Bleeding Disorders

A single intra-articular injection of platelet-rich plasma showed better pain and function scores at 6 months than did weekly injections of hyaluronic acid in patients with hemophilic arthropathy of the knee.

“In patients with chronic knee joint pain, our study shows that treatment with intra-articular [platelet-rich plasma] injection could reduce pain, improve hyperaemia and enhance knee joint function,” wrote Tsung-Ying Li, MD, of Tri-Service General Hospital in Taipei, Taiwan, and his colleagues. The results of the comparison study were published in Haemophilia.

Researchers conducted a nonrandomized, single-center, open-label comparison study of 22 patients with hemophilia A who had chronic hemophilic arthropathy of the knee. Patients were stratified into two treatment groups using a matched sampling method.

“Patients who could commit to hyaluronic acid treatment were allocated to the hyaluronic acid group, otherwise patients were allocated to the platelet‐rich plasma group,” the researchers wrote.

Participants in the hyaluronic acid arm were given five sequential weekly injections and those in the platelet-rich plasma arm received only a single injection. Outcomes were measured via the visual analogue scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Chinese Version, and ultrasonography to determine synovial change.

Pain and function scores were significantly lower in patients administered intra-articular platelet-rich plasma versus hyaluronic acid at 6 months (P less than .05), the researchers reported. However, comparative analysis found no significant differences at earlier follow-up time points.

“Both treatments were found to be effective in reducing pain and improving functional status of the knee,” the researchers wrote.

They acknowledged a key limitation of the study was the short duration of follow-up, which was due to budget restrictions at the treatment facility.

“Further investigation using rigorous research methodology is warranted to establish the benefit of [platelet-rich plasma] on hemophilic arthropathy and standardized [platelet-rich plasma] preparation and dosing regimens,” they wrote.

The study was supported by grant funding from Tri-Service General Hospital in Taiwan. Three of the authors reported receiving research grants from Shire.

SOURCE: Li TY et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13711.

A single intra-articular injection of platelet-rich plasma showed better pain and function scores at 6 months than did weekly injections of hyaluronic acid in patients with hemophilic arthropathy of the knee.

“In patients with chronic knee joint pain, our study shows that treatment with intra-articular [platelet-rich plasma] injection could reduce pain, improve hyperaemia and enhance knee joint function,” wrote Tsung-Ying Li, MD, of Tri-Service General Hospital in Taipei, Taiwan, and his colleagues. The results of the comparison study were published in Haemophilia.

Researchers conducted a nonrandomized, single-center, open-label comparison study of 22 patients with hemophilia A who had chronic hemophilic arthropathy of the knee. Patients were stratified into two treatment groups using a matched sampling method.

“Patients who could commit to hyaluronic acid treatment were allocated to the hyaluronic acid group, otherwise patients were allocated to the platelet‐rich plasma group,” the researchers wrote.

Participants in the hyaluronic acid arm were given five sequential weekly injections and those in the platelet-rich plasma arm received only a single injection. Outcomes were measured via the visual analogue scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Chinese Version, and ultrasonography to determine synovial change.

Pain and function scores were significantly lower in patients administered intra-articular platelet-rich plasma versus hyaluronic acid at 6 months (P less than .05), the researchers reported. However, comparative analysis found no significant differences at earlier follow-up time points.

“Both treatments were found to be effective in reducing pain and improving functional status of the knee,” the researchers wrote.

They acknowledged a key limitation of the study was the short duration of follow-up, which was due to budget restrictions at the treatment facility.

“Further investigation using rigorous research methodology is warranted to establish the benefit of [platelet-rich plasma] on hemophilic arthropathy and standardized [platelet-rich plasma] preparation and dosing regimens,” they wrote.

The study was supported by grant funding from Tri-Service General Hospital in Taiwan. Three of the authors reported receiving research grants from Shire.

SOURCE: Li TY et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13711.

A single intra-articular injection of platelet-rich plasma showed better pain and function scores at 6 months than did weekly injections of hyaluronic acid in patients with hemophilic arthropathy of the knee.

“In patients with chronic knee joint pain, our study shows that treatment with intra-articular [platelet-rich plasma] injection could reduce pain, improve hyperaemia and enhance knee joint function,” wrote Tsung-Ying Li, MD, of Tri-Service General Hospital in Taipei, Taiwan, and his colleagues. The results of the comparison study were published in Haemophilia.

Researchers conducted a nonrandomized, single-center, open-label comparison study of 22 patients with hemophilia A who had chronic hemophilic arthropathy of the knee. Patients were stratified into two treatment groups using a matched sampling method.

“Patients who could commit to hyaluronic acid treatment were allocated to the hyaluronic acid group, otherwise patients were allocated to the platelet‐rich plasma group,” the researchers wrote.

Participants in the hyaluronic acid arm were given five sequential weekly injections and those in the platelet-rich plasma arm received only a single injection. Outcomes were measured via the visual analogue scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Chinese Version, and ultrasonography to determine synovial change.

Pain and function scores were significantly lower in patients administered intra-articular platelet-rich plasma versus hyaluronic acid at 6 months (P less than .05), the researchers reported. However, comparative analysis found no significant differences at earlier follow-up time points.

“Both treatments were found to be effective in reducing pain and improving functional status of the knee,” the researchers wrote.

They acknowledged a key limitation of the study was the short duration of follow-up, which was due to budget restrictions at the treatment facility.

“Further investigation using rigorous research methodology is warranted to establish the benefit of [platelet-rich plasma] on hemophilic arthropathy and standardized [platelet-rich plasma] preparation and dosing regimens,” they wrote.

The study was supported by grant funding from Tri-Service General Hospital in Taiwan. Three of the authors reported receiving research grants from Shire.

SOURCE: Li TY et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13711.

Women with factor XI (FXI) deficiency, particularly those with a history of bleeding and low plasmatic FXI levels, are at risk of experiencing obstetric and gynecologic hemorrhage, according to a retrospective analysis.

“[W]hile spontaneous bleeding episodes are unusual, FXI-deficient patients tend to bleed excessively after trauma or surgery, especially when highly fibrinolytic tissues are involved, such as rhino/oropharyngeal and genitourinary mucosa,” wrote Carlos Bravo-Perez, MD, of Universidad de Murcia in Spain, along with his colleagues. The report is in Medicina Clínica. “Menstruation, pregnancy and birth labour constitute intrinsic haemostatic challenges for FXI deficient women,” they noted.

The researchers conducted a retrospective analysis of 95 women with FXI deficiency. Cohort data was collected over a period of 20 years (1994 to 2014) from the city of Yecla, Spain.

Clinical information obtained included blood group, age, sex, aPTT ratio, and FXI coagulant levels, among others. The team completed a comprehensive molecular and biochemical analysis on all study patients.

“Surgical interventions and postoperative bleeding were recorded, as well as the use of antihemorrhagic prophylaxis or treatment,” the researchers wrote.

Bleeding occurred in 27.4% of women with FXI deficiency, with the majority of events being a single episode. The team reported that 52.5% of hemorrhagic events were provoked by surgical, obstetric, or dental procedures, while 47.5% were spontaneous bleeding events.

Among women who experienced bleeding events, 73.1% were gynecologic or obstetric hemorrhagic episodes. These included abnormal uterine bleeding, postpartum hemorrhage, excessive bleeding after a miscarriage, and bleeding after gynecologic surgery.

Overall, the proportion of abnormal uterine bleeding was 12.6%, the proportion of postpartum hemorrhage was 6.6%, and the proportion of gynecologic postoperative hemorrhage was 16%.

While the proportion of these bleeding events is higher than what has been observed in the general population, it is lower than what has been reported in other reviews for women with FXI deficiency, the researchers noted.

They also found that a positive history of bleeding and low plasmatic FXI levels were associated with a higher prevalence of gynecologic or obstetric bleeding.

The study was funded by Fundación Española de Trombosis y Hemostasia and Sociedad Española de Hematología y Hemoterapia in Spain. The authors reported having no conflicts of interest.

