBE updates.

Poster: HERE

Gene Therapy in Hemophilia A: the Impact of Valoctocogene Roxaparvovec on Patient Outcomes – Initial Results from Patient Reported Outcomes, Burdens and Experiences (PROBE) from the GENEr8-1 Trial

Skinner M, Chen E, Ibrahim Q, Kucher A, Germini F, Karimi M, Clearfield E , O’Mahony B , Jain M. Gene Therapy in Hemophilia A: the Impact of Valoctocogene Roxaparvovec on Patient Outcomes – Initial Results from Patient Reported Outcomes, Burdens and Experiences (PROBE) from the GENEr8-1 Trial. (Abstract). NHF (2023).

Objective

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire is included in the phase 3, open-label, single-arm study (GENEr8-1) as a tertiary endpoint. The aim is to assess the effect of a single intravenous administration of valoctocogene roxaparvovec on patient-reported health and life experiences using PROBE.

Methods

134 adult men with FVIII ≤1 IU/dL without history of FVIII inhibitors and AAV5 antibodies previously receiving FVIII prophylaxis were enrolled in the GENEr8-1 trial for hemophilia A. Results from baseline, week 52 and week 104 were summarized. The PROBE questionnaire comprises four sections: demographics, general health problems, hemophilia-specific problems, and health-related quality of life (HRQoL) with the 5-level EQ-5D tool. While further validation to understand the performance of PROBE in this context of use is ongoing, this study summarized the initial PROBE summary score results (based on section 2) utilizing existing scoring algorithms. Change from baseline summary score was assessed with paired t-tests.

Summary

PROBE score was available for 124/134 (93%) at baseline, 129/132 (98%) at week 52, and 129/130 (99%) at week 104. Mean PROBE scores (SDs) were 0.82 (0.13), 0.87 (0.12) and 0.86 (0.13) at the baseline, week 52 and week 104 respectively. Average changes in score of  0.05 [95% CI: (0.03, 0.07), p <0.001] and 0.05 (0.02, 0.07), p<0.001) were observed at weeks 52 and 104. Item-level analyses suggested fewer participants reported pain, limitations in activities of daily living, and target joints at weeks 52 and 104 vs. baseline. Two years after treatment, the percentage of participants working full-time increased by >10% (Table 1). Overall, these results were consistent with EQ-5D results (Table 2).

Conclusions

Valoctocogene roxaparvovec led to measurable changes in HRQoL 2 years after a single administration. Further research is necessary to interpret clinically meaningful change in PROBE scores.

Disclosures

Er Chen: Bio Marin Pharmaceutical Inc.; Federico Germini: Bayer Bio Marin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Takeda; Mohit Jain: Bio Marin Pharmaceutical Inc.; Milad Karimi: Bio Marin Pharmaceutical Inc.;

Brian O’Mahony BioMarin Pharmaceutical Inc.CSL Behring; Mark Skinner: Bayer, Bio Marin Pharmaceutical Inc., Blue Cross Blue Shield, ICERMASACNHFNORD, Novo Nordisk, Pfizer, Roche/Genentech, Spark, Takeda, WFH, USA

Poster: HERE

 

Initial results of the impact of valoctocogene roxaparvovec on pain occurrence and interference: Insights from PROBE

Skinner M, Chen E, Kucher A, Germini F, Karimi M, Clearfield E , O’Mahony B , Jain M. Initial results of the impact of valoctocogene roxaparvovec on pain occurrence and interference: Insights from PROBE. (Abstract). NHF (2023).

Introduction

People with severe haemophilia A (PwSHA) commonly present with intramuscular bleeding and hemarthrosis, leading to acute and chronic pain with an overall reduction in health-related quality of life. Here, we report the occurrence of pain in PwSHA before and 2 years after administration of valoctocogene roxaparvovec, and its interference on daily life.

Methods

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire was included in the phase 3, open-label, single-arm study (GENEr8-1) as a tertiary endpoint to assess the effect of a single 6 × 1013 vg/kg dose of valoctocogene roxaparvovec on patient-reported health and life experiences. While further validation to understand the performance of PROBE in this context of use is ongoing, this study summarized pain-related outcomes collected within the PROBE questionnaire. This analysis evaluated PROBE completions at baseline and 104 weeks post gene therapy, including any occurrence of acute and chronic pain (recall: 12 months) and during eight activities (walking, stair climbing, nighttime, resting, weight bearing, playing, after falling/trauma, other). Participants also reported pain interference in 11 aspects of life (general activity, mood, walking ability, normal work, attending school, relations with others, sleep, enjoyment of life, playing/participating in sports/exercising, lifting, other). Descriptive statistics including 95% confidence intervals (CI) were presented at baseline and Week 104.

