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

Blood ◽  
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.

scholarly journals 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

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3028-3028
Author(s):  
Katharine Batt ◽  
Bob G Schultz ◽  
Jorge Caicedo ◽  
Christopher S Hollenbeak ◽  
Neha Agrawal ◽  
...  
Keyword(s):  
Real World ◽  
Bayesian Model ◽  
Hemophilia A ◽  
Publicly Traded ◽  
Real World Data ◽  
Population Mean ◽  
Icd 10 ◽  
Bleeding Episodes ◽  
The Mean ◽  
Privately Held

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.

Effect of a Fall Prevention Program on Balance Maintenance Using a Quasi-experimental Design in Real-World Settings

2012 ◽  
Vol 24 (5) ◽  
pp. 827-845 ◽  
Author(s):  
Yvonne Robitaille ◽  
Michel Fournier ◽  
Sophie Laforest ◽  
Lise Gauvin ◽  
Johanne Filiatrault ◽  
...  
Keyword(s):  
Real World ◽  
Fall Prevention ◽  
Prevention Program ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Community Dwelling ◽  
Balance Performance ◽  
Community Based ◽  
Fall Prevention Program ◽  
Quasi Experimental

Objectives: To examine the effect of a fall prevention program offered under real-world conditions on balance maintenance several months after the program. To explore the program’s impact on falls. Method: A quasi-experimental study was conducted among community-dwelling seniors, with pre- and postintervention measures of balance performance and self-reported falls. Ten community-based organizations offered the intervention (98 participants) and 7 recruited participants to the study’s control arm (102 participants). An earlier study examined balance immediately after the 12-week program. The present study focuses on the 12-month effect. Linear regression (balance) and negative binomial regression (falls) procedures were performed.falls. Results: During the 12-month study period, experimental participants improved and maintained their balance as reflected by their scores on three performance tests. There was no evidence of an effect on falls.falls. Discussion: Structured group exercise programs offered in community-based settings can maintain selected components of balance for several months after the program’s end.

scholarly journals Injury-related falls from bicycles, skateboards, roller skates, and non-motorized scooters in the United States: 2005 - 2014

2017 ◽  
Vol 4 (1) ◽  
pp. 16
Author(s):  
William Milczarski ◽  
Peter Tuckel ◽  
Richard Maisel
Keyword(s):  
Public Health ◽  
New York ◽  
Negative Binomial ◽  
Local Level ◽  
Specific Treatment ◽  
Negative Binomial Regression ◽  
The United States ◽  
Treatment Modalities ◽  
Public Health Officials ◽  
National Databases

Purpose: To provide an updated and comparative analysis of injury-related falls from bicycles, skateboards, roller skates and non-motorized scooters.Methods: The study uses two national databases – the Nationwide Emergency Department Sample and the Nationwide Inpatient Sample  – and subnational databases for New York, California, and Maryland.  Univariate and multivariate analyses (negative binomial regression) are performed to identify effects of age, gender, racial-ethnic background, and region on the incidence of injury-related falls from each of the four devices.Results: The rate of injuries due to falls from bicycles far surpasses the rates due to falls from the other devices.  When a measure of “exposure” is taken into consideration, however, the rate of injuries from skateboards outstrips the rates from bicycles or roller skates.  The profile of patients who are injured from falls from each of the four devices is distinctive.  Asian-Americans are greatly underrepresented among those who suffer a fall-related injury from any of the four devices.  The incidence of injuries attributable to falls varies considerably by geographic region.Conclusions: Public health officials need to be mindful that while certain activities such as scootering might be gaining in popularity, the number of injuries sustained from bicycles still dwarfs the number attributable to falls from skateboards, roller skates, and scooters combined.  Thus special attention needs to be paid to both prevent falls from bicycles and specific treatment modalities.  It is important for public health officials to gather injury data at the local level to allocate prevention and treatment resources more efficiently.

scholarly journals Trends in Opioid Prescribing Among Hemodialysis Patients, 2007–2014

2018 ◽  
Vol 49 (1) ◽  
pp. 20-31 ◽  
Author(s):  
Matthew Daubresse ◽  
G. Caleb Alexander ◽  
Deidra C. Crews ◽  
Dorry L. Segev ◽  
Mara A. McAdams-DeMarco
Keyword(s):  
Low Income ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
The United States ◽  
Incidence Rates ◽  
Opioid Prescription ◽  
Opioid Prescribing ◽  
Hispanic Patients ◽  
Estimate Annual Incidence ◽  
National Trends

