scholarly journals Emicizumab Outcomes in Hemophilia A Using Real-World Data from the Canadian Hemophilia Bleeding Disorder Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 347-347
Author(s):  
Man-Chiu Poon ◽  
Adrienne Lee ◽  
Federico Germini ◽  
Arun Keepanasseril ◽  
Quazi Ibrahim ◽  
...  
Keyword(s):  
Stock Options ◽  
Research Funding ◽  
Patient Reported Outcomes ◽  
Hemophilia A ◽  
Severe Disease ◽  
Mild Disease ◽  
Patient Reported ◽  
Privately Held ◽  
Mcmaster University

Abstract Background: The Canadian Hemophilia Bleeding Disorders Registry (CBDR) is a clinical database including data from all Canadian Hemophilia Treatment Centers (HTCs) to assist in the management of hemophilia and other bleeding disorders. The CBDR launched on July 1, 2015 and integrates the data entry platform for patients, myCBDR, allowing direct entry of treatments, bleeding events, and other patient reported outcomes (PRO) data. Health Canada approved emicizumab in August 2018 for the treatment of persons with hemophilia A (PwHA) with factor (F)VIII inhibitors, and for PwHA without FVIII inhibitors in 2019, enabling some patients without FVIII inhibitors to be provided compassionate access beginning November 2019. Our aim for this analysis was to use the CBDR data to describe the demographics of the emicizumab-treated PwHA population and assess its effectiveness, safety, treatment patterns, and the impact on disease burden. Methods: De-identified data were extracted from the CBDR database for all registered PwHA who had received emicizumab at least once up to December 31, 2020. Disease severity is defined by the level of endogenous clotting FVIII activity. Effectiveness outcomes include number of patients (%) with zero treated bleeds, joint bleeds, and spontaneous bleeds; annualized bleeding rates (ABR) for any bleeds and treated bleeds; Hemophilia Joint Health Score (HJHS); Patient Reported Outcomes Burdens and Experiences (PROBE); and EQ-5D-5L index and visual analog scale (VAS). ABRs were calculated as (total number of bleeds/duration of follow-up [days])*365.25. All analyses were performed based on the observed values, without imputation. This study was approved by the research ethics board of McMaster University and other participating centers, and abides by the guiding principles of the Declaration of Helsinki. Results: 73 PwHA who received emicizumab at least once up to December 31, 2020 were identified. Demographic characteristics, severity, inhibitor status, and treatments are described in Table 1. Median (IQR) age for the entire cohort was 19.7 (10.0, 40.6) years with 45.2% ≤18 years. There were 64 PwHA with severe disease, 7 with moderate disease and 2 with mild disease; both cases with mild disease had current FVIII inhibitors. 49 PwHA had current FVIII inhibitors, 12 had a history of FVIII inhibitors, and 12 had no FVIII inhibitors. 5/73 (6.8%) received immune tolerance induction (ITI) treatment while on emicizumab. Two cases of rash (allergic or acute reactions) were reported (2/73, 2.7%) of which one (reported 6 days after administration) was possibly related to emicizumab according to the reporting HTC. No thromboembolisms or thrombotic microangiopathies were observed. Median ABR (IQR) for the entire study population was 0.0 (0, 0) and 59/73 (80.8%) had no recorded bleeds. In the 14/73 (19.2%) with recorded bleeds, median ABR (IQR) was 2 (1, 3); 8 of those 14 had joint bleeds and 7 had spontaneous bleeds. HJHS was recorded for 23, PROBE Score for 9, EQ-5D-5L for 9 and EQ-5D-5L VAS for 4 PwHA (Table 2). Conclusions: The Canadian population treated with emicizumab had severe disease and current or historical FVIII inhibitors. The bleed outcomes are consistent with earlier publications, showing 80.8% had no recorded bleeds. The CBDR will allow for longitudinal follow-up of this patient population. Our results can inform healthcare practitioners and regulatory authorities on the real-world safety and effectiveness outcomes of emicizumab in PwHA with and without FVIII inhibitors. Figure 1 Figure 1. Disclosures Poon: Roche: Honoraria; Pfizer: Honoraria; Novo Nordisk: Honoraria; Bioverativ/Sanofi: Honoraria; CSL-Behring: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; University of Calgary: Current Employment; Takeda: Honoraria. Lee: Roche: Honoraria; Pfizer: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; CSL Behring: Honoraria; Biovertiv/Sanofi: Honoraria, Research Funding; Bayer: Research Funding, Speakers Bureau; Takeda: Honoraria. Keepanasseril: McMaster University: Current Employment; NovoNordisk Canada: Consultancy. Ibrahim: McMaster University: Current Employment. Nissen: F. Hoffmann-La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company; Novartis: Consultancy; Actelion: Consultancy. Sanabria: F. Hoffmann-La Roche Ltd: Current Employment, Current holder of individual stocks in a privately-held company. Santos: F. Hoffmann-La Roche Ltd.: Current Employment; Roche: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Baxter: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Takeda: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Iorio: McMaster University: Current Employment; Bayer (funding to the institution): Research Funding; BioMarin (funding to the institution): Research Funding; NovoNordisk (funding to the institution): Research Funding; Octapharma (funding to the institution): Research Funding; Pfizer (funding to the institution): Research Funding; Roche (funding to the institution): Research Funding; Sanofi (funding to the institution): Research Funding; Sobi (funding to the institution): Research Funding; Takeda (funding to the institution): Research Funding.