Results

Data were available for 124 participants at baseline and 129 at 104 weeks. Median age was 34 (range 21−73 years). Reporting of acute and chronic pain was reduced post gene therapy (acute pain: 60.5% to 41.9%, chronic pain: 65.3% to 57.0%). At 104 weeks, the aggregate instances of self-reported acute pain occurrence decreased from 151 (15.2%) to 113 (10.9%) across the 8 activities (including ‘Other’) [Table 1]. Chronic pain reduced from 238 (24.0%) to 216 (20.9%) [Table 2]. At 104 weeks, the aggregate instances of self-reported acute pain interference decreased from 294 (21.4%) to 204 (14.4%) across the 11 activities (including ‘Other’) [Table 3]. Chronic pain interference was reduced from 332 (24.3%) to 262 (18.5%) [Table 3 and 4].

Conclusions

Initial analysis of PROBE data demonstrates that gene therapy may be associated with a decrease in self-reported acute and chronic pain occurrence and interference with daily life in the study cohort.  Pain is one of the core outcomes of importance to people with haemophilia. The impact of gene therapy on pain, particularly chronic pain as demonstrated from PROBE, a haemophilia-specific tool, has important implications on treatment decision-making and continued disease management.

Disclosures

Er Chen: Bio Marin Pharmaceutical Inc.; Federico Germini: Bayer Bio Marin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Takeda; Mohit Jain: Bio Marin Pharmaceutical Inc.; Milad Karimi: Bio Marin Pharmaceutical Inc.;

Brian O’Mahony BioMarin Pharmaceutical Inc.CSL Behring; Mark Skinner: Bayer, Bio Marin Pharmaceutical Inc., Blue Cross Blue Shield, ICERMASACNHFNORD, Novo Nordisk, Pfizer, Roche/Genentech, Spark, Takeda, WFH, USA

Poster: HERE

 

Self-reflections, lessons learned and suggestions for data quality assurance from a retrospective data analysis from the Canadian Bleeding Disorders Registry

Iorio A, Keepanasseril A, Ibrahim Q, Iserman E, Blaser H. Self-reflections, lessons learned and suggestions for data quality assurance from a retrospective data analysis from the Canadian Bleeding Disorders Registry. (2024), POSTER ABSTRACT (PP-026). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

Real-world evidence (RWE) is used to complement primary evidence from clinical trials on safety and efficacy and to generate clinical effectiveness data. Theoretically, RWE is not subject to ‘on trial effect’, and it shows the true impact of intervention in unselected populations. Barriers to generating RWE are mostly stemming from the incomplete availability of relevant data points in the real-world setting. Aim: Analyse strengths and limitations of the ‘Real-World Effectiveness of PEGylated, recombinant Antihaemophilic Factor (Rurioctocog alfa pegol) Prophylaxis in Patients with Haemophilia A in Canada: A Retrospective, Intra-Patient Comparison with a Before-AfterDesign’.

Methods

A retrospective study, before-after design, comparing PK, clinical and PR outcomes for patient switched from SHL-FVIII or EHL-FVIII products to Rurioctocog alfa pegol. Outcomes: individual PK parameters (half-life, time spent above factor levels of0.01, 0.03 and 0.05 IU/mL), factor utilisation, bleed rates, QoL (PROBE)and joint function (HJHS). Pre-specified subgroups: previous treatment with SHL-FVIII versus EHL-FVIII, history of inhibitors versus no inhibitors, and age ≤12 versus >12 years. Strengths and limitations of the approach, including the amount/quality of data available for the analysis of the different outcomes, were analysed.

Results

Ninety-eight severe haemophilia A inhibitor-free patients qualified for the analysis. Thirty-seven patients had available PK data. There were four patients with history of inhibitors, six <12 years and eight patients formerly treated with SHL; four had HJHS and four had PROBE data. Clinical, PK and utilisation results have been presented elsewhere.

