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Peanut contamination risk prompts Promacta recall
Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.
Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.
Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.
More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.
Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.
Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.
Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.
More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.
Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.
Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.
Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.
More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.
QOL concerns prompt second-line therapy in children with ITP
NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.
Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).
The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).
At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.
QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).
The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).
Reasons for starting second-line treatment varied depending on patients’ phase of disease.
Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).
Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).
Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 109/L and 78% of patients with platelet counts of 20 x 109/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).
On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.
This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.
“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”
Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.
NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.
Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).
The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).
At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.
QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).
The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).
Reasons for starting second-line treatment varied depending on patients’ phase of disease.
Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).
Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).
Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 109/L and 78% of patients with platelet counts of 20 x 109/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).
On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.
This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.
“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”
Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.
NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.
Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).
The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).
At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.
QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).
The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).
Reasons for starting second-line treatment varied depending on patients’ phase of disease.
Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).
Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).
Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 109/L and 78% of patients with platelet counts of 20 x 109/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).
On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.
This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.
“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”
Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.
REPORTING FROM THE 2019 ASPHO CONFERENCE
Key clinical point: Quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Major finding: Quality of life was chosen as a reason to treat in 73% of patients, it was among the top three reasons in 57% of patients, and it was the most important reason in 27%.
Study details: A survey of hematologists treating 120 children in an observational study.
Disclosures: The speaker reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
Source: Shimano KA et al. ASPHO 2019, Abstract 2012.
Study finds lower quality of life for patients with hemophilia A
Real‐world data suggests that patients with hemophilia A with inhibitors had lower health-related quality of life (HRQOL) while receiving standard therapy, according to an international study.
“The objective of this analysis was to characterize disease‐specific HRQOL, overall health status and the effect of bleeding on health status,” wrote Johnny Mahlangu, MD, of the University of the Witwatersrand in Johannesburg, South Africa, and colleagues. The study was published in Haemophilia.
The researchers conducted a prospective, noninterventional study of 103 patients aged 12 years and older with hemophilia A who resided in several different countries, including Australia, Japan, South Africa, and the United States, among others.
The majority of participants (n = 75) received episodic treatment at study enrollment, while others (n = 28) received prophylactic-based therapy. Patients were treated with standard therapy, based on local institutional practice.
HRQOL outcome data were collected in adult and adolescent participants using the Haemophilia Quality of Life Questionnaire for Adults and the Haemophilia‐specific Quality of Life Questionnaire for Children Short Form. Other validated instruments were used to measure additional health‐related outcomes.
After analysis, the researchers found that HRQOL scores revealed impaired quality of life in adult and adolescent participants treated with both episodic and prophylactic regimens. The mean scores in the majority of HRQOL domains showed impairments occurring on average “sometimes” to “often,” the researchers reported.
Adults had highest scores, correlated with greatest impairments, in sports and leisure. Similarly, adolescents reported greatest impairment in the sports and school domain.
“These health‐related outcomes may result from a combination of poor bleed control and treatment burden,” the researchers wrote. “Compliance with prophylactic treatment was low, likely reflecting the high burden associated with standard therapies.”
The researchers acknowledged a key limitation of the study was participant dropout. As a result, some time-related data may be incomplete.
“These [data] demonstrate that patients with hemophilia A with inhibitors have impaired HRQOL, despite standard treatment, and that more effective treatment options are needed,” the researchers concluded.
The study was funded by F. Hoffmann-La Roche. The authors reported financial affiliations with Baxalta, Bayer, CSL Behring, Kaketsuken, Novo Nordisk, Pfizer, and several others.
SOURCE: Mahlangu J et al. Haemophilia. 2019 Apr 24. doi: 10.1111/hae.13731.
Real‐world data suggests that patients with hemophilia A with inhibitors had lower health-related quality of life (HRQOL) while receiving standard therapy, according to an international study.
“The objective of this analysis was to characterize disease‐specific HRQOL, overall health status and the effect of bleeding on health status,” wrote Johnny Mahlangu, MD, of the University of the Witwatersrand in Johannesburg, South Africa, and colleagues. The study was published in Haemophilia.
The researchers conducted a prospective, noninterventional study of 103 patients aged 12 years and older with hemophilia A who resided in several different countries, including Australia, Japan, South Africa, and the United States, among others.
The majority of participants (n = 75) received episodic treatment at study enrollment, while others (n = 28) received prophylactic-based therapy. Patients were treated with standard therapy, based on local institutional practice.
HRQOL outcome data were collected in adult and adolescent participants using the Haemophilia Quality of Life Questionnaire for Adults and the Haemophilia‐specific Quality of Life Questionnaire for Children Short Form. Other validated instruments were used to measure additional health‐related outcomes.
After analysis, the researchers found that HRQOL scores revealed impaired quality of life in adult and adolescent participants treated with both episodic and prophylactic regimens. The mean scores in the majority of HRQOL domains showed impairments occurring on average “sometimes” to “often,” the researchers reported.
Adults had highest scores, correlated with greatest impairments, in sports and leisure. Similarly, adolescents reported greatest impairment in the sports and school domain.
“These health‐related outcomes may result from a combination of poor bleed control and treatment burden,” the researchers wrote. “Compliance with prophylactic treatment was low, likely reflecting the high burden associated with standard therapies.”
The researchers acknowledged a key limitation of the study was participant dropout. As a result, some time-related data may be incomplete.
“These [data] demonstrate that patients with hemophilia A with inhibitors have impaired HRQOL, despite standard treatment, and that more effective treatment options are needed,” the researchers concluded.
The study was funded by F. Hoffmann-La Roche. The authors reported financial affiliations with Baxalta, Bayer, CSL Behring, Kaketsuken, Novo Nordisk, Pfizer, and several others.
SOURCE: Mahlangu J et al. Haemophilia. 2019 Apr 24. doi: 10.1111/hae.13731.
Real‐world data suggests that patients with hemophilia A with inhibitors had lower health-related quality of life (HRQOL) while receiving standard therapy, according to an international study.
“The objective of this analysis was to characterize disease‐specific HRQOL, overall health status and the effect of bleeding on health status,” wrote Johnny Mahlangu, MD, of the University of the Witwatersrand in Johannesburg, South Africa, and colleagues. The study was published in Haemophilia.
The researchers conducted a prospective, noninterventional study of 103 patients aged 12 years and older with hemophilia A who resided in several different countries, including Australia, Japan, South Africa, and the United States, among others.
The majority of participants (n = 75) received episodic treatment at study enrollment, while others (n = 28) received prophylactic-based therapy. Patients were treated with standard therapy, based on local institutional practice.
HRQOL outcome data were collected in adult and adolescent participants using the Haemophilia Quality of Life Questionnaire for Adults and the Haemophilia‐specific Quality of Life Questionnaire for Children Short Form. Other validated instruments were used to measure additional health‐related outcomes.
After analysis, the researchers found that HRQOL scores revealed impaired quality of life in adult and adolescent participants treated with both episodic and prophylactic regimens. The mean scores in the majority of HRQOL domains showed impairments occurring on average “sometimes” to “often,” the researchers reported.
Adults had highest scores, correlated with greatest impairments, in sports and leisure. Similarly, adolescents reported greatest impairment in the sports and school domain.
“These health‐related outcomes may result from a combination of poor bleed control and treatment burden,” the researchers wrote. “Compliance with prophylactic treatment was low, likely reflecting the high burden associated with standard therapies.”
The researchers acknowledged a key limitation of the study was participant dropout. As a result, some time-related data may be incomplete.