SOURCE: Bravo-Perez C et al. Med Clin (Barc). 2019 Mar 26. doi: 10.1016/j.medcli.2019.01.029.

Women with factor XI (FXI) deficiency, particularly those with a history of bleeding and low plasmatic FXI levels, are at risk of experiencing obstetric and gynecologic hemorrhage, according to a retrospective analysis.

“[W]hile spontaneous bleeding episodes are unusual, FXI-deficient patients tend to bleed excessively after trauma or surgery, especially when highly fibrinolytic tissues are involved, such as rhino/oropharyngeal and genitourinary mucosa,” wrote Carlos Bravo-Perez, MD, of Universidad de Murcia in Spain, along with his colleagues. The report is in Medicina Clínica. “Menstruation, pregnancy and birth labour constitute intrinsic haemostatic challenges for FXI deficient women,” they noted.

The researchers conducted a retrospective analysis of 95 women with FXI deficiency. Cohort data was collected over a period of 20 years (1994 to 2014) from the city of Yecla, Spain.

Clinical information obtained included blood group, age, sex, aPTT ratio, and FXI coagulant levels, among others. The team completed a comprehensive molecular and biochemical analysis on all study patients.

“Surgical interventions and postoperative bleeding were recorded, as well as the use of antihemorrhagic prophylaxis or treatment,” the researchers wrote.

Bleeding occurred in 27.4% of women with FXI deficiency, with the majority of events being a single episode. The team reported that 52.5% of hemorrhagic events were provoked by surgical, obstetric, or dental procedures, while 47.5% were spontaneous bleeding events.

Among women who experienced bleeding events, 73.1% were gynecologic or obstetric hemorrhagic episodes. These included abnormal uterine bleeding, postpartum hemorrhage, excessive bleeding after a miscarriage, and bleeding after gynecologic surgery.

Overall, the proportion of abnormal uterine bleeding was 12.6%, the proportion of postpartum hemorrhage was 6.6%, and the proportion of gynecologic postoperative hemorrhage was 16%.

While the proportion of these bleeding events is higher than what has been observed in the general population, it is lower than what has been reported in other reviews for women with FXI deficiency, the researchers noted.

They also found that a positive history of bleeding and low plasmatic FXI levels were associated with a higher prevalence of gynecologic or obstetric bleeding.

The study was funded by Fundación Española de Trombosis y Hemostasia and Sociedad Española de Hematología y Hemoterapia in Spain. The authors reported having no conflicts of interest.

SOURCE: Bravo-Perez C et al. Med Clin (Barc). 2019 Mar 26. doi: 10.1016/j.medcli.2019.01.029.

Women with factor XI (FXI) deficiency, particularly those with a history of bleeding and low plasmatic FXI levels, are at risk of experiencing obstetric and gynecologic hemorrhage, according to a retrospective analysis.

“[W]hile spontaneous bleeding episodes are unusual, FXI-deficient patients tend to bleed excessively after trauma or surgery, especially when highly fibrinolytic tissues are involved, such as rhino/oropharyngeal and genitourinary mucosa,” wrote Carlos Bravo-Perez, MD, of Universidad de Murcia in Spain, along with his colleagues. The report is in Medicina Clínica. “Menstruation, pregnancy and birth labour constitute intrinsic haemostatic challenges for FXI deficient women,” they noted.

The researchers conducted a retrospective analysis of 95 women with FXI deficiency. Cohort data was collected over a period of 20 years (1994 to 2014) from the city of Yecla, Spain.

Clinical information obtained included blood group, age, sex, aPTT ratio, and FXI coagulant levels, among others. The team completed a comprehensive molecular and biochemical analysis on all study patients.

“Surgical interventions and postoperative bleeding were recorded, as well as the use of antihemorrhagic prophylaxis or treatment,” the researchers wrote.

Bleeding occurred in 27.4% of women with FXI deficiency, with the majority of events being a single episode. The team reported that 52.5% of hemorrhagic events were provoked by surgical, obstetric, or dental procedures, while 47.5% were spontaneous bleeding events.

Among women who experienced bleeding events, 73.1% were gynecologic or obstetric hemorrhagic episodes. These included abnormal uterine bleeding, postpartum hemorrhage, excessive bleeding after a miscarriage, and bleeding after gynecologic surgery.

Overall, the proportion of abnormal uterine bleeding was 12.6%, the proportion of postpartum hemorrhage was 6.6%, and the proportion of gynecologic postoperative hemorrhage was 16%.

While the proportion of these bleeding events is higher than what has been observed in the general population, it is lower than what has been reported in other reviews for women with FXI deficiency, the researchers noted.

They also found that a positive history of bleeding and low plasmatic FXI levels were associated with a higher prevalence of gynecologic or obstetric bleeding.

The study was funded by Fundación Española de Trombosis y Hemostasia and Sociedad Española de Hematología y Hemoterapia in Spain. The authors reported having no conflicts of interest.

SOURCE: Bravo-Perez C et al. Med Clin (Barc). 2019 Mar 26. doi: 10.1016/j.medcli.2019.01.029.

The state of Indiana had higher hemophilia incidence and prevalence rates, compared with national estimates, according to results from a statewide epidemiologic analysis.

“[The study] aimed to identify all persons with hemophilia, including those not served by an hemophilia treatment center, who resided in Indiana,” Amanda I. Okolo, MPH, of the Indiana Hemophilia and Thrombosis Center, Indianapolis, and her colleagues wrote in Haemophilia.

The researchers retrospectively reviewed medical chart data from federally identified hemophilia treatment centers in Indiana during 2011-2013. Various data sources were used to find hemophilia cases, including administrative claims, clinic reports, and hospital records. The team estimated incidence and prevalence rates using both confirmed and possible cases of hemophilia. With respect to incidence, the calculation was based on the 10 years leading up to the study surveillance period.

“During the study period, 599, 623, and 634 male cases of hemophilia were identified in 2011, 2012 and 2013, respectively, with a total of 704 unique male cases,” the researchers wrote. Among these cases, 35.2% had factor IX deficiency and 64.8% had factor VIII deficiency.

Health care utilization was high among this group of patients, with more than 80% of cases seen at a hemophilia treatment center at least once during the 3-year study period.

The age-adjusted prevalence rate for hemophilia in 2013 was 19.4 cases per 100,000 males. The mean incidence rate over the 10 years leading up to the study period was 30.1 per 100,000, or 1 per 3,688 live male births, noticeably higher than the generally accepted national frequency of hemophilia at about 1 per 5,000 live male births.

“The estimated hemophilia prevalence in Indiana was 45% higher than previously reported in the United States,” the researchers added.

The higher prevalence could be partly caused by improvements in hemophilia care, namely increased adoption of prophylaxis. But a more important factor may be the reduction in HIV infections and the decreasing mortality from HIV among hemophilia patients.

The researchers acknowledged a key limitation of the study was the lack of data on patients assessed in other clinical settings. As a result, the reported rates could be an underestimation.

“Our results may be relevant to other countries where the hemophilia treatment center model is utilized,” they wrote.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Okolo AI et al. Haemophilia. 2019 Mar 29. doi: 10.1111/hae.13734.


 

The state of Indiana had higher hemophilia incidence and prevalence rates, compared with national estimates, according to results from a statewide epidemiologic analysis.

“[The study] aimed to identify all persons with hemophilia, including those not served by an hemophilia treatment center, who resided in Indiana,” Amanda I. Okolo, MPH, of the Indiana Hemophilia and Thrombosis Center, Indianapolis, and her colleagues wrote in Haemophilia.

The researchers retrospectively reviewed medical chart data from federally identified hemophilia treatment centers in Indiana during 2011-2013. Various data sources were used to find hemophilia cases, including administrative claims, clinic reports, and hospital records. The team estimated incidence and prevalence rates using both confirmed and possible cases of hemophilia. With respect to incidence, the calculation was based on the 10 years leading up to the study surveillance period.

