scholarly journals Real-World Use of Emicizumab in Patients with Hemophilia with and without Inhibitors

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1137-1137 ◽  
Author(s):  
Isabella McCary ◽  
Christine Guelcher ◽  
Jan Kuhn ◽  
Regina Butler ◽  
Gita Massey ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Real World ◽  
National Health System ◽  
Advisory Board ◽  
Inclusion Criteria ◽  
Bleeding Events ◽  
Active Inhibitor ◽  
The Difference

Introduction Emicizumab is a recombinant humanized monoclonal antibody that bridges factor IXa and Factor Xa and is administered via subcutaneous injection. After initial FDA approval for patients with hemophilia A (HA) and inhibitors, it was approved in October 2018 for prophylaxis in patients with HA without inhibitors of all ages. In clinical trials of subjects without inhibitors, emicizumab was studied only in those >12 years of age. The primary objective of this study was to report our "real-world", post-licensure experience with emicizumab across a more heterogenous patient population, comparing annualized bleeding rates prior to and after initiating emicizumab. Secondary objectives included evaluating for serious adverse events including death, thrombosis or drug discontinuation. Methods We conducted a multi-center observational study at 3 federally funded Hemophilia Treatment Centers: Children's Hospital of Philadelphia, Virginia Commonwealth University and Children's National Health System. Inclusion criteria included patients with HA initiated on emicizumab prior to May 15th 2019. Data extraction included: demographics, diagnosis, prior HA history (inhibitor, prophylaxis treatment regimen), emicizumab dosing data, bleeding events (all bleeds, treated bleeds, joint bleeds, traumatic bleeds) and thrombotic events from the 6 months prior to emicizumab until July 15th 2019. Annualized bleeding rates (ABR) were calculated to account for variable follow up. Wilcoxon Sign-Rank Difference Test was used to test the difference in number of bleeds and McNemar's test was used to test the difference in proportions of patients with ABR=0. Results Ninety-two patients met inclusion criteria: 89 male and 89 with severe HA (3 moderate HA) (Table 1). Age at initiation of emicizumab ranged from 5 weeks to 55 years; median 8.6 yrs (IQR 4.8-13.5 yrs). Nineteen patients had an active inhibitor at the time of starting emicizumab; the remaining 73 did not have an inhibitor, and most (86%) were on prophylaxis prior to emicizumab. Sixty-two patients were < 12 years of age (13 with inhibitors). Median duration of emicizumab therapy was 48 weeks (inhibitors) and 22 weeks (non-inhibitors), with a total follow up of 53.3 patient years. In patients with inhibitors, the ABR (treated bleeds) prior to emicizumab was 6.2 events (95% CI, 0.98 to 11.4) compared to 0.3 events (95% CI, 0 to 0.73) on emicizumab, p=0.002. In subjects without inhibitors, the ABR prior to emicizumab was 1.8 events (95% CI, 0.66 to 2.96) compared to 0.22 events (95% CI, 0.05 to 0.39) on emicizumab, p<0.001. Additional data on bleeding events is provided in Table 1. The proportion of patients with ABR=0 increased in both inhibitor (from 46% to 74%, p=0.06) and non-inhibitor subjects (from 60 to 78%, p=0.015). All patients received 1.5 mg/kg weekly x 4 loading doses, followed by either weekly (27%), every other week (70%), or monthly (3%) dosing; patients with inhibitors were more likely to receive weekly dosing. No patients who initiated emicizumab discontinued the drug or developed a neutralizing antibody to FVIII or emicizumab, although patients have not been consistently screened for these antibodies. No thrombotic or thrombotic microangiopathy events or death have occurred. Conclusions Our favorable clinical experience with emicizumab post-licensure in patients with HA is similar to that reported in the clinical trials. Although excluded from the clinical trials, patients with HA without inhibitors < 12 years accounted for the majority (67%) of our cohort. As anticipated, these younger patients appear to experience the same benefit as patients > 12. No serious drug-related adverse events were reported, although the overall study period is relatively short. Ongoing follow up of these patients, and others, will be important to assess the ongoing safety and efficacy profile of this novel therapy. Updated data on this cohort will be presented at the ASH meeting Disclosures Guelcher: NovoNordisk: Other: Advisory Board; Octapharma: Other: Advisory Board; Takeda: Other: Advisory Board; Genetech: Other: Advisory Board. Butler:pfizer: Other: Advisory board; Hema-Biologics: Consultancy; genetech: Other: Advisory board. Guerrera:Genetech: Other: Advisory Board; Kendrion: Other: Advisory Board; Shire: Other: Advisory Board; Bayer: Other: Advisory Board; Bioverativ: Consultancy; Pfizer: Other: Advisory Board; Novo Nordisk: Consultancy. Raffini:Roche: Other: Advisory Board; Bayer: Other: Advisory Board; CSL Behring: Other: Advisory Board.

