Association Between Age and Bleeding Events of Different Severities Among Patients with Nonvalvular Atrial Fibrillation in a Managed Care Population

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4238-4238
Author(s):  
Steven Deitelzweig ◽  
Brett Pinsky ◽  
Erin Buysman ◽  
Michael Lacey ◽  
Yonghua Jing ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Emergency Department ◽  
Older Patients ◽  
Claims Data ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Employment Equity ◽  
Equity Ownership ◽  
Event Rates

Abstract Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF) due to the need for stroke prevention through anticoagulation. Older patients may be at risk for more frequent or more severe bleeding events. Objective: To describe the incidence of bleeding events in various age groups of patients with NVAF. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims data related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were categorized as major, serious non-major, or minor. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Patients were grouped based on their age as of the first atrial fibrillation diagnosis: younger than 65 years or 65 years and older; bleeding events in the subgroup of patients aged 75 years and older were also examined. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Event rates for major bleeds were 5.2 events per 100 patient-years for patients aged younger than 65 years and 13.9 major bleeds per 100 patient-years for patients aged 65 years and older. Patients aged 75 and older had 15.6 major bleeds per 100 patient-years. Approximately 38.9% of all bleeding events experienced by patients aged 65 years and older were major. Approximately 23.3%, 33.6%, and 35.8% of major bleeds among patients younger than 65 years, 65 years and older, and 75 years and older, respectively, were associated with a hospitalization. Corresponding event rates for incident bleeds associated with an inpatient stay were 4.7 bleeding events per 100 patient-years for patients aged younger than 65 years, 12.0 events per 100 patient-years for patients aged 65 years and older, and 13.6 events per 100 patient-years for patients aged 75 years and older. Conclusions: Increasing age was associated with increased rate of any type of bleeding. The increase in rate with increasing age was particularly notable for major bleeds. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Jing:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

Type of Bleeding Among Patients with Nonvalvular Atrial Fibrillation in a Large Managed Care Population

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2073-2073
Author(s):  
Steven Deitelzweig ◽  
Brett Pinsky ◽  
Erin Buysman ◽  
Michael Lacey ◽  
Dinara Makenbaeva ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Rate ◽  
Administrative Claims ◽  
Anatomical Site ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Employment Equity ◽  
Diagnosis Codes ◽  
Equity Ownership

Abstract Abstract 2073 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF), and different anatomical sites may carry greater risk for bleeding. Objective: To describe the incidence of critical anatomical site bleeding events among patients with NVAF in the pre-NOAC (novel oral anticoagulation) era. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were considered major if they were associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Anatomical bleeding sites were identified based on diagnosis codes. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Over 105,419 patient-years, the critical site with the highest rate of major bleeding events was the gastrointestinal tract, followed by intracranial bleeding (TABLE). Conclusions: Gastrointestinal, intracranial, and pericardial bleedings were the most frequently observed major bleedings in the pre-NOAC era. Patients with NVAF have a high rate of major gastrointestinal bleedings. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

