scholarly journals Individualized prophylactic treatment of patients with hemophilia A to improve effectiveness and optimize product consumption on the example of octocog alpha and rurioctocog alpha pegol. A systematic literature review

2021 ◽  
pp. 22-29
Author(s):  
A. G. Tolkushin ◽  
M. E. Holownia-Voloskova ◽  
N. L. Pogudina
Keyword(s):  
Observational Studies ◽  
Prophylactic Treatment ◽  
Pediatric Patients ◽  
Hemophilia A ◽  
Controlled Study ◽  
Bleeding Rate ◽  
Risk Of Bleeding ◽  
Product Consumption ◽  
Annual Consumption ◽  
International Data

Objective: to review the data on the efficacy and consumption of octocog alfa and rurioctoctog alfa pegol in standard prophylaxis and individualized prophylaxis in hemophilia A patients based on published international data. Material and methods: a systematic literature search and review were performed. Among 25 sources identified within the systematic search 7 relevant sources describing the comparison of treatment with octocog alfa and rurioctocog alfa pegol in adult and pediatric patients with severe and moderate hemophilia A based on personalized assessment of the pharmacokinetic curve using the interactive tool myPKFit versus the standard (non-personalized) dosage regimen were selected. Data on individual patients, as well as data from secondary subgroups defined by age, bleeding rate, risk of bleeding associated with the daily physical activity were combined and analyzed. Results. In observational studies, adjustments of the dose and administration of octocog alfa in patients with severe hemophilia based on personalized assessment of the pharmacokinetic curve using myPKFit resulted in the reduced consumption and/or increased efficacy of prophylaxis — a reduced annual bleeding rate. In an extended controlled study of rurioctocog alpha pegol a trend toward reduced bleeding rate and increased mean annual consumption of the drug was reported in patients who received myPKFit guided prophylaxis compared to a non-personalized treatment regimen. In the single-cut studies, myPKFiT use resulted in the regimen revisions in less than a quarter of patients. Summary. Personalized dosing for octocog alpha and rurioctocog alpha pegol based on pharmacokinetic curve built using pharmacokinetic population model enables reasonable dose adjustments and improves outcomes.

scholarly journals Effects of replacement therapies with clotting factors in patients with hemophilia: A systematic review and meta-analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262273
Author(s):  
Carolina J. Delgado-Flores ◽  
David García-Gomero ◽  
Stefany Salvador-Salvador ◽  
José Montes-Alvis ◽  
Celina Herrera-Cunti ◽  
...  
Keyword(s):  
Low Dose ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Clotting Factor ◽  
High Dose ◽  
Bleeding Rate ◽  
Episodic Treatment ◽  
Grade Methodology ◽  
Inform Decision Making ◽  
Intermediate Dose

Background Different prophylactic and episodic clotting factor treatments are used in the management of hemophilia. A summarize of the evidence is needed inform decision-making. Objective To compare the effects of factor replacement therapies in patients with hemophilia. Methods We performed a systematic search in PubMed, Central Cochrane Library, and Scopus. We included randomized controlled trials (RCTs) published up to December 2020, which compared different factor replacement therapies in patients with hemophilia. Random-effects meta-analyses were performed whenever possible. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The study protocol was registered in PROSPERO (CRD42021225857). Results Nine RCTs were included in this review, of which six compared episodic with prophylactic treatment, all of them performed in patients with hemophilia A. Pooled results showed that, compared to the episodic treatment group, the annualized bleeding rate was lower in the low-dose prophylactic group (ratio of means [RM]: 0.27, 95% CI: 0.17 to 0.43), intermediate-dose prophylactic group (RM: 0.15, 95% CI: 0.07 to 0.36), and high-dose prophylactic group (RM: 0.07, 95% CI: 0.04 to 0.13). With significant difference between these subgroups (p = 0.003, I2 = 82.9%). In addition, compared to the episodic treatment group, the annualized joint bleeding rate was lower in the low-dose prophylactic group (RM: 0.17, 95% CI: 0.06 to 0.43), intermediate-dose prophylactic group (RM of 0.14, 95% CI: 0.07 to 0.27), and high-dose prophylactic group (RM of 0.08, 95% CI: 0.04 to 0.16). Without significant subgroup differences. The certainty of the evidence was very low for all outcomes according to GRADE methodology. The other studies compared different types of clotting factor concentrates (CFCs), assessed pharmacokinetic prophylaxis, or compared different frequencies of medication administration. Conclusions Our results suggest that prophylactic treatment (at either low, intermediate, or high doses) is superior to episodic treatment for bleeding prevention. In patients with hemophilia A, the bleeding rate seems to have a dose-response effect. However, no study compared different doses of prophylactic treatment, and all results had a very low certainty of the evidence. Thus, future studies are needed to confirm these results and inform decision making.