scholarly journals Trial in Progress: Real-World Safety and Effectiveness of Brentuximab Vedotin in Adults with CD30+ Lymphoma in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4552-4552
Author(s):  
Pengpeng Xu ◽  
Mingci Cai ◽  
Wendy Zhang ◽  
Wei Li Zhao
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Informed Consent ◽  
Survival Rate ◽  
Real World ◽  
Brentuximab Vedotin ◽  
Routine Clinical Practice ◽  
Inclusion Criteria ◽  
Real World Data

Abstract Background: Clinical trials have demonstrated the effectiveness of the CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) for the treatment of classical Hodgkin lymphoma (HL) and non-Hodgkin lymphoma(e.g. ALCL, PTCL-NOS, AITL, CTCL and etc.). While clinical trials are critical for establishing efficacy, collection of real-world data outside of the controlled trial setting is important to evaluate how interventions are applied and assess the effectiveness of new treatments in routine clinical practice. Inclusion criteria are often rather restrictive compared with the patient populations seen by physicians in daily practice. There are limited real-world data related to treatment with BV in China. Our study aims to obtain timely real-world knowledge in terms of safety and effectiveness of BV in CD30+ lymphoma patients in China. Study Design and Methods: The study (NCT04837222) is a real-world, prospective, multicenter study to evaluate the safety and effectiveness of BV in patients with CD30+ lymphoma in China. Consecutive CD30+ lymphoma patients treated with BV as a part of standard clinical practice will be enrolled. Key inclusion criteria includes adult patients undergoing treatment with BV or to be received with BV, patient/legal guardian must be able to read, understand, and sign the Informed Consent Form, CD30+ lymphoma by INV (any CD30 expression). Exclusion criteria includes patient who currently participates in or with plan to participate in any interventional clinical trial, any other reason that, in the investigator's opinion, makes the patient unsuitable to participate in this study. As CD30+ lymphoma is not a common disease and the affordability of novel treatment is limited, 1000 patients with CD30+ lymphoma will be recruited from almost 30 hematology centers. The physician will determine the treatment regimen, as well as the frequency of laboratory and clinical assessment according to her/his routine practice. All patients will be followed up per routine clinical practice and data will be documented at baseline/3/6/9/12/18/24 months unless withdrawal of Informed Consent, death or loss of follow-up, whichever comes first. Loss to follow-up will be minimized through active contact with participating patients thereafter to ensure almost all clinically relevant outcomes will be captured. The primary endpoint is serious adverse events. Secondary endpoints include adverse events, adverse drug reaction, dose adjustment, characteristics of patients receiving BV, use of BV, number of BV cycles administered, disease characteristics, time to next treatment, overall response rate, duration of response, progression free survival rate, overall survival rate, quality of life and cost-effectiveness ratio. Descriptive analysis will be performed for data analysis. Disclosures Zhang: Takeda Pharmaceuticals: Current Employment.