Romiplostim in Thrombocytopenic Patients with Low- or Int-1- Risk MDS Results in Reduced Bleeding without Impacting Leukemic Progression: Final Follow-up Results from a Randomized, Double-Blind, Placebo-Controlled Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2000-2000
Author(s):  
Hagop Kantarjian ◽  
Pierre Fenaux ◽  
Mikkael A. Sekeres ◽  
Jeffrey Szer ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Disease Progression ◽  
Board Of Directors ◽  
Research Funding ◽  
Study Drug ◽  
Controlled Study ◽  
Bleeding Events ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Background: Thrombocytopenia occurs in ~50% of patients with low/int-1 risk myelodysplastic syndrome (MDS) and is associated with reduced survival. In a placebo (PBO)-controlled study, 250 patients with MDS were randomized 2:1 to receive weekly romiplostim or PBO. In the original June 2011 analysis, romiplostim reduced clinically significant bleeding events [hazard ratio (HR) romiplostim vs PBO 0.83, 95% CI: 0.66−1.05, P = 0.13] and platelet transfusions (relative risk 0.77, 95% CI: 0.66−0.88, P<0.001) and increased IWG hematologic improvement platelets (HI-P) incidence (odds ratio 15.6, 95% CI: 4.7−51.8, P<0.001). Peripheral blast count increases >10% were more frequent with romiplostim (25/167, 15%) than PBO (3/83, 3.6%) and resolved after discontinuation in most cases. In February 2011, the DMC recommended that treatment with study drug be discontinued as the potential benefit seen in the reduction of bleeding did not outweigh the potential risk for disease progression to AML, and that transient increases in blast cell counts might put patients at risk for diagnosis of and treatment for AML. Patients were moved into long-term follow-up (LTFU). Previously reported (Giagounidis et al, Cancer 2014) 58-week incidence of AML was 6.0% (N = 10) for romiplostim and 4.9% for PBO (N = 4); HR 1.20 (95% CI: 0.38−3.84). This report provides final 5-year LTFU data. Methods: Eligible patients were receiving only supportive care and had IPSS low/int-1 risk MDS and platelets 1) ≤20 × 109/L or 2) ≤50 × 109/L with a history of bleeding. Disease progression to AML was defined as 1) ≥20% blasts in bone marrow or peripheral blood after 4 weeks following discontinuation of romiplostim; 2) pathology consistent with leukemia; or 3) antileukemic treatment. Results are presented by treatment group. Results: At baseline, median (Q1, Q3) age was 70 (61, 77) years, the majority (59%) of patients were male; 27.6% were IPSS low risk and 72.4% were int-1 risk. WHO classifications were RCMD: 67.6%, RAEB-1: 13.2%, MDS-U: 11.2%, RA: 4.4%, RCMD-RS: 2.4%, RARS: 0.8%, and RAEB-2: 0.4%. Of 250 patients in the study, 210 entered LTFU and 66 completed the 5 years of LTFU; median (Q1, Q3) follow-up was 27.5 (10.8, 58.7) months. Reasons for discontinuation (death, lost to follow-up, and consent withdrawal) during LTFU were similar in both groups. During the active study period and LTFU, death was reported in 93 (55.7%) patients in the romiplostim group and 45 (54.2%) patients in the PBO group (HR romiplostim vs PBO 1.03, 95% CI: 0.72−1.47) (Figure); mortality rates were greater in those with IPSS int-1 vs low risk for both groups (Table). AML was reported in 20 (11.9%) patients in the romiplostim group and 9 (11.0%) patients in the PBO group (HR 1.06, 95% CI: 0.48−2.33). The proportions of patients who either died or developed AML were 56.9% (N = 95) in the romiplostim group and 55.4% (N = 46) in the PBO group (HR for AML-free survival 1.04, 95% CI: 0.73−1.48) (Figure). Nearly half (N = 14, 48%) of the 29 AML cases occurred in patients who were RAEB-1 at screening (none RAEB-2), and 6 cases were diagnosed because of anti-AML treatment use alone (Table). In LTFU, patient-reported use of MDS therapy (eg, azacitidine or cyclosporine) was 42.8% (N = 59, 95% CI: 34.4%−51.5%) in the romiplostim group and 31.4% (N = 22, 95% CI: 20.9%−43.6%) in the PBO group. AML therapy (eg, chemotherapy) was used in 14 (10.2%) patients in the romiplostim group and 7 (10.0%) patients in the PBO group. Conclusions: Following the decision in 2011 to stop study drug secondary to increased AML rates at that time and transient blasts increases, final 5-year LTFU HRs (romiplostim vs placebo) for death or progression to AML, respectively, are 1.03 (95% CI: 0.72−1.47) and 1.06 (95% CI: 0.48−2.33). In conclusion, romiplostim reduced bleeding events and platelet transfusions, with no increase in AML incidence or impact on survival. Disclosures Kantarjian: Amgen Inc.: Research Funding. Fenaux:Amgen Inc.: Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees. Szer:Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Australia: Consultancy, Honoraria; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Platzbecker:Celgene Corporation: Honoraria, Research Funding; TEVA Pharmaceutical Industries: Honoraria, Research Funding; Janssen-Cilag: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Kuendgen:Celgene: Research Funding. Gaidano:Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wiktor-Jedrzejczak:Angelini: Consultancy; Novartis: Consultancy, Research Funding; Celgene: Consultancy; Janssen-Cilag: Consultancy; Novartis: Consultancy, Research Funding; BMS: Research Funding; Sandoz: Consultancy; Amgen Inc.: Research Funding. Carpenter:Amgen Inc.: Employment, Equity Ownership. Mehta:Amgen Inc.: Employment, Equity Ownership. Franklin:Amgen Inc.: Employment, Equity Ownership. Giagounidis:Amgen Inc.: Consultancy, Honoraria.

scholarly journals Enasidenib Monotherapy Is Effective and Well-Tolerated in Patients with Previously Untreated Mutant- IDH2 (m IDH2) Acute Myeloid Leukemia (AML)

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 638-638 ◽  
Author(s):  
Daniel A. Pollyea ◽  
Martin S. Tallman ◽  
Stephane De Botton ◽  
Courtney D. DiNardo ◽  
Hagop M. Kantarjian ◽  
...  
Keyword(s):  
Median Duration ◽  
Dose Escalation ◽  
Older Patients ◽  
Research Funding ◽  
Standard Treatment ◽  
Phase 1 ◽  
Tumor Lysis Syndrome ◽  
Employment Equity ◽  
Equity Ownership

