A Real-World Study of Pre-Post Annualized Bleed Rates and All Cause Costs Among Non-Inhibitor Patients with Hemophilia a Switching from FVIII Prophylaxis to Emicizumab

Abstract Background Hemophilia A (HA) is a rare genetic disease characterized by a deficiency in clotting factor VIII (FVIII). Persons with HA suffer from spontaneous and traumatic bleeds which significantly impact short- and long-term quality of life. Prophylaxis treatment with FVIII replacement or non-factor replacement (e.g. emicizumab) intends to prevent bleeding episodes. To date, clinical comparisons between FVIII and emicizumab are limited to non-interventional studies and indirect comparisons. Comparisons of costs are limited to cost-effectiveness models or observational studies that include patients with and without inhibitors. An increase in availability of real-world data since emicizumab's approval in 2018 has created opportunity for comparative outcomes research in the non-inhibitor HA population. Objective To compare billed annualized bleed rates (ABR b) and all-cause costs (ACC) among non-inhibitor HA patients switching from prophylaxis with FVIII replacement to emicizumab. Methods This retrospective, observational, pre-post study used the IQVIA PharMetrics® Plus database (2015-2020)-a large longitudinal US commercial health plan database with over 190 million lives. International Classification of Diseases codes (ICD-10), National Drug Codes, and Healthcare Common Procedure Coding System were used to identify diagnoses, therapies, and procedures. Males with ≥1 claim for emicizumab who were on prophylaxis treatment with FVIII prior to initiating emicizumab were included in the analysis. Patients who received bypassing agents, immune tolerance induction, or rituximab were assumed to have inhibitors and were excluded. Patients with ≥2 occurrences of any of the following diagnoses were excluded: von Willebrand disease, hemophilia B, acquired HA, or other coagulation disorders. Annualized bleed rate was defined as billed ABR and represents bleeding episodes that required evaluation, treatment, or procedure resulting in an ICD-10 claim. Therefore, bleeds treated at home and untreated bleeds were not captured. A clinical review of ICD-10 codes resulted in a list of 535 codes used to identify HA-related bleeding episodes (e.g. hemarthrosis). The ACC were calculated as the mean cost per patient per year in 2020 US dollars actually paid by the insurer. Descriptive statistics were used to summarize, and Bayesian models were developed to compare, ABR b and ACC in the pre- and post-switch periods. Bayesian inferences estimated the population mean difference in ABR b and ACC after switching from FVIII prophylaxis to emicizumab. Inferences were conducted by computing posterior probabilities for hypotheses and summarized with 95% credible intervals (CrI). Results A total of 121 patients were included with mean age [range] of 25.9 [2-63] years. The majority of patients were over the age of 18 (60.3%), 33.1% were ≥7-18, and 6.6% were <7. The mean (SD) years on FVIII replacement (pre-switch) and emicizumab (post-switch) were 2.5 (1.5) and 1.1 (0.4), respectively (Table 1). Descriptive In the majority of patients, ABR b remained unchanged from pre-switch to post-switch (42%) while 38% had some magnitude of improvement, and 20% experienced a worsening of ABR b. The mean observed ABR b and ACC were 0.68 and $518,151, respectively, in the pre-switch period, and 0.55 and $652,679, respectively, in the post-switch period. Bayesian Model The Bayesian model demonstrated a mean change in ABR b of -0.128 [95% CrI: -0.441 to 0.184] after switch (Table 2). The mean change in ACC was +$159,680 [95% CrI: $74,842 to $247,841] after switch. The model determined there is a 21.0% probability ABR b will worsen after switch and a 99.9% probability ACC will increase after switch. Conclusions Prophylaxis with FVIII replacement and emicizumab result in similar prevention of billed bleeds in a real-world switch population. Although the population mean ABR b is more likely to fall after switching from FVIII replacement to emicizumab, there is only a 1.02% posterior probability the population mean ABR b will fall by ≥0.5 after switching to emicizumab and a 21.0% probability the ABR b will worsen after switch. Additionaly, ACC are almost certain to substantially increase after switching to emicizumab (99.9%). As additional real-world data becomes available in the non-inhibitor HA population, further research should help to strengthen clinical and economic outcomes for different prophylaxis treatment options. Figure 1 Figure 1. Disclosures Batt: Sanofi: Current equity holder in publicly-traded company; Bayer Therapeutics: Consultancy; Sprouts Consulting: Other: CEO, Principal Consultant; Merck: Current equity holder in publicly-traded company; Forma: Consultancy, Current equity holder in publicly-traded company; Precision Health: Consultancy; Takeda Pharmaceuticals U.S.A.: Consultancy. Schultz: Takeda Pharmaceuticals U.S.A., Inc.: Current Employment, Current holder of individual stocks in a privately-held company. Caicedo: Takeda Pharmaceuticals U.S.A., Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Hollenbeak: Takeda Pharmaceuticals U.S.A., Inc.: Consultancy. Agrawal: Takeda Pharmaceuticals U.S.A., Inc.: Consultancy. Chatterjee: Takeda Pharmaceuticals U.S.A., Inc.: Consultancy. Dayma: Takeda Pharmaceuticals U.S.A., Inc.: Consultancy. Bullano: Takeda Pharmaceuticals U.S.A., Inc.: Current Employment, Current holder of individual stocks in a privately-held company.

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Prospective Controlled Monitoring of Hemlibra Prophylaxis Initiation in a Large Cohort of Hemophilia a Patients- Real World Data

Blood ◽

10.1182/blood-2019-122010 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2397-2397

Author(s):

Assaf Arie Barg ◽

Tami Livnat ◽

Tami Brutman-Barazani ◽

Nurit Rosenberg ◽

Ivan Budnik ◽

...