scholarly journals Real-World Outcomes for 205 Danish Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1767-1767
Author(s):  
Kathrine Aarup ◽  
Lisbeth Enggaard ◽  
Robert Schou Pedersen ◽  
Rasmus Heje Thomsen ◽  
Olav Jonas Bergmann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Population Based ◽  
Advisory Board ◽  
Lymphocytic Leukemia ◽  
Travel Grant ◽  
Tract Infections

Introduction Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase for treatment of chronic lymphocytic leukemia (CLL). Ibrutinib has demonstrated superior efficacy for patients with TP53 aberration or relapsed/refractory (R/R) CLL; and more recently superior progression free survival (PFS) has been demonstrated compared to chemoimmunotherapy as first line therapy. However, knowledge about the outcomes and adverse events (AE) upon ibrutinib among patients at a population-based level are still limited. The aim of the here presented study is to explore outcomes of ibrutinib treatment in a population-based cohort of patients with CLL treated with ibrutinib in Denmark. Methods In this retrospective study, patients from 8 hospitals in Denmark, who were diagnosed with CLL and treated with ibrutinib from April 2014 until February 2019 were included. Medical records were retrospectively reviewed to obtain information. Patients receiving ibrutinib within clinical trials were excluded. Overall survival (OS) was defined as time from ibrutinib start to death from any cause while PFS was defined as time from ibrutinib start to progression or death from any cause. PFS and OS were analyzed with the Kaplan-Meier method while cumulative incidence was calculated with the Aalen-Johansen estimator. Results In total, 205 patients with CLL receiving ibrutinib treatment were identified from hospital records and registries. The median follow-up was 21.4 months (IQR, 11.9-32.8) and the median time on ibrutinib was 16.8 months (IQR, 6.0-28.1). The median age at treatment initiation was 72.8 years (IQR, 65.7-77.8), 128 (62.4%) were male, and 111 (63.4%) were Binet stage B/C at treatment initiation out of 175 with available information regarding clinical stage. Thirty-nine (19.0%) received ibrutinib as first-line, and 166 for R/R CLL with a median of 2 (range, 1-8) prior treatment regimens. Information on TP53 aberration was available for 149 and regarding IGHV mutation for 147 patients, 111 (74.5%) had TP53 aberration and 107 (72.8%) were IGHV unmutated. Eighty-six patients (42.0%) discontinued ibrutinib during follow-up with a median time until discontinuation of 9.3 months (IQR, 3.0-23.2). Forty-seven (54.7%) discontinued due to AEs, 19 (22.1%) due to progression (12 had progression of CLL and 7 had Richter's transformation) while the remaining 20 (23.2%) discontinued due to other reasons. The estimated cumulative incidence of discontinuation at 12 months was 24.8% (95% CI: 18.6-30.9). The estimated OS after 12 and 24 months was 88.8% (95%CI: 84.3-93.3) and 76.8% (95%CI: 70.4-83.2) and the estimated PFS after 12 and 24 months was 87.3% (95%CI: 82.5-92.1) and 72.4% (95%CI: 65.5-79.2). One hundred and eighty-eight (91.7%) experienced at least one AE, among these 45 (23.9%) experienced a grade 3+. The most common AEs were hemorrhage (tendency to bruise, epistaxis etc.) which occurred in 86 (42.0%) of all and musculoskeletal and connective tissue disorders (arthralgia, myalgia etc.) which occurred in 82 (40.0%). Thirty-one (15.1%) patients experienced atrial fibrillation while on ibrutinib and 14 (6.8%) developed hypertension. One hundred and thirty-seven patients (66.8%) had at least one infection and among these 80 (58.4%) were hospitalized with an infection. The most common infections were lower respiratory tract infections and urinary tract infections that occurred for 88 (42.9%) and 41 (20.0%). The estimated cumulative incidence for any infection was 58.9% (95%CI: 52.0-65.9) at 12 months. Conclusion This is the first study describing outcomes for a population-based cohort of CLL patients treated with ibrutinib in Denmark. Real-world studies are warranted, to confirm the results from clinical trials. In this study, patients appear to have comparable OS and types of AE compared with the RESONATE trial. Differences in frequency of AEs compared to the clinical trial may reflect the focus of clinicians in routine practice. Discontinuation in this cohort was higher compared to clinical trials but comparable to previously reported real-world studies. While ibrutinib can be safely managed in routine clinical practice, this study demonstrates that a quarter of patients discontinue treatment due to mainly AEs. Further patient training and information, and in some instances personalized treatment with other targeted agents based on adverse event profile, may improve treatment adherence. Disclosures Aarup: Research Committee, Rigshospitalet: Research Funding. Enggaard:Abbie: Other: Advisory board; Gilead: Other: Advisory board; Janssen: Other: Advisory board. Frederiksen:Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding; Alexion: Research Funding. Niemann:Novo Nordisk Foundation: Research Funding; AstraZeneca: Consultancy, Other: Travel Grant, Research Funding; Sunesis: Consultancy; Acerta: Consultancy; CSL Behring: Consultancy; Roche: Other: Travel Grant; Janssen: Consultancy, Other: Travel Grant, Research Funding; Gilead: Other: Travel Grant; Abbvie: Consultancy, Other: Travel Grant, Research Funding.