Background: Hemodialysis (HD) patients frequently experience pain. Previous studies of HD patients suggest increased opioid prescribing through 2010. It remains unclear if this trend continued after 2010 or declined with national trends. Methods: Longitudinal cohort study of 484,745 HD patients in the United States Renal Data System/Medicare data. We used Poisson/negative binomial regression to estimate annual incidence rates of opioid prescribing between 2007 and 2014. We compared prescribing rates with the general US population using IQVIA’s National Prescription Audit data. Outcomes included the following: percent of HD patients receiving an opioid prescription, rate of opioid prescriptions, quantity, days supply, morphine milligram equivalents (MME) dispensed per 100 person-days, and prescriptions per person. Results: In 2007, 62.4% of HD patients received an opioid prescription. This increased to 63.2% in 2010 then declined to 53.7% by 2014. Opioid quantity peaked in 2011 at 73.5 pills per 100 person-days and declined to 62.6 pills per 100 person-days in 2014. MME peaked between 2010 and 2012 then declined through 2014. In 2014, MME rates were 1.8-fold higher among non-Hispanic patients and 1.6-fold higher among low-income patients. HD patients received 3.2-fold more opioid prescriptions per person compared to the general US population and were primarily prescribed oxycodone and hydrocodone. Between 2012 and 2014, HD patients experienced greater declines in opioid prescriptions per person (18.2%) compared to the general US population (7.1%). Conclusion: Opioid prescribing among HD patients declined between 2012 and 2014. However, HD patients continue receiving substantially more opioids than the general US population.

scholarly journals Impact of Switching to Fingolimod Versus Injectable Disease-Modifying Therapy Cycling on Risk of Multiple Sclerosis–Related Relapses: A Retrospective Analysis

2020 ◽  
pp. 0000-0000
Author(s):  
Maria Cecilia Vieira ◽  
Yunfeng Li ◽  
Xiangyi Meng ◽  
Huanxue Zhou ◽  
Olivia Wenxian Piao ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Relapse Rate ◽  
Real World ◽  
Negative Binomial ◽  
Office Visit ◽  
Negative Binomial Regression ◽  
Negative Binomial Regression Model ◽  
Corticosteroid Administration ◽  
Disease Modifying Therapy ◽  
Disease Modifying

Abstract Background: Clinical and real-world studies have shown significant reductions in MS relapses in patients receiving fingolimod versus injectable disease-modifying therapies (iDMTs). The objective was to compare MS relapse rate and incidence in patients switching from an iDMT to fingolimod with those cycling from one iDMT to another or those remaining on their original iDMT. Methods: A retrospective analysis was performed using MarketScan® Commercial and Medicare Supplemental claims data (July-1-2010–June-30-2016). Adult MS patients receiving ≥1 iDMT during the study were included. Relapses were identified from an MS-related hospitalization, outpatient ER or office visit, and corticosteroid administration. Annualized relapse rate ratio was estimated by negative binomial regression model with repeat-measures. Results: Of 16,352 patients, 1,110 were switchers to fingolimod, 908 were iDMT cyclers, and 14,334 were non-switchers. At baseline, rate and incidence of MS relapses were higher in switchers and iDMT cyclers versus non-switchers (P < .001); mean (SD) relapse rates declined from 0.4 (0.7), 0.4 (0.7), and 0.2 (0.5) at baseline to 0.2 (0.5), 0.3 (0.6), and 0.1 (0.4) after follow-up in switchers, iDMT cyclers, and non-switchers, respectively. Relapse incidence also declined in each cohort. The highest reductions in relapse rate and incidence were observed in switchers to fingolimod, where relapse risk was significantly reduced versus iDMT cyclers (22%; P = .0433) and non-switchers (47%; P < .001). Conclusions: This real-world study provides evidence that patients switching from an iDMT to fingolimod have the highest reductions in annualized rate and incidence of MS relapses, and significantly reduced risk of relapse, versus iDMT cyclers and non-switchers.

scholarly journals Emicizumab-Kxwh for Previously Untreated Patients with Haemophilia: The Conversation Begins