Keyword(s):

Real World ◽

Research Funding ◽

Hemophilia A ◽

Previous History ◽

Peak Height ◽

Real World Data ◽

World Data ◽

Young Infants ◽

Bleeding Episodes ◽

Supplemental Therapy

Background: Hemlibra is a bispecific antibody that bridges factor IXa and factor X to restore hemostasis in patients with Hemophilia A (HA). It has proven efficacy and safety in multicenter trials. However, real world data is currently lacking. Ancillary tests' results for monitoring Hemlibra's hemostatic effect are scarce. Aim: To evaluate laboratory monitoring and any clinical correlations to hemostasis in patients with HA who initiate prophylactic treatment with Hemlibra, per standard protocol. Methods: Any severe HA patient with or without inhibitors treated by Hemlibra and followed by our National Hemophilia Center was eligible for the study, as approved by our institutional review board. The first two subcutaneous loading injections (3 mg/kg body weight given once weekly for 4 weeks) were administered in the clinic, as was the first post-loading maintenance dose (1.5 mg/kg given once weekly) injection. The patients were instructed to contact and consult the center about any trauma, bleeding or other adverse events. Bleeding episodes as well as any surgical intervention were documented. Blood samples were obtained before initiation of therapy, during the loading period (week 2), and following the initiation of maintenance therapy (week 5). Platelet-poor plasma (PPP) was obtained and activated partial thromboplastin time (aPTT), FVIII activity and inhibitor Bethesda units (BU) assay were performed. Hemlibra levels were evaluated as previously described.1 Thrombin generation (TG) was measured in PPP and thrombin peak height and endogenous thrombin potential (ETP) were calculated.2 Results: Forty patients with HA, median age 10 years (range 6 month- 76 years) were enrolled. The group consisted of 25 children and 15 adults, of whom 18 patients had FVIII inhibitors (median 16, range 1-900BU) and 22 were without inhibitors, including 9 patients with previous history of inhibitor. Patients were clinically followed for a median of 18 weeks (range 9-76 weeks). During follow-up only one patient experienced spontaneous bleeding episodes. Hemarthroses (mainly target joints) occurred in 4/40 patients (1 child only) and post traumatic bleeds were documented in 8 patients. However, 17/40 experienced trauma that did not cause any bleeding. For 32/40 patients, Hemlibra prophylaxis was sufficient to maintain hemostasis without additional supplemental therapy. Five minor surgeries were safely performed in 4 children (2/5 without supplemental therapy), yet another procedure (circumcision of a 3-months-old baby) was complicated by major bleeding. Laboratory analyses, presented as median (interquartile range), disclosed statistically significant increase of Hemlibra plasma levels from 19 (15-22) µg/ml to 50 (42-57) µg/ml between week 2 and week 5, respectively (Fig 1A). The extended aPTT values measured before treatment of 85(61-127) sec were normalized at week 2 [28 (26-30) sec] with additional significant shortening at week 5 [23 (22-25) sec; Fig 1B]. Both ETP and peak height significantly increased from baseline 43 (0-374) nM×min and 14 (6-22) nM to 700 (202-1043) nM×min and 47 (12-76) nM after 2 weeks and further to 981 (476-1396) nM×min and 72 (35-100) nM after 5 weeks; however, TG did not reach the levels observed in normal controls [ETP 1594 (1505-1722) nM×min and peak height 221 (199-273) nM]; Fig 1C,D. No differences were found between adults and children or between inhibitor and non- inhibitor patients yet notably, initial aPTT was significantly prolonged among patients with inhibitors as compared to non- inhibitor patients and the same difference persisted at week 2 and disappeared at week 5. No differences were noted between patients experiencing any bleeding or non- bleeders, probably as most bleeding episodes were trauma related. Positive correlations were found between aPTT, Hemlibra levels and TG parameters. Notably lower TG was observed in very young infants, thus interpretation of laboratory results in this age required caution. Conclusion: This study confirms the safety and efficacy of Hemlibra prophylaxis in patients with HA, including young infants. Laboratory analyses prove that Hemlibra loading, results in higher drug levels and correlates with aPTT shortening and improved TG parameters. While aPTT normalizes during Hemlibra loading, TG is still lower than the normal range observed in controls and may be a more sensitive ancillary test to predict patients' hemostasis. Disclosures Kenet: Roche: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Research Funding; Opko Biologics: Consultancy, Honoraria, Research Funding; CSL: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria, Research Funding; Alnylam: Consultancy, Honoraria, Research Funding; BPL: Research Funding.

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Improvement in Annualized Bleed Rate in Patients with Hemophilia A Initiating Emicizumab - Physician Reported Outcomes from the Adelphi Hemophilia a Disease Specific Programme™

Blood ◽

10.1182/blood-2021-147945 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1961-1961

Author(s):

Rahul Khairnar ◽

Marquita Decker-Palmer ◽

Jennifer Mellor ◽

Keisha Golden ◽

Susanna Libby ◽

...

Keyword(s):