scholarly journals Risk definition and outcomes with the application of the PEGASUS-TIMI 54 trial inclusion criteria to a “real world” STEMI population: results from the Italian “CARDIO-STEMI SANREMO” registry

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Federico Sanchez ◽  
Valentina Boasi ◽  
Matteo Vercellino ◽  
Chiara Tacchi ◽  
Pierpaolo Cannarile ◽  
...  
Keyword(s):  
Real World ◽  
Risk Scores ◽  
Hospital Death ◽  
Cumulative Number ◽  
Inclusion Criteria ◽  
Bleeding Events ◽  
Hemorrhagic Risk ◽  
The Impact

Abstract Background The PEGASUS-TIMI 54 trial inclusion criteria effectively identified high-risk patients with recent myocardial infarction (MI) who would benefit from continuing dual antiplatelet therapy (DAPT) with ticagrelor for more than 12 months. It is unknown how many real-world patients meet these criteria during the acute phase of ST-elevation MI (STEMI), or the extent to which these criteria predict a patient's risk and prognosis. Study objectives were: (1) determine the proportion of PEGASUS-TIMI 54-like patients (PG-l) in a real-world cohort of patients hospitalized with STEMI and to assess their ischemic and hemorrhagic risk; (2) examine their ischemic and hemorrhagic in-hospital events (major adverse cardiovascular and cerebrovascular events [MACCE] and clinically relevant bleeding); (3) evaluate their long-term outcomes and the impact on the long-term prognosis of the type of DAPT prescribed at discharge. Methods This observational study was conducted in 1086 patients admitted to hospital with a diagnosis of STEMI between February 2011 and March 2018 and enrolled in the CARDIO-STEMI Sanremo registry. Patients’ demographic and clinical characteristics, procedural variables, and individual ischemic and hemorrhagic risk scores were assessed in-hospital. Four-year survival was also analyzed. Results The proportion of PG-I patients was 69.2%. Compared with non-PG-l patients, PG-l patients were older, had more multivessel disease and comorbidities, and experienced more frequent MACCE (8.3% vs. 3.6%, p = 0.005) and clinically significant bleeding events (6.7% vs. 2.7%, p = 0.008), a higher rate of in-hospital death (6.5% vs. 1.5%, p < 0.001), and higher follow-up mortality rate (14.8% vs. 7.7%; p = 0.002). Four-year survival was significantly lower in the PG-l group (83.9% vs. 91.8%; Log-rank = 0.001) and was related to the cumulative number of concurrent risk factors. In the unadjusted analysis, survival was greater in patients discharged on ticagrelor than on another P2Y12 inhibitor (90.2% vs. 76.7%, Log-rank = 0.001), and the difference was particularly evident in PG-l patients. Conclusions The risk of MACCE for PG-l patients increased with the number of concurrent PEGASUS-TIMI 54 risk features. Treatment with ticagrelor on discharge was associated with improved survival rates during 4 years of follow-up.