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

Blood ◽  
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.

scholarly journals Efficacy of rFVIIIFc for First-Time Immune Tolerance Induction (ITI) Therapy: Final Results from the Global, Prospective VerITI-8 Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 2) ◽  
pp. LBA-5-LBA-5
Author(s):  
Lynn Malec ◽  
An Van Damme ◽  
Anthony Chan ◽  
Mariya Spasova ◽  
Nisha Jain ◽  
...  
Keyword(s):  
Half Life ◽  
Stock Options ◽  
Research Funding ◽  
Hemophilia A ◽  
High Titer ◽  
High Dose ◽  
Severe Hemophilia ◽  
First Time ◽  
Inhibitor Titer ◽  
Privately Held

Abstract Introduction: Inhibitor development is a major complication of factor VIII (FVIII) replacement therapy, affecting approximately 30% of people with severe hemophilia A (Peyvandi et al Lancet 2016). Inhibitor eradication is the standard of care to restore responsiveness to FVIII; however, ITI regimens often require frequent high-dose factor injections over a long period (DiMichele et al Haemophilia 2007; Carcao et al Haemophilia 2021). Median (interquartile range [IQR]) time (months) to negative titer in the International ITI Study with high-dose FVIII was 4.6 (2.8-13.8) (n=31); negative titer to normal recovery was 6.9 (3.5-12.0) (n=23); and normal recovery to tolerance was 10.6 (6.3-20.5) (n=22) (Hay and DiMichele Blood 2012). Recombinant factor VIII Fc fusion protein (rFVIIIFc) is an extended half-life (EHL) FVIII that showed potential benefits for ITI in retrospective clinical data and case reports (Malec et al Haemophilia 2016; Groomes et al Pediatr Blood Cancer 2016; Carcao et al Haemophilia 2021). VerITI-8 (NCT03093480) is the first prospective study of rFVIIIFc in first-time ITI and follows on from the reITIrate (NCT03103542) study of rFVIIIFc for rescue ITI (Königs et al Res Pract Thromb Haemost, ISTH 2021). Aim: Describe outcomes in the verITI-8 study of first-time ITI with rFVIIIFc over 48 weeks in subjects with severe hemophilia A and high-titer inhibitors. Methods: VerITI-8 is a prospective, single-arm, open-label, multicenter study exploring efficacy of rFVIIIFc for first-time ITI in people with severe hemophilia A with high-titer inhibitors. Initial screening was followed by an ITI period in which all subjects received rFVIIIFc 200 IU/kg/day until tolerization or 48 weeks had elapsed (Figure). This was followed by tapered dose reduction to standard prophylaxis and follow-up. Key inclusion criteria included males with severe hemophilia A, high-titer inhibitors (historical peak ≥5 Bethesda units [BU]/mL), and prior treatment with any plasma-derived or recombinant standard half-life or EHL FVIII. Key exclusion criteria included coagulation disorder(s) other than hemophilia A and previous ITI. The primary endpoint was time to tolerization (successful ITI) with rFVIIIFc defined by inhibitor titer <0.6 BU/mL, incremental recovery (IR) ≥66% of expected IR (IR ≥1.32 IU/dL per IU/kg) (both at 2 consecutive visits), and t ½ ≥7 hours (h) within 48 weeks. Secondary endpoints included number of subjects achieving ITI success, annualized bleed rates (ABR), and adverse events (AEs). Results: Sixteen subjects were enrolled and received ≥1 rFVIIIFc dose. Median (range) age at baseline was 2.1 (0.8-16.0) years, and historical peak inhibitor titer was 22.4 (6.2-256.0) BU/mL (Table). Twelve (75%), 11 (69%), and 10 (63%) subjects, respectively, achieved a negative inhibitor titer, an IR >66%, and a t½ ≥7 h (ie, tolerance) within 48 weeks. Median (IQR) times in weeks to achieve these markers of success were 7.4 (2.2-17.8), 6.8 (5.4-22.4), and 11.7 (9.8-26.2) (ie, 2.7 [2.3-6.0] months to tolerance), respectively. One subject achieved partial success (negative inhibitor titer and IR ≥66%), and 5 subjects failed ITI, of which 2 had high inhibitors throughout, 2 experienced an increase in inhibitor levels, and 1 recorded a negative inhibitor titer at 282 days. Most bleeds occurred in the ITI period when median (IQR) ABRs (n=13) were 3.8 (0-10.1) overall, 0 (0-2.6) for spontaneous, 1 (0-4) for traumatic, and 0 (0-3.1) for joint. During tapering, median (IQR) ABRs (n=10) were overall, 0 (0-2.4); spontaneous, 0 (0-0); traumatic, 0 (0-1.3); and joint, 0 (0-0). All 16 subjects experienced ≥1 treatment-emergent AE (TEAE), the most frequent of which was pyrexia in 7 subjects (44%). One subject reported ≥1 related TEAE (injection site pain). Nine subjects (56%) experienced ≥1 treatment-emergent serious AE (TESAE). TESAEs occurring in ≥2 subjects included vascular device infection, contusion, and hemarthrosis. No treatment-related TESAEs, discontinuations due to AEs, or deaths were reported. Conclusions: rFVIIIFc is the first EHL FVIII with prospective data for first-time ITI in patients with severe hemophilia A with historical high-titer inhibitors. Evaluated within a 48-week timeframe, rFVIIIFc offered rapid time to tolerization (median 11.7 weeks; 2.7 months) with durable responses in almost two-thirds of subjects and was well tolerated. Optimizing ITI to eradicate inhibitors remains a priority. Figure 1 Figure 1. Disclosures Malec: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy, Research Funding; Takeda: Consultancy; Bioverativ: Consultancy, Research Funding, Speakers Bureau; Shire: Consultancy; Bayer: Consultancy. Van Damme: Pfizer: Consultancy; Shire: Consultancy; Bayer: Consultancy. Chan: Bioverativ: Consultancy. Jain: Sanofi: Ended employment in the past 24 months; Takeda: Current Employment, Current holder of stock options in a privately-held company. Sensinger: Sanofi: Current Employment, Current holder of stock options in a privately-held company. Dumont: Sanofi: Current Employment, Current holder of stock options in a privately-held company. Lethagen: Sobi: Current Employment, Current holder of stock options in a privately-held company. Carcao: Bayer, Bioverativ/Sanofi, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, and Shire/Takeda: Research Funding; Bayer, Bioverativ/Sanofi, CSL Behring, Grifols, LFB, Novo Nordisk, Pfizer, Roche, and Shire/Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Peyvandi: Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Ablynx, Grifols, Kedrion, Novo Nordisk, Roche, Shire, and Sobi: Other: Personal Fees. OffLabel Disclosure: adheres to routine clinical practice