Real World ◽

Negative Binomial ◽

Hemophilia A ◽

Negative Binomial Regression ◽

The United States ◽

Publicly Traded ◽

Bleeding Events ◽

Treatment Centre ◽

Disease Specific ◽

Privately Held

Abstract Introduction: Emicizumab is indicated for prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (PwHA) with or without factor VIII inhibitors. There is a paucity of research on real-world effectiveness of emicizumab in PwHA, particularly in non-severe hemophilia A (HA). We aimed to describe characteristics of PwHA initiating emicizumab, and examine the change in annualized bleed rate (ABR) in these patients after initiating emicizumab in the real world. Methods: Data were collected via the Adelphi HA Disease Specific Programme™, a point-in-time survey of physicians treating PwHA collected in the United States of America from February 2020 - April 2021. Participating physicians completed a patient record form for their next consulting eligible HA patients using information from their medical charts and physician recall. Data on socio-demographics, clinical characteristics and HA treatment were collected. The sample included patients receiving emicizumab and had been receiving it for at least 12 months at the time of survey completion with the index date defined as the date of emicizumab initiation. The analysis was restricted to patients with complete data on bleeding events in the 12 months before and ≥12 months after emicizumab initiation. We calculated the annual bleed rate in the pre-index period, and annualized the bleed rate in the post-index period for those with >12 months follow-up. Change in proportion of patients with zero bleeds pre- and post-emicizumab was evaluated using the McNemar test. Changes in ABR over time in the overall cohort and subgroups of disease severity (severe vs. mild/moderate) and inhibitor status were examined using unadjusted negative binomial regression models. Results: A total of 19 patients, 14 (74%) severe and 5 (26%) mild/moderate met the inclusion criteria. 18 patients were adult (95%) with a mean age of 31 (standard deviation [SD] = 11.5) years; 15 (79%) patients were white, 8 (42%) patients had active inhibitors at the time of survey completion [5 (36%) of the 14 severe, and 3 (60%) of the 5 mild/ moderate patients], 14 (74%) patients previously received prophylactic treatment, 14 (74%) patients were commercially insured and 12 (63%) patients received at least some care at a Hemophilia Treatment Centre. Mean age at diagnosis was 4.1 (SD=8.9) years; 13.9 (SD=12.2) years in mild/ moderate patients, and 0.1 (SD=0.27) years for severe patients. The most common comorbidities were hypertension (n=3, 16%), anxiety (n=2, 11%) and depression (n=2, 11%). The average time since starting treatment with emicizumab was approximately 20.8 (SD=7.0) months. A larger proportion of patients experienced zero bleeds in the post-emicizumab compared to pre-emicizumab period (79% vs. 21%, p=0.003).The ABR was 2.10 events (95% confidence interval [CI]: 1.22 -2.99) before initiating emicizumab compared to 0.29 events (95% CI: 0.02 - 0.56) in the post-emicizumab period, indicating an 86% lower ABR after initiating emicizumab prophylaxis (ABR rate ratio [RR]: 0.14; 95% CI: 0.06 - 0.34; p<0.001). In the pre-emicizumab period, the ABR in severe patients was 1.71 events (95% CI: 0.72 -2.70) and 3.2 events (95% CI: 1.63 - 4.77) in mild/moderate patients compared to 0.19 events (95% CI: -0.08 - 0.47) and 0.57 events (95% CI: -0.09 - 1.22) respectively, in the post-emicizumab period, suggesting an 89% (ABR RR: 0.11; 95% CI: 0.03 - 0.40; p=0.001) and 82% (ABR RR: 0.18; 95% CI: 0.05 - 0.63; p=0.007) lower ABR in these subgroups respectively, after initiating emicizumab. Similarly, the ABR in patients with active inhibitors was 2.13 events (95% CI: 0.81 - 3.44) and 2.09 events (95% CI: 0.9 - 3.28) in patients without inhibitors in the pre-emicizumab period compared to 0.21 events (95% CI: -0.25 - 0.66) and 0.35 events (95% CI: 0.00 - 0.71) respectively, in the post-emicizumab period, suggesting a 90% (ABR RR: 0.10; 95% CI: 0.02 - 0.48; p=0.004) and 83% (ABR RR: 0.17; 95% CI: 0.06 - 0.50; p=0.001) lower ABR in these subgroups respectively, after initiating emicizumab. Conclusion: This real-world survey is one of the first to examine the change in ABR in PwHA initiating emicizumab. Significant bleed reductions were seen after initiating emicizumab, regardless of patient's inhibitor status. Disclosures Khairnar: University of Maryland, Baltimore: Ended employment in the past 24 months; Genentech Inc - A Member of The Roche Group: Current Employment; Roche: Current equity holder in publicly-traded company. Decker-Palmer: Genentech Inc - A Member of The Roche Group: Current Employment, Current equity holder in publicly-traded company. Mellor: Adelphi Real World: Current Employment. Golden: Adelphi Real World: Current Employment. Libby: Adelphi Real World: Current Employment. Olsen: Adelphi Real World: Current Employment. Taylor: Adelphi Real World: Current Employment. Meyer: Genentech: Current Employment; Hoffman La-Roche: Current holder of individual stocks in a privately-held company. Pike: Adelphi Real World: Current Employment. Ko: Genentech, Inc.: Current Employment; Genentech, Inc.-Roche: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company.

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A Novel Methodology for Building Longitudinal, Patient-Centric Real World Datasets in Hemophilia A

Blood ◽

10.1182/blood-2021-146160 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 594-594

Author(s):

Mark W Skinner ◽

Gillian Hanson ◽

Tao Xu ◽

Richard Ofori-Asenso ◽

Richard H. Ko ◽

...

Keyword(s):