scholarly journals Real-world experience with tofacitinib in ulcerative colitis - a systematic review and meta-analysis

2021 ◽  
Author(s):  
Laura Alexandra Lucaciu ◽  
Nathan Samuel Constantine-Cooke ◽  
Nikolas Plevris ◽  
Spyros Siakavellas ◽  
Lauranne AAP Derikx ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Clinical Response ◽  
Real World ◽  
Meta Analysis ◽  
Inclusion Criteria ◽  
Random Effects Models ◽  
Real World Evidence ◽  
Previously Treated

Background and aims Evidence on the outcomes of tofacitinib therapy in real world ulcerative colitis (UC) patients is needed, as a number of these patients would not match the inclusion criteria for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe ulcerative colitis (UC) patients. Methods We searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30/05/2018 and 24/01/2021. Pooled induction (8-14 weeks) and maintenance (16-26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models. Results Nine studies were included, comprising 830 patients, of which 81% were previously treated with anti-TNF and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% CI 41-60%) and 37% (26-45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31-50%) and 29% (23-36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%). Conclusions Tofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.

scholarly journals Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Rosa Escudero-Sánchez ◽  
María Ruíz-Ruizgómez ◽  
Jorge Fernández-Fradejas ◽  
Sergio García Fernández ◽  
María Olmedo Samperio ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Recurrence Rates ◽  
Factors Associated ◽  
Clostridioides Difficile ◽  
Multicentre Cohort Study ◽  
Clostridioides Difficile Infection ◽  
Prevention Of Recurrence ◽  
Multicentre Cohort

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S75-S75
Author(s):  
Scott D Lee ◽  
Anand Singla ◽  
Caitlin Kerwin ◽  
Kindra Clark-Snustad
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Real World ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Clinical Disease ◽  
Endoscopic Remission ◽  
Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with &gt;3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

scholarly journals Patterns and Predictors of Emicizumab Adherence in People with Hemophilia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2178-2178
Author(s):  
Ang Li ◽  
Catlin Goodfriend ◽  
John Sokol ◽  
Rebecca Kruse-Jarres
Keyword(s):  
Clinical Trials ◽  
Half Life ◽  
Clinical Care ◽  
Multivariable Analysis ◽  
Skewed Distribution ◽  
Prior Exposure ◽  
Age Group ◽  
Active Inhibitor ◽  
Routine Prophylaxis