Abstract Background: Enasidenib (AG-221) is an oral, selective inhibitor of mIDH2 proteins. Results from the AG221-C-001 phase 1/2 dose-escalation and expansion study of enasidenib monotherapy showed an overall response rate (ORR) of 40.3% and median overall survival (OS) of 9.3 months in patients with m IDH2 relapsed or refractory (R/R) AML (Stein, Blood, 2017). Like patients with R/R AML, older patients with untreated AML who are not candidates for standard induction therapy due to advanced age, poor performance status, comorbidities, poor-risk cytogenetics, or other factors, pose a therapeutic challenge. Treatment options for these patients are limited and outcomes are poor. Reported here are clinical outcomes for older patients with previously untreated m IDH 2 AML who received enasidenib monotherapy in the AG221-C-001 study (NCT01915498). Methods: The phase 1 dose-escalation and expansion portions of the study included patients aged ≥ 60 years with previously untreated AML who were not candidates for standard treatment and had ECOG PS scores of 0-2. Patients in the dose-escalation phase received enasidenib doses of 50-650 mg/day, and all patients in the expansion phase received enasidenib 100 mg/day, in continuous 28-day treatment cycles. ORR included complete remission (CR), CR with incomplete count recovery (CRi/CRp), partial remission (PR), and morphologic leukemia-free state (MLFS), per modified IWG 2003 response criteria for AML. OS was defined as the time from first dose to death from any cause. Event-free survival (EFS) was defined as the time from first dose to relapse, progressive disease (PD), or death, whichever came first. Safety was assessed by treatment-emergent adverse event (TEAE) reporting and TEAEs were graded for severity per CTCAE version 4.0. Results: Of 239 patients in the phase 1 dose-escalation and study expansion, 37 patients (15.5%) had previously untreated m IDH2 AML. At data cutoff (14 Oct 2016), 4 patients with previously untreated AML (11%) remained on-study: 3 patients in CR, and 1 patient with stable disease at cycle 13. Median age was 77 years (range 58-87); 62% of patients were aged ≥ 75 years (Table 1). Median number of enasidenib treatment cycles was 6 (range 1-23) and median follow-up was 7.9 months (range 0.5-23.7). Seven patients (19%) attained CR, with a median time to CR of 5.6 months (range 3.4-12.9) (Table 2). ORR was 37.8% (95%CI 22.5, 55.2). The median duration of CR was not reached (NR) (95%CI 3.7, NR) and median duration of any response was 12.2 months (2.9, NR) (Table 2). Three patients proceeded to transplant; at data cutoff, all 3 patients remained in remission. Among all 37 patients, median OS was 10.4 months (95%CI 5.7, 15.1) and median EFS was 11.3 months (3.9, NR). Median OS for responding patients (n=14) was 19.8 months (95%CI 10.4, NR) and for non-responders was 5.4 months (2.8, 12.4). The most frequent TEAEs (any grade or cause) were fatigue (43%), nausea (41%), and decreased appetite (41%). The most frequent treatment-related TEAEs were hyperbilirubinemia (30%) and nausea (22%) (Table 3). The only serious treatment-related TEAEs reported for more than 1 patient were IDH differentiation syndrome (n=3, 8%) and tumor lysis syndrome (n=2, 5%). Treatment-related TEAEs led to dose modification for 3 patients (8%), dose interruption for 7 patients (19%), and treatment discontinuation for 1 patient (3%). Conclusions: Enasidenib induced hematologic responses in these older patients with previously untreated m IDH2 AML who were not candidates for standard treatment. Approximately 1 in 5 of these patients attained CR and 1 in 3 patients had a response with enasidenib monotherapy. Responses were durable: at a median of 7.9 months of follow-up, median CR duration was not reached and median duration of any response was &gt; 1 year. Median OS and EFS were also promising (10.4 months and 11.3 months, respectively). Rates of treatment-related TEAEs were low and only 1 patient discontinued treatment due to a TEAE. These results suggest enasidenib may benefit older adults with m IDH2 AML who are not fit to receive cytotoxic chemotherapy. These encouraging findings have prompted follow-up studies of enasidenib in older patients with previously untreated m IDH2 AML, such as the Beat AML Master Trial (NCT03013998). Disclosures Pollyea: Takeda, Ariad, Alexion, Celgene, Pfizer, Pharmacyclics, Gilead, Jazz, Servier, Curis: Membership on an entity's Board of Directors or advisory committees; Agios, Pfizer: Research Funding. De Botton: Servier: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Agios: Honoraria, Research Funding. DiNardo: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding. Kantarjian: Bristol-Meyers Squibb: Research Funding; Amgen: Research Funding; Novartis: Research Funding; ARIAD: Research Funding; Pfizer: Research Funding; Delta-Fly Pharma: Research Funding. Collins: BMS: Research Funding; Arog: Research Funding; Agios: Research Funding; Celgene Corporation: Research Funding. Stein: Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy. Xu: Celgene Corporation: Employment, Equity Ownership. Tosolini: Celgene Corporation: Employment, Equity Ownership. Gupta: Celgene Corporation: Employment, Equity Ownership. Agresta: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Stein: Seattle Genetics: Research Funding; GSK: Other: Advisory Board, Research Funding; Constellation Pharma: Research Funding; Celgene Corporation: Consultancy, Other: Travel expenses, Research Funding; Agios Pharmaceuticals, Inc.: Consultancy, Research Funding; Pfizer: Consultancy, Other: Travel expenses; Novartis: Consultancy, Research Funding.