“During the study period, 599, 623, and 634 male cases of hemophilia were identified in 2011, 2012 and 2013, respectively, with a total of 704 unique male cases,” the researchers wrote. Among these cases, 35.2% had factor IX deficiency and 64.8% had factor VIII deficiency.

Health care utilization was high among this group of patients, with more than 80% of cases seen at a hemophilia treatment center at least once during the 3-year study period.

The age-adjusted prevalence rate for hemophilia in 2013 was 19.4 cases per 100,000 males. The mean incidence rate over the 10 years leading up to the study period was 30.1 per 100,000, or 1 per 3,688 live male births, noticeably higher than the generally accepted national frequency of hemophilia at about 1 per 5,000 live male births.

“The estimated hemophilia prevalence in Indiana was 45% higher than previously reported in the United States,” the researchers added.

The higher prevalence could be partly caused by improvements in hemophilia care, namely increased adoption of prophylaxis. But a more important factor may be the reduction in HIV infections and the decreasing mortality from HIV among hemophilia patients.

The researchers acknowledged a key limitation of the study was the lack of data on patients assessed in other clinical settings. As a result, the reported rates could be an underestimation.

“Our results may be relevant to other countries where the hemophilia treatment center model is utilized,” they wrote.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Okolo AI et al. Haemophilia. 2019 Mar 29. doi: 10.1111/hae.13734.


 

The state of Indiana had higher hemophilia incidence and prevalence rates, compared with national estimates, according to results from a statewide epidemiologic analysis.

“[The study] aimed to identify all persons with hemophilia, including those not served by an hemophilia treatment center, who resided in Indiana,” Amanda I. Okolo, MPH, of the Indiana Hemophilia and Thrombosis Center, Indianapolis, and her colleagues wrote in Haemophilia.

The researchers retrospectively reviewed medical chart data from federally identified hemophilia treatment centers in Indiana during 2011-2013. Various data sources were used to find hemophilia cases, including administrative claims, clinic reports, and hospital records. The team estimated incidence and prevalence rates using both confirmed and possible cases of hemophilia. With respect to incidence, the calculation was based on the 10 years leading up to the study surveillance period.

“During the study period, 599, 623, and 634 male cases of hemophilia were identified in 2011, 2012 and 2013, respectively, with a total of 704 unique male cases,” the researchers wrote. Among these cases, 35.2% had factor IX deficiency and 64.8% had factor VIII deficiency.

Health care utilization was high among this group of patients, with more than 80% of cases seen at a hemophilia treatment center at least once during the 3-year study period.

The age-adjusted prevalence rate for hemophilia in 2013 was 19.4 cases per 100,000 males. The mean incidence rate over the 10 years leading up to the study period was 30.1 per 100,000, or 1 per 3,688 live male births, noticeably higher than the generally accepted national frequency of hemophilia at about 1 per 5,000 live male births.

“The estimated hemophilia prevalence in Indiana was 45% higher than previously reported in the United States,” the researchers added.

The higher prevalence could be partly caused by improvements in hemophilia care, namely increased adoption of prophylaxis. But a more important factor may be the reduction in HIV infections and the decreasing mortality from HIV among hemophilia patients.

The researchers acknowledged a key limitation of the study was the lack of data on patients assessed in other clinical settings. As a result, the reported rates could be an underestimation.

“Our results may be relevant to other countries where the hemophilia treatment center model is utilized,” they wrote.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Okolo AI et al. Haemophilia. 2019 Mar 29. doi: 10.1111/hae.13734.


 

Interim data suggest SB-525, an investigational gene therapy, may be safe and effective for patients with severe hemophilia A.

In the phase 1/2 Alta trial, SB-525 produced dose-dependent increases in factor VIII activity, with two of eight patients achieving normal factor VIII levels.

In addition, SB-525 was considered well tolerated. One patient did experience treatment-related serious adverse events – hypotension and fever – but these resolved within 24 hours.

Sangamo Therapeutics and Pfizer recently released these data in a press release and conference call.

The data include eight patients with severe hemophilia A who received SB-525 at 9e11 vg/kg, 2e12 vg/kg, 1e13 vg/kg, and 3e13 vg/kg.

Patient 1 (9e11 vg/kg), Patient 2 (9e11 vg/kg), and Patient 3 (2e12 vg/kg) did not experience clinically relevant increases in factor VIII levels and still require prophylactic recombinant factor VIII therapy.

Patient 4 (2e12 vg/kg) and Patient 5 (1e13 vg/kg) discontinued factor VIII therapy but have experienced spontaneous bleeds. Patient 4 had three bleeds in 48 weeks of follow-up, and Patient 5 had two bleeds in 40 weeks of follow-up.

Patient 6 (1e13 vg/kg), Patient 7 (3e13 vg/kg), and Patient 8 (3e13 vg/kg) have stopped factor VIII therapy and remain free of spontaneous bleeds at 28 weeks, 12 weeks, and 6 weeks of follow-up, respectively.

Patients 7 and 8 have achieved normal factor VIII levels. At 6 weeks, their factor VIII levels reached 140% and 94% of normal, respectively, according to a one-stage clotting assay, and 93% and 65%, respectively, according to a chromogenic assay.

“It appears the patients achieve their peak factor level at week 5 to 7 and maintain that level,” Edward Conner, MD, chief medical officer of Sangamo, said during the conference call.

The adverse events observed in this trial include grade 1 tachycardia (n = 1), grade 1 fatigue (n = 1), grade 1 alanine aminotransferase increase (n = 3), grade 1 myalgia (n = 1), grade 2 pyrexia (n = 2), and grade 3 hypotension (n = 1).

“These interim results indicate that SB-525 has the potential to comprise a well-tolerated, reliable, and predictable treatment, features that we believe will be a hallmark of the future gene therapy treatment of hemophilia A,” Dr. Conner said during the call.

Sangamo and Pfizer are enrolling additional patients in this trial, with the goal of expanding the 3e13 vg/kg cohort by up to five patients. The companies plan to present longer-term follow-up data at an upcoming scientific meeting.

The Alta trial is sponsored by Sangamo Therapeutics in collaboration with Pfizer.

[email protected]

Interim data suggest SB-525, an investigational gene therapy, may be safe and effective for patients with severe hemophilia A.

In the phase 1/2 Alta trial, SB-525 produced dose-dependent increases in factor VIII activity, with two of eight patients achieving normal factor VIII levels.

In addition, SB-525 was considered well tolerated. One patient did experience treatment-related serious adverse events – hypotension and fever – but these resolved within 24 hours.

Sangamo Therapeutics and Pfizer recently released these data in a press release and conference call.

The data include eight patients with severe hemophilia A who received SB-525 at 9e11 vg/kg, 2e12 vg/kg, 1e13 vg/kg, and 3e13 vg/kg.

Patient 1 (9e11 vg/kg), Patient 2 (9e11 vg/kg), and Patient 3 (2e12 vg/kg) did not experience clinically relevant increases in factor VIII levels and still require prophylactic recombinant factor VIII therapy.

Patient 4 (2e12 vg/kg) and Patient 5 (1e13 vg/kg) discontinued factor VIII therapy but have experienced spontaneous bleeds. Patient 4 had three bleeds in 48 weeks of follow-up, and Patient 5 had two bleeds in 40 weeks of follow-up.

Patient 6 (1e13 vg/kg), Patient 7 (3e13 vg/kg), and Patient 8 (3e13 vg/kg) have stopped factor VIII therapy and remain free of spontaneous bleeds at 28 weeks, 12 weeks, and 6 weeks of follow-up, respectively.

Patients 7 and 8 have achieved normal factor VIII levels. At 6 weeks, their factor VIII levels reached 140% and 94% of normal, respectively, according to a one-stage clotting assay, and 93% and 65%, respectively, according to a chromogenic assay.

“It appears the patients achieve their peak factor level at week 5 to 7 and maintain that level,” Edward Conner, MD, chief medical officer of Sangamo, said during the conference call.