Introduction: Emicizumab is a subcutaneously administered, humanized bispecific monoclonal antibody that is recently approved for hemostatic prophylaxis in people with hemophilia A (PWH) with or without factor VIII inhibitors. We hypothesize that the new route and frequency of administration would lead to better treatment adherence compared to factor or bypass products in PWH outside of clinical trials. We performed the current study to test the hypothesis and to examine potential predictors of non-adherence associated with emicizumab treatment. Methods: We performed a retrospective cohort study at the Washington Center for Bleeding Disorders. Inclusion criteria included PWH with moderate to severe hereditary hemophilia (FVIII <5%), clinician recommendation for routine prophylaxis, receipt of clinical care and medication from a hemophilia treatment center (HTC), at least 12 months of prior exposure to factor or bypass products, and at least 3 months of emicizumab treatment. For patients who were previously enrolled in emicizumab clinical trials, adherence data were collected from the time of first commercial product administration. Adherence percentage (%) was estimated as days of drug dispensed / days elapsed x 100 and non-adherence % was determined as 100 - adherence %. Relevant patient, condition, treatment, and socioeconomic variable data were collected from review of medical records. To assess the difference in drug adherence, we compared the adherence % of emicizumab versus that of factor or bypass product in the same patients using the paired t test. To assess predictors of non-adherence %, we used a generalized linear model (GLM) with log link and gamma distribution to account for the right skewed distribution of the outcome. A multivariable GLM was built to incorporate the most significant predictors of non-adherence. Results: We identified 56 PWH that initiated commercial emicizumab from 1/2018 to 5/2019 at our HTC. Five patients were excluded for fewer than 3 months of follow-up on treatment and 3 patients were excluded for not having prior exposure to factor therapy. The remaining 48 patients had a median duration on emicizumab of 7 months (IQR 5-9) at the time of study. The most common dosing frequency was weekly administration (77%). The median age at treatment index date was 17 years (IQR 9-36), 65% were Caucasian, and 46% had Medicaid or Medicare insurance. The majority of patients had a diagnosis of severe hemophilia (90%), 42% had a history of inhibitor (15% active inhibitor), and 25% were previously enrolled in an emicizumab interventional trial. Prior to emicizumab initiation, 46% of patients had 5 or more self-reported annualized bleeds. The most common reason for emicizumab initiation was patient preference (35%), followed by breakthrough bleeding (33%), difficult venipuncture (21%), and shortened factor half-life (10%). Among 12 patients who previously received only on demand treatment, their adherence on emicizumab was 89%. Among 36 patients who previously received routine prophylaxis, their adherence was significantly higher on emicizumab (98%) than factor/bypass products (89%) (p=0.002). Specifically, 18 out of 48 patients (38%) had factor/bypass adherence <75% (or refused prophylaxis) and 2 out of 48 patients (4%) had emicizumab adherence <75%. Various factors were associated with increased emicizumab non-adherence (Table 1). Age group had the strongest association where young and older adult PWH had more non-adherence % than children and adolescents (Figure 1). On multivariable analysis, age group, active inhibitor, and prior factor/bypass agent non-adherence (episodic or <75% usage) were significantly associated with increased emicizumab non-adherence. Conclusions: In the current study, we found that PWH requiring routine prophylaxis were more likely to be adherent to emicizumab than previous factor or bypass agents. Age group (young adult), active inhibitor, and prior non-adherence to factor product were significant predictors for decreased emicizumab adherence but the differences were small. Given the long half-life of the drug, the significance of non-perfect adherence on bleeding outcomes needs to be studied prospectively with longer clinical follow-up. Disclosures No relevant conflicts of interest to declare.

scholarly journals Veleszületett szemhéjcsüngés műtéti megoldása a szemhéjemelő izom kötőhártya felőli redőzésével

2021 ◽  
Vol 162 (18) ◽  
pp. 705-711
Author(s):  
Zsuzsanna Antus ◽  
Olga Lukáts ◽  
Irén Szalai ◽  
Zoltán Zsolt Nagy ◽  
Nóra Szentmáry
Keyword(s):  
Success Rate ◽  
Posterior Approach ◽  
Treatment Method ◽  
Inclusion Criteria ◽  
Upper Eyelid ◽  
Congenital Ptosis ◽  
Surgical Success ◽  
Suitable Treatment ◽  
The Difference