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2409-2409
Author(s):  
Tiffany Lin Lucas ◽  
Shveta Gupta ◽  
Joanna A. Davis ◽  
Fernando F. Corrales-Medina
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Hemophilia A ◽  
The United States ◽  
Haemophilia A ◽  
Advisory Committees ◽  
Inhibitor Development ◽  
Increased Risk ◽  
Prophylaxis Therapy

Introduction: With the Federal Drug and Administration approval of the use of emicizumab from birth to adulthood, clinicians will now grapple with when to choose and offer emicizumab for routine prophylaxis, especially in previously untreated patients (PUPs). Given the overall limited real-world reported data and experience using emicizumab in PUPs, we created and administered a survey to medical providers in the United States who care for paediatric patients with haemophilia to investigate real-world practice strategies and treatment selection for PUPs. Methods: After review and endorsement by the Haemostasis and Thrombosis Research Society (HTRS), the survey was electronically distributed by e-mail to all providers included in the HTRS core member list. The survey was also sent to those providers included in a list of Haemophilia Treatment Centre (HTC) physicians (with duplicate emails reconciled). Providers needed to self-identify as ones that treat pediatric patients to be included. The survey was developed as a tiered survey with questions presented to each recipient based on their prior responses. Results: Seventy-seven completed surveys were included and analysed. All participants were active providers at a comprehensive HTC and the majority (93.4%) were practicing at an academically affiliated site. In terms of characteristics of those that answered the survey, forty-eight percent of responders reported that 1-20% of their patients had expressed interest in emicizumab. 46% of participants (34/74) reported that they would personally consider emicizumab as their prophylaxis recommendation for the majority (>50%) of their hemophilia A patients without inhibitors. 57% (44/76) reported that 1-10% of their non-inhibitor hemophilia A patients were already prescribed emicizumab prophylaxis. Each participant was then asked about his or her consideration of emicizumab as prophylaxis therapy for a 2 month old PUP. Just over the majority were unsure or said no to this consideration (51.3%) and their concerns were lack of information on safety and efficacy in this young age group and increased risk for inhibitor development. If the 2 month old PUP had a high risk of inhibitor, the majority of providers who initially were hesitant to start emicizumab prophylaxis would remain so. Of note, those providers went on to be asked if the patient had gone on to complete 50 exposure days without inhibitor development, they would then become more likely to initiate emicizumab prophylaxis therapy. Use of concurrent factor replacement was posed to all participants and there were varied responses. Discussion: Overall, our results reflect a widespread practice variation and a not yet well-standardized or defined approach for the use of emicizumab in PUPs with haemophilia A. In this survey, patient preference and individual bleeding risk were the top reasons for which a provider would consider using switching to emicizumab prophylaxis in both severe and mild/moderate haemophilia A patients. This pattern of practice reflects the current era of individualized medicine. Overall, our findings reinforce the need for more studies to investigate the outcomes of a combined treatment approach with FVIII concentrates and emicizumab focusing in the potential benefit of this approach in decreasing the risk for inhibitor development PUPs. Clinicians also feel the need for further data to help clarifying the safety of emicizumab in this population. Figure Disclosures Gupta: Novartis: Honoraria, Speakers Bureau; CSL Behring: Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Davis:Sanofi: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Shire: Consultancy; Spark Therapeutics: Consultancy. Corrales-Medina:Kedrion: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees.

Inhibitor Development In Patients with Mild and Moderate Hemophilia A: Results From a Single Centre.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1407-1407 ◽  
Author(s):  
Yohann Repesse ◽  
Philippe Gautier ◽  
Annie Borel-Derlon
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Direct Sequencing ◽  
Immunosuppressive Treatment ◽  
Gene Promoter ◽  
Missense Mutations ◽  
Bleeding Events ◽  
Inhibitor Development ◽  
Treatment Centre