“These [data] demonstrate that patients with hemophilia A with inhibitors have impaired HRQOL, despite standard treatment, and that more effective treatment options are needed,” the researchers concluded.
The study was funded by F. Hoffmann-La Roche. The authors reported financial affiliations with Baxalta, Bayer, CSL Behring, Kaketsuken, Novo Nordisk, Pfizer, and several others.
SOURCE: Mahlangu J et al. Haemophilia. 2019 Apr 24. doi: 10.1111/hae.13731.
FROM HAEMOPHILIA
New recommendations on immune tolerance induction in hemophilia A
New treatment recommendations, released by a panel of nine experts, offer consensus advice on the use of immune tolerance induction (ITI) therapy in patients with hemophilia A with inhibitors.
The recommendations from the Future of Immunotolerance Treatment (FIT) group were authored by a nine-member committee with expertise in the treatment of hemophilia. The authors attended three meetings from 2017-2018 to form a consensus on the use of nonfactor therapies with current inhibitor management strategies.
“The treatment of hemophilia A has evolved and a number of molecules that potentially can be used in the setting of patients with inhibitors have been developed, or are in various phases of development,” wrote Manuel Carcao, MD, of the University of Toronto and colleagues. The report is published in Haemophilia.
The current body of literature is lacking high-quality evidence on the concomitant use of nonfactor treatments, such as emicizumab, and current inhibitor therapies. The recommendations included the panel’s consensus opinions on treatment of inhibitors, with and without the use of nonreplacement therapies. The concurrent use of factor VIII replacement therapy and emicizumab could inhibit bleeding with lower dose immunotolerance strategies, according to the recommendations.
The group hypothesized that increased uptake of lower dose and lower frequency factor VIII ITI treatment strategies could reduce the likelihood of requiring central venous access while retaining a high probability of treatment success.
“In our new algorithm, we have indicated that one option might be to start patients on low-dose ITI with emicizumab regardless of their historical peak inhibitor titre. Patients could then escalate their ITI regimen should their response to low-dose ITI be deemed insufficient,” they wrote.
The experts provided a novel treatment algorithm for immune tolerance induction without emicizumab in addition to a new theoretical strategy with emicizumab.
Other recommendations included that patients with inhibitors should be offered at least one attempt at ITI and that monthly monitoring should be done and ITI dose and frequency should be adjusted based on changes in bleeding phenotype and inhibitor titer.
The authors acknowledged a current limitation is the lack of published evidence pertaining to the concurrent use of emicizumab and factor VIII replacement therapy.
“The FIT group sees the need for properly conducted prospective studies to evaluate the impact of adding emicizumab, and in the future, other nonfactor therapies, into the management of patients with inhibitors,” the experts wrote.
The manuscript was supported by Grifols. The authors reported financial disclosures related to Grifols and other companies.
SOURCE: Carcao M et al. Haemophilia. 2019 Apr 29. doi: 10.1111/hae.13762.
New treatment recommendations, released by a panel of nine experts, offer consensus advice on the use of immune tolerance induction (ITI) therapy in patients with hemophilia A with inhibitors.
The recommendations from the Future of Immunotolerance Treatment (FIT) group were authored by a nine-member committee with expertise in the treatment of hemophilia. The authors attended three meetings from 2017-2018 to form a consensus on the use of nonfactor therapies with current inhibitor management strategies.
“The treatment of hemophilia A has evolved and a number of molecules that potentially can be used in the setting of patients with inhibitors have been developed, or are in various phases of development,” wrote Manuel Carcao, MD, of the University of Toronto and colleagues. The report is published in Haemophilia.
The current body of literature is lacking high-quality evidence on the concomitant use of nonfactor treatments, such as emicizumab, and current inhibitor therapies. The recommendations included the panel’s consensus opinions on treatment of inhibitors, with and without the use of nonreplacement therapies. The concurrent use of factor VIII replacement therapy and emicizumab could inhibit bleeding with lower dose immunotolerance strategies, according to the recommendations.
The group hypothesized that increased uptake of lower dose and lower frequency factor VIII ITI treatment strategies could reduce the likelihood of requiring central venous access while retaining a high probability of treatment success.
“In our new algorithm, we have indicated that one option might be to start patients on low-dose ITI with emicizumab regardless of their historical peak inhibitor titre. Patients could then escalate their ITI regimen should their response to low-dose ITI be deemed insufficient,” they wrote.
The experts provided a novel treatment algorithm for immune tolerance induction without emicizumab in addition to a new theoretical strategy with emicizumab.
Other recommendations included that patients with inhibitors should be offered at least one attempt at ITI and that monthly monitoring should be done and ITI dose and frequency should be adjusted based on changes in bleeding phenotype and inhibitor titer.
The authors acknowledged a current limitation is the lack of published evidence pertaining to the concurrent use of emicizumab and factor VIII replacement therapy.
“The FIT group sees the need for properly conducted prospective studies to evaluate the impact of adding emicizumab, and in the future, other nonfactor therapies, into the management of patients with inhibitors,” the experts wrote.
The manuscript was supported by Grifols. The authors reported financial disclosures related to Grifols and other companies.
SOURCE: Carcao M et al. Haemophilia. 2019 Apr 29. doi: 10.1111/hae.13762.
New treatment recommendations, released by a panel of nine experts, offer consensus advice on the use of immune tolerance induction (ITI) therapy in patients with hemophilia A with inhibitors.
The recommendations from the Future of Immunotolerance Treatment (FIT) group were authored by a nine-member committee with expertise in the treatment of hemophilia. The authors attended three meetings from 2017-2018 to form a consensus on the use of nonfactor therapies with current inhibitor management strategies.
“The treatment of hemophilia A has evolved and a number of molecules that potentially can be used in the setting of patients with inhibitors have been developed, or are in various phases of development,” wrote Manuel Carcao, MD, of the University of Toronto and colleagues. The report is published in Haemophilia.
The current body of literature is lacking high-quality evidence on the concomitant use of nonfactor treatments, such as emicizumab, and current inhibitor therapies. The recommendations included the panel’s consensus opinions on treatment of inhibitors, with and without the use of nonreplacement therapies. The concurrent use of factor VIII replacement therapy and emicizumab could inhibit bleeding with lower dose immunotolerance strategies, according to the recommendations.
The group hypothesized that increased uptake of lower dose and lower frequency factor VIII ITI treatment strategies could reduce the likelihood of requiring central venous access while retaining a high probability of treatment success.
“In our new algorithm, we have indicated that one option might be to start patients on low-dose ITI with emicizumab regardless of their historical peak inhibitor titre. Patients could then escalate their ITI regimen should their response to low-dose ITI be deemed insufficient,” they wrote.
The experts provided a novel treatment algorithm for immune tolerance induction without emicizumab in addition to a new theoretical strategy with emicizumab.
Other recommendations included that patients with inhibitors should be offered at least one attempt at ITI and that monthly monitoring should be done and ITI dose and frequency should be adjusted based on changes in bleeding phenotype and inhibitor titer.
The authors acknowledged a current limitation is the lack of published evidence pertaining to the concurrent use of emicizumab and factor VIII replacement therapy.
“The FIT group sees the need for properly conducted prospective studies to evaluate the impact of adding emicizumab, and in the future, other nonfactor therapies, into the management of patients with inhibitors,” the experts wrote.
The manuscript was supported by Grifols. The authors reported financial disclosures related to Grifols and other companies.