Conclusions

PROBE data shows a good cross-section of people with Haemophilia A, B and carriers. Brazil has free Selection bias is anticipated to be lower in retrospective design versus post-marketing surveillance (PMS) studies, which also threaten national registries data integrity. Included (n = 37) and excluded (n = 61) patients were similar in terms of age distributions, BMI, and number of surgery or traumatic bleedings, confirming that the retrospective analysis did not identify a selected population. Lim-ited availability of HJHS and PROBE data suggests that routine clinical practice does not yet include standardised recording of patient centred/reported outcomes, hampering the measurement of health care interventions’ value. There is a significant opportunity to improve the breadth/quality of data generation in the future to demonstrate the true impact of factor replacement in routine clinical practice.

Disclosures

Alfonso Iorio: Bayer, CSL, Pfizer, Roche, Sanofi/Sobi, Takeda; Heiko Blaser: Takeda.

View Poster: PP_26_WFH2024

PROBE: Brazil data

Pietrobelli T, Skinner M. PROBE: Brazil data. (2024), POSTER ABSTRACT (PP-165). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The Brazilian Haemophilia Federation (FBH) carried out a campaign to increase responses to the PROBE (Patient Reported Outcomes, Burdens, and Experiences) questionnaire, which collaborates with the World Haemophilia Federation and was integrated into myWBDR and GTR. To have robust data on the quality of life, treatment and daily life of people with Haemophilia A and B. The data collected is intended to be used in FBH advocacy actions, to improve Public Policies in Brazil.

Methods

PROBE has real-life data from patients, which is why FBH has been a partner in the study since 2018 and has a specific response link that allows you to know the state where the person lives and the distance from their home to the HTC. The information collected by PROBE allows FBH to hold meetings with government authorities and propose improvements for the treatment of people with haemophilia in all 27 federative units in Brazil.

Results

PROBE has 679 contributions to the questionnaire in Brazil. With 321 people with Haemophilia A, 49 with Haemophilia B, 35 carriers and 274 people without coagulopathy, this last group is considered a comparative group for quality of life. Considering 405 people with Haemophilia A, B and carriers, 168 have Severe Haemophilia and 45 Moderate. Around 65% undergo treatment at home and 28% go tothe HTC for treatment. 75% perform 2–3 infusions per week and only 2.25% infuse daily. 41.75% do not have chronic pain and 58.25% admit to living with chronic pain, of which 85% have chronic pain in the target joints.

Conclusions

PROBE data shows a good cross-section of people with Haemophilia A, B and carriers. Brazil has free treatment through the Public Health System, which is an example for the world and, even so, there are windows of improvement that should be taken advantage of. With this data, FBH will work to improve Public Policies with government authorities to improve access to treatment and quality of life.

Disclosures

Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics.

View Poster: PP_165_WFH2024

Global Efforts in Uniting all stakeholders in ensuring safety of hemophilia gene therapy patients: the World Federation of Hemophilia Gene Therapy Registry

Naccache M, Konkle B, Peyvandi F, Miesbach W, O’Mahony B, Pile S, Youttananukorn T, Coffin D, Pierce G. Global Efforts in Uniting all stakeholders in ensuring safety of hemophilia gene therapy patients: the World Federation of Hemophilia Gene Therapy Registry. (2024), POSTER ABSTRACT (MP-021). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The World Federation of Haemophilia (WFH) launched the Gene Therapy Registry (GTR) aimed at gathering comprehensive data on all people with haemophilia (PWH) who receive gene therapy worldwide.

Methods

The GTR was designed to standardise and centralise global data collection for the gathering and dissemination of gene therapy data. The GTR is a prospective, observational, and longitudinal registry. Data entry occurs once, either directly from haemophilia treatment centre (HTC) into the GTR or through data transfer from National Registries. The GTR Scientific Advisory Board oversees all data entered into the GTR and its dissemination. Specificde-identified data will be shared with various stakeholders: participating patients will have access to view their own data; HTCs and National Registries will receive aggregated global safety data; industry part-ners will receive product-specific data, and regulatory agencies and health technology assessment organisations can request specific data to inform their decisions.

Results

The WFH is engaged with a broad network of collabora-tors, and the GTR National Registries & HTC Consortium has been established to foster dialogue, obtain feedback from our collaborators, and establish mutually beneficial collaboration. This group includes representatives from Brazil, Ireland, Saudi Arabia and Sweden, and registries from Australia, Canada, France, Germany, Japan, the Netherlands, Spain, the United Kingdom and the United States. The European Medicines Agency (EMA) issued a pivotal letter of support to the WFHGTR. The CHMP endorses the GTR as the worldwide registry for consolidating all international data on PWH who receive gene therapy and encourages collaboration of all HTCs and National Registries, stating that the WFH GTR is of particular value for post approval safety and efficacy studies of gene therapies and recommending its use as a planned data source for mandated Phase IV studies.