Board Of Directors ◽

Real World ◽

Stock Options ◽

Research Funding ◽

Hemophilia A ◽

Advisory Board ◽

Real World Data ◽

Advisory Committees ◽

Patient Reported ◽

Privately Held

Abstract Background: There are limited real-world data (RWD) available on the unmet needs of people with mild or moderate hemophilia A (PwHA). This population accounts for 40-52% of all PwHA, including nearly all women with hemophilia A (HA), and is under-represented in scientific literature (Michele, et al. Haemophilia 2014; Benson, et al. Blood Transfus 2018; Peyvandi, et al. Haemophilia 2019). Available claims data from payer databases are confined to billing codes, and lack key information on outcomes and disease characterization (e.g. severity, treatment response.) (Tyree, et al. Am J Med Qual 2006). Registry datasets can require resource-intensive data entry and potentially miss key information about care received at outside facilities, at home, or after patients switch providers (Gliklich, et al. Registries for Evaluating Patient Outcomes: A User's Guide. 2014). To address these data gaps, we developed a novel, patient-centered approach to create a longitudinal healthcare database from individuals with mild and moderate HA in the United States. This study assessed the feasibility of this approach, which integrates medical record data collected during routine clinical care along with patient-reported outcomes (PROs) to provide needed insights into this under-represented population. Methods: Recruitment began in June 2020 via a broad strategy of social media outreach, healthcare provider partnerships, and patient advocacy groups. Eligibility was confined to mild or moderate PwHA, confirmed via physician report within provider notes in combination with baseline factor VIII levels (>5-50% mild, 1-5% moderate.) This study received research ethics board approval and abides by the guiding principles of the Declaration of Helsinki. PwHA enrolled via an online record management platform, PicnicHealth. After signing authorization forms for collection of their electronic health records (EHR) and informed consent to share their de-identified data for research, participants were prompted to enter information on their care providers. Records were gathered from all providers, across any facility, retrospectively as records were available. (Figure 1) All records obtained were made available to the participants via a medical timeline. Records were translated to text via optical character recognition with human review. Data elements from structured text as well as disease-specific elements from narrative text were captured using natural language processing and supervised machine learning. All elements, including visit metadata, conditions, measurements, drugs, and procedures were mapped to standardized medical ontologies and reviewed by a team of nurses. (Table 1) Quality control was assessed via inter-abstractor agreement on outputs with physician review. Patient-reported bleed, treatment, and pain data were collected via online questionnaire for a subset of PwHA, with participants prompted to enter data every 2 weeks. Abstracted EHR data was linked to PRO responses in a de-identified dataset. Cohort and abstraction characteristics were summarized descriptively. Results: From June 1, 2020 to June 30, 2021, 104 PwHA met eligibility criteria for enrollment (65 [62.5%] mild; 39 [37.5%] moderate). Participants saw providers across 34 states in the US, 22.1% (23/104) were female, and 20.6% (14/68) of those with known race/ethnicity status were from minority groups. Records were gathered from a median of six care sites and 16 providers per participant. A median of 50 (IQR [21-93]) clinical documents from 11 years were processed for each PwHA. (Table 2) Inter-abstractor agreement to assess abstraction quality averaged 95.9% for condition, 99.5% for drug name, and 95.4% for drug start date. As of June 2021, the average PRO response rate was 90.3% (150/166 of all requests) and continues prospectively. Conclusions: The patient-centric data collection methods implemented in this study provide a novel approach to build longitudinal real-world data sets. Technology-enabled data abstraction showed consistent high quality when processing the heterogeneous clinical records across disparate providers and care sites, and direct engagement with patients complements potential gaps in the clinical record. Additionally, this approach provides needed data on groups under-represented in RWD and traditional PwHA cohorts, including those with mild and moderate disease and women with HA. Figure 1 Figure 1. Disclosures Skinner: ICER: Membership on an entity's Board of Directors or advisory committees; Spark (DMC): Honoraria; Sanofi: Honoraria; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Honoraria; Pfizer (DMC): Honoraria; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; uniQure: Research Funding; Takeda: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Freeline: Research Funding; BioMarin: Honoraria, Research Funding; IPA Ltd.: Current holder of individual stocks in a privately-held company; National Hemophilia Foundation: Consultancy; Institute for Policy Advancement Ltd: Current Employment; WFH USA: Membership on an entity's Board of Directors or advisory committees; BCBS MAP: Membership on an entity's Board of Directors or advisory committees. Hanson: PicnicHealth: Current Employment, Current holder of stock options in a privately-held company. Xu: F. Hoffmann-La Roche AG: Current Employment. Ofori-Asenso: F. Hoffmann-La Roche Ltd: Current Employment. Ko: Genentech, Inc.: Current Employment; Genentech, Inc.-Roche: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Cibelli: PicnicHealth: Current Employment. Nissen: Novartis: Consultancy; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company. Witkop: Roche Advisory Panel: Consultancy; National Hemophilia Foundation: Current Employment. Sanabria: F. Hoffmann-La Roche Ltd: Current Employment, Current holder of individual stocks in a privately-held company. Shapiro: Novartis: Research Funding; Novo Nordisk: Other: Advisory board fees, Research Funding, Speakers Bureau; Octapharma: Research Funding; Pfizer: Research Funding; OPKO: Research Funding; Prometric BioTherapeutics: Research Funding; Sangamo: Other: Advisory board fees, Research Funding; Sigilon Therapeutics: Other: Advisory board fees, Research Funding; Takeda: Research Funding; Kedrion Biopharma: Research Funding; Glover Blood Therapeutics: Research Funding; Genentech: Other: Advisory board fees, Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; Bioverativ (a Sanofi company): Other: Advisory board fees, Research Funding; BioMarin: Research Funding; Agios: Research Funding.

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Real-World Data on Bleeding Patterns of Hemophilia A Patients Treated with Emicizumab

Journal of Clinical Medicine ◽

10.3390/jcm10194303 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4303

Author(s):

Sarina Levy-Mendelovich ◽

Tami Brutman-Barazani ◽

Ivan Budnik ◽

Einat Avishai ◽

Assaf A. Barg ◽

...

Keyword(s):

Real World ◽

Hemophilia A ◽

Real World Data ◽

Spontaneous Bleeding ◽

World Data ◽

Breakthrough Bleeding ◽

Time Points ◽

Observational Cohort ◽

Bleeding Episodes ◽

One Year

Emicizumab (Hemlibra™) is approved for prophylaxis of hemophilia A (HA) patients. The HAVEN studies addressed bleeding reduction in emicizumab-treated patients, but real-world data on bleeding patterns during emicizumab therapy are lacking. We aimed to compare the occurrence of breakthrough bleeding at different time points, starting from emicizumab initiation. This longitudinal prospective observational cohort study included HA patients (n = 70, aged 1 month to 74.9 years) that completed at least 18 months of follow-up in our center. We analyzed the number of spontaneous and traumatic bleeds during selected time points of the study (“bleeding periods”). The percentage of traumatic and spontaneous bleeding episodes was not significantly different among “bleeding periods” (P = 0.053 and P = 0.092, respectively). Most trauma-related treated bleeds resulted from either hemarthrosis (53%) or head trauma (33%). Spontaneous bleeding episodes were mostly hemarthroses (80%). Potential associations of the patients’ age, annualized bleeding rate before emicizumab treatment, and the presence of inhibitors with spontaneous bleed occurrence were analyzed with binomial logistic regression. The odds of bleeding while on emicizumab increased by a factor of 1.029 (P = 0.034) for every one year of age. Conclusions: Our real-world data revealed that the risk of bleeding persists, especially in older patients, despite therapy with emicizumab. These data may help clinicians in counselling their patients and in planning their management.