Evaluation of Extended-Interval Dabigatran Dosing in Older Patients With Non-Valvular Atrial Fibrillation

2020 ◽  
pp. 107424842097722
Author(s):  
Lianfang Ni ◽  
Xiahuan Chen ◽  
Meilin Liu ◽  
Yan Fan ◽  
Zhifang Fu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Creatinine Clearance ◽  
Partial Thromboplastin Time ◽  
Older Patients ◽  
Low Dose ◽  
Activated Partial Thromboplastin Time ◽  
Chinese Patients ◽  
Bleeding Events ◽  
Dosing Intervals

Objective: To evaluate the safety and efficacy of extended-interval dabigatran dosing in older Chinese patients with non-valvular atrial fibrillation. Methods: We conducted an observational study on non-valvular atrial fibrillation patients administered dabigatran at different dosing intervals at the Department of Geriatrics, Peking University First Hospital, China. We enrolled 121 consecutive non-valvular atrial fibrillation patients aged ≥60 years on dabigatran therapy (mean age, 79.6 ± 7.4 years); they were administered conventional low-dose dabigatran (110 mg twice daily) or extended-interval dosing with dabigatran (110 mg every 16 h or every 24 h). All patients received follow-up care, and we evaluated the presence of bleeding and thromboembolic events. Results: All patients exhibited creatinine clearance greater than 30 mL/min with an average of 56.6 ± 17.3 mL/min. Sixty-two patients received extended-interval dosing with dabigatran at a mean dose of 117.1 ± 18.6 mg daily. Patients on extended-interval dosing were older; they exhibited lower creatinine clearance and bodyweight and higher CHA2DS2-VASc and HAS-BLED scores. The mean follow-up time was 25.8 ± 15.6 months. No significant differences were observed in the trough and peak values of the activated partial thromboplastin time and in thromboembolic or bleeding events between the 2 groups. Conclusion: Extended-interval dabigatran dosing in older patients with non-valvular atrial fibrillation and lower creatinine clearance can maintain activated partial thromboplastin time trough and peak values comparable to the conventional low dose. Physician-prescribed practices regarding dabigatran dosing intervals do not lead to worse outcomes in the above-mentioned population.

scholarly journals Eculizumab Prevents Thrombotic Microangiopathy: Long-Term Follow-up Study of Patients with Atypical Hemolytic Uremic Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2252-2252 ◽  
Author(s):  
Laurence A. Greenbaum ◽  
Yahsou Delmas ◽  
Fadi Fakhouri ◽  
John F. Kincaid ◽  
Christoph Licht ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Employment Equity ◽  
Advisory Committees ◽  
Long Term Follow Up ◽  
Uremic Syndrome ◽  
Equity Ownership ◽  
Event Rates

Abstract Background: Eculizumab was demonstrated to effectively treat and prevent thrombotic microangiopathy (TMA) and to improve renal function and hematologic parameters for up to 2 years in4 previous prospective clinical trials and in 1 retrospective study of patients with atypical hemolytic uremic syndrome (aHUS). Patients in these studies enrolled in a long-term follow-up study, in which rates of TMA were evaluated during eculizumab treatment and during discontinuation from eculizumab. Methods: Data were gathered from an ongoing, observational, multicenter study of aHUS patients treated with eculizumab in 5 prior clinical studies. The primary endpoint was TMA event rate post-parent study during on-treatment (ON; among patients receiving eculizumab) and off-treatment (OFF; among patients who discontinued eculizumab) periods. Results: As of March 28, 2015, 87 patients, including 35 children <18 years of age (40%) and 52 adults ≥18 years of age (60%), enrolled in the study (Table). Of these, 76 patients had ON and 39 patients had OFF treatment periods with median follow-up of 26.1 and 20.1 months, respectively. A reduced dosage of eculizumab was received by 33 of 87 patients (38%). Seventeen of 39 patients (44%) reinitiated eculizumab after therapy discontinuation. The TMA event rates were 7.3 and 19.9 per 100 patient-years for ON and OFF patients, respectively. The rate of TMA in ON patients was greater in those receiving reduced dosing compared with label recommendations (Table). OFF patients had higher estimated glomerular filtration rates at time of discontinuation than ON patients. Age, frequencies of higher-risk complement factor mutations (CFH, C3, or CFB) and kidney transplant status were not different between ON and OFF patients. Factors that independently predicted TMA events included: ON treatment status (compared with OFF; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.07‒0.49; P<0.001), higher-risk mutations (compared with no mutation; HR, 5.51; 95% CI, 1.61‒18.84; P=0.007), and lower-risk mutations (compared with no mutation; HR, 3.70; 95% CI, 1.05‒13.02; P=0.04). Conclusions: The TMA event rate was 2.7-fold higher after eculizumab discontinuation compared with patients receiving ongoing eculizumab therapy. TMA event rates were lowest during on-label dosing, higher during reduced dosing, and highest during off-treatment periods. These findings suggest that patients with aHUS have a progressive increase in the risk of TMA events during periods of reduced dosing and after discontinuation of eculizumab, compared with on-label eculizumab dosing. Disclosures Greenbaum: Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fakhouri:Alexion Pharmaceuticals: Consultancy. Kincaid:Alexion Pharmaceuticals: Employment, Equity Ownership. Licht:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillon: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mix:Alexion Pharmaceuticals: Employment, Equity Ownership. Provôt:Alexion Pharmaceuticals: Honoraria. Rondeau:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sheerin:Alexion Pharmaceuticals: Honoraria. Wang:Alexion Pharmaceuticals: Employment, Equity Ownership. Menne:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Comparison of Medical Costs Avoided When New Oral Anticoagulants Are Used for the Treatment of Patients with Atrial Fibrillation and Venous Thromboembolism in the U.S