Abstract Abstract 1407 The development of factor VIII (FVIII) inhibitors is usually considered uncommon among patients with mild and moderate hemophilia A (HA) and less frequent than in patients with severe HA. We report here the prevalence of FVIII inhibitors and their caracteristics in 167 patients with mild and moderate HA followed in Caen Hemophilia Treatment Centre (Table). FVIII molecular defects were identified by direct sequencing in 167 patients including 30 and 137 with mild and moderate HA, respectively. Following FVIII concentrates infusions, FVIII inhibitors occured in 7.8% of patients (13/167). Fifteen percent (2/13) were low-responding inhibitors. The risk of inhibitor development appeared to be associated with high-risk FVIII genotypes clustered in the A2 and C2 domains, especially p.Arg2150His (50%) and p.Arg593Cys mutations. Interestingly, we described inhibitor development associated with novel missense-mutations (p.Tyr1786Ser, p.Asp115Tyr and -219C>T substitutions in FVIII gene promoter). In addition, high regimen infusion of FVIII concentrates appeared as risk factor for FVIII inhibitors development. Indeed, 60% (8/13) developped FVIII inhibitors following massive infusion of FVIII concentrates associated with FVIII:C levels above 1.2 UI/dL. Inhibitors in mild HA usually cross-react with endogenous factor VIII reducing the circulating basal FVIII:C level and are associated with more bleeding events. Similarly, we observed the evolution of bleeding patterns in our cohort to severe phenotypes. Bleedings were treated with FVIII concentrates and bypassing therapies (activated FVII and activated-prothrombin complex). About 25% (3/13) of these inhibitors disappeared spontaneously. Induction of Immune Tolerance (ITI) protocoles with high doses of FVIII were initiated for 7 high-responding patients with a success rate of 85 % (6/7). However, inhibitors persisted long-term and remained troublesome in 1 of these patients despite of ITI protocole. For two patients, immunosuppressive treatment with corticosteroids was started. Inhibitors disappeared and the levels of FVIII:C became detectable within 6 months. Development of FVIII inhibitors, their disappearance and the efficacy of ITI regimen seem to be different from our experience between patients with mild or moderate HA and severe HA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Current Clinical Practice and Decision-Making in Multiple Myeloma Treatment in the United States of America: A Real-World Survey

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3001-3001
Author(s):  
Amanda Ribbands ◽  
Boris Gorsh ◽  
Abigail Bailey ◽  
Natalie Boytsov ◽  
Emily Luke ◽  
...  
Keyword(s):  
Decision Making ◽  
Real World ◽  
United States Of America ◽  
Drug Class ◽  
The United States ◽  
Treatment Patterns ◽  
Treatment Choice ◽  
Current Clinical Practice ◽  
Publicly Traded ◽  
Factors Influencing

Abstract Introduction: With each successive line of therapy (LOT), treatment choice for patients with multiple myeloma (MM) becomes increasingly complicated due to existing regimens and the lack of consensus on the standard of care for relapsed/refractory disease. There is a need for more real-world (RW) information on current MM treatments and clinical practices. More insight into the complexity of treatment choices for MM, increasing with each LOT, is also needed to better understand and inform patient treatment as their MM progresses. We aimed to examine current clinical practice and decision-making in the RW setting in MM. Methods: Data were derived from the Adelphi MM Disease Specific Programme™, a point-in-time survey of hematologists and hemato-oncologists conducted in the United States of America between August 2020 and July 2021, collating descriptive information on MM treatment patterns and decision-making from first-line (1L) to fourth-line therapy and beyond (4L+). Physicians completed online patient record forms for their next 8 consulting patients who had a confirmed diagnosis of MM and were actively receiving 1L-4L+ treatment (ie, a quota of ≥2 patients on each LOT). Results: A total of 63 physicians were included in the interim analysis, reporting patients who ever received, or are on at the time of data collection, a specific LOT. Data were provided for 259 patients with 1L treatment, 186 with second-line (2L), 120 with third-line (3L), 60 with 4L, and 2 with fifth-line treatment. Of the patients included in the study, 66% were male with a mean age of 67.7 years (standard deviation 8.16 years); 59% of patients used Medicare for their health insurance and 32% of patients had commercial insurance. The majority of patients received triplet regimens in each LOT (1L: 72%, 2L: 72%, 3L: 68%, 4L: 43%). The top 5 triplet regimens are shown in Table 1. Regimens including cluster of differentiation (CD)38-targeted treatments were used across all LOTs, with the most frequent use seen in earlier relapsed/refractory settings (1L: 8%, 2L: 45%, 3L: 26%, 4L: 19%). Retreatment with the same drug class occurred in 53% of patients treated with a proteasome inhibitor, 50% of patients treated with immunomodulatory drugs, and 4% of patients treated with CD38-targeted treatment. Disease progression/relapse was the most frequent reason for treatment cessation across all LOTs among patients who used either mono, doublet, triplet, or quad regimens (1L: n=92 [48%], 2L: n=72 [61%], 3L: n=37 [63%], 4L: n=2 [100%]). For all LOTs, the leading factors influencing physicians' treatment choice were good clinical data regarding overall survival (OS) (1L: 59%, 2L: 65%, 3L: 52%, 4L: 48%) followed by better efficacy overall (1L: 48%, 2L: 53%, 3L: 45%, 4L: 41%). In 3L, high overall response rate was also important (24%). Good clinical data regarding OS was the most frequent factor influencing choice of triplet regimens at 1L, 2L, and 3L (56%, 62%, and 50%, respectively), whereas manageable side effects profile was the leading factor driving choice of triplet regimen at 4L+ (43%). Other factors that influenced treatment choice included long-term safety, transplant eligibility, and effective use of the treatment as part of a combination therapy. Conclusion: We provide valuable RW data on current treatment patterns and decision-making in MM. Interim analyses revealed a trend for use of triplet therapies across all LOTs, high retreatment rate with the same drug class, and the importance of survival data and clinical efficacy as key factors influencing physician selection of treatment. Additional analyses will be conducted as physicians complete their patient reporting for the study to identify unmet needs and opportunities for new treatment strategies in MM. Funding: GlaxoSmithKline (Study 209997). Figure 1 Figure 1. Disclosures Ribbands: Adelphi Real World, paid employee: Current Employment. Gorsh: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Boytsov: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Luke: Adelphi Real World, paid employee: Current Employment. Lambert: Adelphi Real World, paid employee: Current Employment. Hogea: GlaxoSmithKline, paid employee: Current equity holder in publicly-traded company, Ended employment in the past 24 months.