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P592 Costs savings associated with ferric maltol and the reduced use of intravenous iron based on real world data

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.713 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S541-S542

Author(s):

S Howaldt ◽

C K Becker ◽

J A Becker ◽

A C Poinas

Keyword(s):

Real World ◽

Productivity Loss ◽

Drug Acquisition ◽

Cost Savings ◽

Intravenous Iron ◽

Ferric Carboxymaltose ◽

Real World Data ◽

Iv Iron ◽

Acquisition Costs ◽

The Mean

Abstract Background Intravenous (IV) iron is frequently used in patients with iron deficiency (ID) when conventional oral ferrous products are ineffective or cannot be used (e.g. due to poor tolerability). Oral ferric maltol is a new iron ferric product registered in Europe and US. The aim of this study was to quantify the use of IV iron before and after the introduction of the new oral ferric maltol in real world settings and extrapolate the overall costs involved. Methods Data were collected from a single centre German clinical practice, MVZ für Immunologie, in inflammatory bowel disease (IBD) patients treated with iron therapy for ID with or without anaemia between 2013 and 2019 through the systematic CEDUR IBD registry and local medical records. The first cohort was formed of patients treated between 2013 and 2015, receiving only IV iron as ferric carboxymaltose (FCM). The second cohort was formed of patients treated between 2017 and 2019, receiving either oral ferric maltol only or ferric maltol in combination with FCM. Costs involved in each cohort were extrapolated using a societal perspective. Results Following the introduction of oral ferric maltol, the actual total number of FCM infusions observed was 138, showing a decrease of 70% compared to the first cohort in which oral ferric maltol was not available. This decreased number of infusions between the two cohorts was associated with total costs-savings of €56,933. In the first cohort, the administration costs were €44,536, the drug acquisition costs were €59,536 and the productivity loss were €30,944. In the second cohort, the administration costs were €13,597 the drug acquisition costs were €55,028 and the productivity loss were €9,447. A secondary scenario strictly applying the doses taken from respective SmPCs was tested and resulted in greater costs-savings. Noteworthy, the mean (SD) haemoglobin (Hb) level at baseline in the first cohort was lower with 11.5g/dl (1.19) vs. 12.2g/dl (1.18) in the second cohort. Three to six months after the treatment had been stopped, the mean (SD) Hb level was 13g/dl in both the first and second cohort with a SD of 1.31 and 1.37 respectively, showing that Hb levels were maintained in both cohorts. Conclusion The introduction of the new oral ferric maltol resulted in a decrease of 70% in terms of number of FCM infusions which was associated with costs-savings of €56,933 in terms of administration, drug acquisition and productivity loss costs. Considering that Hb levels were maintained in both cohorts, these results indicate that ID patients with or without anaemia previously treated with IV iron can also be managed effectively with oral ferric maltol resulting in overall societal cost-savings.

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Glucocorticoid management of adrenal insufficiency in the United Kingdom: assessment using real-world data

Endocrine Connections ◽

10.1530/ec-18-0418 ◽

2019 ◽

Vol 8 (1) ◽

pp. 20-31 ◽

Cited By ~ 4

Author(s):

Kamran Iqbal ◽

Kate Halsby ◽

Robert D Murray ◽

Paul V Carroll ◽

Robert Petermann

Keyword(s):

United Kingdom ◽

Adrenal Insufficiency ◽

Real World ◽

Hospital Admissions ◽

Immediate Release ◽

Resource Utilisation ◽

Health Improvement ◽

Real World Data ◽

The United Kingdom ◽

The Mean

Background and objectives Glucocorticoids are used to manage adrenal insufficiency (AI). We describe treatments used in the United Kingdom and real-world clinical outcomes for each treatment. Methods We used 2010–2016 primary care data from The Health Improvement Network (THIN). Descriptive analyses were conducted, and differences in variables between patients prescribed immediate-release hydrocortisone (IR HC), prednisolone or modified-release hydrocortisone (MR HC) were assessed using Fisher’s exact test. Results Overall, 2648 patients were included: 1912 on IR HC (72%), 691 on prednisolone (26%) and 45 (2%) on MR HC. A total of 1174 (44.3%) had primary and 1150 (43.4%) had secondary AI. Patients on prednisolone were older (P < 0.001) and had a greater history of smoking (292/691, P < 0.001) and CVD (275/691, P < 0.001). Patients on MR HC had more PCOS (3/45, P = 0.001) and diabetes (27/45, P = 0.004). The number of GP visits/patient/year was 6.50 in IR HC, 9.54 in prednisolone and 9.11 in MR HC cohorts. The mean number of A&E visits and inpatient and outpatient hospital admissions ranged from 0.42 to 0.93 visits/patient/year. The mean number of adrenal crises/patient/year was between 0.02 and 0.03 for all cohorts. Conclusion IR HC is most commonly used for the management of AI in the United Kingdom, followed by prednisolone. Few patients receive MR HC. The prednisolone and MR HC cohorts displayed a greater prevalence of vascular risk factors compared with IR HC. The occurrence of AC and primary and secondary resource use were similar between treatment cohorts, and they indicate significant resource utilisation. Improved treatment and management of patients with AI is needed.