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2181-2181
Author(s):  
Alpesh N Amin ◽  
Amanda Bruno ◽  
Jeffrey Trocio ◽  
Jay Lin ◽  
Melissa Lingohr-Smith
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Medical Cost ◽  
Oral Anticoagulants ◽  
Medical Costs ◽  
Nonvalvular Atrial Fibrillation ◽  
Equity Ownership ◽  
Acute Venous Thromboembolism ◽  
Event Rates

Abstract Introduction: Clinical trials have demonstrated that the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban are either superior or non-inferior to standard therapies/placebo for the treatment of nonvalvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). This study estimated and compared the medical costs from a U.S. payer perspective that may be potentially avoided when NOACs are used instead of standard therapies/placebo for the treatment of patients with NVAF or VTE. Methods: Event rates of efficacy and safety clinical endpoints as defined in clinical trials (Table), were obtained from published trial data. Medical cost avoidances associated with NOAC usage vs. standard therapies/placebo for NVAF patients, acute VTE treatment patients, and extended VTE treatment patients were derived from previous publications. All costs were inflation adjusted to 2013 cost level. A hypothetical health plan population with 1 million members in 2014 was used to estimate and compare the NVAF and VTE combined medical cost avoidances for patients treated with NOACs vs. standard therapies/placebo. Prevalence rates of NVAF and VTE were derived from published literature. The same usage rate for each NOAC was assumed for comparison purpose. The medical cost avoidances are also projected in the years 2015-2018 and compared among the NOACs. Results: In 2014, in the hypothetical population of one million insured lives, the medical costs were projected to be reduced by -$3.0, -$2.1, and -$7.3 million for NVAF patients treated with dabigatran, rivaroxaban, and apixaban, respectively; by -$0.7, -$2.2, and -$4.1 million for patients treated for acute VTE with dabigatran, rivaroxaban, and apixaban, respectively; and by -$6.3, -$6.6, -$9.6, and -$9.5 million for VTE patients treated for extended periods with dabigatran, rivaroxaban, 2.5 mg apixaban, and 5.0 mg apixaban, respectively (2 arms with different apixaban dosages were included in extended VTE treatment trial). In 2014, for the combined NVAF and VTE patient populations, within the hypothetical population of one million insured lives, medical costs were projected to be reduced by -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5.0 mg apixaban, respectively. In the model, the reductions in medical costs associated with usage of the NOACs were projected to steadily increase in the years 2015 to 2018 (Figure). Conclusions: Medical costs are reduced, when any of the three NOACs are used instead of standard therapy/placebo for the treatment of NVAF or VTE. Apixaban is associated with the greatest reduction in medical costs, which is driven by medical cost reductions associated with both efficacy and safety endpoints among patients with NVAF or VTE. Further evaluation may be needed to validate these results in the real-world setting. Table 1 Clinical Trials from which Clinical Event Rates were Obtained Trial Drug Indication RE-LY Dabigatran Nonvalvular atrial fibrillation ROCKET-AF Rivaroxaban Nonvalvular atrial fibrillation ARISTOTLE Apixaban Nonvalvular atrial fibrillation RE-COVER I Dabigatran Acute venous thromboembolism RE-COVER II Dabigatran Acute venous thromboembolism EINSTEIN-Pooled Rivaroxaban Acute venous thromboembolism AMPLIFY Apixaban Acute venous thromboembolism RE-SONATE Dabigatran Extended venous thromboembolism EINSTEIN-EXT Rivaroxaban Extended venous thromboembolism AMPLIFY-EXT Apixaban Extended venous thromboembolism Figure 1 Figure 1. Disclosures Amin: Bristol-Myers Squibb, Pfizer: Consultancy. Off Label Use: Apixaban for the indication of VTE.. Bruno:Bristol-Myers Squibb: Employment, Equity Ownership. Trocio:Pfizer: Employment, Equity Ownership. Lin:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding. Lingohr-Smith:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding.

scholarly journals Updated Follow-up of the Alta Study, a Phase 1/2, Open Label, Adaptive, Dose-Ranging Study to Assess the Safety and Tolerability of SB-525 Gene Therapy in Adult Patients with Severe Hemophilia A

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2060-2060 ◽  
Author(s):  
Barbara A. Konkle ◽  
Kimo Stine ◽  
Nathan Visweshwar ◽  
Thomas J. Harrington ◽  
Andrew D. Leavitt ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hemophilia A ◽  
High Dose ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
Employment Equity ◽  
Dose Cohort ◽  
Fviii Activity ◽  
Equity Ownership