The adverse events observed in this trial include grade 1 tachycardia (n = 1), grade 1 fatigue (n = 1), grade 1 alanine aminotransferase increase (n = 3), grade 1 myalgia (n = 1), grade 2 pyrexia (n = 2), and grade 3 hypotension (n = 1).

“These interim results indicate that SB-525 has the potential to comprise a well-tolerated, reliable, and predictable treatment, features that we believe will be a hallmark of the future gene therapy treatment of hemophilia A,” Dr. Conner said during the call.

Sangamo and Pfizer are enrolling additional patients in this trial, with the goal of expanding the 3e13 vg/kg cohort by up to five patients. The companies plan to present longer-term follow-up data at an upcoming scientific meeting.

The Alta trial is sponsored by Sangamo Therapeutics in collaboration with Pfizer.

[email protected]

Interim data suggest SB-525, an investigational gene therapy, may be safe and effective for patients with severe hemophilia A.

In the phase 1/2 Alta trial, SB-525 produced dose-dependent increases in factor VIII activity, with two of eight patients achieving normal factor VIII levels.

In addition, SB-525 was considered well tolerated. One patient did experience treatment-related serious adverse events – hypotension and fever – but these resolved within 24 hours.

Sangamo Therapeutics and Pfizer recently released these data in a press release and conference call.

The data include eight patients with severe hemophilia A who received SB-525 at 9e11 vg/kg, 2e12 vg/kg, 1e13 vg/kg, and 3e13 vg/kg.

Patient 1 (9e11 vg/kg), Patient 2 (9e11 vg/kg), and Patient 3 (2e12 vg/kg) did not experience clinically relevant increases in factor VIII levels and still require prophylactic recombinant factor VIII therapy.

Patient 4 (2e12 vg/kg) and Patient 5 (1e13 vg/kg) discontinued factor VIII therapy but have experienced spontaneous bleeds. Patient 4 had three bleeds in 48 weeks of follow-up, and Patient 5 had two bleeds in 40 weeks of follow-up.

Patient 6 (1e13 vg/kg), Patient 7 (3e13 vg/kg), and Patient 8 (3e13 vg/kg) have stopped factor VIII therapy and remain free of spontaneous bleeds at 28 weeks, 12 weeks, and 6 weeks of follow-up, respectively.

Patients 7 and 8 have achieved normal factor VIII levels. At 6 weeks, their factor VIII levels reached 140% and 94% of normal, respectively, according to a one-stage clotting assay, and 93% and 65%, respectively, according to a chromogenic assay.

“It appears the patients achieve their peak factor level at week 5 to 7 and maintain that level,” Edward Conner, MD, chief medical officer of Sangamo, said during the conference call.

The adverse events observed in this trial include grade 1 tachycardia (n = 1), grade 1 fatigue (n = 1), grade 1 alanine aminotransferase increase (n = 3), grade 1 myalgia (n = 1), grade 2 pyrexia (n = 2), and grade 3 hypotension (n = 1).

“These interim results indicate that SB-525 has the potential to comprise a well-tolerated, reliable, and predictable treatment, features that we believe will be a hallmark of the future gene therapy treatment of hemophilia A,” Dr. Conner said during the call.

Sangamo and Pfizer are enrolling additional patients in this trial, with the goal of expanding the 3e13 vg/kg cohort by up to five patients. The companies plan to present longer-term follow-up data at an upcoming scientific meeting.

The Alta trial is sponsored by Sangamo Therapeutics in collaboration with Pfizer.

[email protected]

NEW ORLEANS – A novel targeted ticagrelor reversal agent demonstrated rapid and sustained reversal of the potent antiplatelet agent in a phase 1 proof-of-concept study, Deepak L. Bhatt, MD, reported at the annual meeting of the American College of Cardiology.

“Hopefully the FDA will view this as something that really is a breakthrough,” commented Dr. Bhatt, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard University, both in Boston.

Why a breakthrough? Because despite recent major advances in the ability to reverse the action of the direct-acting oral anticoagulants and thereby greatly improve their safety margin, there have been no parallel developments with regard to the potent antiplatelet agents ticagrelor (Brilinta), prasugrel (Effient), and clopidogrel. The effects of these antiplatelet drugs take 3-5 days to dissipate after they’ve been stopped, which is highly problematic when they’ve induced catastrophic bleeding or a patient requires emergent or urgent surgery, the cardiologist explained.

“The ability to reverse tigracelor’s antiplatelet effects rapidly could distinguish it from other antiplatelet agents such as prasugrel or even generic clopidogrel and, for that matter, even aspirin,” Dr. Bhatt said.

The ticagrelor reversal agent, known for now as PB2452, is an intravenously administered recombinant human immunoglobulin G1 monoclonal antibody antigen-binding fragment. It binds specifically and with high affinity to ticagrelor and its active metabolite. In the phase 1, placebo-controlled, double-blind study conducted in 64 healthy volunteers pretreated with ticagrelor for 48 hours, it reversed oral ticagrelor’s antiplatelet effects within 5 minutes and, with prolonged infusion, showed sustained effect for at least 20 hours.

The only adverse events observed in blinded assessment were minor injection site issues.

PB2452 is specific to ticagrelor and will not reverse the activity of other potent antiplatelet agents. Indeed, because of their chemical structure, neither prasugrel nor clopidogrel is reversible, according to Dr. Bhatt.

[email protected]

NEW ORLEANS – A novel targeted ticagrelor reversal agent demonstrated rapid and sustained reversal of the potent antiplatelet agent in a phase 1 proof-of-concept study, Deepak L. Bhatt, MD, reported at the annual meeting of the American College of Cardiology.

“Hopefully the FDA will view this as something that really is a breakthrough,” commented Dr. Bhatt, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard University, both in Boston.

Why a breakthrough? Because despite recent major advances in the ability to reverse the action of the direct-acting oral anticoagulants and thereby greatly improve their safety margin, there have been no parallel developments with regard to the potent antiplatelet agents ticagrelor (Brilinta), prasugrel (Effient), and clopidogrel. The effects of these antiplatelet drugs take 3-5 days to dissipate after they’ve been stopped, which is highly problematic when they’ve induced catastrophic bleeding or a patient requires emergent or urgent surgery, the cardiologist explained.

“The ability to reverse tigracelor’s antiplatelet effects rapidly could distinguish it from other antiplatelet agents such as prasugrel or even generic clopidogrel and, for that matter, even aspirin,” Dr. Bhatt said.

The ticagrelor reversal agent, known for now as PB2452, is an intravenously administered recombinant human immunoglobulin G1 monoclonal antibody antigen-binding fragment. It binds specifically and with high affinity to ticagrelor and its active metabolite. In the phase 1, placebo-controlled, double-blind study conducted in 64 healthy volunteers pretreated with ticagrelor for 48 hours, it reversed oral ticagrelor’s antiplatelet effects within 5 minutes and, with prolonged infusion, showed sustained effect for at least 20 hours.

The only adverse events observed in blinded assessment were minor injection site issues.

PB2452 is specific to ticagrelor and will not reverse the activity of other potent antiplatelet agents. Indeed, because of their chemical structure, neither prasugrel nor clopidogrel is reversible, according to Dr. Bhatt.

[email protected]

NEW ORLEANS – A novel targeted ticagrelor reversal agent demonstrated rapid and sustained reversal of the potent antiplatelet agent in a phase 1 proof-of-concept study, Deepak L. Bhatt, MD, reported at the annual meeting of the American College of Cardiology.

“Hopefully the FDA will view this as something that really is a breakthrough,” commented Dr. Bhatt, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard University, both in Boston.

Why a breakthrough? Because despite recent major advances in the ability to reverse the action of the direct-acting oral anticoagulants and thereby greatly improve their safety margin, there have been no parallel developments with regard to the potent antiplatelet agents ticagrelor (Brilinta), prasugrel (Effient), and clopidogrel. The effects of these antiplatelet drugs take 3-5 days to dissipate after they’ve been stopped, which is highly problematic when they’ve induced catastrophic bleeding or a patient requires emergent or urgent surgery, the cardiologist explained.