SOURCE: Carcao M et al. Haemophilia. 2019 Apr 29. doi: 10.1111/hae.13762.
FROM HAEMOPHILIA
Study identifies GI bleed risk factors in von Willebrand disease
Researchers have identified several risk factors associated with gastrointestinal (GI) bleeding in adult patients with von Willebrand disease (VWD), based on findings from a retrospective analysis.
“[We] evaluated prevalence and risk factors of GIB among individuals with and without VWD, using a large national database,” wrote Anastasia Tsagianni, MD, of the University of Pittsburgh, and colleagues. The findings were published in Thrombosis Research.
The researchers retrospectively reviewed discharge data from the National Inpatient Sample database. The team analyzed correlates of GI bleeding among patients with VWD and estimated prevalence rates using measures in the database. Risk factors for GI bleeding in VWD were correlated via multivariable logistic regression.
Between Jan. 1, 2009, and Dec. 31, 2014, there were 16,640 admissions with VWD and 618 were admitted with GI bleeding, the researchers reported. After analysis, the researchers found that the prevalence of GI bleeding was 3.7% and 1.49% in VWD and non-VWD patients, respectively – a 2.5-fold greater rate in VWD patients.
“Comorbidities associated with greater [GI bleeding] risk in individuals with VWD include past surgery, hypertension, hyperlipidemia, smoking, renal disease, hepatitis C, thrombocytopenia, or liver disease,” the researchers wrote.
In the multivariable analysis, the factors associated with GI bleeding were smoking status (odds ratio, 1.40), African American race (OR, 1.80), male gender (OR, 1.61), angiodysplasia (OR, 104.06), colonic diverticulitis (OR, 16.66), and hepatitis C (OR 2.17). These variables were similar to risk factors identified in the non-VWD group, the researchers noted.
“Although significant, age did not appear to be a strong risk factor for either group,” they wrote. “Steroids were not associated with increased risk for [GI bleeding] in either group.”
A key limitation of the study was the use of discharge diagnosis codes as an inclusion method, the researchers noted. As a result, misclassification bias could be present, they added.
The Pennsylvania Department of Health and the Health Resources and Services Administration funded the study. The authors reported having no conflicts of interest.
SOURCE: Tsagianni A et al. Thromb Res. 2019 Apr 17. doi: 10.1016/j.thromres.2019.04.017.
Researchers have identified several risk factors associated with gastrointestinal (GI) bleeding in adult patients with von Willebrand disease (VWD), based on findings from a retrospective analysis.
“[We] evaluated prevalence and risk factors of GIB among individuals with and without VWD, using a large national database,” wrote Anastasia Tsagianni, MD, of the University of Pittsburgh, and colleagues. The findings were published in Thrombosis Research.
The researchers retrospectively reviewed discharge data from the National Inpatient Sample database. The team analyzed correlates of GI bleeding among patients with VWD and estimated prevalence rates using measures in the database. Risk factors for GI bleeding in VWD were correlated via multivariable logistic regression.
Between Jan. 1, 2009, and Dec. 31, 2014, there were 16,640 admissions with VWD and 618 were admitted with GI bleeding, the researchers reported. After analysis, the researchers found that the prevalence of GI bleeding was 3.7% and 1.49% in VWD and non-VWD patients, respectively – a 2.5-fold greater rate in VWD patients.
“Comorbidities associated with greater [GI bleeding] risk in individuals with VWD include past surgery, hypertension, hyperlipidemia, smoking, renal disease, hepatitis C, thrombocytopenia, or liver disease,” the researchers wrote.
In the multivariable analysis, the factors associated with GI bleeding were smoking status (odds ratio, 1.40), African American race (OR, 1.80), male gender (OR, 1.61), angiodysplasia (OR, 104.06), colonic diverticulitis (OR, 16.66), and hepatitis C (OR 2.17). These variables were similar to risk factors identified in the non-VWD group, the researchers noted.
“Although significant, age did not appear to be a strong risk factor for either group,” they wrote. “Steroids were not associated with increased risk for [GI bleeding] in either group.”
A key limitation of the study was the use of discharge diagnosis codes as an inclusion method, the researchers noted. As a result, misclassification bias could be present, they added.
The Pennsylvania Department of Health and the Health Resources and Services Administration funded the study. The authors reported having no conflicts of interest.
SOURCE: Tsagianni A et al. Thromb Res. 2019 Apr 17. doi: 10.1016/j.thromres.2019.04.017.
Researchers have identified several risk factors associated with gastrointestinal (GI) bleeding in adult patients with von Willebrand disease (VWD), based on findings from a retrospective analysis.
“[We] evaluated prevalence and risk factors of GIB among individuals with and without VWD, using a large national database,” wrote Anastasia Tsagianni, MD, of the University of Pittsburgh, and colleagues. The findings were published in Thrombosis Research.
The researchers retrospectively reviewed discharge data from the National Inpatient Sample database. The team analyzed correlates of GI bleeding among patients with VWD and estimated prevalence rates using measures in the database. Risk factors for GI bleeding in VWD were correlated via multivariable logistic regression.
Between Jan. 1, 2009, and Dec. 31, 2014, there were 16,640 admissions with VWD and 618 were admitted with GI bleeding, the researchers reported. After analysis, the researchers found that the prevalence of GI bleeding was 3.7% and 1.49% in VWD and non-VWD patients, respectively – a 2.5-fold greater rate in VWD patients.
“Comorbidities associated with greater [GI bleeding] risk in individuals with VWD include past surgery, hypertension, hyperlipidemia, smoking, renal disease, hepatitis C, thrombocytopenia, or liver disease,” the researchers wrote.
In the multivariable analysis, the factors associated with GI bleeding were smoking status (odds ratio, 1.40), African American race (OR, 1.80), male gender (OR, 1.61), angiodysplasia (OR, 104.06), colonic diverticulitis (OR, 16.66), and hepatitis C (OR 2.17). These variables were similar to risk factors identified in the non-VWD group, the researchers noted.
“Although significant, age did not appear to be a strong risk factor for either group,” they wrote. “Steroids were not associated with increased risk for [GI bleeding] in either group.”
A key limitation of the study was the use of discharge diagnosis codes as an inclusion method, the researchers noted. As a result, misclassification bias could be present, they added.
The Pennsylvania Department of Health and the Health Resources and Services Administration funded the study. The authors reported having no conflicts of interest.
SOURCE: Tsagianni A et al. Thromb Res. 2019 Apr 17. doi: 10.1016/j.thromres.2019.04.017.
FROM THROMBOSIS RESEARCH
Key clinical point: Researchers identified several risk factors associated for gastrointestinal bleeding in adult patients with von Willebrand disease.
Major finding: In a multivariate analysis, the most significant factors associated with gastrointestinal bleeding in von Willebrand disease were smoking status, African American race, male gender, angiodysplasia, diverticulitis, and hepatitis C.
Study details: A retrospective analysis of 16,640 patients with the disease.
Disclosures: The Pennsylvania Department of Health and the Health Resources and Services Administration funded the study. The authors reported having no conflicts of interest.
Source: Tsagianni A et al. Thromb Res. 2019 Apr 17. doi: 10.1016/j.thromres.2019.04.017.
LentiGlobin reduces transfusion dependence in young thalassemia patients
NEW ORLEANS – The gene therapy LentiGlobin can reduce transfusion dependence in children and young adults with non-beta0/beta0 thalassemia, according to two trials.