Conclusions

The GTR facilitates the accumulation of data in one registry and supports the efficient dissemination of valuable information to all stakeholders, advancing our understanding of gene therapy’s safety, efficacy, and long-term effects. In the current landscape of numerous registries in haemophilia around the world, the success of the GTR depends on collaborative relationships with all stakeholders, including patients, HTCs, National Registries, industry partners and regulatory bodies.

Disclosures

Barbara Konkle: Be Biotherapy, Biomarin, Novo Nordisk, Pfizer, Sanofi; Flora Peyvandi: BioMarin Pharmaceutical Inc., CSL Behring, F. Hoffmann-La Roche Ltd., Grifols, Sanofi, Sobi, Takeda; Wolfgang Miesbach: Bayer, BioMarin, Biotest, Chugai, CSL Behring, Free-line, LFB, Novo Nordisk, Octapharma, Pfizer, Regeneron, Roche, Sanofi, Sigilon, Sobi, Takeda/shire; Brian O’Mahony: Biomarin, CSL Behring, Freeline, Irish Haemophilia Society, Pfizer, Roche; Mike Makris: Grifols, Novo Nordisk, Sanofi, Takeda; Steven Pipe: Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Genentech/Roche, GeneVentiv and Equilibra Bioscience, Sanofi, Takeda, Spark Therapeutics, uniQure, Siemens; Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics; Glenn F. Pierce: ASC Therapeutics, Be Bio, BioMarin, Decibel Therapeutics, Frontera, Intellia, Metagenomi, Novo Nordisk, Pfizer, Regeneron, Spark Therapeutics, Third Rock Ventures.

View Poster: MP_21_WFH2024

Long-term retention plan through myGTR – a patient engagement tool from World Federation of Hemophilia Gene Therapy Registry

Youttananukorn T, Konkle B, Peyvandi F, Naccache M, Miesbach W, O’Mahony B, Makris M, Pipe S, Skinner M, Coffin D, Pierce G.Long-term retention plan through myGTR – a patient engagement tool from World Federation of Hemophilia Gene Therapy Registry. (2024), POSTER ABSTRACT (PP-054). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The World Federation of Haemophilia (WFH) Gene Therapy Registry (GTR) is designed to collect comprehensive clinical data on all people with haemophilia (PWH) who receive gene therapy (GT) globally. To complement data from the GTR, the WFH developed myGTR – a patient engagement tool aimed at collecting patient-reported outcome (PRO) data. PRO data are important and are part of shared decision-making process that could lead to meaningful care and treatment.

Methods

To reduce potential data gap after GT and to ensure long-term engagement between haemophilia treatment centre (HTC) and PWH, the GTR is developing a retention plan. The patient engagement plan of the GTR includes myGTR – the foundational element, data visualisation through dashboards, video/podcasts with experts, and a dedicated website with latest news about GT.

Results

Whilst developing myGTR, the WFH held focus groups to discuss which PRO data are important to collect, at which frequency, and how to capture PWH’s experience on GT. The groups indicated mobile app fatigue and requested a simple tool. myGTR is not available at any app store. It was developed as a web-based application. Patients can choose their preferred contact method – email or text message – to access myGTR and provide PRO data via an interactive digital assis-tant. The PRO data are bleeds, treatments and health related quality of life (HR-QOL) including the Patient Reported Outcomes Burdens and Experiences (PROBE), coreHEM Mental Health Outlook (core-HEM MHO) and EQ-5D-5L. At regular interval (4 times during the first year, 2 times per year thereafter), the patients will be prompted to answer two simple questions about their health status since GT infusion, and complete two out of three HR-QOL questionnaires on a rotational basis.

Conclusions

To monitor GT’s safety, efficacy and long-term effects, engagement from both HTCs and patients is critical. The GTR is a platform for HTCs whereas myGTR allows the patients to continue providing data on their health status and HR-QOL in a simple manner. When working hand-in-hand, both tools can improve patient care and treatment outcomes as well as our understanding of benefits and risks of GT.