“The ability to reverse tigracelor’s antiplatelet effects rapidly could distinguish it from other antiplatelet agents such as prasugrel or even generic clopidogrel and, for that matter, even aspirin,” Dr. Bhatt said.

The ticagrelor reversal agent, known for now as PB2452, is an intravenously administered recombinant human immunoglobulin G1 monoclonal antibody antigen-binding fragment. It binds specifically and with high affinity to ticagrelor and its active metabolite. In the phase 1, placebo-controlled, double-blind study conducted in 64 healthy volunteers pretreated with ticagrelor for 48 hours, it reversed oral ticagrelor’s antiplatelet effects within 5 minutes and, with prolonged infusion, showed sustained effect for at least 20 hours.

The only adverse events observed in blinded assessment were minor injection site issues.

PB2452 is specific to ticagrelor and will not reverse the activity of other potent antiplatelet agents. Indeed, because of their chemical structure, neither prasugrel nor clopidogrel is reversible, according to Dr. Bhatt.

[email protected]

A novel whole blood assay was unable to predict clinical severity in patients with type 1 von Willebrand disease (VWD).

The whole blood ristocetin-induced platelet agglutination (WB-RIPA) assay has shown potential for use as a diagnostic test for patients with type 1 VWD. However, the ability of the assay to predict clinical severity of the disease is unknown.

Yuto Nakajima, MD, of the Nara (Japan) Medical University and his colleagues studied the diagnostic and clinical capabilities of the assay in 55 patients with type 1 VWD and 20 healthy controls. The results of the study were published in Haemophilia.

The team examined relationships between WB-RIPA levels, VWF-associated measurements, and bleeding scores using whole blood samples. Bleeding severity was assessed using scores from a standardized assessment tool.

After analysis, the team found that assay values were significantly lower in patients with type 1 VWD versus healthy controls (P less than .0001), which validated the detection abilities of the test.

However, correlations between WB-RIPA levels and specific VWF-associated measurements were found to be weak. Similar results were reported with assay levels and bleeding scores. There were no significant differences seen in WB-RIPA between patients with a bleeding score of 4 or greater (abnormal bleeding tendency) and less than 4 (no abnormal bleeding tendency).

“Our study indicated that the WB-RIPA assay would not be useful for assessing and predicting the clinical severity in type 1 VWD,” they wrote.

The authors acknowledged that a key limitation was that the definition of type 1 VWD used in the study was not based on the most current classification.

The study was supported by grant funding from the Ministry of Education, Culture, Sports, Science and Technology (Japan). The authors reported having no conflicts of interest.

SOURCE: Nakajima Y et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13725.

A novel whole blood assay was unable to predict clinical severity in patients with type 1 von Willebrand disease (VWD).

The whole blood ristocetin-induced platelet agglutination (WB-RIPA) assay has shown potential for use as a diagnostic test for patients with type 1 VWD. However, the ability of the assay to predict clinical severity of the disease is unknown.

Yuto Nakajima, MD, of the Nara (Japan) Medical University and his colleagues studied the diagnostic and clinical capabilities of the assay in 55 patients with type 1 VWD and 20 healthy controls. The results of the study were published in Haemophilia.

The team examined relationships between WB-RIPA levels, VWF-associated measurements, and bleeding scores using whole blood samples. Bleeding severity was assessed using scores from a standardized assessment tool.

After analysis, the team found that assay values were significantly lower in patients with type 1 VWD versus healthy controls (P less than .0001), which validated the detection abilities of the test.

However, correlations between WB-RIPA levels and specific VWF-associated measurements were found to be weak. Similar results were reported with assay levels and bleeding scores. There were no significant differences seen in WB-RIPA between patients with a bleeding score of 4 or greater (abnormal bleeding tendency) and less than 4 (no abnormal bleeding tendency).

“Our study indicated that the WB-RIPA assay would not be useful for assessing and predicting the clinical severity in type 1 VWD,” they wrote.

The authors acknowledged that a key limitation was that the definition of type 1 VWD used in the study was not based on the most current classification.

The study was supported by grant funding from the Ministry of Education, Culture, Sports, Science and Technology (Japan). The authors reported having no conflicts of interest.

SOURCE: Nakajima Y et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13725.

A novel whole blood assay was unable to predict clinical severity in patients with type 1 von Willebrand disease (VWD).

The whole blood ristocetin-induced platelet agglutination (WB-RIPA) assay has shown potential for use as a diagnostic test for patients with type 1 VWD. However, the ability of the assay to predict clinical severity of the disease is unknown.

Yuto Nakajima, MD, of the Nara (Japan) Medical University and his colleagues studied the diagnostic and clinical capabilities of the assay in 55 patients with type 1 VWD and 20 healthy controls. The results of the study were published in Haemophilia.

The team examined relationships between WB-RIPA levels, VWF-associated measurements, and bleeding scores using whole blood samples. Bleeding severity was assessed using scores from a standardized assessment tool.

After analysis, the team found that assay values were significantly lower in patients with type 1 VWD versus healthy controls (P less than .0001), which validated the detection abilities of the test.

However, correlations between WB-RIPA levels and specific VWF-associated measurements were found to be weak. Similar results were reported with assay levels and bleeding scores. There were no significant differences seen in WB-RIPA between patients with a bleeding score of 4 or greater (abnormal bleeding tendency) and less than 4 (no abnormal bleeding tendency).

“Our study indicated that the WB-RIPA assay would not be useful for assessing and predicting the clinical severity in type 1 VWD,” they wrote.

The authors acknowledged that a key limitation was that the definition of type 1 VWD used in the study was not based on the most current classification.

The study was supported by grant funding from the Ministry of Education, Culture, Sports, Science and Technology (Japan). The authors reported having no conflicts of interest.

SOURCE: Nakajima Y et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13725.

Switching from the sucrose‐formulated recombinant factor VIII replacement therapy rFVIII‐FS (Kogenate) to the rFVIII product BAY 81‐8973 (Kovaltry) resulted in a longer half-life and improved bleeding rates in patients with hemophilia A, according to a recent report.

Juan Eduardo Megías‐Vericat, PharmD, of the Hospital Universitari i Politècnic La Fe, Valencia, Spain, and his colleagues conducted a comparative, cross‐sectional, pharmacokinetic analysis of switching from rFVIII‐FS to BAY 81‐8973 in patients with hemophilia A. The results of the analysis were reported in a letter to the editor published in Haemophilia.

“All the patients of this cohort were switched in a short period of time, while maintaining the same dose and frequency of infusions,” the researchers wrote.

The study included 14 patients who had moderate (n = 3) or severe (n = 11) hemophilia A and received pharmacokinetic-guided prophylaxis with rFVIII. The median weekly doses were 60.6 IU/kg and 61.6 IU/kg for rFVIII‐FS and BAY 81‐8973, respectively.

After analysis, the researchers found that the half-life of BAY 81‐8973 was significantly longer than rFVIII‐FS (median half-life, 16.9 hours vs. 15.4 hours; P = .001), with a median improvement of 3.0 hours (range, 1.5-4.0 hours). No significant differences were seen in any other pharmacokinetic factors.

With respect to bleeding, significant reductions were seen in annualized joint bleeding rate (P = .021), annualized bleeding rate (P = .038), and the number of spontaneous bleeds (P = .028) after the switch to BAY 81-8973.

The researchers acknowledged that the external validity of the study was a key limitation. As a result, Dr. Megías‐Vericat and his colleagues recommended that the findings be interpreted with discretion.

“The results of this study should be validated with an independent and larger cohort of patients, analyzing also the differences between adult and pediatric patients,” they concluded.

The study was partially funded by an unrestricted grant from Bayer. The authors reported having no conflicts of interest.

SOURCE: Megías-Vericat JE et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13733.