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 >100 and >80 countries, respectively. Emicizumab has been used by >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 >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 >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.

scholarly journals Updated Follow-up of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (SB-525) Gene Therapy in Adults with Severe Hemophilia a

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Andrew D. Leavitt ◽  
Barbara A. Konkle ◽  
Kimo Stine ◽  
Nathan Visweshwar ◽  
Thomas J. Harrington ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stock Options ◽  
Research Funding ◽  
Hemophilia A ◽  
Phase 1 ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
Dose Cohort ◽  
Fviii Activity

Introduction: Hemophilia A is a rare bleeding disorder caused by pathogenic variants in the F8 gene, resulting in insufficient factor VIII (FVIII) activity. Adeno-associated virus (AAV)-mediated gene transfer enables the delivery of a modified functional F8 gene to hepatocytes that subsequently synthesize FVIII at levels that may prevent bleeding events in the absence of exogenous FVIII. Updated results and follow-up from the Alta study, an ongoing gene therapy study in patients with severe hemophilia A, are presented. Methods: The Alta study is a phase 1/2 dose-ranging, single-dose study of giroctocogene fitelparvovec (also known as SB-525 and PF-07055480), a recombinant AAV serotype 6 (rAAV6) vector encoding a modified F8 gene. Adults aged ≥18 years with severe hemophilia A were eligible for inclusion. Giroctocogene fitelparvovec was infused into patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11, 2e12, 1e13, and 3e13 vg/kg). The 3e13 vg/kg dose cohort was expanded with 3 additional patients. Key end points included safety, circulating FVIII activity, use of FVIII replacement therapy, and frequency of bleeding events. Presented data are from the ongoing Alta study (NCT#03061201; data cutoff date, 26 May 2020; database not locked; data reflect those at time of data cutoff, have not undergone standard quality checks, and may be subject to change). Results: Eleven male patients participated in the study (mean [SD] age, 30.3 [7.8] years; white, 81.8%). As of the cutoff date, patients have been followed for 35 to 144 weeks; one patient in the 1e13 vg/kg cohort discontinued from the study. Overall, the most commonly reported adverse events (AEs; n) included increased alanine aminotransferase (ALT; 8 [72.7%]), increased aspartate aminotransferase (AST; 5 [45.5%]), upper respiratory tract infection (4 [36.4%]), and pyrexia (4 [36.4%]). Treatment-related serious AEs were reported in 1 patient (in the 3e13 vg/kg cohort) who experienced hypotension and fever ≈6 hours after giroctocogene fitelparvovec infusion; the events fully resolved with treatment and did not delay post-infusion discharge. In the 3 lower-dose cohorts, no ALT elevation requiring more than 7 days of corticosteroid treatment was observed. Of the 5 patients in the 3e13 vg/kg cohort, 4 had elevations in ALT that were managed with a tapering course of corticosteroids (ranging from 10-134 days) without loss of clinically relevant FVIII activity through 40 weeks, as evidenced by a lack of bleeding events before and after treatment with corticosteroids. Increases in FVIII activity from baseline were generally dose-dependent. Patients in the 3e13 vg/kg cohort achieved a mean normal-range of FVIII activity within 5 weeks post-infusion, with mean FVIII activity maintained through week 40, which is the last time point with data for all 5 patients in this cohort (Table). Following the initial prophylactic period of up to ≈3 weeks after giroctocogene fitelparvovec administration, no bleeding events occurred in any patient treated in the 3e13 vg/kg cohort. Use of FVIII replacement therapy ≥3 weeks after giroctocogene fitelparvovec administration was reported in 5/6 patients in the lower-dose cohorts (range: 9-115 infusions); none of the patients in the 3e13 vg/kg cohort required FVIII replacement beyond initial use of prophylactic factor for up to ≈3 weeks (prophylactic coverage stopped 3 weeks and 2 days after giroctocogene fitelparvovec administration in 1 patient in the 3e13 vg/kg cohort). Conclusions: To date, a single infusion of giroctocogene fitelparvovec gene therapy in patients with severe hemophilia A resulted in dose-dependent and sustained increases in FVIII levels without administration of exogenous FVIII, bleeding episodes or sustained adverse events in the highest-dose cohort (3e13 vg/kg). Additionally, patients treated in the highest-dose cohort achieved a mean FVIII activity in the normal range within 5 weeks, which was maintained through week 40. Data on all patients with more than 1 year of follow-up will also be presented. The study is ongoing, and these interim results support further development of giroctocogene fitelparvovec for the treatment of patients with severe hemophilia A. Disclosures Leavitt: BioMarin: Membership on an entity's Board of Directors or advisory committees. Konkle:Sanofi: Consultancy, Research Funding; Takeda: Research Funding; Uniquire: Research Funding; CSL Behring: Consultancy; BioMarin: Consultancy; Baxalta: Research Funding; Spark: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sigilon: Consultancy, Research Funding; Roche: Consultancy. Stine:Biomarin: Consultancy; Applied Stem Cell Therapeutics: Consultancy. Visweshwar:Biogen Idec: Membership on an entity's Board of Directors or advisory committees. Giermasz:uniQure: Consultancy, Research Funding; Sangamo Therapeutics: Research Funding; Bioverativ/Sanofi: Consultancy, Research Funding, Speakers Bureau; BioMarin: Consultancy, Research Funding, Speakers Bureau; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau. Arkin:Pfizer: Current Employment, Current equity holder in publicly-traded company, Other: own stock/options in the company. Fang:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Plonski:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Smith:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Tseng:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Di Russo:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Cockroft:Sangamo Therapeutics: Current Employment, Other: Shareholder of Sangamo Therapeutics. Rupon:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Rouy:Sangamo Therapeutics: Current Employment, Other: Shareholder of Sangamo Therapeutics.

scholarly journals Tisagenlecleucel Demonstrates Safety, Efficacy and CNS Trafficking in Primary CNS Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 258-258
Author(s):  
Matthew J. Frigault ◽  
Jorg Dietrich ◽  
Kathleen M.E. Gallagher ◽  
Irene Scarfò ◽  
Mark Roschewski ◽  
...  
Keyword(s):  
Stock Options ◽  
Research Funding ◽  
Response Rate ◽  
Unmet Need ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Publicly Traded ◽  
Car T ◽  
Privately Held