Introduction: Hemophilia A is a rare blood disorder caused by an F8 variant resulting in insufficient Factor VIII (FVIII) activity. Updated results and follow-up of an ongoing gene therapy study in patients with severe hemophilia A are presented. Methods: The Alta study is a dose-ranging, single-dose study of SB-525 gene therapy, a recombinant adeno-associated virus (rAAV6) vector encoding an F8 gene. SB-525 was injected into 11 patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11, 2e12, 1e13 and 3e13 vg/kg) with expansion of the high dose cohort by 3 additional patients. Endpoints included: safety events, changes in circulating FVIII activity, FVIII antigen, FVIII usage, and frequency and severity of bleeding. Results: In the third cohort (1e13 vg/kg), a single infusion of SB-525 resulted in stable and clinically relevant increases in FVIII activity. Patients in the fourth cohort (high dose, 3e13 vg/kg) achieved FVIII levels within the normal range (Table 1), with no bleeding events reported up to 24 weeks post-injection. Patients treated at 3e13 vg/kg did not require FVIII replacement therapy following the initial prophylactic period of up to approximately 3 weeks post-SB-525 administration. No bleeding events were observed in any of the patients treated at the 3e13 vg/kg dose. One patient had a treatment-related serious adverse event of hypotension and fever, with symptoms of headache and tachycardia, which occurred ~6 hours after completion of the vector infusion and resolved with treatment within 24 hours. In the three first cohorts, no ALT elevation requiring more than 7 days of corticosteroid treatment was observed. Of the 5 patients treated to date in the high dose cohort, 3 followed for at least 8 weeks showed transient and mild (grade 1) ALT elevations. All responded to corticosteroids within one week. At the time of abstract submission, all patients were off corticosteroids. FVIII antigen was assessed by ELISA, and preliminary results from the high dose cohort showed a good correlation by chromogenic assay between the specific activity of SB-525 derived FVIII and Xyntha, a recombinant B-domain deleted protein control. Dosing in the fourth cohort is ongoing, and additional analyses of the trial data including FVIII levels, bleeding rate and factor usage will be presented as available. Four- to 11-month follow-up data on all patients in the fourth dose cohort will also be presented. Conclusions: To date, treatment with a single infusion of SB-525 gene therapy resulted in dose-dependent and sustained increases in FVIII levels, with a substantial decrease in FVIII usage, and no bleeding episodes recorded in the highest dose cohort. Patients treated in the highest dose cohort achieved FVIII activity in the normal range. No ALT elevations persisting longer than 7 days were observed in the first three dose cohorts. The study is ongoing, and the results support further development of SB-525 for the treatment of severe Hemophilia A. Disclosures Giermasz: uniQure: Consultancy, Other: Research; Sangamo: Other: Research; Bioverativ/Sanofi: Consultancy, Speakers Bureau; BioMarin: Consultancy, Other: Research; Genentech/Roche: Consultancy, Other: Research, Speakers Bureau. Arkin:Pfizer: Employment, Equity Ownership. Di Russo:Pfizer: Employment, Equity Ownership. Snyder:Sangamo Therapeutics: Employment. Woolfson:Sangamo Therapeutics: Employment, Equity Ownership. Rouy:Sangamo Therapeutics: Employment, Equity Ownership.

scholarly journals Burden of CRAB Events By Relapse in Patients with Newly Diagnosed Multiple Myeloma Not Eligible for Stem Cell Transplant

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4770-4770
Author(s):  
Shivani Pandya ◽  
Zoe Clancy ◽  
Sulena Shrestha ◽  
Li Wang ◽  
Onur Baser
Keyword(s):  
Economic Burden ◽  
Index Date ◽  
Stem Cell Transplant ◽  
Event Rate ◽  
Cell Transplant ◽  
Employment Equity ◽  
Equity Ownership ◽  
Line Of Therapy ◽  
Event Rates