Switching from the sucrose‐formulated recombinant factor VIII replacement therapy rFVIII‐FS (Kogenate) to the rFVIII product BAY 81‐8973 (Kovaltry) resulted in a longer half-life and improved bleeding rates in patients with hemophilia A, according to a recent report.

Juan Eduardo Megías‐Vericat, PharmD, of the Hospital Universitari i Politècnic La Fe, Valencia, Spain, and his colleagues conducted a comparative, cross‐sectional, pharmacokinetic analysis of switching from rFVIII‐FS to BAY 81‐8973 in patients with hemophilia A. The results of the analysis were reported in a letter to the editor published in Haemophilia.

“All the patients of this cohort were switched in a short period of time, while maintaining the same dose and frequency of infusions,” the researchers wrote.

The study included 14 patients who had moderate (n = 3) or severe (n = 11) hemophilia A and received pharmacokinetic-guided prophylaxis with rFVIII. The median weekly doses were 60.6 IU/kg and 61.6 IU/kg for rFVIII‐FS and BAY 81‐8973, respectively.

After analysis, the researchers found that the half-life of BAY 81‐8973 was significantly longer than rFVIII‐FS (median half-life, 16.9 hours vs. 15.4 hours; P = .001), with a median improvement of 3.0 hours (range, 1.5-4.0 hours). No significant differences were seen in any other pharmacokinetic factors.

With respect to bleeding, significant reductions were seen in annualized joint bleeding rate (P = .021), annualized bleeding rate (P = .038), and the number of spontaneous bleeds (P = .028) after the switch to BAY 81-8973.

The researchers acknowledged that the external validity of the study was a key limitation. As a result, Dr. Megías‐Vericat and his colleagues recommended that the findings be interpreted with discretion.

“The results of this study should be validated with an independent and larger cohort of patients, analyzing also the differences between adult and pediatric patients,” they concluded.

The study was partially funded by an unrestricted grant from Bayer. The authors reported having no conflicts of interest.

SOURCE: Megías-Vericat JE et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13733.

Switching from the sucrose‐formulated recombinant factor VIII replacement therapy rFVIII‐FS (Kogenate) to the rFVIII product BAY 81‐8973 (Kovaltry) resulted in a longer half-life and improved bleeding rates in patients with hemophilia A, according to a recent report.

Juan Eduardo Megías‐Vericat, PharmD, of the Hospital Universitari i Politècnic La Fe, Valencia, Spain, and his colleagues conducted a comparative, cross‐sectional, pharmacokinetic analysis of switching from rFVIII‐FS to BAY 81‐8973 in patients with hemophilia A. The results of the analysis were reported in a letter to the editor published in Haemophilia.

“All the patients of this cohort were switched in a short period of time, while maintaining the same dose and frequency of infusions,” the researchers wrote.

The study included 14 patients who had moderate (n = 3) or severe (n = 11) hemophilia A and received pharmacokinetic-guided prophylaxis with rFVIII. The median weekly doses were 60.6 IU/kg and 61.6 IU/kg for rFVIII‐FS and BAY 81‐8973, respectively.

After analysis, the researchers found that the half-life of BAY 81‐8973 was significantly longer than rFVIII‐FS (median half-life, 16.9 hours vs. 15.4 hours; P = .001), with a median improvement of 3.0 hours (range, 1.5-4.0 hours). No significant differences were seen in any other pharmacokinetic factors.

With respect to bleeding, significant reductions were seen in annualized joint bleeding rate (P = .021), annualized bleeding rate (P = .038), and the number of spontaneous bleeds (P = .028) after the switch to BAY 81-8973.

The researchers acknowledged that the external validity of the study was a key limitation. As a result, Dr. Megías‐Vericat and his colleagues recommended that the findings be interpreted with discretion.

“The results of this study should be validated with an independent and larger cohort of patients, analyzing also the differences between adult and pediatric patients,” they concluded.

The study was partially funded by an unrestricted grant from Bayer. The authors reported having no conflicts of interest.

SOURCE: Megías-Vericat JE et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13733.

The recombinant factor IX (FIX) product rIX‐FP (albutrepenonacog alfa) can maintain high steady‐state FIX trough levels in both adult and pediatric patients with severe hemophilia B, according to a pharmacokinetic study.

“rIX‐FP is a fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin and has an extended half‐life compared with standard products, allowing a prolonged dosing interval,” wrote Joan C. Gill, MD, of the Medical College of Wisconsin, Milwaukee, along with her colleagues. The findings of the study were published in Haemophilia.

Safety and efficacy of rIX-FP was previously demonstrated for both adults/adolescents and children in two phase 3 trials. In the current analysis, the researchers evaluated mean steady state and observed trough FIX:C levels during prophylaxis with rIX-FP in the two previous trials and assessed the impact on hemophilia B patients.

The researchers studied 90 patients with severe hemophilia B, which included both adult/adolescent (n = 63) and pediatric (n = 27) patients. The adult/adolescent group was administered 35‐50 IU/kg or 50‐75 IU/kg of rIX‐FP every 7 and 10 or 14 days, respectively, while pediatric participants (younger than 12 years old) were given 35‐50 IU/kg of rIX‐FP every 7 days. Only the 7‐ and 14‐day dosing intervals were included in the analysis.

After analysis, the researchers reported that steady‐state FIX trough levels were higher than 5% across all doses in 96.2% and 97.9% of adult/adolescent and pediatric patients, respectively.

Among adults/adolescents, including all dose levels, the mean FIX:C trough levels were 22.26% for 7-day regimens and 12.48% for 14-day regimens. Among children in the study, the mean steady-state FIX:C trough level was 12.80%.

The team reported that these results, which are consistent with low median annualized bleeding rates observed, indicate that sustaining high FIX trough levels may successfully change a case of severe disease into a mild bleeding phenotype.

The authors acknowledged a key limitation of the study was the unknown effects of rIX‐FP remaining within the extravascular space. Further biodistribution studies are required to fully understand these effects.

“Patients may find that an extended dosing regimen would still provide protection from bleeds but be easier to maintain,” they concluded.

The study was funded by CSL Behring. The authors reported financial disclosures related to Bayer, CSL Behring, Kedrion Biopharma, Novo Nordisk, Pfizer, and others.

SOURCE: Gill JC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13735.

The recombinant factor IX (FIX) product rIX‐FP (albutrepenonacog alfa) can maintain high steady‐state FIX trough levels in both adult and pediatric patients with severe hemophilia B, according to a pharmacokinetic study.

“rIX‐FP is a fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin and has an extended half‐life compared with standard products, allowing a prolonged dosing interval,” wrote Joan C. Gill, MD, of the Medical College of Wisconsin, Milwaukee, along with her colleagues. The findings of the study were published in Haemophilia.

Safety and efficacy of rIX-FP was previously demonstrated for both adults/adolescents and children in two phase 3 trials. In the current analysis, the researchers evaluated mean steady state and observed trough FIX:C levels during prophylaxis with rIX-FP in the two previous trials and assessed the impact on hemophilia B patients.

The researchers studied 90 patients with severe hemophilia B, which included both adult/adolescent (n = 63) and pediatric (n = 27) patients. The adult/adolescent group was administered 35‐50 IU/kg or 50‐75 IU/kg of rIX‐FP every 7 and 10 or 14 days, respectively, while pediatric participants (younger than 12 years old) were given 35‐50 IU/kg of rIX‐FP every 7 days. Only the 7‐ and 14‐day dosing intervals were included in the analysis.

After analysis, the researchers reported that steady‐state FIX trough levels were higher than 5% across all doses in 96.2% and 97.9% of adult/adolescent and pediatric patients, respectively.

Among adults/adolescents, including all dose levels, the mean FIX:C trough levels were 22.26% for 7-day regimens and 12.48% for 14-day regimens. Among children in the study, the mean steady-state FIX:C trough level was 12.80%.