Human-Cl Rhfviii Effectively and Safely Prevents Bleeding Episodes in Previously Treated Adult Patients with Severe Haemophilia A

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1132-1132
Author(s):  
Sigurd Knaub ◽  
Toshko Lissitchkov ◽  
Kingsley Hampton ◽  
Mario Von Depka ◽  
Savita Rangarajan ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Research Funding ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Open Label ◽  
Bleeding Rate ◽  
Previously Treated

Abstract Abstract 1132 The main purpose of this prospective, multi-center, open-label phase 3 study was to assess the efficacy of prophylactic treatment with Human-cl rhFVIII, the first human cell-line derived recombinant FVIII, in previously treated patients (PTPs) with severe haemophilia A. Patients were to receive 30–40 international units (IU) FVIII of Human-cl rhFVIII per kg every other day for 6 months. Efficacy of preventing and treating bleeds were judged using objective criteria taking the monthly bleeding rate and the number of infusions needed to manage a break-through bleed into account. In-vivo recovery (IVR) was determined at the beginning of the study and after 3 and 6 months. FVIII:C was measured by validated chromogenic (CHR) and one-stage (OS) assays in a central laboratory, which also assigned drug potencies. Inhibitor activity was determined using the Nijmegen modification of the Bethesda assay before the first administration and at defined intervals thereafter. Thirty-two patients between 18 and 75 years of age were enrolled from 11 centres in Europe and treated prophylactically for 6.0±0.9 months (mean ± SD) with a mean prophylactic dose of 32.8 IU/kg. Sixteen patients never bled, 11 patients bled once and 5 more than once. The mean total and spontaneous monthly bleeding rate was 0.188±0.307 and 0.095±0.211, respectively. Efficacy of the prophylactic treatment was “excellent” in all patients for spontaneous BEs and “excellent” or “good” in all patients but one for all types of bleeds. All treatments of bleeds were rated as “excellent” (71.4%) or “good” (28.6%). The IVR at baseline was 2.6±0.5 % per IU/kg for the CHR and 2.2±0.5 % per IU/kg for the OS assay and remained stable during the study. A total of 2921 infusions were given in the study. Human-cl rhFVIII was well tolerated and no patient experienced a related serious adverse event. No FVIII inhibitors were detected. Conclusion: The data indicate that Human-cl rh FVIII is safe and efficacious in preventing and treating bleeds in PTPs with severe haemophlia A. Disclosures: Knaub: Octapharma AG: Employment. Lissitchkov:Octapharma AG: PI Other. Tuddenham:College London: Consultancy, Employment, Gene therapy for hemophilia A, Gene therapy for hemophilia A Patents & Royalties, Research Funding. Collins:Octapharma AG: Consultancy. Oldenburg:d and e: Baxter, Bayer, Biotest, CSL-Behring, Grifols, Inspiration, NovoNordisk, Octapharma, Pfizer e: Biogen IDec, Swedish Orphan Biovitrum: Honoraria, Research Funding. Bichler:Octapharma AG: Employment.