Összefoglaló. Bevezetés: Szemhéjcsüngésnek (ptosis vagy blepharoptosis) nevezzük azt az állapotot, amikor a felső szemhéj abnormálisan alacsony pozícióban van. A szemhéjcsüngésnek lehetnek veleszületett és szerzett formái. Célkitűzés: Célunk volt bemutatni a szemhéjemelő izom (levator) – veleszületett szemhéjcsüngés korrekciója céljából végzett – kötőhártya felőli redőzésének eredményeit retrospektív módszerrel. Módszer: 20 beteg 22 szemhéján végeztük el a műtétet (átlagéletkor: 19,4 ± 9,9 év, férfi: 12 [60%], nő: 8 [40%]). Beválasztási kritérium volt a közepes (5–8 mm) vagy jó (9 mm felett) levatorfunkció. Kizártuk a korábban szemhéjkorrekciós műtéten átesett és a 3 hónapnál rövidebb követési idővel rendelkező betegeket. A műtét előtt megmértük a levatorfunkciót és a margó–reflex-távolságot. A műtét után megmértük a margó–reflex-távolságot, a szemhéjak magassága közti aszimmetria mértékét, és elemeztük a szemhéj posztoperatív kontúrját. Eredmények: A preoperatív levatorfunkció 10,6 ± 3,0 mm, a preoperatív margó–reflex-távolság 1,8 ± 0,8 mm volt. A 7,8 ± 7,2 hónap átlagos követési idő alatt a posztoperatív margó–reflex-távolság 3,2 ± 0,8 mm volt. A preoperatív és a posztoperatív margó–reflex-távolság különbsége nem tért el szignifikánsan a sikeres és a sikertelen műtétek között (p = 0,523). A szemhéjak magassága közti aszimmetria mértéke 3 betegnél haladta meg az 1 mm-t. A szemhéj posztoperatív kontúrja minden esetben megfelelő volt. A műtét összességében 86,4%-ban (19/22) volt sikeres. A helyi érzéstelenítésben és altatásban végzett műtétek közt nem találtunk szignifikáns különbséget a sikeresség tekintetében (p = 0,227). Következtetés: Tanulmányunk alapján az elvégzett műtéteink eredményessége a nemzetközi irodalomban közöltekhez hasonló volt. A veleszületett szemhéjcsüngés korrekciójára a kötőhártya felőli levatorredőzés megfelelő kezelési mód közepes vagy annál jobb levatorfunkció esetén. Orv Hetil. 2021; 162(18): 705–711. Summary. Introduction: Droopy eyelid (ptosis or blepharoptosis) is defined through abnormally low upper eyelid position. Ptosis can be classified as congenital or acquired. Objective: Our purpose was to report the results of posterior approach levator plication for congenital ptosis in a retrospective review. Method: 22 eyelids of 20 patients were included in this study (age: 19.4 ± 9.9 years, male: 12 [60%], female: 8 [40%]). The inclusion criteria were moderate (5–8 mm) or good (more than 9 mm) levator function. Patients with postoperative follow-up time shorter than 3 months and those who underwent previous eyelid surgery were excluded. The data collected included preoperative levator function and margin reflex distance, postoperative margin reflex distance, inter-eyelid height asymmetry and postoperative eyelid contour. Results: Preoperative levator function was 10.6 ± 3.0 mm, preoperative margin reflex distance was 1.8 ± 0.8 mm. During 7.8 ± 7.2 months postoperative follow-up, postoperative margin reflex distance was 3.2 ± 0.8 mm. The difference between preoperative and postoperative margin reflex distance was not significant (p = 0.523) in the group of successful operations compared with unsuccessful operations. Inter-eyelid height asymmetry was more than 1 mm in 3 cases. Satisfactory postoperative eyelid contour was achieved in all cases. Overall success rate was 86.4% (19/22). Surgical success did not differ significantly between surgeries in local or general anaesthesia (p = 0.227). Conclusion: Our study shows an overall success rate of the procedures comparable to those in international publications. Posterior approach levator plication for congenital ptosis with moderate or better levator function seems to be a suitable treatment method. Orv Hetil. 2021; 162(18): 705–711.

Abstract 16784: Under-Enrollment of Real-World Heart Failure With Preserved Ejection Fraction Patients in Major HFpEF Clinical Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Joban Vaishnav ◽  
Lisa R Yanek ◽  
Virginia S Hahn ◽  
Eunice Yang ◽  
Rishi Trivedi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Real World ◽  
Loop Diuretic ◽  
Nyha Class ◽  
Clinic Visit ◽  
Inclusion Criteria ◽  
Pulmonary Capillary ◽  
Number Of Patients ◽  
Wedge Pressure