The team reported that these results, which are consistent with low median annualized bleeding rates observed, indicate that sustaining high FIX trough levels may successfully change a case of severe disease into a mild bleeding phenotype.

The authors acknowledged a key limitation of the study was the unknown effects of rIX‐FP remaining within the extravascular space. Further biodistribution studies are required to fully understand these effects.

“Patients may find that an extended dosing regimen would still provide protection from bleeds but be easier to maintain,” they concluded.

The study was funded by CSL Behring. The authors reported financial disclosures related to Bayer, CSL Behring, Kedrion Biopharma, Novo Nordisk, Pfizer, and others.

SOURCE: Gill JC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13735.

The recombinant factor IX (FIX) product rIX‐FP (albutrepenonacog alfa) can maintain high steady‐state FIX trough levels in both adult and pediatric patients with severe hemophilia B, according to a pharmacokinetic study.

“rIX‐FP is a fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin and has an extended half‐life compared with standard products, allowing a prolonged dosing interval,” wrote Joan C. Gill, MD, of the Medical College of Wisconsin, Milwaukee, along with her colleagues. The findings of the study were published in Haemophilia.

Safety and efficacy of rIX-FP was previously demonstrated for both adults/adolescents and children in two phase 3 trials. In the current analysis, the researchers evaluated mean steady state and observed trough FIX:C levels during prophylaxis with rIX-FP in the two previous trials and assessed the impact on hemophilia B patients.

The researchers studied 90 patients with severe hemophilia B, which included both adult/adolescent (n = 63) and pediatric (n = 27) patients. The adult/adolescent group was administered 35‐50 IU/kg or 50‐75 IU/kg of rIX‐FP every 7 and 10 or 14 days, respectively, while pediatric participants (younger than 12 years old) were given 35‐50 IU/kg of rIX‐FP every 7 days. Only the 7‐ and 14‐day dosing intervals were included in the analysis.

After analysis, the researchers reported that steady‐state FIX trough levels were higher than 5% across all doses in 96.2% and 97.9% of adult/adolescent and pediatric patients, respectively.

Among adults/adolescents, including all dose levels, the mean FIX:C trough levels were 22.26% for 7-day regimens and 12.48% for 14-day regimens. Among children in the study, the mean steady-state FIX:C trough level was 12.80%.

The team reported that these results, which are consistent with low median annualized bleeding rates observed, indicate that sustaining high FIX trough levels may successfully change a case of severe disease into a mild bleeding phenotype.

The authors acknowledged a key limitation of the study was the unknown effects of rIX‐FP remaining within the extravascular space. Further biodistribution studies are required to fully understand these effects.

“Patients may find that an extended dosing regimen would still provide protection from bleeds but be easier to maintain,” they concluded.

The study was funded by CSL Behring. The authors reported financial disclosures related to Bayer, CSL Behring, Kedrion Biopharma, Novo Nordisk, Pfizer, and others.

SOURCE: Gill JC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13735.

The PROBE (Patient Reported Outcomes Burdens and Experience) questionnaire was found to be a valid instrument to evaluate health status in patients with hemophilia in an cross‐cultural context, according to an international study.

PeopleImages/gettyimages

“This study [aimed] to investigate the variation in the PROBE questionnaire–driven measurements across four broad geographical regions,” wrote Chatree Chai‐Adisaksopha, MD, of McMaster University in Hamilton, Ontario, and his colleagues. The results of the study were published in Haemophilia.

The researchers analyzed data from 862 study participants who resided in various geographical regions, including North America, South America, Europe, and the Western Pacific. The majority of participants were male and had greater than 12 years of education.

The team assessed common characteristics of participants through collection of demographic data, including age, gender, years of education, among others. With respect to hemophilia, they evaluated patient‐reported outcome measures across these four regions.

“Outcome measurement in haemophilia has been developed to capture clinically relevant outcomes like bleeding rates, pharmacokinetics, joint pain, joint function scores, radiologic changes and mortality rates,” the researchers wrote.

After analysis, Dr. Chai‐Adisaksopha and his colleagues found that the PROBE questionnaire showed low variability when used on a multinational, cross‐cultural level. In particular, limited variation was found with respect to years of education and geographical region in all subcategories, with the exception of mobility score. In contrast, diagnosis and age had the highest levels of variation.

Region contributed 0.26% of variance in the PROBE score. Similarly, education level contributed 0.34% of the variance. However, age contributed 3.42% and diagnosis contributed 22.42% of the variance in the PROBE score.

The authors acknowledged a key limitation of the study was the inability to include all geographical regions, largely due to an inadequate number of participants in certain areas, such as Africa.

“Despite being used in disparate groups of patients, in 14 countries, in four regions and in 20 languages, the tool produced comparable results, suggesting it can be reliably used across these groups,” the researchers wrote.

The study was funded by Baxalta, Bayer, Bioverativ, CSL Behring, Novo Nordisk, Roche, and Sobi, with additional support from the U.S. National Hemophilia Foundation. Co-author Mark W. Skinner is the principal investigator and no other investigators reported relevant conflicts of interest.

SOURCE: Chai-Adisaksopha C et al. Haemophilia. 2019 Mar 12. doi: 10.1111/hae.13703 .

The PROBE (Patient Reported Outcomes Burdens and Experience) questionnaire was found to be a valid instrument to evaluate health status in patients with hemophilia in an cross‐cultural context, according to an international study.

PeopleImages/gettyimages

“This study [aimed] to investigate the variation in the PROBE questionnaire–driven measurements across four broad geographical regions,” wrote Chatree Chai‐Adisaksopha, MD, of McMaster University in Hamilton, Ontario, and his colleagues. The results of the study were published in Haemophilia.

The researchers analyzed data from 862 study participants who resided in various geographical regions, including North America, South America, Europe, and the Western Pacific. The majority of participants were male and had greater than 12 years of education.

The team assessed common characteristics of participants through collection of demographic data, including age, gender, years of education, among others. With respect to hemophilia, they evaluated patient‐reported outcome measures across these four regions.

“Outcome measurement in haemophilia has been developed to capture clinically relevant outcomes like bleeding rates, pharmacokinetics, joint pain, joint function scores, radiologic changes and mortality rates,” the researchers wrote.

After analysis, Dr. Chai‐Adisaksopha and his colleagues found that the PROBE questionnaire showed low variability when used on a multinational, cross‐cultural level. In particular, limited variation was found with respect to years of education and geographical region in all subcategories, with the exception of mobility score. In contrast, diagnosis and age had the highest levels of variation.

Region contributed 0.26% of variance in the PROBE score. Similarly, education level contributed 0.34% of the variance. However, age contributed 3.42% and diagnosis contributed 22.42% of the variance in the PROBE score.

The authors acknowledged a key limitation of the study was the inability to include all geographical regions, largely due to an inadequate number of participants in certain areas, such as Africa.

“Despite being used in disparate groups of patients, in 14 countries, in four regions and in 20 languages, the tool produced comparable results, suggesting it can be reliably used across these groups,” the researchers wrote.

The study was funded by Baxalta, Bayer, Bioverativ, CSL Behring, Novo Nordisk, Roche, and Sobi, with additional support from the U.S. National Hemophilia Foundation. Co-author Mark W. Skinner is the principal investigator and no other investigators reported relevant conflicts of interest.

SOURCE: Chai-Adisaksopha C et al. Haemophilia. 2019 Mar 12. doi: 10.1111/hae.13703 .

The PROBE (Patient Reported Outcomes Burdens and Experience) questionnaire was found to be a valid instrument to evaluate health status in patients with hemophilia in an cross‐cultural context, according to an international study.

PeopleImages/gettyimages

“This study [aimed] to investigate the variation in the PROBE questionnaire–driven measurements across four broad geographical regions,” wrote Chatree Chai‐Adisaksopha, MD, of McMaster University in Hamilton, Ontario, and his colleagues. The results of the study were published in Haemophilia.

The researchers analyzed data from 862 study participants who resided in various geographical regions, including North America, South America, Europe, and the Western Pacific. The majority of participants were male and had greater than 12 years of education.