Abstract Background: Three CD19 directed CAR-T products have gained FDA approval for systemic large B-cell lymphoma. Due to heightened concerns of immune cell associated neurotoxicity syndrome (ICANS), patients with primary CNS lymphoma (PCNSL) were excluded from all pivotal CAR-T studies. Consequently, all three products carry a limitation of use in the PCNSL patient population per their FDA labels . Due to these exclusions, little is known about the treatment-related toxicities and therapeutic potential of the currently available CD19 directed CAR-T products in this challenging patient population with significant unmet need. Methods: Based on our prior experience of tisagenlecleucel in secondary CNS lymphoma (PMID: 31320380) we conducted a pilot study with expansion of tisagenlecleucel in adults with relapsed or refractory PCNSL (NCT04134117). Patients had to be 18 years of age or older and have had progression or relapse following methotrexate-based therapy. All patients needed a confirmed diagnosis of PCNSL without evidence of systemic disease. Patients received a standard regimen of fludarabine (25 mg/m 2) and cyclophosphamide (250 mg/m 2) daily on days -5, -4, and -3 of infusion and a dose of 0.6-6.0 x 10 8 tisagenlecleucel CAR+ T-cells. Patients who had progressed on prior BTKi were allowed to continue given its beneficial effect on CAR-T expansion and function with cessation by month 3. The primary endpoint of this study was tolerability and toxicity including the rate and grade of CRS and ICANS per the 2019 ASTCT (American Society of Transplantation and Cellular Therapy) consensus criteria. Secondary endpoints included overall response rate and complete response rate to tisagenlecleucel per the international PCNSL Collaborative Group (IPCG) criteria which included MRI and CSF assessments. Exploratory endpoints included long-term efficacy, expansion, persistence and phenotype of tisagenlecleucel, cytokine profiling of the blood and CSF and CNS trafficking of CAR-T cells. Results: As of April 1, 2021, 10 subjects (ages 35-70 years) were enrolled and 9 were infused with a median age of 67 years (range, 34-81). Of the 9 infused patients, the median time from leukapheresis to infusion was 30 days (range, 27-37). Patients were heavily pretreated prior to study enrollment and received a median of 4 prior lines of anti-neoplastic therapy. All patients had progressed or failed first line high-dose methotrexate (HD-MTX); two had a history of prior thiotepa based autologous stem cell transplant (ASCT). Eight out of 9 patients had progressed following a prior BTKi and/or an immunomodulatory drug (IMiD) as part of TEDDI-R (temozolomide, etoposide, doxil, dexamethasone, ibrutinib and rituximab, n = 3), ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab and Revlimid, n = 3), or as monotherapy (n = 5) and 2 patients had received prior stereotactic radiotherapy. All patients had measurable disease at time of lymphodepletion (pre-infusion). Grade 1 CRS was observed in 6 patients with a median onset of 4 days (range, 1-5) following tisagenlecleucel and no patients required intervention for CRS. ICANS developed in 5 out of the 9 patients, only a single case of grade 3 ICANS, with a median time of onset was 5 days (range, 3-11). With a median follow-up of 7.43 months for survivors, 6/9 patients were alive with 4/9 showing ongoing responses (Figure 1). Expansion of tisagenlecleucel was demonstrated in the peripheral blood and CSF. Nanostring and RNA pathway analysis of CSF infiltrates demonstrated higher degrees of CNS CAR-T penetration in responding patients and increased T-cell and macrophage gene signatures. Peripheral and CSF cytokines were assessed. Conclusion: Tisagenlecleucel in r/r PCNSL was safe and efficacious in a highly refractory group of patients with significant unmet need. The majority of patients demonstrated a response per IPCG, including responses beyond 12 months. Tisagenlecleucel was found to expand in the peripheral blood and CNS with CSF gene signatures suggestive of higher CAR-T cell infiltrates in responding patients. Full trial safety data as well as additional follow-up and correlative studies will be presented. Figure 1 Figure 1. Disclosures Frigault: Editas: Consultancy; Iovance: Consultancy; Arcellx: Consultancy; Kite: Consultancy, Research Funding; Takeda: Consultancy; Novartis: Consultancy, Research Funding; BMS: Consultancy. Dietrich: Unum: Consultancy; Blue Earth Diagnostics: Consultancy; Magnolia: Consultancy; Gamaka Bio: Consultancy; Beacon Biosignals: Research Funding; Boehringer Ingelheim: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Acerta: Research Funding; Orbus: Research Funding. Jordan: CereXis: Consultancy; Recursion: Consultancy; Navio Theragnostics: Consultancy. Forst: Eli Lilly: Current holder of individual stocks in a privately-held company. Plotkin: AstraZeneca: Consultancy; Akuous: Consultancy; NFlection Therapeutics: Other: Co-founder; NF2 Therapeutics: Other: Co-founder. Spitzer: Qihan Bio: Consultancy; Bluebird Bio: Consultancy; Jazz Pharmaceuticals: Consultancy; Syneos Health: Consultancy. Defilipp: Omeros, Corp.: Consultancy; Incyte Corp.: Research Funding; Regimmune Corp.: Research Funding; Syndax Pharmaceuticals, Inc: Consultancy. Maus: Tmunity: Consultancy; Novartis: Consultancy; Micromedicine: Consultancy, Current holder of stock options in a privately-held company; Kite Pharma: Consultancy, Research Funding; GSK: Consultancy; Intellia: Consultancy; In8bio (SAB): Consultancy; CRISPR therapeutics: Consultancy; Cabaletta Bio (SAB): Consultancy; BMS: Consultancy; Bayer: Consultancy; Atara: Consultancy; AstraZeneca: Consultancy; Astellas: Consultancy; Arcellx: Consultancy; Agenus: Consultancy; Adaptimmune: Consultancy; tcr2: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months; century: Current equity holder in publicly-traded company; ichnos biosciences: Consultancy, Current holder of stock options in a privately-held company; Torque: Consultancy, Current holder of stock options in a privately-held company; WindMIL: Consultancy. Chen: Gamida: Consultancy; Incyte: Consultancy.