Disclosures

Barbara Konkle: Be Biotherapy, Biomarin, Novo Nordisk, Pfizer, Sanofi; Flora Peyvandi: BioMarin Pharmaceutical Inc., CSL Behring, F. Hoffmann-La Roche Ltd., Grifols, Sanofi, Sobi, Takeda; Wolfgang Miesbach: Bayer, BioMarin, Biotest, Chugai, CSL Behring, Free-line, LFB, Novo Nordisk, Octapharma, Pfizer, Regeneron, Roche, Sanofi, Sigilon, Sobi, Takeda/shire; Brian O’Mahony: Biomarin, CSL Behring, Freeline, Irish Haemophilia Society, Pfizer, Roche; Mike Makris: Grifols, Novo Nordisk, Sanofi, Takeda; Steven Pipe: Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Genentech/Roche, GeneVentiv and Equilibra Bioscience, Sanofi, Takeda, Spark Therapeutics, uniQure, Siemens; Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics; Glenn F. Pierce: ASC Therapeutics, Be Bio, BioMarin, Decibel Therapeutics, Frontera, Intellia, Metagenomi, Novo Nordisk, Pfizer, Regeneron, Spark Therapeutics, Third Rock Ventures.

View Poster: PP_54_WFH2024

Physical functioning and pain in older men with haemophilia

O’Callaghan S, Parikh S, Bishop L, Caris S. Physical functioning and pain in older men with haemophilia. (2024), POSTER ABSTRACT (PP-161). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

It is well recognised that physical functioning can be impaired and pain common as men with haemophilia (MWH) age, due to complications from their bleeding disorder. However, it can be difficult to quantify the difference between their experience and that of men without a bleeding disorder (MNBD)of equivalent age in the general population. The PROBE (Patient Reported Outcomes Burdens Experiences) questionnaire is an internationally validated tool defining the impact of haemophilia on quality of life from the patient perspective. In 2020 the PROBE Australia Study compared the experience of MWH and MNBD, all of whom were aged 45 years and over.

Methods

A total of 106 questionnaire respondents aged 45 years and over (MWH: n = 57; MNBD: n = 49) were recruited via Australian community networks. PROBE questions included use of a mobility aid or assistive device, difficulties with activities of daily liv-ing, acute and chronic pain and use of medications for pain in the last 12 months.

Results

Differences between MWH and MNBD were pronounced. Overall MWH reported that 44% (25/57) used a mobility aid, 54% (31/57) had difficulties with activities of daily living, 58% (33/57) experienced acute pain, 74% (42/57) chronic pain and 79% (45/57) used medication for pain in the last 12 months. This was markedly higher than MNBD: none reported problems with mobility, 6% (3/49) reported problems with activities of daily living, 27% (13/49) had acute pain, 41% (20/49) chronic pain, and 61% (30/49) used medication for pain. A higher proportion of men with moderate or severe haemophilia (n = 28) reported physical function problems or pain: 61% (17/28) needed mobility aids, 79% (22/28) had difficulties with activities of daily living, 79% (22/28) had acute pain, 86% (24/28) chronic pain, and 89% (25/28) had used medi-cation for pain. Men with mild haemophilia (n = 29) also reported problems and pain more often than MNBD, including 28% (8/29) reporting mobility problems and 31% (9/29) with activities of daily living.

Conclusions

Validated haemophilia-specific tools such as PROBE are an important way to quantify the substantial differences in quality of life between older men with haemophilia and men without a bleeding disorder of equivalent age.

View Poster: PP_161_WFH2024

Gene therapy with the Padua variant of a codon-optimized human factor IX gene etranacogene dezaparvovec in people with hemophilia B: effects on patient-oriented outcomes measured using thePatient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire in the HOPE-B study

Pipe S, Abdelkader W, Clearfield E, Kucher A, Joseph B, Braverman J, Galante N, Monahan P, Ibrahim Q, Iorio A, Germini F, Skinner M. Gene therapy with the Padua variant of a codon-optimized human factor IX gene etranacogene dezaparvovec in people with hemophilia B: effects on patient-oriented outcomes measured using thePatient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire in the HOPE-B study. (2024), POSTER ABSTRACT (PP-164). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire was used to measure patient-oriented outcomes in the HOPE-B trial. Determine the effect of a single dose of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec) on the quality of life and the burden of the disease as measured by the PROBE questionnaire.

Methods

In this phase 3, open-label, single-arm trial, people with severe to moderately severe haemophilia B, after factor IX prophylaxis for ≥6 months (lead-in period), received one infusion of etranacogene dezaparvovec. The PROBE questionnaire was admin-istered at enrolment, during the lead-in period, and at 6 months, 1, 2and 3 years after the treatment. The PROBE score was calculated and ranged from 0 to 1 (worst to best health status possible). Intra-patientchanges in PROBE scores were analysed using a two-level linear mixed model (within patient repeated observations and random intercepts).