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FEIBA® and Novoseven® Neutralize the Anticoagulant Effects of a Novel Small Molecule FXIa Inhibitor BMS-986177/JNJ-70033093 in Human Plasma and Whole Blood in Vitro

Blood ◽

10.1182/blood-2020-136378 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 10-11

Author(s):

Matthew W Bunce ◽

Zheng Huang Devine ◽

Madhu Chintala

Keyword(s):

Human Plasma ◽

Whole Blood ◽

Thrombin Generation ◽

Hemophilia A ◽

Lag Time ◽

Publicly Traded ◽

Routine Prophylaxis ◽

Control And Prevention ◽

Bleeding Episodes

Background: FXIa inhibition is a promising antithrombotic drug target. BMS-986177/JNJ-70033093 (BMS-177/JNJ-3093) is a novel small molecular inhibitor of FXIa currently in Phase II clinical trials with the potential for reduced bleeding risk as compared to the currently approved oral anticoagulantsHowever, reversal of anticoagulation may still be required in patients who have uncontrolled or life-threatening bleeding or need an urgent surgical procedure. Aim: To evaluate the ability of nonspecific reversal agents (NSRAs) FEIBA®, NovoSeven®, Kcentra®, Profilnine®, BeneFix®, Novoeight®, and Cyklokapron® to neutralize the anticoagulation of BMS-177/JNJ-3093 in the activated partial thromboplastin time (aPTT), thromboelastography (TEG) and thrombin generation assay (TGA) in vitro using human plasma or whole blood. Method: aPTT and TEG were performed in human plasma and whole blood, respectively, using standard assay procedures. TGA was performed in human plasma using diluted kaolin aPTT reagent (1:10,000). JNJ-3093 was evaluated at different concentrations (0.3 -10 µM) to cover the anticipated exposures in the Phase II clinical trials. The NSRAs were evaluated at the anticipated concentrations according to the dosing information in their respective labels. Results: BMS-177/JNJ-3093 produced concentration dependent increases in aPTT (up to 4.4x at 10 μM); prolongations of lag time in TEG (2.6X); prolongations of lag time (3X) as well as reductions in peak thrombin generation (70%) in TGA. FEIBA® effectively neutralized the anticoagulant effects of JNJ-3093 in aPTT, TEG and TGA. NovoSeven® neutralized the BMS-177/JNJ-3093-induced prolongations in aPTT, prolongations in lag time in TEG and TGA assays and partially restored the peak thrombin generation in TGA. In contrast, all other NSRAs tested had negligible effects or did not show neutralization of anticoagulation induced by BMS-177/JNJ-3093 in the referenced assays Conclusion: These results demonstrate that FEIBA® and NovoSeven® can effectively neutralize the anticoagulant effects of BMS-177/JNJ-3093 in vitro. A clinical study is required to determine if these agents can reverse the anticoagulant effects of BMS-177/JNJ-3093 in patients. Table Disclosures Bunce: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Huang Devine:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Chintala:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. OffLabel Disclosure: FEIBA: hemophilia A and B patients with inhibitors for: control and prevention of bleeding episodes; use around the time of surgery; routine prophylaxis to prevent or reduce the frequency of bleeding episodes NovoSeven: Treatment of bleeding and prevention of bleeding for surgeries and procedures in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmanns thrombasthenia with a decreased or absent response to platelet transfusions; treatment of bleeding and prevention of bleeding for surgeries and procedures in adults with acquired hemophilia Kcentra: urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist therapy in adult patients with need for urgent surgery/invasive procedure or acute major bleeding Profilnine: prevention and control of bleeding in patients with Factor IX deficiency due to hemophilia B BeneFix: control and prevention of bleeding episodes or peri-operative management in adult and pediatric patients with hemophilia B Novoeight: for use in adults and children with hemophilia A for control and prevention of bleeding, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes Cyklokapron: patients with hemophilia for short-term use to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction)

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Estimating the Burden of Intracranial Hemorrhage in Persons with Hemophilia A using Administrative Claims Data

Blood ◽

10.1182/blood-2019-123713 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2398-2398

Author(s):

Arash Mahajerin ◽

Anisha M. Patel ◽

Erru Yang ◽

Chinelo C. Orji ◽

Richard H. Ko

Keyword(s):