In a phase 1/2 trial, 8 of 10 of patients achieved transfusion independence at a median follow-up of 36.0 months. In a phase 3 trial, transfusion independence was achieved by 2 of 3 patients with follow-up of at least 12 months.
Timothy S. Olson, MD, PhD, of Children’s Hospital of Philadelphia, presented results from the phase 1/2 HGB-204 trial and the phase 3 HGB-207 trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Treatment
In both trials, patients received granulocyte colony-stimulating factor and plerixafor for hematopoietic stem cell mobilization. Their cells were collected via apheresis and transduced with the betibeglogene darolentivec (BB305) lentiviral vector. The patients received busulfan (for an average of 4 days) as conditioning and were infused with the transduced cells.
The manufacturing process for LentiGlobin was refined in the HGB-207 trial, which translated to a product with a higher vector copy number and higher proportion of CD34+ cells transduced, Dr. Olson said.
The median vector copy number was 3.1 in the HGB-207 trial and 0.7 in the HGB-204 trial. The median proportion of CD34+ cells transfused was 81% and 29%, respectively. The median cell dose was 7.7 x 106 CD34+ cells/kg and 7.1 x 106 CD34+ cells/kg, respectively.
HGB-204 patients and efficacy
The HGB-204 trial included 10 patients with non-beta0/beta0 genotypes – 6 with betaE/beta0, 1 with beta+/beta0, 2 with beta+/beta+, and 1 with an “other” genotype.
The patients’ median age at consent was 19.5 years (range, 16-34). The annualized median prestudy red blood cell (RBC) transfusion volume was 151 mL/kg per year.
At a median follow-up of 36 months, 8 of the 10 patients achieved transfusion independence. The median duration of transfusion independence was 38 months. The median weighted average hemoglobin during transfusion independence was 10.2 g/dL.
“Two patients did not achieve transfusion independence, and both patients were on the lower end of the spectrum both in terms of vector copy number per cell and the percentage of CD34+ cells that were successfully transduced,” Dr. Olson said. “Both patients actually experienced a reduction in the annualized transfusion volume requirements of between 43% and 77%.”
HGB-207 patients and efficacy
The HGB-207 trial included 16 patients with non-beta0/beta0 genotypes – 6 with betaE/beta0, 7 with beta+/beta0, and 3 with the beta+/beta+ genotype.
The patients’ median age at consent was 19 years . The annualized median prestudy RBC transfusion volume was 192 mL/kg per year.
The median follow-up in this trial is 9.3 months. Ten of 11 patients with at least 3 months of follow-up are transfusion-free with hemoglobin levels greater than 11 g/dL.
Two patients have achieved transfusion independence according to the protocol definition, which is weighted average hemoglobin of 9 g/dL or greater without any RBC transfusions for at least 12 months.
“In the one patient in this study who did not achieve transfusion independence, the vector-derived hemoglobin was quite low, and this correlated with a very low vector copy number seen in circulating peripheral blood mononuclear cells,” Dr. Olson said.
It isn’t clear why this occurred, however, as the vector copy number wasn’t especially low in the LentiGlobin product the patient received. Therefore, the researchers are still investigating why this patient failed to achieve transfusion independence.
Safety in both trials
“Very importantly, there were no deaths, there were no engraftment failures, there was no evidence of vector-mediated replication-competent lentivirus, and integration site analysis revealed no evidence of clonal dominance,” Dr. Olson said.
He added that most of the grade 3 or greater adverse events seen in both trials were directly attributable to busulfan-based myeloablative conditioning, including four episodes of veno-occlusive disease.
Nonhematologic grade 3 or higher adverse events in HGB-204 included stomatitis (n = 8), febrile neutropenia (n = 6), irregular menstruation (n = 3), pharyngeal inflammation (n = 2), and veno-occlusive liver disease (n = 1).
Nonhematologic grade 3 or higher adverse events in HGB-207 included stomatitis (n = 9), febrile neutropenia (n = 4), pharyngeal inflammation (n = 2), epistaxis (n = 3), pyrexia (n = 3), veno-occlusive liver disease (n = 3), ALT increase (n = 2), bilirubin increase (n = 2), and hypoxia (n = 2).
One patient in HGB-207 had grade 3 thrombocytopenia considered possibly related to LentiGlobin.
Dr. Olson reported advisory board engagement with bluebird bio, which sponsored both trials.
SOURCE: Olson TS et al. ASPHO 2019. Abstract 2002.
NEW ORLEANS – The gene therapy LentiGlobin can reduce transfusion dependence in children and young adults with non-beta0/beta0 thalassemia, according to two trials.
In a phase 1/2 trial, 8 of 10 of patients achieved transfusion independence at a median follow-up of 36.0 months. In a phase 3 trial, transfusion independence was achieved by 2 of 3 patients with follow-up of at least 12 months.
Timothy S. Olson, MD, PhD, of Children’s Hospital of Philadelphia, presented results from the phase 1/2 HGB-204 trial and the phase 3 HGB-207 trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Treatment
In both trials, patients received granulocyte colony-stimulating factor and plerixafor for hematopoietic stem cell mobilization. Their cells were collected via apheresis and transduced with the betibeglogene darolentivec (BB305) lentiviral vector. The patients received busulfan (for an average of 4 days) as conditioning and were infused with the transduced cells.
The manufacturing process for LentiGlobin was refined in the HGB-207 trial, which translated to a product with a higher vector copy number and higher proportion of CD34+ cells transduced, Dr. Olson said.
The median vector copy number was 3.1 in the HGB-207 trial and 0.7 in the HGB-204 trial. The median proportion of CD34+ cells transfused was 81% and 29%, respectively. The median cell dose was 7.7 x 106 CD34+ cells/kg and 7.1 x 106 CD34+ cells/kg, respectively.
HGB-204 patients and efficacy
The HGB-204 trial included 10 patients with non-beta0/beta0 genotypes – 6 with betaE/beta0, 1 with beta+/beta0, 2 with beta+/beta+, and 1 with an “other” genotype.
The patients’ median age at consent was 19.5 years (range, 16-34). The annualized median prestudy red blood cell (RBC) transfusion volume was 151 mL/kg per year.
At a median follow-up of 36 months, 8 of the 10 patients achieved transfusion independence. The median duration of transfusion independence was 38 months. The median weighted average hemoglobin during transfusion independence was 10.2 g/dL.
“Two patients did not achieve transfusion independence, and both patients were on the lower end of the spectrum both in terms of vector copy number per cell and the percentage of CD34+ cells that were successfully transduced,” Dr. Olson said. “Both patients actually experienced a reduction in the annualized transfusion volume requirements of between 43% and 77%.”
HGB-207 patients and efficacy
The HGB-207 trial included 16 patients with non-beta0/beta0 genotypes – 6 with betaE/beta0, 7 with beta+/beta0, and 3 with the beta+/beta+ genotype.
The patients’ median age at consent was 19 years . The annualized median prestudy RBC transfusion volume was 192 mL/kg per year.
The median follow-up in this trial is 9.3 months. Ten of 11 patients with at least 3 months of follow-up are transfusion-free with hemoglobin levels greater than 11 g/dL.
Two patients have achieved transfusion independence according to the protocol definition, which is weighted average hemoglobin of 9 g/dL or greater without any RBC transfusions for at least 12 months.
“In the one patient in this study who did not achieve transfusion independence, the vector-derived hemoglobin was quite low, and this correlated with a very low vector copy number seen in circulating peripheral blood mononuclear cells,” Dr. Olson said.