Results

Fifty-four adult males received the treatment, and PROBE data were available for 48 participants. The characteristics of the population and the mean PROBE score at the various time points are reported in Table 1. Using the baseline as a reference, there was an average change (95% confidence interval) in the PROBE score of 0.04 (0.02, 0.07) at 6 month/1 year, which persisted at 2–3 years, 0.04(0.02, 0.06). Nine (22.5%) participants had an improvement of at least0.1 in the PROBE score, five (12.5%) had a worsening of at least 0.1. Changes in the responses to the core PROBE questions are reported in Table 2. At three years, there was a 23.8% (95% CI -41.7, −5.8) reduction in the prevalence of participants having experienced acute pain in the previous 12 months. Participants with at least one target joint at baseline demonstrated a trend towards reduction in the proportion of participants experiencing difficulties with activity of daily life, without reaching the cut off for statistical significance.

Conclusions

Administering a single dose of etranacogene dezaparvovec to patients with hemophilia B led to improvement of mean Probe score maintained through at three years.

Disclosures

Steven Pipe: Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Genentech/Roche, GeneVentiv and Equilibra Bioscience, Sanofi, Takeda, Spark Therapeutics, uniQure, Siemens; Bernard Joseph: CSL Behring; Julia Braverman: CSL Behring; Nicholas Galante: CSL Behring; Paul Monahan: CSL Behring; Alfonso Iorio: Bayer, CSL, Pfizer, Roche, Sanofi/Sobi, Takeda; Federico Germini: Bayer, Biomarin, CSL Behring, Novo Nordisk, Pfizer, Roche, Takeda; Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics

View Poster: PP_164_WFH2024

Incorporating Patient Reported Outcomes into Clinical Practice: a 360-degree Clinical Evaluation for Better Care and Treatment of People with Hemophilia through myWBDR and myPROBE

Youttananukorn T, Coffin D, Diop S, Hermans C, Konkle B, Lambert C, Noone D, O’Hara J, Pierce G, W Skinner M, Iorio A. Incorporating Patient Reported Outcomes into Clinical Practice: A 360-degree Clinical Evaluation for Better Care and Treatment of People with Hemophilia through myWBDR and myPROBE [abstract]. Res Pract Thromb Haemost. 2021;5(Suppl 2). https://abstracts.isth.org/abstract/incorporating-patient-reported-outcomes-into-clinical-practice-a-360-degree-clinical-evaluation-for-better-care-and-treatment-of-people-with-hemophilia-through-mywbdr-and-myprobe/. Accessed March 12, 2022

Background

The World Federation of Hemophilia (WFH) World Bleeding Disorders Registry (WBDR) is designed to fill gaps in hemophilia care and knowledge that exist globally. The WBDR is a tool for clinicians to collect real world data on patient clinical care and quality of life, and a tool to empower people with hemophilia (PWH) to manage their own care and treatment.  The WFH will be introducing myWBDR – a mobile application for PWH participating in the WBDR through the participating hemophilia treatment centers.

Aims

To collect bleed and other patient-reported outcome (PRO) data in the WBDR.

Methods

myWBDR is designed to track bleeds, associated pain, treatments, and health status using EQ-5D-5L and the Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaires (Table).  Initially, myWBDR will be available in English, French, Hindi, Spanish, and Vietnamese.

Results

myWBDR is undergoing field testing in non-WBDR PWH and will follow with a testing cohort of PWH within the WBDR.  Implementation will be regional, starting with 5 countries (2 regions) in Q2 2021. myWBDR is a simple tool, allowing users to record accurate bleeds and treatment in under 1 minute. The inclusion of the EQ-5D-5L and PROBE questionnaires, both available in a large number of languages, will allow users to track changes in their health status over time. Both myWBDR and myPROBE include an off-line feature so data can be entered at anytime and offer simple data visualization on bleeds (number, location), level of pain and health-status.

Conclusions

Integration of PRO via the myWBDR will allow PWH to play an active role in their care and treatment. With the 360-degree data, researchers can better understand hemophilia and work to improve quality of care and treatment for PWH around the world. A data dashboard for PWH to visualize and compare their personal data is in development.

View Poster: myWBDR and myPROBE