scholarly journals Real World Use of Extended Half-Life Products and the Impact on Bleeding Events and Joint Health in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1195-1195 ◽  
Author(s):  
Lynn M. Malec ◽  
Char M Witmer ◽  
Julie Jaffray ◽  
Peter A. Kouides ◽  
Kristina M. Haley ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Hemophilia A ◽  
Advisory Board ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
On Demand ◽  
Joint Health

Abstract Background : The hemophilia treatment landscape has evolved substantially in the last several years with the approval of extended half-life (EHL) products which reduce the burden of prophylaxis. Data reported from the American Thrombosis and Hemostasis Network (ATHN) as of June 2017 indicate that 21% of patients with moderate or severe hemophilia A, and 42% of patients with moderate or severe hemophilia B, receive prophylaxis utilizing an EHL. As new treatments become available and are adopted into practice, it is important to recognize the need for evaluation of efficacy, safety, and economic impact of their use outside of the clinical trial setting. We aimed to characterize the real world impact of EHL products by collecting detailed information on bleeding rates, joint health and quality of life amongst patients cared for at ATHN-affiliated Hemophilia Treatment Centers. We hypothesized that use of EHL products were utilized in at least 30% of patients and would lead to decreased ABRs and improved joint health. To date 67 of a planned 135 subjects have been enrolled, constituting this interim analysis. Methods:Subjects were recruited from seven U.S. Hemophilia Treatment Centers. Subjects with severe hemophilia A or B ≤ 30 years of age on prophylaxis or demand therapy were eligible for enrollment. Subjects excluded from study were those with a recent joint bleed (within the last 2 weeks) or those unwilling to complete all elements of the study. Data were collected during a one-time encounter concurrent with an appointment for clinical evaluation, including demographic information, treatment regimen, product type, frequency, location and severity of all bleeds, Hemophilia Joint Health Scores (HJHS), and Quality of life (QoL). Bleeding rates in subjects receiving prophylaxis were compared with those receiving on demand therapy by type treatment, EHL vs standard half-life (SHL), and by hemophilia type. Severity of bleeding events (mild, moderate, or severe) and HJHS were compared by prophylaxis groups. Results: A total of 67 patients were enrolled and eligible for analysis. This included 58 subjects with severe hemophilia A, and 9 subjects with severe hemophilia B. The mean age of the cohort was 15 years (median 12 years, IQR 8 - 21 years). For these patients whose race information was known, 89.1% were Caucasian, 3.3% African-American, 3.3% Asian, and 4.7% were of mixed or 'other' race. Eleven out of 61 (18.0%) subjects with known ethnicity were Hispanic. Among 59 patients whose treatment type were available, the majority were on prophylaxis (n=53; 89.8%) as compared to on demand therapy (n=6; 10.2%). The average annualized bleeding rate (ABR) was 2.8 amongst all individuals. As expected, the ABR was substantially lower in those receiving prophylaxis (ABR=1.0) as compared to on demand therapy (ABR=18.6) (p<0.001). Additionally, HJHS in those receiving prophylaxis was lower (mean