It isn’t clear why this occurred, however, as the vector copy number wasn’t especially low in the LentiGlobin product the patient received. Therefore, the researchers are still investigating why this patient failed to achieve transfusion independence.
Safety in both trials
“Very importantly, there were no deaths, there were no engraftment failures, there was no evidence of vector-mediated replication-competent lentivirus, and integration site analysis revealed no evidence of clonal dominance,” Dr. Olson said.
He added that most of the grade 3 or greater adverse events seen in both trials were directly attributable to busulfan-based myeloablative conditioning, including four episodes of veno-occlusive disease.
Nonhematologic grade 3 or higher adverse events in HGB-204 included stomatitis (n = 8), febrile neutropenia (n = 6), irregular menstruation (n = 3), pharyngeal inflammation (n = 2), and veno-occlusive liver disease (n = 1).
Nonhematologic grade 3 or higher adverse events in HGB-207 included stomatitis (n = 9), febrile neutropenia (n = 4), pharyngeal inflammation (n = 2), epistaxis (n = 3), pyrexia (n = 3), veno-occlusive liver disease (n = 3), ALT increase (n = 2), bilirubin increase (n = 2), and hypoxia (n = 2).
One patient in HGB-207 had grade 3 thrombocytopenia considered possibly related to LentiGlobin.
Dr. Olson reported advisory board engagement with bluebird bio, which sponsored both trials.
SOURCE: Olson TS et al. ASPHO 2019. Abstract 2002.
NEW ORLEANS – The gene therapy LentiGlobin can reduce transfusion dependence in children and young adults with non-beta0/beta0 thalassemia, according to two trials.
In a phase 1/2 trial, 8 of 10 of patients achieved transfusion independence at a median follow-up of 36.0 months. In a phase 3 trial, transfusion independence was achieved by 2 of 3 patients with follow-up of at least 12 months.
Timothy S. Olson, MD, PhD, of Children’s Hospital of Philadelphia, presented results from the phase 1/2 HGB-204 trial and the phase 3 HGB-207 trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Treatment
In both trials, patients received granulocyte colony-stimulating factor and plerixafor for hematopoietic stem cell mobilization. Their cells were collected via apheresis and transduced with the betibeglogene darolentivec (BB305) lentiviral vector. The patients received busulfan (for an average of 4 days) as conditioning and were infused with the transduced cells.
The manufacturing process for LentiGlobin was refined in the HGB-207 trial, which translated to a product with a higher vector copy number and higher proportion of CD34+ cells transduced, Dr. Olson said.
The median vector copy number was 3.1 in the HGB-207 trial and 0.7 in the HGB-204 trial. The median proportion of CD34+ cells transfused was 81% and 29%, respectively. The median cell dose was 7.7 x 106 CD34+ cells/kg and 7.1 x 106 CD34+ cells/kg, respectively.
HGB-204 patients and efficacy
The HGB-204 trial included 10 patients with non-beta0/beta0 genotypes – 6 with betaE/beta0, 1 with beta+/beta0, 2 with beta+/beta+, and 1 with an “other” genotype.
The patients’ median age at consent was 19.5 years (range, 16-34). The annualized median prestudy red blood cell (RBC) transfusion volume was 151 mL/kg per year.
At a median follow-up of 36 months, 8 of the 10 patients achieved transfusion independence. The median duration of transfusion independence was 38 months. The median weighted average hemoglobin during transfusion independence was 10.2 g/dL.
“Two patients did not achieve transfusion independence, and both patients were on the lower end of the spectrum both in terms of vector copy number per cell and the percentage of CD34+ cells that were successfully transduced,” Dr. Olson said. “Both patients actually experienced a reduction in the annualized transfusion volume requirements of between 43% and 77%.”
HGB-207 patients and efficacy
The HGB-207 trial included 16 patients with non-beta0/beta0 genotypes – 6 with betaE/beta0, 7 with beta+/beta0, and 3 with the beta+/beta+ genotype.
The patients’ median age at consent was 19 years . The annualized median prestudy RBC transfusion volume was 192 mL/kg per year.
The median follow-up in this trial is 9.3 months. Ten of 11 patients with at least 3 months of follow-up are transfusion-free with hemoglobin levels greater than 11 g/dL.
Two patients have achieved transfusion independence according to the protocol definition, which is weighted average hemoglobin of 9 g/dL or greater without any RBC transfusions for at least 12 months.
“In the one patient in this study who did not achieve transfusion independence, the vector-derived hemoglobin was quite low, and this correlated with a very low vector copy number seen in circulating peripheral blood mononuclear cells,” Dr. Olson said.
It isn’t clear why this occurred, however, as the vector copy number wasn’t especially low in the LentiGlobin product the patient received. Therefore, the researchers are still investigating why this patient failed to achieve transfusion independence.
Safety in both trials
“Very importantly, there were no deaths, there were no engraftment failures, there was no evidence of vector-mediated replication-competent lentivirus, and integration site analysis revealed no evidence of clonal dominance,” Dr. Olson said.
He added that most of the grade 3 or greater adverse events seen in both trials were directly attributable to busulfan-based myeloablative conditioning, including four episodes of veno-occlusive disease.
Nonhematologic grade 3 or higher adverse events in HGB-204 included stomatitis (n = 8), febrile neutropenia (n = 6), irregular menstruation (n = 3), pharyngeal inflammation (n = 2), and veno-occlusive liver disease (n = 1).
Nonhematologic grade 3 or higher adverse events in HGB-207 included stomatitis (n = 9), febrile neutropenia (n = 4), pharyngeal inflammation (n = 2), epistaxis (n = 3), pyrexia (n = 3), veno-occlusive liver disease (n = 3), ALT increase (n = 2), bilirubin increase (n = 2), and hypoxia (n = 2).
One patient in HGB-207 had grade 3 thrombocytopenia considered possibly related to LentiGlobin.
Dr. Olson reported advisory board engagement with bluebird bio, which sponsored both trials.
SOURCE: Olson TS et al. ASPHO 2019. Abstract 2002.
REPORTING FROM 2019 ASPHO CONFERENCE
TTP death linked to elevated troponin and neurological signs
GLASGOW – , according to retrospective analysis of 475 patients from the United Kingdom TTP registry.
In addition, low ADAMTS13 activity (less than 10%) was present in 92% of immune-mediated of TTP upon acute presentation, reported lead author Jin-Sup Shin, MD, of University College London Hospital, and colleagues.
Presenting at the annual meeting of the British Society for Haematology, Dr. Shin provided some background on TTP, a condition that most clinicians encounter infrequently.
“As recently as the 1980s and 90s, when etiology was not that well understood, TTP was associated with an untreated mortality of up to 90%,” Dr. Shin said. “However, based on improved understanding of pathophysiology, and through the creation of TTP registries worldwide, there have been major advances in diagnosis, treatment, and outcomes.”
To gain insight into diagnostic and prognostic characteristics of TTP, the investigators turned to data from 602 patients with clinically suspected TTP, based on an ADAMTS13 activity level less than 10% of normal and associated clinical signs. Out of these 602 patients, 475 consented to registry participation and data analysis.
The analysis revealed a mortality rate of 4%, although Dr. Shin said that “this is probably an underestimate of the true figure,” as it excludes those who died before treatment could be initiated.
Nearly three-quarters of patients were female. The median age at presentation was 43 years, with a range of 1-93 years. The most commonly represented racial/ethnic groups were white (60%) and Afro-Caribbean (22%). Some cases were congenital (16%), but the majority were immune mediated (84%).