scholarly journals Follow-up of More Than 5 Years in a Cohort of Patients with Hemophilia B Treated with Fidanacogene Elaparvovec Adeno-Associated Virus Gene Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3975-3975
Author(s):  
Ben J. Samelson-Jones ◽  
Spencer K. Sullivan ◽  
John E.J. Rasko ◽  
Adam Giermasz ◽  
Lindsey A. George ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Stock Options ◽  
Research Funding ◽  
Phase 1 ◽  
Hemophilia B ◽  
Advisory Committees ◽  
Adeno Associated Virus ◽  
Privately Held

Abstract Fifteen patients with moderately severe to severe hemophilia B (factor IX [FIX] activity ≤2%) were treated with fidanacogene elaparvovec at a dose of 5e11 vg/kg as part of a phase 1/2a study. The study was 52 weeks in duration, after which patients were eligible to enroll in the long-term follow-up (LTFU) study of up to 5 years. All 15 patients completed the phase 1/2a study, and 14 patients were subsequently enrolled in the LTFU study. At the time of the data cut (December 2020), 13 patients were enrolled in the LTFU study, with follow-up ranging from >2.5 years to >5 years following vector administration. Over this period of time, fidanacogene elaparvovec remained generally well tolerated. As reported previously, 3 patients were treated with corticosteroids within the first 6 months of the phase 1/2a study. No patients have required treatment or re-treatment with corticosteroids in the LTFU study. There were no serious adverse events (SAEs) in the phase 1/2a study, and 3 patients reported SAEs in the LTFU study, none of which were considered treatment related. No patient developed an inhibitor or had a thrombotic event. No patients have developed hepatic masses or significant elevations in alpha-fetoprotein (AFP). Annual liver ultrasounds revealed only hepatic steatosis in one patient. Mean FIX activity levels by year remain in the mild hemophilia severity range: 22.8%, year 1 (n=15); 25.4%, year 2 (n=14); 22.9%, year 3 (n=14); 24.9%, year 4 (n=9); and 19.8%, year 5 (n=7) when evaluated centrally using the ACTIN/FSL one-stage assay. These levels have been associated with mean annualized bleeding rates ranging from 0-0.9 over the course of follow-up, and no patients have resumed FIX prophylaxis. Four patients have undergone 6 surgical procedures during the LTFU study, 4 elective and 2 emergent. There were no bleeding complications with these procedures, and the 2 emergent procedures (appendectomy and lumbar discectomy) were performed without the need of additional FIX. Overall, this represents the largest cohort of hemophilia B patients with a duration of follow-up up to 5 years following treatment with an adeno-associated virus gene therapy expressing a highly active variant of FIX. Fidanacogene elaparvovec remains generally well tolerated over a period up to 5 years postinfusion. While encouraging, more long-term data in a larger cohort of patients are needed to further characterize the safety and durability of fidanacogene elaparvovec, which is under way in an ongoing phase 3 study. Disclosures Samelson-Jones: Pfizer: Consultancy, Research Funding; Spark: Research Funding. Sullivan: Genentech: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees. Rasko: Imago: Consultancy; Cynata: Honoraria, Speakers Bureau; Gene Technology Technical Advisory Board: Membership on an entity's Board of Directors or advisory committees; NHMRC Mitochondrial Donation Expert Working Committee: Membership on an entity's Board of Directors or advisory committees; Australian Cancer Research: Membership on an entity's Board of Directors or advisory committees; Cure the Future Foundation: Membership on an entity's Board of Directors or advisory committees; FSHD Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Australian Government: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Pfizer Inc: Honoraria, Speakers Bureau; Glaxo-Smith-Kline: Honoraria, Speakers Bureau; Spark: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; bluebird bio: Honoraria, Speakers Bureau; Genea: Current equity holder in publicly-traded company; Celgene: Honoraria, Speakers Bureau. Giermasz: BioMarin: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Bayer: Consultancy; ATHN: Consultancy; NovoNordisk: Consultancy; UniQure: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Bioverativ/Sanofi: Consultancy, Research Funding, Speakers Bureau; Sangamo Therapeutics,: Research Funding. George: CSL Behring: Consultancy; Bayer: Consultancy; Avrobio: Other: Data Safety Monitoring Committee . Ducore: Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Speakers Bureau; HEMA Biologics: Consultancy, Honoraria. Teitel: Pfizer: Consultancy, Research Funding; Spark: Research Funding; Bayer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Novo Nordisk: Consultancy; Octapharma: Consultancy; CSL Behring: Consultancy. McGuinn: Biogen: Research Funding; Roche/Genentech: Research Funding; Shire/Baxalta: Consultancy, Research Funding; Spark: Research Funding. O'Brien: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Winburn: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Smith: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Chhabra: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Rupon: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company.