Healthcare Costs ◽

Hemophilia A ◽

Administrative Claims ◽

Index Event ◽

Major Bleed ◽

Diagnosis Codes ◽

Icd 10 ◽

Equity Ownership ◽

The Mean

Introduction Intracranial hemorrhage (ICH) is a serious, life-threatening complication of hemophilia A (HA). Previous studies have reported an incidence rate of ICH between 2-4% in persons with hemophilia A (PwHA); however, a single episode of ICH can result in significant morbidity and mortality. Few studies have assessed the long-term consequences of ICH among PwHA. We aimed to examine the downstream clinical, healthcare resource utilization (HRU), and cost burden of ICH in PwHA. Methods We utilized commercial administrative claims data from US MarketScan Commercial Research Database and PharMetrics Plus Database from 01/01/06 to 12/30/18 (MarketScan data available until 9/30/18 at the time of analysis). PwHA aged ≤65y were identified using a validated claims-based HA algorithm (Lyons et al. 2018). Further, PwHA with ICH were identified as those with ≥1 claim involving ICD-9-CM/ICD-10-CM diagnosis codes for ICH. The first ICH event was identified as the index event. PwHA with ICH were required to have ≥6 months of continuous enrollment from the index event (follow-up period). Clinical conditions were identified using ICD-9-CM/ICD-10-CM diagnosis codes, and major bleeds were identified using a previously developed algorithm (Shrestha et al. 2017). Physical therapy (PT), durable medical equipment (DME) use, factor VIII (FVIII), and bypassing agents (BPAs) were identified using NDC, CPT, or other HCPCS codes. Patient demographics, clinical characteristics, HRU, and costs were descriptively examined during the follow-up period. Results Of the total 4539 PwHA, 94 (2.1%) had ≥1 ICH diagnosis. Of these, 69 individuals with ≥6 months of continuous enrollment constituted the current study cohort. The majority (59.4%, n=41) had their index ICH event recorded in an ICU or inpatient setting. The mean age was 21.1y (SD±18.9) with 33 adults (range: 19-65y) and 36 children (range: 0-16y); 16 (23.2%) were aged <5y; all were male; 27 (39.1%) were in the northeast/east US; 37 (53.6%) had a Preferred Provider Organization health plan. In the ICH cohort, 26 (37.7%) individuals had evidence of ≥1 major bleed in the 6 months following the index ICH event, while 11 (15.9%) had evidence of inhibitors (i.e. claim for a BPA). The mean Charlson Comorbidity Index score of those in the ICH cohort was 0.9 (SD±1.8); 23 (33.3%) had a diagnosis of joint/musculoskeletal conditions including arthropathy, 22 (31.9%) had chronic pain diagnosis, 12 (17.4%) had evidence of fracture, 11 (15.9%) had a mental health-related diagnosis including depression/anxiety, and 10 (14.5%) had evidence of paraplegia/hemiplegia. In the 6 months following the index ICH event, 26 (37.7%) of the individuals had ≥1 ICU visit (mean no. of visits=0.6, SD±1.0), 23 (33.3%) had ≥1 non-ICU in-patient stay (mean=0.6, SD±1.5) and a mean length of stay of 5.5 (SD±14.9) days, 44 (63.8%) had ≥1 ER visit (mean=1.6, SD±2.3), 55 (79.7%) had ≥1 outpatient hospital visit (mean=6.2, SD±11.8), 64 (92.8%) had ≥1 office visit (mean=7.9, SD±7.4), 19 (27.5%) had evidence of DME or PT, and 47 (68.1%) had ≥1 claim for FVIII prescription/administration with an average of 5.2 (SD±11.4) claims in the post 6-month period. The average all-cause healthcare costs among PwHA with ICH was $201,595 (SD±205,388, median=$135,374) over 6 months following the ICH event, and medical costs accounted for 25.3% ($50,937) of these costs. The average healthcare costs associated with the index ICH episode were estimated to be $63,369 (SD±97,925, median=$16,813). To contextualize these findings, we estimated the average 6-month healthcare costs of PwHA without any ICH diagnosis to be $102,548 (SD±214,065, median=$40,401). Among the 69 PwHA in the ICH cohort, 51 had continuous enrollment for 6 months prior to the index event. Of these, 31 (60.8%) had evidence of any FVIII or BPA use while 15 (29.4%) had a diagnosis of ≥1 non-ICH related major bleed in the 6 months preceding the index event. Conclusions Although rare, ICH still occurs in PwHA including younger children. ICH was associated with high comorbidity burden, health care service utilization, and costs. Due to unavailability of mortality data, the current analysis may still be an underestimate of the true burden of ICH in PwHA. Based on our findings, two out of five PwHA with ICH had no evidence of HA treatments prior to the incidence of ICH. Early management and treatment of HA may reduce the burden of ICH in this population. Disclosures Mahajerin: Genentech: Consultancy, Speakers Bureau; Alexion: Speakers Bureau; Spark: Speakers Bureau; Kedrion: Membership on an entity's Board of Directors or advisory committees. Patel:Roche/Genentech: Equity Ownership; Genentech: Employment. Yang:Genentech, Inc.: Employment, Equity Ownership. Orji:Genentech: Employment. Ko:Genentech, Inc.: Employment.

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Straightforward Transition to Bay 81-8973 Prophylaxis in Patients with Hemophilia A: Prospective Real-World Data from the Taurus Non-Interventional Study Show That Number of Infusions per Week Is Maintained or Reduced

Blood ◽

10.1182/blood-2018-99-116622 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5045-5045

Author(s):

Michael Wang ◽

Beng Fuh ◽

Philip Maes ◽

Maria Eva Mingot-Castellano ◽

Rubén Berrueco ◽

...

Keyword(s):

Clinical Trials ◽

Real World ◽

Hemophilia A ◽

Weekly Dose ◽

Real World Data ◽

World Data ◽

Real World Setting ◽

Patient Reported ◽

Dosing Frequency

Abstract BACKGROUND: BAY 81-8973 (Kovaltry®, Bayer) is an unmodified full-length recombinant FVIII indicated for prophylaxis and treatment of bleeds in patients with hemophilia A; BAY 81-8973 was launched in 2016 and has since accumulated 6765 patient-years of exposure. The TAURUS study (NCT02830477) was established to investigate BAY 81-8973 prophylaxis dosing regimens chosen in clinical practice and confirm the established safety and efficacy results from the LEOPOLD clinical trials in a real world setting. OBJECTIVES: To analyse the proportion of patients on specific BAY 81-8973 prophylaxis regimens, bleeds, and patient-reported outcomes at baseline and most recent follow-up. METHODS: TAURUS is an international, open label, prospective, non-interventional, single arm study with a target recruitment of 350 previously treated patients with hemophilia A of all ages with moderate or severe hemophilia A (≤ 5% FVIII:C) with ≥ 50 exposure days to any FVIII product who have been switched to prophylaxis with BAY 81-8973. At baseline, physicians document clinical information including age, BMI, severity of hemophilia, number of target joints, prior treatment regimen, bleed history, inhibitor history, and reason for choosing a specific prophylaxis regimen. Patients/caregivers reported bleeds in ongoing patient diaries, and completed questionnaires on treatment satisfaction (HEMOSAT) and adherence (VERITAS-PRO) at baseline and follow-up. A scheduled interim analysis (30% of patients recruited) was conducted with data collected up to 2 July 2018. RESULTS: At the cut-off, 160 enrolled patients were included in the baseline analysis set, of whom 89 had ≥ 6 months of follow-up data available (median observation period 201 days), 33% of whom had completed one year of the study. Median (range) patient age was 22 (2‒69) years, time since diagnosis was 15 (0.5‒64) years, and most patients (76/89, 85%) had baseline FVIII level of <1%. Treatment assignments are shown in the table. All patients had received pre-study prophylaxis, for a median of 15 years, with 66% of patients using rFVIII-FS as their most recent FVIII treatment prior to BAY 81-8973. Most (91%) had been treated with BAY 81-8973 for <3 months prior to study entry. Pre-study, 72% of patients were treated ≥3 times per week (xW). At baseline, most patients (59%) were assigned treatment ≥3xW (every day, 1%; every other day, 16%; 3xW, 41%). The majority remained on their previous regimen (78% on ≤2xW and 97% on ≥3xW); any changes were mainly a reduction in frequency on BAY 81-8973 vs previous treatment (22%), with only 2% increasing frequency on BAY 81-8973. At last follow up, most patients remained on the same regimen: 60% on ≥3xW (≥ every other day, 17%; 3xW, 42%). Most patients (92%) did not alter their dosing frequency. Of the 8% who changed dosing frequency, the majority (6 patients) changed from ≥3xW to ≤2xW; 1 patient changed from ≤2xW to ≥3xW. The median prescribed weekly dose was 52 IU/kg (64 IU/kg for ≥3xW and 43 IU/kg for ≤2xW) on study, slightly lower than those with previous product: 56 IU/Kg overall, 64 IU/kg for ≥3xW and 50 IU/kg for ≤2xW. Median (Q1; Q3) patient diary-reported annualized joint bleed rates were 1.5 (0.0; 5.3), 1.2 (0.0; 5.3) and 1.4 (0.0; 6.1); for ≤2xW, ≥3xW, and all patients, respectively. HEMO-SAT and VERITAS-PRO data will be presented in the poster. No recruited patients developed inhibitors with BAY 81-8973. CONCLUSIONS: These real-world data from 89 patients show that the range of dosing options available for BAY 81-8973 allowed the majority of patients to become established quickly on this treatment upon switching. In the few instances where patients changed dosing frequency either upon switching to BAY 81-8973 or once established on treatment, most moved to less frequent treatment. Joint bleeding rates confirm and extend findings from the clinical trials and speak to effective bleeding prophylaxis with BAY 81-8973 in a real-world setting. Therefore, BAY 81-8973 treatment may be successfully individualized according to patient need and disease characteristics. Disclosures Wang: Terumo BCT: Other: CPC Clinical Research; CSL Behring: Consultancy; Bayer, Bioverative, Novo Nordisk, Octapharma, Shire, Genentech, Biomarain, Pfizer, CSL Behring, HEMA Biologics, Daiichi Sankyo: Research Funding; Bayer: Consultancy; Bayer, Novo Nordisk, Octapharma, Genentech, HEMA Biologics, Shire, CSL Behring: Honoraria; Novo Nordisk: Consultancy. Maes:Bayer: Honoraria. Rauchensteiner:Bayer: Employment.