The immune-mediated group was the primary focus of Dr. Shin’s report. In this cohort, 76% of cases were idiopathic, while the remainder had a defined precipitant; most common were infection, autoimmune disease, pregnancy, and HIV. The relapse rate among those with immune-mediated TTP was 19%, after a median time to relapse of 26 months.
In total, 71% of patients presented with neurological abnormalities, while slightly less than half (48%) had symptomatic thrombocytopenia (bleeding/petechiae).
Diagnostic tools showed that 64% of patients had an elevated troponin level, 92% had ADAMTS13 activity less than 10%, and 25% had a platelet count lower than 10 x 109/L.
Median platelet count upon presentation was 15 x 109/L, and median lactate dehydrogenase (LDH) exceeded 1,000 units/L. After 7 days of therapy, 58% of patients were still severely deficient in ADAMTS13 activity and 36% of patients still had a platelet count lower than 150 x 109/L.
Where information was available, 30% of patients had positive auto-antibody screens, although not necessarily with signs or symptoms of autoimmune disease. A total of 93% of patients had elevated ADAMTS13 IgG antibody upon presentation. The median ADAMTS13 IgG antibody level at presentation was 37%, with a normal value being less than 6%.
Nearly half of patients with immune-mediated TTP (45%) required intensive care, and 10% of these patients were intubated and ventilated. Most patients were treated with steroids upon admission (81%). On average, 11 plasma exchanges (PEXs) were required before remission.
The investigators noted that “[t]he number of PEXs to remission appears to have decreased over the years.” As an example, a median of 14 PEXs were needed from 2009 to 2010, compared with 8 from 2017 to 2018.
Although rituximab usage in the acute setting held steady over the 10-year period, elective use increased. Out of 89 instances of subacute relapse, elective rituximab was given twice from 2009 to 2010, compared with 26 times from 2017 to 2018.
Comparing features of survival, the investigators found that the median ADAMTS13 IgG antibody level was higher among those who died. Other factors related to increased mortality risk included raised troponin (sevenfold increased risk) and neurological abnormalities, defined by reduced Glasgow Coma Scale score (sixfold increased risk).
“Our data confirm other registries worldwide; in particular, increased susceptibility in women, the Afro-Caribbean population, and those who are middle-aged,” Dr. Shin said. “Our data also show that elevated cardiac troponin and neurological involvement are indicators of poor prognosis. Also, raised antibody levels appear to be associated with a worse clinical outcome and increased mortality rate. These are clearly valuable markers in clinical practice, allowing for intensive care of high-risk patients.”
The investigators reported having no conflicts of interest.
GLASGOW – , according to retrospective analysis of 475 patients from the United Kingdom TTP registry.
In addition, low ADAMTS13 activity (less than 10%) was present in 92% of immune-mediated of TTP upon acute presentation, reported lead author Jin-Sup Shin, MD, of University College London Hospital, and colleagues.
Presenting at the annual meeting of the British Society for Haematology, Dr. Shin provided some background on TTP, a condition that most clinicians encounter infrequently.
“As recently as the 1980s and 90s, when etiology was not that well understood, TTP was associated with an untreated mortality of up to 90%,” Dr. Shin said. “However, based on improved understanding of pathophysiology, and through the creation of TTP registries worldwide, there have been major advances in diagnosis, treatment, and outcomes.”
To gain insight into diagnostic and prognostic characteristics of TTP, the investigators turned to data from 602 patients with clinically suspected TTP, based on an ADAMTS13 activity level less than 10% of normal and associated clinical signs. Out of these 602 patients, 475 consented to registry participation and data analysis.
The analysis revealed a mortality rate of 4%, although Dr. Shin said that “this is probably an underestimate of the true figure,” as it excludes those who died before treatment could be initiated.
Nearly three-quarters of patients were female. The median age at presentation was 43 years, with a range of 1-93 years. The most commonly represented racial/ethnic groups were white (60%) and Afro-Caribbean (22%). Some cases were congenital (16%), but the majority were immune mediated (84%).
The immune-mediated group was the primary focus of Dr. Shin’s report. In this cohort, 76% of cases were idiopathic, while the remainder had a defined precipitant; most common were infection, autoimmune disease, pregnancy, and HIV. The relapse rate among those with immune-mediated TTP was 19%, after a median time to relapse of 26 months.
In total, 71% of patients presented with neurological abnormalities, while slightly less than half (48%) had symptomatic thrombocytopenia (bleeding/petechiae).
Diagnostic tools showed that 64% of patients had an elevated troponin level, 92% had ADAMTS13 activity less than 10%, and 25% had a platelet count lower than 10 x 109/L.
Median platelet count upon presentation was 15 x 109/L, and median lactate dehydrogenase (LDH) exceeded 1,000 units/L. After 7 days of therapy, 58% of patients were still severely deficient in ADAMTS13 activity and 36% of patients still had a platelet count lower than 150 x 109/L.
Where information was available, 30% of patients had positive auto-antibody screens, although not necessarily with signs or symptoms of autoimmune disease. A total of 93% of patients had elevated ADAMTS13 IgG antibody upon presentation. The median ADAMTS13 IgG antibody level at presentation was 37%, with a normal value being less than 6%.
Nearly half of patients with immune-mediated TTP (45%) required intensive care, and 10% of these patients were intubated and ventilated. Most patients were treated with steroids upon admission (81%). On average, 11 plasma exchanges (PEXs) were required before remission.
The investigators noted that “[t]he number of PEXs to remission appears to have decreased over the years.” As an example, a median of 14 PEXs were needed from 2009 to 2010, compared with 8 from 2017 to 2018.
Although rituximab usage in the acute setting held steady over the 10-year period, elective use increased. Out of 89 instances of subacute relapse, elective rituximab was given twice from 2009 to 2010, compared with 26 times from 2017 to 2018.
Comparing features of survival, the investigators found that the median ADAMTS13 IgG antibody level was higher among those who died. Other factors related to increased mortality risk included raised troponin (sevenfold increased risk) and neurological abnormalities, defined by reduced Glasgow Coma Scale score (sixfold increased risk).
“Our data confirm other registries worldwide; in particular, increased susceptibility in women, the Afro-Caribbean population, and those who are middle-aged,” Dr. Shin said. “Our data also show that elevated cardiac troponin and neurological involvement are indicators of poor prognosis. Also, raised antibody levels appear to be associated with a worse clinical outcome and increased mortality rate. These are clearly valuable markers in clinical practice, allowing for intensive care of high-risk patients.”
The investigators reported having no conflicts of interest.
GLASGOW – , according to retrospective analysis of 475 patients from the United Kingdom TTP registry.
In addition, low ADAMTS13 activity (less than 10%) was present in 92% of immune-mediated of TTP upon acute presentation, reported lead author Jin-Sup Shin, MD, of University College London Hospital, and colleagues.
Presenting at the annual meeting of the British Society for Haematology, Dr. Shin provided some background on TTP, a condition that most clinicians encounter infrequently.
“As recently as the 1980s and 90s, when etiology was not that well understood, TTP was associated with an untreated mortality of up to 90%,” Dr. Shin said. “However, based on improved understanding of pathophysiology, and through the creation of TTP registries worldwide, there have been major advances in diagnosis, treatment, and outcomes.”
To gain insight into diagnostic and prognostic characteristics of TTP, the investigators turned to data from 602 patients with clinically suspected TTP, based on an ADAMTS13 activity level less than 10% of normal and associated clinical signs. Out of these 602 patients, 475 consented to registry participation and data analysis.