Consumption Of FVIII Concentrate During On-Demand and Prophylactic Treatment With Human-cl rhFVIII In Prospective Clinical Studies In Adult Patients With Severe Hemophilia A

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3595-3595 ◽  
Author(s):  
Andreas Tiede ◽  
Sigurd Knaub ◽  
Johannes Oldenburg ◽  
Johann Bichler
Keyword(s):  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Fold Increase ◽  
Human Cell Line ◽  
Adult Patients ◽  
Study Entry ◽  
Severe Hemophilia ◽  
Ample Evidence ◽  
Bleeding Rate ◽  
On Demand

Abstract Background There is ample evidence to support prophylactic treatment with factor VIII (FVIII) in children with severe hemophilia A (HA). Adults with severe HA are often treated on-demand and the potential benefit of regular prophylaxis is linked to a higher consumption of FVIII concentrates. During the clinical development of Human-cl rhFVIII, the first recombinant FVIII concentrate from a human cell line, its efficacy and safety was evaluated in previously treated adult patients (PTPs) during on-demand treatment only (GENA-01) and prophylaxis (GENA-08). Aims To compare post-hoc the annualized bleeding rate (ABR) and the consumption of FVIII concentrate in patients treated exclusively on-demand with those treated prophylactically. Methods Both prospective multi-centre studies were approved by the Ethics Committees of each participating institution and informed consent was obtained from the patient prior to any trial activity. In GENA-01, patients were to be treated on-demand for ≥6 months and ≥50 exposure days with protocol recommended doses ranging from 20 to 60 IU/kg, depending on the severity of the bleed. In GENA-08, patients were to be treated prophylactically with Human-cl rhFVIII every other day with 30-40 IU/kg for ≥6 months. Human-cl rhFVIII was also to be used in case of breakthrough bleeds. Results 22 PTPs with severe HA were enrolled in GENA-01, and 32 in GENA-08. The study populations were reasonably well comparable to each other (GENA-01 vs. GENA-08, mean±SD), regarding age (39.6±14.1 vs. 37.3±13.6 years), body mass index (23.9±4.8 vs. 25.8±4.9 kg/m2), hemophilia joint health score (38.4±30.3 vs. 34.6±32.2), race (>80% White in both studies) and historical bleeding sites. In GENA-08, the majority of patients (65.6%) had been treated prophylactically prior to study entry. Their historical mean±SD ABR was 6.6 ±11.3 (median: 2.0, range: 0-48.7) and their mean prophylactic dose/month was 293 IU/kg. The other 11 patients who had been treated on-demand had a mean±SD ABR of 47.4±34.6 (median: 36.5, range: 12.2-121.7). In GENA-01, all but 2 patients were treated on-demand prior to study entry. The historical mean±SD ABR of all GENA-01 patients was 49.5±35.9 (median: 44.6, range: 2.0-158.7). The ABR and FVIII consumption during the studies are shown in Table 1. Conclusion The data suggest that regular prophylactic treatment with Human-cl rhFVIII in adult PTPs with severe HA resulted in an approximately 25-fold reduction of bleeding rate, and a 3-fold increase of FVIII concentrate consumption. Disclosures: Tiede: Octapharma AG: Consultancy, Investigator Other. Knaub:Octapharma AG: Employment. Oldenburg:Octapharma AG: Consultancy, Investigator Other. Bichler:Octapharma AG: Employment.

scholarly journals Bleeding and Response to Hemostatic Therapy in Acquired Hemophilia A (AHA): Results from the GTH-AH 01/2010 Study

Blood ◽  
2020 ◽  
Author(s):  
Katharina Holstein ◽  
Xiaofei Liu ◽  
Andrea Smith ◽  
Paul Knöbl ◽  
Robert Klamroth ◽  
...  
Keyword(s):  
Partial Remission ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Individual Risk ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Bleeding Rate ◽  
Risk Of Bleeding ◽  
Fviii Activity ◽  
Hemostatic Therapy

Acquired hemophilia A (AHA) is due to autoantibodies against coagulation factor VIII (FVIII) and most often presents with unexpected bleeding. In contrast to congenital hemophilia, the patient's residual FVIII activity does not seem to correlate with the risk of bleeding as suggested from previous studies. Risk factors for bleeding have not been described. We used data from the prospective GTH-AH 01/2010 study to assess the risk of bleeding and the efficacy of hemostatic therapy. FVIII activity was measured at baseline and weekly thereafter. Bleeding events were assessed by treating physicians. A total of 289 bleeds was recorded in 102 patients. 141 new bleeds starting after day 1 were observed in 59% of the patients, with a mean rate of 0.13 bleeds per patient-week in weeks 1 to 12, or 0.27 bleeds per patient-week before achieving partial remission. Weekly measured FVIII activity was significantly associated with the bleeding rate, but only achieving FVIII ≥50% abolished the risk of bleeding. A good WHO performance status assessed at baseline (score 0 vs. higher) was associated with a lower bleeding rate. Hemostatic treatment was reported to be effective in 96% of bleeds. In conclusion, the risk of new bleeds after a first diagnosis of AHA remains high until partial remission is achieved, and weekly measured FVIII activity may help to assess the individual risk of bleeding. These results will help to define future strategies for prophylaxis of bleeding in AHA.