Individualized cancer follow-up supported by electronic Patient-Reported Outcomes: Development and evaluation (Preprint)

2020 ◽  
Author(s):  
Sissel Ravn ◽  
Henriette Vind Thaysen ◽  
Lene Seibaek ◽  
Victor Jilbert Verwaal ◽  
Lene Hjerrild Iversen
Keyword(s):  
Ct Scan ◽  
Advanced Cancer ◽  
Patient Reported Outcomes ◽  
Cost Benefit Analysis ◽  
Cost Benefit ◽  
Structured Interviews ◽  
European Organization ◽  
Individualized Care ◽  
Patient Reported

BACKGROUND Cancer survivors experience unmet needs during follow-up. Besides recurrence, a follow-up includes detection of late side effects, rehabilitation, palliation and individualized care. OBJECTIVE We aimed to describe the development and evaluate the feasibility of an intervention providing individualized cancer follow-up supported by electronic patient-reported outcomes (e-PRO). METHODS The study was carried out as an interventional study at a Surgical and a Gynecological Department offering complex cancer surgery and follow-up for advanced cancer. The e-PRO screened for a priori defined clinical important symptoms and needs providing individualized follow-up. We included following questionnaires in the e-PRO; the general European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC validated for colorectal and ovarian cancer patients. To support individualization, we included three prioritized issues of the patient’s preference in each e-PRO. The response-algorithm was aggregated based on the severity of the patient’s response. To ensure the sensitivity of the e-PRO, we performed semi-structured interviews with five patients. All clinicians (surgeons and gynecologists) performing the consultations reviewed the e-PRO. The evaluation was divided in two, 1)The feasibility was assessed by a)Patients’ response rate of the e-PRO, b)Number of follow-up visits documenting the use of e-PRO and c)Patients’ prioritized issues prior to the consultation(‘yes’ / ‘no’), and after the follow-up 2)Patients assessment of a)The need and purpose of the follow-up visit and b)the support provided during the follow-up visit. RESULTS In total, 187 patients were included in the study, of which 73%(n=136/187) patients responded to the e-PRO and were subjected to an individualized follow-up. The e-PRO was documented as applied in 79% of the follow-up visits. In total, 23% of the prioritized issues did not include a response. Stratified by time since surgery, significantly more patients did not fill out a prioritized issue had a follow-up >6 months since surgery. In total, 72 % follow-up visits were evaluated to be necessary in order to discuss the outcome of the CT scan, symptoms, and/or prioritized issues. Contrary, 19% of the follow-up visits were evaluated to be necessary only to discuss the result of the CT scan. A range from 19.3–56.3% of patients assessed the follow-up visit to provide support with respect to physical (42% of patients), mental (56%), sexual (19%) or dietary (27%) issues. Further, a range from 34–60% of the patients reported that they did not need support regarding physical (43% of patients), mental (34%), sexual (63%) or dietary (57%) issues. CONCLUSIONS An individualized follow-up based on e-PRO is feasible, and support most patients surgically treated for advanced cancer. However, results indicate that follow-up based on e-PRO may not be beneficial for all patients and circumstances. A thorough cost-benefit analysis may be warranted before implementation in routine clinic.