The analysis revealed a mortality rate of 4%, although Dr. Shin said that “this is probably an underestimate of the true figure,” as it excludes those who died before treatment could be initiated.
Nearly three-quarters of patients were female. The median age at presentation was 43 years, with a range of 1-93 years. The most commonly represented racial/ethnic groups were white (60%) and Afro-Caribbean (22%). Some cases were congenital (16%), but the majority were immune mediated (84%).
The immune-mediated group was the primary focus of Dr. Shin’s report. In this cohort, 76% of cases were idiopathic, while the remainder had a defined precipitant; most common were infection, autoimmune disease, pregnancy, and HIV. The relapse rate among those with immune-mediated TTP was 19%, after a median time to relapse of 26 months.
In total, 71% of patients presented with neurological abnormalities, while slightly less than half (48%) had symptomatic thrombocytopenia (bleeding/petechiae).
Diagnostic tools showed that 64% of patients had an elevated troponin level, 92% had ADAMTS13 activity less than 10%, and 25% had a platelet count lower than 10 x 109/L.
Median platelet count upon presentation was 15 x 109/L, and median lactate dehydrogenase (LDH) exceeded 1,000 units/L. After 7 days of therapy, 58% of patients were still severely deficient in ADAMTS13 activity and 36% of patients still had a platelet count lower than 150 x 109/L.
Where information was available, 30% of patients had positive auto-antibody screens, although not necessarily with signs or symptoms of autoimmune disease. A total of 93% of patients had elevated ADAMTS13 IgG antibody upon presentation. The median ADAMTS13 IgG antibody level at presentation was 37%, with a normal value being less than 6%.
Nearly half of patients with immune-mediated TTP (45%) required intensive care, and 10% of these patients were intubated and ventilated. Most patients were treated with steroids upon admission (81%). On average, 11 plasma exchanges (PEXs) were required before remission.
The investigators noted that “[t]he number of PEXs to remission appears to have decreased over the years.” As an example, a median of 14 PEXs were needed from 2009 to 2010, compared with 8 from 2017 to 2018.
Although rituximab usage in the acute setting held steady over the 10-year period, elective use increased. Out of 89 instances of subacute relapse, elective rituximab was given twice from 2009 to 2010, compared with 26 times from 2017 to 2018.
Comparing features of survival, the investigators found that the median ADAMTS13 IgG antibody level was higher among those who died. Other factors related to increased mortality risk included raised troponin (sevenfold increased risk) and neurological abnormalities, defined by reduced Glasgow Coma Scale score (sixfold increased risk).
“Our data confirm other registries worldwide; in particular, increased susceptibility in women, the Afro-Caribbean population, and those who are middle-aged,” Dr. Shin said. “Our data also show that elevated cardiac troponin and neurological involvement are indicators of poor prognosis. Also, raised antibody levels appear to be associated with a worse clinical outcome and increased mortality rate. These are clearly valuable markers in clinical practice, allowing for intensive care of high-risk patients.”
The investigators reported having no conflicts of interest.
REPORTING FROM BSH 2019
Key clinical point: Neurological abnormalities and elevated troponin predict mortality in patients with thrombotic thrombocytopenic purpura (TTP).
Major finding: ADAMTS13 IgG antibody level, elevated troponin, and neurological abnormalities were all linked to an increased mortality risk.
Study details: A retrospective analysis of 475 patients with clinically suspected thrombotic thrombocytopenic purpura (TTP) from the U.K. registry (2009-2018).
Disclosures: The investigators reported having no conflicts of interest.
Extended half-life clotting factors cut infusions, hike prices
More than a fifth of patients with hemophilia may now be using extended half-life (EHL) clotting factors, although the economic impact of these new treatments remains unclear.
Use of EHL factor VIII (FVIII) and IX (FIX) products surged from 10% of patients to 22% over an 18-month period ending in late 2017, Dr. Stacy E. Croteau and her colleagues reported in Haemophilia.
The increase appears to be mostly driven by prescribed prophylaxis rather than on-demand use of the products, wrote Dr. Croteau of Boston Children’s Hospital, and her coauthors. EHL dosages were similar to standard half-life (SHL) dosages and extended the time between infusions. But in the end, the higher cost of the EHL products actually drove up the price of prophylaxis, with a year of EHL FIX topping $1 million.
“Careful assessment of factor consumption and patient outcomes is needed to ensure general cost neutrality of this expensive therapy,” the researchers wrote. “Unless demonstrably offset by reduction in bleed doses, the net effect could be further increases in annual cost of care for this patient population.”
The study examined the use of SHL and EHL clotting factors in 7,893 adults and children with hemophilia A or B, who were being followed in the American Thrombosis and Hemostasis Network (ATHN) database. The authors sought to characterize changes in usage patterns for SHL and EHL factors, and to identify demographic and economic influences on them.
During the study, the number of patients using EHL products for both on-demand and prophylactic factor replacement increased. EHL FVIII use rose from 9% to 21%, and EHL FIX from 14% to 21%, especially among those with hemophilia B.
There were 6,437 patients with full data at both initial and final sampling. Among these, there was a 9.6% increase in the use of an EHL clotting factor by the end of the study (P less than .001). Patients with hemophilia A were less likely than hemophilia B patients to use an EHL product for prophylaxis.
While the EHL products did reduce the number of prophylactic infusions, they also cost much more, the investigators found.
The standard dose of SHL FVIII is 40 IU/g infused three times a week. The projected cost of 156 annual infusions is $690,144. EHL FVII, dosed at 50 IU/kg, cuts infusions to twice a week. The annual projected cost of the 104 infusions is $753,480.
The standard dose of SHL FIX is 67 IU/kg, infused twice a week. The annual projected cost of 104 infusions is $697,497. EHL FIX, dosed at 75 IU/Kg, halves the number of infusions. But the price for those 52 treatments exceeds $1 million ($1,015,560). Despite the cost, however, just 43 patients switched from an EHL product to a SHL factor product during the study period.
Insurance type appeared to have little influence on the choice of SHL or EHL clotting factors. Across payer types, a similar proportion of patients started using them, and 71% were covered by private insurance or Medicaid.
The study was funded HTRS/ATHN Dataset Research Engagement and a DREAM Award from the Hemostasis and Thrombosis Research Society. Dr. Croteau reported consulting for Bayer, Bioverativ, Biomarin, CSL-Behring, and other companies.
SOURCE: Croteau SE et al. Haemophilia. 2019 Apr 17. doi: 10.1111/hae.13758.
More than a fifth of patients with hemophilia may now be using extended half-life (EHL) clotting factors, although the economic impact of these new treatments remains unclear.
Use of EHL factor VIII (FVIII) and IX (FIX) products surged from 10% of patients to 22% over an 18-month period ending in late 2017, Dr. Stacy E. Croteau and her colleagues reported in Haemophilia.
The increase appears to be mostly driven by prescribed prophylaxis rather than on-demand use of the products, wrote Dr. Croteau of Boston Children’s Hospital, and her coauthors. EHL dosages were similar to standard half-life (SHL) dosages and extended the time between infusions. But in the end, the higher cost of the EHL products actually drove up the price of prophylaxis, with a year of EHL FIX topping $1 million.
“Careful assessment of factor consumption and patient outcomes is needed to ensure general cost neutrality of this expensive therapy,” the researchers wrote. “Unless demonstrably offset by reduction in bleed doses, the net effect could be further increases in annual cost of care for this patient population.”