The team assessed common characteristics of participants through collection of demographic data, including age, gender, years of education, among others. With respect to hemophilia, they evaluated patient‐reported outcome measures across these four regions.

“Outcome measurement in haemophilia has been developed to capture clinically relevant outcomes like bleeding rates, pharmacokinetics, joint pain, joint function scores, radiologic changes and mortality rates,” the researchers wrote.

After analysis, Dr. Chai‐Adisaksopha and his colleagues found that the PROBE questionnaire showed low variability when used on a multinational, cross‐cultural level. In particular, limited variation was found with respect to years of education and geographical region in all subcategories, with the exception of mobility score. In contrast, diagnosis and age had the highest levels of variation.

Region contributed 0.26% of variance in the PROBE score. Similarly, education level contributed 0.34% of the variance. However, age contributed 3.42% and diagnosis contributed 22.42% of the variance in the PROBE score.

The authors acknowledged a key limitation of the study was the inability to include all geographical regions, largely due to an inadequate number of participants in certain areas, such as Africa.

“Despite being used in disparate groups of patients, in 14 countries, in four regions and in 20 languages, the tool produced comparable results, suggesting it can be reliably used across these groups,” the researchers wrote.

The study was funded by Baxalta, Bayer, Bioverativ, CSL Behring, Novo Nordisk, Roche, and Sobi, with additional support from the U.S. National Hemophilia Foundation. Co-author Mark W. Skinner is the principal investigator and no other investigators reported relevant conflicts of interest.

SOURCE: Chai-Adisaksopha C et al. Haemophilia. 2019 Mar 12. doi: 10.1111/hae.13703 .

The use of concurrent anticoagulation and emicizumab prophylaxis eliminated the need for bypassing therapy and improved a life-threatening central venous access device (CVAD)–associated thrombus in a patient with severe hemophilia A.

“Systemic anticoagulation with concomitant emicizumab has not been previously described,” Angela Weyand, MD, of the University of Michigan, Ann Arbor, and her colleagues wrote in a letter to the editor published in Haemophilia.

The researchers reported findings from a case of a 6-year-old boy with severe hemophilia A who developed a CVAD‐associated thrombus during immune tolerance induction with recombinant factor VIII (rFVIII). As his clinical condition worsened, the team hypothesized thrombus development was being caused by the ongoing use of bypassing therapy.

Dr. Weyand and her colleagues started prophylaxis with subcutaneous emicizumab (3 mg/kg once weekly for 4 weeks followed by 1.5 mg/kg weekly thereafter) and anticoagulation therapy (low-molecular-weight heparin given twice daily; anti‐Xa target of 0.3‐0.5 IU/ mL, later increased to 0.5‐0.7 IU/mL).

After 2 months of concurrent therapy, the team saw major symptomatic improvement and the thrombus had substantially decreased in size. One month later, his port access was removed without any bleeding complications and no further hemostatic agents were required.

“Follow‐up echocardiogram 3 months after discontinuation of anticoagulation demonstrated continued improvement with increasing organization of the thrombus,” they wrote.

Afterward, the patient was continued on emicizumab prophylaxis and did not require additional bypassing agent therapy.

“Consideration was given to surgical thrombectomy as that would be the recommendation in a non-haemophilic patient, but ultimately anticoagulation was deemed to be a safer alternative,” they wrote.

The researchers acknowledged that very little evidence is available to guide treatment of patients similar to the one described in this case. “Although this particular scenario is rare, its real‐life efficacy data in these types of settings will help inform emicizumab use, which is critical given its expanding indications,” they concluded.

No funding sources were reported. The authors reported financial disclosures related to Bayer, CSL Behring, Novo Nordisk, Octapharma, Shire, and others.

SOURCE: Weyand AC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13721.

The use of concurrent anticoagulation and emicizumab prophylaxis eliminated the need for bypassing therapy and improved a life-threatening central venous access device (CVAD)–associated thrombus in a patient with severe hemophilia A.

“Systemic anticoagulation with concomitant emicizumab has not been previously described,” Angela Weyand, MD, of the University of Michigan, Ann Arbor, and her colleagues wrote in a letter to the editor published in Haemophilia.

The researchers reported findings from a case of a 6-year-old boy with severe hemophilia A who developed a CVAD‐associated thrombus during immune tolerance induction with recombinant factor VIII (rFVIII). As his clinical condition worsened, the team hypothesized thrombus development was being caused by the ongoing use of bypassing therapy.

Dr. Weyand and her colleagues started prophylaxis with subcutaneous emicizumab (3 mg/kg once weekly for 4 weeks followed by 1.5 mg/kg weekly thereafter) and anticoagulation therapy (low-molecular-weight heparin given twice daily; anti‐Xa target of 0.3‐0.5 IU/ mL, later increased to 0.5‐0.7 IU/mL).

After 2 months of concurrent therapy, the team saw major symptomatic improvement and the thrombus had substantially decreased in size. One month later, his port access was removed without any bleeding complications and no further hemostatic agents were required.

“Follow‐up echocardiogram 3 months after discontinuation of anticoagulation demonstrated continued improvement with increasing organization of the thrombus,” they wrote.

Afterward, the patient was continued on emicizumab prophylaxis and did not require additional bypassing agent therapy.

“Consideration was given to surgical thrombectomy as that would be the recommendation in a non-haemophilic patient, but ultimately anticoagulation was deemed to be a safer alternative,” they wrote.

The researchers acknowledged that very little evidence is available to guide treatment of patients similar to the one described in this case. “Although this particular scenario is rare, its real‐life efficacy data in these types of settings will help inform emicizumab use, which is critical given its expanding indications,” they concluded.

No funding sources were reported. The authors reported financial disclosures related to Bayer, CSL Behring, Novo Nordisk, Octapharma, Shire, and others.

SOURCE: Weyand AC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13721.

The use of concurrent anticoagulation and emicizumab prophylaxis eliminated the need for bypassing therapy and improved a life-threatening central venous access device (CVAD)–associated thrombus in a patient with severe hemophilia A.

“Systemic anticoagulation with concomitant emicizumab has not been previously described,” Angela Weyand, MD, of the University of Michigan, Ann Arbor, and her colleagues wrote in a letter to the editor published in Haemophilia.

The researchers reported findings from a case of a 6-year-old boy with severe hemophilia A who developed a CVAD‐associated thrombus during immune tolerance induction with recombinant factor VIII (rFVIII). As his clinical condition worsened, the team hypothesized thrombus development was being caused by the ongoing use of bypassing therapy.

Dr. Weyand and her colleagues started prophylaxis with subcutaneous emicizumab (3 mg/kg once weekly for 4 weeks followed by 1.5 mg/kg weekly thereafter) and anticoagulation therapy (low-molecular-weight heparin given twice daily; anti‐Xa target of 0.3‐0.5 IU/ mL, later increased to 0.5‐0.7 IU/mL).

After 2 months of concurrent therapy, the team saw major symptomatic improvement and the thrombus had substantially decreased in size. One month later, his port access was removed without any bleeding complications and no further hemostatic agents were required.

“Follow‐up echocardiogram 3 months after discontinuation of anticoagulation demonstrated continued improvement with increasing organization of the thrombus,” they wrote.

Afterward, the patient was continued on emicizumab prophylaxis and did not require additional bypassing agent therapy.

“Consideration was given to surgical thrombectomy as that would be the recommendation in a non-haemophilic patient, but ultimately anticoagulation was deemed to be a safer alternative,” they wrote.

The researchers acknowledged that very little evidence is available to guide treatment of patients similar to the one described in this case. “Although this particular scenario is rare, its real‐life efficacy data in these types of settings will help inform emicizumab use, which is critical given its expanding indications,” they concluded.

No funding sources were reported. The authors reported financial disclosures related to Bayer, CSL Behring, Novo Nordisk, Octapharma, Shire, and others.

SOURCE: Weyand AC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13721.