Minimum 10-Year Outcomes of Primary Arthroscopic Transosseous-Equivalent Double-Row Rotator Cuff Repair

2021 ◽  
pp. 036354652110154
Author(s):  
Adam M. Johannsen ◽  
Justin W. Arner ◽  
Bryant P. Elrick ◽  
Philip-C. Nolte ◽  
Dylan R. Rakowski ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Revision Surgery ◽  
Rotator Cuff Repair ◽  
Patient Reported Outcomes ◽  
Long Term Results ◽  
Double Row ◽  
Kaplan Meier ◽  
Patient Reported ◽  
Cuff Repair

Background: Modern rotator cuff repair techniques demonstrate favorable early and midterm outcomes, but long-term results have yet to be reported. Purpose: To determine 10-year outcomes and survivorship after arthroscopic double-row transosseous-equivalent (TOE) rotator cuff repair. Study Design: Case series; Level of evidence 4. Methods: The primary TOE rotator cuff repair procedure was performed using either a knotted suture bridge or knotless tape bridge technique on a series of patients with 1 to 3 tendon full-thickness rotator cuff tears involving the supraspinatus. Only patients who were 10 years postsurgery were included. Patient-reported outcomes were collected pre- and postoperatively, including American Shoulder and Elbow Surgeons (ASES), 12-Item Short Form Health Survey (SF-12), Single Assessment Numeric Evaluation (SANE), shortened version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH), and satisfaction. Kaplan-Meier survivorship analysis was performed. Failure was defined as progression to revision surgery. Results: A total of 91 shoulders (56 men, 31 women) were included between October 2005 and December 2009. Mean follow-up was 11.5 years (range, 10.0-14.1 years). Of 91 shoulders, 5 (5.5%) failed and required revision surgery. Patient-reported outcomes for patients who survived were known for 80% (69/86). Outcomes scores at final follow-up were as follows: ASES, 93.1 ± 10.8; SANE, 87.5 ± 14.2; QuickDASH, 11.1 ± 13.5; and SF-12 physical component summary (PCS), 49.2 ± 10.1. There were statistically significant declines in ASES, SANE, and SF-12 PCS from the 5-year to 10-year follow-up, but none of these changes met the minimally clinically important difference threshold. Median satisfaction at final follow-up was 10 (range, 3-10). From this cohort, Kaplan-Meier survivorship demonstrated a 94.4% survival rate at a minimum of 10 years. Conclusion: Arthroscopic TOE rotator cuff repair demonstrates high patient satisfaction and low revision rates at a mean follow-up of 11.5 years. This information may be directly utilized in surgical decision making and preoperative patient counseling regarding the longevity of modern double-row rotator cuff repair.

scholarly journals Sex differences in outcomes after arthroscopic bankart repair

2020 ◽  
Vol 6 (1) ◽  
pp. e000965
Author(s):  
Natalie A Lowenstein ◽  
Peter J Ostergaard ◽  
Daniel B Haber ◽  
Kirsten D Garvey ◽  
Elizabeth G Matzkin
Keyword(s):  
Mental Health ◽  
Sex Differences ◽  
Patient Reported Outcomes ◽  
Strength Function ◽  
Bankart Repair ◽  
Level Of Evidence ◽  
Arthroscopic Bankart Repair ◽  
Patient Reported ◽  
Males And Females

ObjectivesRisk factors for anterior shoulder dislocation include young age, contact activities and male sex. The influence of sex on patient-reported outcomes of arthroscopic Bankart repair (ABR) is unclear, with few studies reporting potential differences. This study’s purpose was to compare patient-reported outcomes of males and females following ABR.MethodsProspectively collected data was analysed for 281 patients (males: 206, females: 75) after ABR with preoperative, 1-year and 2-year follow-up responses. The Wilcoxon signed-rank and χ2 tests, preoperative, 1 year and 2 year follow-up results were examined to determine differences of scores in males versus females.ResultsNo statistically significant sex differences were observed in Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES), Visual Analogue Scale (VAS) or Single Assessment Numerical Evaluation (SANE) Scores at 1-year or 2-year follow-up. Females had lower Veterans RAND 12-item health survey (VR-12) mental health subscores at 2-year follow-up (females: 52.3±9.0, males: 55.8±7.6, p=0.0016). Females were more likely to report that treatment had ‘exceeded expectations’ at 2-year follow-up regarding motion, strength, function and normal sports activities.ConclusionResults of study demonstrate that ABR has similar outcomes for both males and females. There were no statistically significant sex-related differences in SST, ASES, VAS or SANE scores following ABR. VR-12 mental health subscores showed a minimal difference at 2-year follow-up, with lower scores in females.Level of evidenceRetrospective cohort study; level II.

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