scholarly journals Impact of Prophylaxis Usage on Bleeding Rates Among Persons with Hemophilia A: Evidence from Longitudinal Analyses in the USA

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 494-494
Author(s):  
Michael B. Nichol ◽  
Randall Curtis ◽  
Yuchen Ding ◽  
Elmar R. Aliyev ◽  
Marion A. Koerper ◽  
...  
Keyword(s):  
Health Insurance ◽  
Health Outcomes ◽  
Joint Pain ◽  
Research Funding ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Age Groups ◽  
Clotting Factor ◽  
Bleeding Rate

Abstract BACKGROUND There are limited longitudinal studies following up persons with hemophilia (PWH) in adherence to clotting factor treatment and health outcomes. The Hemophilia Utilization Group Studies part Va (HUGS Va) was a two-year observational study of persons with hemophilia A conducted from 2005-2007. Participants from HUGS Va were enrolled to the long-term follow-up study (HUGS LTS) in 2014. OBJECTIVES To compare participants' characteristics between baseline of HUGS Va and follow-up in LTS; and investigate the impacts of changes of participants' characteristics on annualized bleeding rates. METHODS We collected data on sociodemographic and clinical characteristics. Self-reported bleedings were obtained from periodic surveys for 2-years in HUGS Va, and a survey that asked bleedings in the past 6-month in HUGS LTS. Clotting factor dispensing records were collected prospectively for two years in HUGS Va, and retrospectively for six months prior to HUGS LTS enrollment. Annualized bleeding rates and factor dispensing (unit/kg body weight) were calculated. Adherence to factor treatment was determined by the ratio of dispensed clotting factor to clinical recommended factor usage. We classified age at baseline of HUGS Va into three groups: children (aged 2-11 years), adolescents (aged 12-20 years), and adults (aged ≥21 years). The characteristics of participants were compared among the three age groups using Chi-square tests for categorical variables and ANOVA for continuous variables for each study. Annualized factor dispensed and bleeding rates were compared between HUGS Va and HUGS LTS using paired T-tests. RESULTS A total of 74 persons participated in both HUGS Va and LTS with completed data to calculate annualized factor dispensed and bleeding rates were included to the analyses. The mean age was 17.8±11.4 years in HUGS Va, and 26.2±11.5 years in LTS, respectively. The sample had 43% of children, 22% adolescents, and 35% adults at baseline. All adolescents at baseline transitioned to young adults in LTS. Approximately 80% of participants were severe hemophilia. Adults (73%) were less likely to have an entire year of health insurance as compared to children (100%) or adolescents (93.8%, P<0.01) in HUGS Va. Health insurance status was not significantly different among age groups in LTS. In HUGS Va, children had the highest rate of prophylactic treatment (74%), adherence to factor treatment (62%), highest mean annualized factor dispensed (4724±4090 u/kg), lowest rate of self-reported moderate or severe joint pain (31%), and lowest mean annualized bleeding rate (4.2±4.7); while adults had the lowest rate of prophylactic treatment (31%), adherence (28%), lowest mean annualized factor dispensed (2084±1870 u/kg), highest rate of self-reported moderate or severe joint pain (73%), and highest mean annualized bleeding rate (11.9±9.3), all P<0.05 among age group comparisons for these variables. There were 18 (26%) people (22% children, 17% adolescents, and 61% adults) switching from episodic treatment to prophylactic treatment from HUGS Va to LTS; others remained on the same treatment regimens. Adolescents and adults increased in prophylactic treatment (63% to 80% for adolescents, 31% to 69% for adults, respectively), adherence (36% to 75%, 28% to 61%), and mean annualized factor dispensed (3206±2581 to 4931±2945 u/kg, 2084±1870 to 4612±2577 u/kg) from HUGS Va to LTS. Mean annualized bleeding rates were not statistically significant different between HUGS Va (7.3±8.4) and LTS (10.6±22.0, P>0.05). The bleeding rates were not significantly different among age groups in LTS (P=0.06). CONCLUSIONS Although current literature indicated that PWH in transition from childhood to adulthood maybe at high risk of adverse health outcomes due to poor management of their condition with diminishing influence from parents, adolescents showed a significant increase in prophylactic treatment, adherence to factor treatment, and annualized factor dispensed, which may be associated with unchanged annualized bleed rates after they transitioned to adulthood in this study. Adults had a larger increase in dispensed factors than adolescents. Prophylaxis and adherence to clotting factor treatment were associated with a lower bleeding rate. Our current analyses reinforce the importance of prophylaxis and adherence to factor treatment for decreasing bleedings in persons with hemophilia A. Disclosures Nichol: Bayer: Research Funding; CSL Behring: Research Funding; Bioverativ: Research Funding; Shire/Baxter: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Genentech: Research Funding. Curtis:Gilead: Honoraria; Pfizer: Research Funding; Novo Nordisk: Honoraria, Research Funding; Shire/Baxter: Research Funding; Bioverativ: Research Funding; National Hemophilia Foundation: Honoraria; CSL Behring: Research Funding; Bayer: Research Funding, Speakers Bureau; Genentech: Honoraria, Research Funding. Ding:Novo Nordisk: Employment; Bioverativ: Research Funding. Aliyev:Genentech: Research Funding. Lou:Bioverativ: Research Funding; Novo Nordisk: Research Funding; Genentech: Research Funding; Bayer: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Shire/Baxter: Research Funding. Ullman:Genentech: Research Funding. Tran:Bioverativ: Honoraria; Novo Nordisk: Honoraria; Bayer: Honoraria; Genentech: Research Funding. Baker:Genentech: Research Funding. Riske:Genentech: Research Funding. Wu:Pfizer: Research Funding; Genentech: Research Funding; Bioverativ: Research Funding; CSL Behring: Research Funding; Bayer: Research Funding; Shire/Baxter: Research Funding; Novo Nordisk: Research Funding.