HJHS= 3.9), meaning less evidence of joint damage, than in those receiving demand therapy (mean HJHS= 8.8) (p=0.162). For patients with severe hemophilia A, the ABR was lower in those individuals receiving EHL (ABR= 0.5) versus SHL (ABR= 1.5), although this did not reach statistical significance (p=0.136). All subjects with severe hemophilia B enrolled to date receive EHL products (n=9) therefore no comparison of ABR could be made between EHL and SHL products; the ABR in this group was 0.9. In patients with severe hemophilia A, there was a higher HJHS for those receiving EHL (mean HJHS= 7.0) versus those receiving SHL (mean HJHS = 2.1) (p=0.053). For patients with severe hemophilia B, all of whom received EHL, the mean HJHS was lower than in the hemophilia A cohort (mean HJHS=1.2). Conclusions: We report real-world bleeding events and joint health in patients with severe hemophilia A and B utilizing EHL and SHL products across a wide U.S. geographic distribution. As anticipated, there is substantial bleed reduction with prophylaxis versus on demand therapy. In our severe hemophilia A cohort, the ABR for patients receiving EHL products was similar to ABRs reported in clinical trials, suggesting clinical trial data may be reflective of real world use. Patients with severe hemophilia A receiving EHL for prophylaxis had a lower ABR than those receiving SHL, although the early impact is not reflected in the HJHS score. Longer follow-up will be necessary to determine the impact of EHL on HJHS. Disclosures Malec: Bioverativ: Research Funding; Bayer: Consultancy; Bioverativ: Consultancy; Shire: Consultancy. Jaffray:Octapharma: Consultancy; Bayer: Consultancy; CSL Behring: Consultancy, Research Funding. Kouides:UniQure: Other: DSMB; Octapharma: Research Funding. Sidonio:Octapharma: Other: Advisory Board; Genentech: Other: Advisory Board, Research Funding; CSL Behring: Other: Advisory Board; Shire: Other: Advisory Board, Research Funding; Novo Nordisk: Other: Advisory Board; Kedrion: Research Funding; Biomarin: Other: Advisory Board; Grifols: Other: Advisory Board, Research Funding; Bioverativ: Other: Advisory Board, Research Funding; Uniqure: Other: Advisory Board. Abshire:CSL: Consultancy; Shire: Consultancy; Novo Nordisk: Other: DSMB. White:Asklepios: Other: Scientific Advisory Board; Novo Nordisk: Consultancy; Shire: Other: Physician Leadership Group; Bayer: Other: GRAC; Bioverativ: Other: DSMB; Biomarin: Other: DSMB; Invitrox: Other: Scientific Advisory Board; Pfizer: Equity Ownership. Ragni:CSL Behring: Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees, Research Funding; SPARK: Consultancy, Research Funding; Shire: Research Funding; Bioverativ: Consultancy, Research Funding; Alnylam: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Sangamo: Research Funding; MOGAM: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Evaluation of the Safety of Emicizumab Prophylaxis in Persons with Hemophilia A: An Updated Summary of Thrombotic Events and Thrombotic Microangiopathies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3186-3186
Author(s):  
Monet Howard ◽  
Derrick McKinley ◽  
Fabian Sanabria ◽  
Richard H. Ko ◽  
Francis Nissen
Keyword(s):  
Risk Factors ◽  
Stock Options ◽  
Hemophilia A ◽  
Publicly Traded ◽  
Thrombotic Microangiopathies ◽  
Off Label ◽  
Coronary Syndrome ◽  
Patient Reported ◽  
Post Marketing ◽  
Privately Held