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Final Primary Results from the Defifrance Registry Study: Effectiveness and Safety of Defibrotide in the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood-2020-136685 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 35-36

Author(s):

Mohamad Mohty ◽

Ibrahim Yakoub-Agha ◽

Myriam Labopin ◽

Didier Blaise ◽

Delphine Lebon ◽

...

Keyword(s):

Board Of Directors ◽

Real World ◽

Research Funding ◽

Pediatric Patients ◽

Hematopoietic Cell Transplantation ◽

Sinusoidal Obstruction Syndrome ◽

Publicly Traded ◽

Real World Data ◽

Advisory Committees ◽

World Data

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication that occurs after hematopoietic cell transplantation (HCT) conditioning. In its most severe form, VOD/SOS is associated with multi-organ failure (MOF) and a mortality rate of >80% if untreated. Defibrotide is approved for the treatment of hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT in adult and pediatric patients in the United States and severe hepatic VOD/SOS post-HCT in patients aged >1 month in the European Union. The DEFIFrance study collected real-world data on the safety and effectiveness of defibrotide in France. This analysis presents final primary data on the subgroup of DEFIFrance patients who received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT. This post-marketing study collected retrospective and prospective real-world data on patients receiving defibrotide at 53 HCT centers in France from July 15, 2014 to March 31, 2020. VOD/SOS severity was categorized using European Society for Blood and Marrow Transplantation criteria (adults) or study steering committee member adjudication (pediatric patients). The primary endpoints included Kaplan-Meier (KM)-estimated Day 100 (post-HCT) survival and Day 100 complete response (CR; total serum bilirubin <2 mg/dL and MOF resolution per investigators' assessment) in patients with severe/very severe VOD/SOS post-HCT. Secondary endpoints included evaluation of adverse events (AEs) of interest, such as hemorrhage, coagulopathy, injection-site reactions, infections, and thromboembolic events, irrespective of their relationship to treatment. Of the 775 defibrotide-treated patients included in the study analysis, 250 received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT (severe: 119 [48%]; very severe: 131 [52%]). The median patient age was 45 years (range: 5 months, 74 years) and 52 (21%) patients were less than 18 years of age. A total of 219 (88%) patients had received allogeneic HCT and 95 (38%) patients had an unrelated donor. The Day 100 KM-estimated survival was 58% (95% confidence interval [CI]: 52%, 64%) in patients with severe/very severe VOD/SOS post-HCT. The estimated Day 100 survival rate was higher in patients with severe (74% [95% CI: 65%, 81%]) versus very severe (43% [95% CI: 35%, 52%]) VOD/SOS. Among patients with severe/very severe VOD/SOS post-HCT, the CR rate at Day 100 was 53% (95% CI: 47%, 59%). The Day 100 CR rate was higher in patients with severe (68% [95% CI: 60%, 77%]) versus very severe (39% [95% CI: 30%, 47%]) VOD/SOS. Treatment emergent AEs of interest occurred in 41% of patients with severe/very severe VOD/SOS, with infection (23%) and bleeding (17%) being the most commonly reported. The DEFIFrance study represents the largest collection of real-world data on the use of defibrotide. The effectiveness and safety observed in this study build upon prior studies supporting the utility of defibrotide for treating severe/very severe VOD/SOS post-HCT in a real-world setting. Among patients receiving defibrotide for VOD/SOS post-HCT, outcomes were better in patients with severe versus very severe disease, highlighting the importance of early diagnosis and treatment of VOD/SOS before patients reach the most severe stage of VOD/SOS. Disclosures Mohty: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau. Yakoub-Agha:Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria. Labopin:Jazz Pharmaceuticals: Honoraria. Blaise:Jazz Pharmaceuticals: Honoraria. Renard:Jazz Pharmaceuticals: Research Funding. Jubert:Jazz Pharmaceuticals: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Bouvatier:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Dalle:Bellicum: Consultancy, Honoraria; Sanofi-Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Consultancy, Honoraria; Gilead: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orchard: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Peffault De Latour:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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