Soy Consumption with Risk of Coronary Heart Disease and Stroke: A Meta-Analysis of Observational Studies

2016 ◽  
Vol 46 (4) ◽  
pp. 242-252 ◽  
Author(s):  
Danfei Lou ◽  
Yuehua Li ◽  
Guoliang Yan ◽  
Jianhong Bu ◽  
Haihui Wang
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cohort Studies ◽  
Observational Studies ◽  
Meta Analysis ◽  
Case Control ◽  
Inverse Association ◽  
Case Control Studies ◽  
Relative Risks ◽  
Product Consumption

Background: The association of soy product consumption with the relative risk of cardiovascular disease remains controversial. This meta-analysis aimed at investigating whether an association exists between soy consumption and the risk of stroke and coronary heart disease (CHD) in observational studies. Methods: A systematic search of the PubMed and EMBASE databases was performed for case-control and cohort studies that assessed soy consumption and the risk of stroke and CHD. Summary relative risks (SRRs) and 95% CIs were combined by using a random-effects model. Results: Of a total of 1,266 abstracts, 5 prospective cohort and 6 case-control studies met our inclusion criteria, and comprised 4,954 stroke and 7,616 CHD events. Based on the high vs. low analyses, combining cohort studies showed no association between soy intake and risk of stroke (SRR 0.92; 95% CI 0.70-1.10; Pheterogeneity = 0.236; I2 = 29.4%) or CHD (SRR 0.97; 95% CI 0.74-1.27; Pheterogeneity = 0.020; I2 = 62.7%), although a significantly inverse association between soy intake and the risk of stroke (SRR 0.54; 95% CI 0.34-0.87; Pheterogeneity = 0.001; I2 = 79.3%) and CHD (SRR 0.66; 95% CI 0.56-0.77; Pheterogeneity = 0.421; I2 = 0) was observed in case-control studies. No association between soy isoflavone intake and the risk of stroke and CHD was identified. Conclusion: There was limited evidence to indicate that soy consumption was inversely associated with the risk of stroke and CHD, although further studies, with prospective designs that use validated questionnaires and control for important confounders, are warranted.

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