Abstract Background: For decades, CRAB criteria (hypercalcemia, renal impairment, anemia, and bone disease) have been used to diagnose multiple myeloma (MM), but little is known about the economic burden of CRAB in patients with MM who have relapsed. The only category 1 doublet regimens recommended by NCCN Guidelines for non-transplant candidates are lenalidomide-based (NCCN Myeloma v4.2018). This study aims to evaluate CRAB event rates and the associated economic burden among newly diagnosed MM (NDMM) patients on doublet therapy who were not eligible for stem cell transplant (SCT) and were followed to next line of therapy. Methods: This retrospective study identified patients with ≥ 2 claims of MM (ICD-9-CM code: 203.0x; ICD-10-CM code: C90.0x) ≥ 30 days apart and ≥ 1 treatment (first claim date was used as index date) between January 1, 2011 and December 31, 2015 from the Medicare database. Eligible patients were required to have continuous enrollment from 6 months pre-index or first MM diagnosis date until ≥ 12 months post-index date unless patients died < 12 months post-index date (the follow-up period); ≥ 1 full cycle of therapy; no evidence of prior MM diagnosis or treatment (including autologous SCT [ASCT]); and no evidence of ASCT in the follow-up period. First line of therapy (LOT1) included all treatments prescribed within 60 days of the index date, and patients were included in the doublet therapy cohort based on the index treatment regimen. Progression to a subsequent LOT (LOT2) was defined by the earliest occurrence of an addition or switch to new non-maintenance treatment > 60 days post-index date, restart of any non-maintenance MM treatment after a > 180-day gap, or a dose increase from maintenance to relapse therapy. CRAB event rate per 1,000 person-years (PYs), CRAB event-related healthcare resource utilization (HRU) per patient per month (PPPM), and costs PPPM were evaluated during the LOT1 (the time from index date to end of LOT1) and LOT2 (the time from initiation of LOT2 to end of LOT2) among patients on doublet therapy with LOT1 and those who progressed to LOT2, respectively. Mean was calculated for the continuous variables, while categorical variables were presented as percentage values. Since the LOT2 population was a subset of the LOT1 population and they were not mutually exclusive cohorts, no statistical comparisons were made. Results: The study included 4,970 patients with MM not eligible for ASCT, of which 3,065 (61.7%) patients were prescribed doublet therapy in LOT1. Among these patients on doublet therapy, 1,122 (36.6%) initiated LOT2. The mean age was approximately 77 years, and most patients were white (LOT1, 77.0%; LOT2, 79.7%). The majority of the patients had hypertension (LOT1, 88.3%; LOT2, 86.1%), followed by anemia (LOT1, 79.0%; LOT2, 75.6%) and osteoarthritis (LOT1, 75.7%; LOT2, 76.7%), as comorbidities during the 6 months prior to the index date. CRAB event rates declined from LOT1 to LOT2, with the highest event rate per 1,000 PYs observed for anemia (LOT1, 1,965.1; LOT2, 1,808.2), followed by bone disease (LOT1, 258.1; LOT2, 244.1), renal impairment (LOT1, 167.9; LOT2, 159.9), and hypercalcemia (LOT1, 106.9; LOT2, 99.6); a decline in event rate was observed from LOT1 to LOT2 (Figure 1). CRAB event-related HRU PPPM increased from LOT1 to LOT2, including number of inpatient visits (LOT1, 0.1; LOT2, 0.2), length of inpatient stay (LOT1, 0.8 days; LOT2, 1.0 days), and number of outpatient hospital visits (LOT1, 2.0; LOT2, 2.2). However, the number of outpatient office visits PPPM decreased from LOT1 to LOT2 (LOT1, 0.9; LOT2, 0.8). Similarly, there was a trend toward increased CRAB event-related healthcare costs PPPM from LOT1 to LOT2 (Figure 2) including inpatient (LOT1, USD 1,548; LOT2, USD 2,031), outpatient hospital (LOT1, USD 214; LOT2, USD 301), outpatient office (LOT1, USD 77; LOT2, USD 89), and total medical costs (LOT1, USD 2,120; LOT2, USD 2,593). Conclusions: This study shows that CRAB events were more expensive to treat as patients relapse. Delaying disease progression may be associated with lower HRU and potential cost savings, thereby reducing the burden of MM. A potential limitation of this study is that claims data do not include clinical parameters. Future studies should be considered to evaluate the impact of age and comorbidities on the economic burden associated with CRAB events. This study also highlights the value of delaying progression and the time to next treatment. Disclosures Pandya: Celgene Corporation: Consultancy; STATinMED Research: Employment. Clancy:Celgene Corporation: Employment, Equity Ownership, Research Funding. Shrestha:STATinMED Research: Employment, Equity Ownership. Wang:STATinMED Research: Employment, Equity Ownership.

Abstract 169: Bleeding Incidence By Stroke Risk Among Patients With Nonvalvular Atrial Fibrillation In A Large Managed Care Population

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Steven B Deitelzweig ◽  
Brett Pinsky ◽  
Erin Buysman ◽  
Michael Lacey ◽  
Dinara Makenbaeva ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Emergency Department ◽  
Managed Care ◽  
Real World ◽  
Stroke Risk ◽  
Anticoagulation Therapy ◽  
Administrative Claims ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Outpatient Hospital

Introduction Stroke prevention among patients with nonvalvular atrial fibrillation (NVAF) requires careful assessment of both the risk of stroke and bleeding. Hypothesis We hypothesized that in a real-world managed care population of patients with NVAF, bleeding incidence increases with CHADS2 stroke risk. Methods Administrative claims data were used for this retrospective study. Adults with healthcare claims related to AF (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Patients were categorized based on CHADS2 scores of 0, 1, 2, or ≥3, with higher scores indicating more risk factors. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, death, physician guided medical or surgical treatment, or intracranial bleed. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Results The mean (SD) age of the study sample (N=48,260) was 67±13 years and 62% of the patients were male. Mean follow-up duration was 802±540 days (median 673 days). Mean (SD) baseline CHADS2 score was 1.48±1.15. Event rates for each bleeding category increased with increasing CHADS2 scores (Table). Conclusions Patients with NVAF in a real-world managed care setting who had high stroke risk also had a high rate of bleeding events, including major events. Patients at high risk for stroke might require more careful selection of anticoagulation therapy to avoid bleeding events.