Abstract Background: Emicizumab is indicated for routine prophylaxis in persons with congenital hemophilia A (PwcHA) with/without factor (F)VIII inhibitors in &gt;100 and &gt;80 countries, respectively. Emicizumab has been used by &gt;11,400 persons across the globe (data cut-off 15 May 2021). The pivotal HAVEN 1-4 trials established the efficacy and safety of emicizumab prophylaxis; however, the HAVEN 1 trial identified an increased risk of thrombotic events (TEs) and thrombotic microangiopathies (TMAs) when used in conjunction with &gt;100 U/kg/24 hours activated prothrombin complex concentrate (aPCC) for ≥24 hours (Oldenburg, et al. New Engl J Med 2017). Here we report an updated safety evaluation of emicizumab prophylaxis focusing on TEs and TMAs. Methods: All individual safety reports for emicizumab from clinical trials, registries, expanded access programs, compassionate use and the post-marketing setting were collated with a cut-off date of 15 May 2021 and analyzed for TEs and TMAs. Number of TEs/TMAs, clinical factors (indication, age, FVIII inhibitor status, comorbidities) and drug factors (co-exposure to medications affecting coagulation) are presented in aggregate. Individual case reports (cases) were reviewed to exclude non-TEs and any duplicate reports. TEs were identified using the Medical Dictionary for Regulatory Activities (MedDRA) search strategy: 'Embolic and Thrombotic Events' Standardized Medical Query ([SMQ] Wide) and Preferred Term 'Acute Coronary Syndrome'. TMAs were defined as hemolytic uremic syndrome, microangiopathic hemolytic anemia, microangiopathy, thrombotic microangiopathy and thrombotic thrombocytopenic purpura. Results: In total, 52 cases (56 events) meeting the search criteria were identified on the Roche Global Safety Database as of 15 May 2021 (Figure). After review, 39 cases were reported in PwcHA and 10 cases were determined to be off-label (acquired hemophilia A, n=7; or unknown indication, n=3). Two additional cases were determined to be duplicates. One case of 'hemiparesis' was identified through SMQ review, but did not fit the clinical definition of a true TE. Six cases occurred with concomitant aPCC use, of which four were TMAs. In total, 33 cases were not associated with concomitant aPCC use, and these comprised 37 TEs and no TMAs in PwcHA. No new TEs or TMAs associated with aPCC were reported since the last update (Lee, et al. Haemophilia 2020). For the 37 TEs reported in PwcHA and not associated with aPCC, the median age (range) at time of event was 49 years (0.42-84) and the median (range) emicizumab treatment duration at time of event was 330 days (0-1076). In total, 36 (97.3%) TEs were medically confirmed and one (2.7%) was patient reported. Seventeen (45.9%) TEs occurred in PwcHA with FVIII inhibitors. Seven (18.9%) TEs were associated with central venous access devices (CVADs), of which four were reported to be resolving/recovering at last report. All except for two (with limited information) non-aPCC associated TEs in PwcHA were associated with ≥1 cardiovascular (CV) risk factors (e.g. previous myocardial infarction, ischemic heart disease, coronary artery disease, hypertension, hyperlipidemia, smoking, advanced age) or other risk factors for thrombosis (e.g. sepsis/bacteremia, device use, coinciding injury, hepatitis C). Of the non-aPCC and non-CVAD associated events reported, six (20.0%) TEs led to the discontinuation of emicizumab. Across all non-aPCC associated events, an evaluation of latency or duration of treatment did not reveal any patterns or trends. In total, four TEs were fatal: two myocardial infarctions, both in medically complex patients; and two disseminated intravascular coagulation events in patients &gt;70 years of age with pneumonia. Where reported, 20/31 (64.5%) TEs were recovered/resolving at the time of this analysis, with the majority of these cases reporting no change to emicizumab prophylaxis as a result of the event. Conclusions: The reporting rate for TEs without concomitant aPCC remains low as exposure increases. Notably, all cases with adequate information available were associated with CV risk factors and/or risk factors for thrombosis. All TMAs were associated with concomitant use of aPCC. This post-marketing analysis does not support TEs and TMAs without concomitant aPCC as an identified risk for PwcHA receiving emicizumab prophylaxis. The risk-benefit profile of emicizumab remains unchanged. Figure 1 Figure 1. Disclosures Howard: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. McKinley: Pro Unlimited: Current Employment. Sanabria: F. Hoffmann-La Roche Ltd: Current Employment, Current holder of individual stocks in a privately-held company. 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. Nissen: Novartis: Consultancy; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company. OffLabel Disclosure: The enclosed analysis of the Roche Hemlibra internal database was produced by submitted safety reports, including reports of off-label use. These data will be discussed in aggregate, and not individually described.

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