Introduction: Inclusion criteria for enrollment in HFpEF clinical trials vary considerably and often exclude patients with co-morbidities such as obesity. We tested the hypotheses that: 1) a large number of patients with clinical and hemodynamic evidence of HFpEF are excluded from major HFpEF clinical trials; and 2) there is no difference in clinical outcomes between patients excluded versus those who met enrollment criteria by evaluating reasons for exclusion from HFpEF clinical trials and comparing clinical outcomes in a real-world HFpEF cohort. Methods: Patients referred to the Johns Hopkins HFpEF Clinic with clinical and hemodynamic evidence of HFpEF (pulmonary capillary wedge pressure [PCWP] ≥ 12 mmHg on a loop diuretic or PCWP ≥ 15 mmHg) were assessed for inclusion into 4 major HFpEF trials (TOPCAT, I-PRESERVE, PARAGON-HF, and RELAX). Cumulative hazard of HF hospitalization or death at 2 years from index clinic visit was compared between patients included and excluded by each trial. Results: Of 132 HFpEF patients, the median PCWP was 19 mmHg (IQR: 15-22 mmHg). Forty-four (33%) of patients met enrollment criteria for TOPCAT, 39 (29%) for I-PRESERVE, 21 (16%) for PARAGON-HF, and 50 (38%) for RELAX. The top 5 criteria that would have excluded patients included low natriuretic peptide level, obesity, elevated blood pressure, young age, and low hemoglobin (Figure 1A) . There was no difference in HF burden (hospitalizations, diuretic dosing, or NYHA class), or in clinical outcomes including HF hospitalization or death between patients who did or did not meet inclusion criteria for each clinical trial (Figure 1B ). Conclusion: We demonstrate that in a real-world cohort of hemodynamically-proven HFpEF few patients would have met criteria for enrollment in major HFpEF clinical trials, yet HF burden and outcomes were no different. Given the lack of proven therapies in HFpEF, consideration should be given to unifying and broadening enrollment criteria in HFpEF clinical trials.

Abstract 15829: Temporal Characteristics of Intra-thoracic Impedance Before and After Heart Failure Hospitalizations in a Large Real-world Population of Patients With Cardiovascular Implanted Electronic Devices

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shantanu Sarkar ◽  
Jodi L Koehler ◽  
Eddy Warman
Keyword(s):  
Real World ◽  
Electronic Devices ◽  
Primary Diagnosis ◽  
Implantable Devices ◽  
World Population ◽  
Inclusion Criteria ◽  
Temporal Characteristics ◽  
Before And After ◽  
Intrathoracic Impedance

Introduction: Intrathoracic impedance (IMP), measured in ICD/CRTD implantable devices, is a measure of intravascular blood volume and have been shown to correlate with intracardiac pressures. We investigated the temporal characteristics of IMP before and after HF events (HFE) in a large real-world cohort of patients (pts) with ICD/CRTD devices. Methods: We linked Optum© deidentified EHR dataset during the period from 2007-2017 to the Medtronic CareLink data warehouse. Pts with ICD/CRTD implants with IMP measurements were included. HFE was defined as an inpatient, ED, or observation unit stay with primary diagnosis of HF and IV diuretics administration. Temporal average of IMP measurement across all pts in the 60 days pre and post HFE were compared for HFE with and without readmission for HF within 60 days and in pts with no HFE. Results: A total of 17,886 pts with 1.8±1.2 years of follow-up met inclusion criteria. The average age was 66.6 ±12.3 years, with 72% being males, and 51% with ICD devices. A total of 1174 pts had 1425 HFE with no readmission and 282 pts had 295 HFE which were followed by readmission. A total of 17,839 pts had no HFE over 86,858 follow-up months. The average IMP during HFE, with and without readmission, and in pts with no HFE are shown in Fig. IMP decreases over a period of time prior to HFE and recovers due to treatment during HFE. The average IMP across all patients was lower on all 60 days pre and post HFE with readmission compared to HFE with no readmission (p<0.001) and both were lower compared to follow-up period with no HFE (p<0.001). The IMP recovers less often after HF events which are followed by readmission within 60 days compared to HF events with no readmission. Conclusions: In a large real-world population of pts with ICD/CRTD devices, on an average IMP reduces prior to and recovers during HFE. IMP was lower before and after HFE with readmission compared to HFE with no readmission. Readmission is more likely in pts with smaller impedance recovery after HF events.

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