An Open-Label Extension Study Evaluating the Long-Term Safety and Efficacy of Romiplostim in Thrombocytopenic Patients (Pts) with Myelodysplastic Syndromes (MDS).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2765-2765 ◽  
Author(s):  
Pierre Fenaux ◽  
Hagop Kantarjian ◽  
Roger Lyons ◽  
Richard A. Larson ◽  
Mikkael A. Sekeres ◽  
...  
Keyword(s):  
Research Funding ◽  
Extension Study ◽  
Platelet Response ◽  
Bleeding Events ◽  
Open Label ◽  
Employment Equity ◽  
Open Label Extension ◽  
Equity Ownership

Abstract Abstract 2765 Poster Board II-741 Background: Romiplostim is a peptibody protein that increases platelet production by binding to and activating the thrombopoietin receptor. Currently, platelet transfusion is the only supportive treatment for thrombocytopenia in MDS. In a phase 1/2 study of romiplostim in lower-risk thrombocytopenic MDS pts receiving supportive care only, about half achieved a platelet response (Sekeres et al., ASCO 2009, Kantarjian et al, JCO 2009, in press). We report results from an interim analysis of the subsequent ongoing open-label extension study evaluating the long-term safety and efficacy of romiplostim in MDS pts. Methods: MDS pts who, after completing the parent study, had platelets '50×109/L and no evidence of disease progression were eligible to enroll in this extension. The primary endpoint of this extension was adverse event (AE) incidence with long-term use of romiplostim; incidence of bleeding events was a secondary endpoint. Pts received romiplostim at a dose of 250, 500, 750, 1000, or 1500 μg weekly or every two weeks based on previous dosing, with subsequent adjustment between 250 and 1000 μg. If after 4 weeks at the increased dose there was an inadequate platelet response (using IWG 2006 criteria), the dose could be further escalated (with 4 weeks at each dose) up to a maximum of 1000 μg/week. If no response was observed after 4 weeks at 1000 μg/week, treatment was discontinued. Results: At the reference date of Feb 18, 2009, 28 pts had enrolled in this open-label extension study: 68% male, median age 71.5 y [interquartile range (Q1-Q3): 63.5-76.5 y], median baseline platelets 31×109/L (Q1-Q3: 20–41×109/L), 32% with platelets <20×109/L. During the parent study, 24 of the 28 pts had a platelet response. At the end of the parent study, there was a 4-week washout period. At initiation of the open-label extension study, IPSS status was low (13 pts), int-1 (12), int-2 (1), or missing (2), and MDS subtypes were RA (11 pts), RCMD (7), MDS-U (4), RAEB-1 (2), RCMD-RS (1), RARS (1), or missing (2). Ten pts (36%) had bleeding events in the previous year. Median duration of treatment in the extension study was 41 weeks (Q1-Q3: 23–58 weeks), with a median weekly dose of 748 μg (Q1-Q3: 493–821 μg). All 28 pts received μ8 weeks of romiplostim. Most AEs were mild-to-moderate; the most common being epistaxis (36%), arthralgia (29%), anemia (21%), and cough (21%). No neutralizing antibodies to romiplostim or TPO were observed. Nine pts withdrew from the study, 6 of these due to AEs. By investigator assessment, five of these AEs were related to romiplostim: 3 pts with increased blast cells, 1 pt with early-stage chronic myeloid leukemia (CML) diagnosed 519 days after romiplostim initiation, with bcr-abl first detected 1 year after romiplostim initiation (negative at baseline), and 1 pt with a history of chronic obstructive pulmonary disease and congestive heart failure who subsequently experienced the acute and rapid development of fatal pulmonary fibrosis after treatment with romiplostim. Two of these AEs were severe (pulmonary fibrosis and CML). For the increased blast cells, in cases 1 and 2, peripheral blasts were detected: in case 1 bone marrow (bm) blasts of 7% fell to <1% after drug discontinuation, while in case 2, bm blasts were 3% (no follow-up blast count). In both cases 1 and 2, peripheral blasts disappeared after drug discontinuation. In case 3, increase in blasts was reported by the investigator, with no peripheral blasts detected (follow-up bm biopsy was not evaluable). One AE leading to study withdrawal was not related to romiplostim (follicular B-cell lymphoma). As of the reference date, no progression to AML was reported. Eighteen pts (64%) reported ≥1 bleeding events, with 6 pts (21%) reporting ≥1 clinically significant bleeding events (i.e., CTCAE grade ≥3, serious AE, or any bleeding AE requiring intervention). Eight pts (29%) received platelet transfusions. From Study Week 4 on, the median platelet count was ≥50×109/L. Twenty-three pts (82%) had a platelet response (per IWG 2006 guidelines), including 6 of 9 pts with baseline platelet counts <20×109/L. The median platelet response lasted 30 weeks (Q1-Q3: 16–52 weeks). Over half of pts (54%) demonstrated an initial platelet response by Study Week 3. Conclusion: In this long-term, follow-up, open-label extension study in thrombocytopenic MDS pts, romiplostim demonstrated an acceptable toxicity profile, with the majority of pts achieving a durable platelet response. Disclosures: Fenaux: Cephalon: Research Funding; Amgen Inc.: Research Funding; Merck: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Off Label Use: Nplate (romiplostim) is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Kantarjian:Amgen Inc.: Research Funding. Lyons:Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy; Johnson&Johnson: Consultancy, Honoraria, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau. Larson:Amgen Inc.: Equity Ownership, Research Funding. Sekeres:Celgene: Honoraria, Research Funding, Speakers Bureau. Becker:Amgen Inc.: Research Funding, Speakers Bureau. Muus:Amgen Inc.: Speakers Bureau. Hu:Amgen Inc.: Employment, Equity Ownership. Berger:Amgen Inc.: Employment, Equity Ownership. Franklin:Amgen Inc.: Employment, Equity Ownership.

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