The study examined the use of SHL and EHL clotting factors in 7,893 adults and children with hemophilia A or B, who were being followed in the American Thrombosis and Hemostasis Network (ATHN) database. The authors sought to characterize changes in usage patterns for SHL and EHL factors, and to identify demographic and economic influences on them.
During the study, the number of patients using EHL products for both on-demand and prophylactic factor replacement increased. EHL FVIII use rose from 9% to 21%, and EHL FIX from 14% to 21%, especially among those with hemophilia B.
There were 6,437 patients with full data at both initial and final sampling. Among these, there was a 9.6% increase in the use of an EHL clotting factor by the end of the study (P less than .001). Patients with hemophilia A were less likely than hemophilia B patients to use an EHL product for prophylaxis.
While the EHL products did reduce the number of prophylactic infusions, they also cost much more, the investigators found.
The standard dose of SHL FVIII is 40 IU/g infused three times a week. The projected cost of 156 annual infusions is $690,144. EHL FVII, dosed at 50 IU/kg, cuts infusions to twice a week. The annual projected cost of the 104 infusions is $753,480.
The standard dose of SHL FIX is 67 IU/kg, infused twice a week. The annual projected cost of 104 infusions is $697,497. EHL FIX, dosed at 75 IU/Kg, halves the number of infusions. But the price for those 52 treatments exceeds $1 million ($1,015,560). Despite the cost, however, just 43 patients switched from an EHL product to a SHL factor product during the study period.
Insurance type appeared to have little influence on the choice of SHL or EHL clotting factors. Across payer types, a similar proportion of patients started using them, and 71% were covered by private insurance or Medicaid.
The study was funded HTRS/ATHN Dataset Research Engagement and a DREAM Award from the Hemostasis and Thrombosis Research Society. Dr. Croteau reported consulting for Bayer, Bioverativ, Biomarin, CSL-Behring, and other companies.
SOURCE: Croteau SE et al. Haemophilia. 2019 Apr 17. doi: 10.1111/hae.13758.
More than a fifth of patients with hemophilia may now be using extended half-life (EHL) clotting factors, although the economic impact of these new treatments remains unclear.
Use of EHL factor VIII (FVIII) and IX (FIX) products surged from 10% of patients to 22% over an 18-month period ending in late 2017, Dr. Stacy E. Croteau and her colleagues reported in Haemophilia.
The increase appears to be mostly driven by prescribed prophylaxis rather than on-demand use of the products, wrote Dr. Croteau of Boston Children’s Hospital, and her coauthors. EHL dosages were similar to standard half-life (SHL) dosages and extended the time between infusions. But in the end, the higher cost of the EHL products actually drove up the price of prophylaxis, with a year of EHL FIX topping $1 million.
“Careful assessment of factor consumption and patient outcomes is needed to ensure general cost neutrality of this expensive therapy,” the researchers wrote. “Unless demonstrably offset by reduction in bleed doses, the net effect could be further increases in annual cost of care for this patient population.”
The study examined the use of SHL and EHL clotting factors in 7,893 adults and children with hemophilia A or B, who were being followed in the American Thrombosis and Hemostasis Network (ATHN) database. The authors sought to characterize changes in usage patterns for SHL and EHL factors, and to identify demographic and economic influences on them.
During the study, the number of patients using EHL products for both on-demand and prophylactic factor replacement increased. EHL FVIII use rose from 9% to 21%, and EHL FIX from 14% to 21%, especially among those with hemophilia B.
There were 6,437 patients with full data at both initial and final sampling. Among these, there was a 9.6% increase in the use of an EHL clotting factor by the end of the study (P less than .001). Patients with hemophilia A were less likely than hemophilia B patients to use an EHL product for prophylaxis.
While the EHL products did reduce the number of prophylactic infusions, they also cost much more, the investigators found.
The standard dose of SHL FVIII is 40 IU/g infused three times a week. The projected cost of 156 annual infusions is $690,144. EHL FVII, dosed at 50 IU/kg, cuts infusions to twice a week. The annual projected cost of the 104 infusions is $753,480.
The standard dose of SHL FIX is 67 IU/kg, infused twice a week. The annual projected cost of 104 infusions is $697,497. EHL FIX, dosed at 75 IU/Kg, halves the number of infusions. But the price for those 52 treatments exceeds $1 million ($1,015,560). Despite the cost, however, just 43 patients switched from an EHL product to a SHL factor product during the study period.
Insurance type appeared to have little influence on the choice of SHL or EHL clotting factors. Across payer types, a similar proportion of patients started using them, and 71% were covered by private insurance or Medicaid.
The study was funded HTRS/ATHN Dataset Research Engagement and a DREAM Award from the Hemostasis and Thrombosis Research Society. Dr. Croteau reported consulting for Bayer, Bioverativ, Biomarin, CSL-Behring, and other companies.
SOURCE: Croteau SE et al. Haemophilia. 2019 Apr 17. doi: 10.1111/hae.13758.
FROM HAEMOPHILIA
HAVEN 4: Monthly emicizumab shows value
For many patients with hemophilia A, with or without inhibitors, a monthly emicizumab injection is enough to ensure a high level of bleed control, based on results from the ongoing HAVEN 4 trial.
Most patients reported three or fewer treated bleeds, while slightly more than half had no treated bleeds at all, according to lead author Steven W. Pipe, MD, of the University of Michigan, Ann Arbor, and his colleagues. The investigators noted that results from this trial have already led to approval of a monthly dosing schedule in the United States and several other countries.
“This convenient regimen has the potential to improve the care of patients by decreasing their treatment burden, and increasing uptake and adherence to effective prophylaxis, which is known to decrease the development of debilitating secondary complications,” the investigators wrote. The report is in The Lancet Haematology.
The data were collected at 20 centers in 8 countries. Eligibility required that patients have severe congenital hemophilia A (less than 1% normal FVIII activity), or hemophilia A with FVIII inhibitors and concurrent treatment with bypassing agents or FVIII concentrates.
An initial run-in cohort that included seven patients assessed pharmacokinetics and safety. These patients received 6 mg/kg of emicizumab subcutaneously every 4 weeks for at least 24 weeks. After this group showed good responses, 41 additional patients were enrolled in an expansion cohort, which involved an initial loading phase of weekly doses at 3 mg/kg for the first month, followed by monthly dosing at 6 mg/kg for at least 6 months (24 weeks).
The efficacy endpoint of the study was bleed prevention, as measured by treated target joint bleeds, treated joint bleeds, treated spontaneous bleeds, all bleeds (untreated and treated), and annualized bleed rates for treated bleeds.
In the expansion cohort, the median number of bleeds in the 24-week period preceding enrollment was five. In the same group, five patients (12%) had FVIII inhibitors and 61% of patients exhibited at least one target joint.
After a median treatment of 25.6 weeks, the model-based annualized bleed rate for treated bleeds was 2.4, while the median annualized bleed rate was zero.
Slightly more than half of the patients (56.1%) reported no treated bleeds, 90% of patients reported 0-3 treated bleeds, and 85% of patients did not require treatment for targeted joint bleeds.
When untreated bleeds were included, the model-based annualized bleed rate was 4.5, while the median annualized bleed rate was 2.1. Almost one-third of patients (29%) had no bleeding events of any kind and most (80%) had 0-3 treated or untreated bleeds.
Overall, treatment was well tolerated, with no patients withdrawing from the study, discontinuing treatment, or requiring dose modifications. Laboratory parameters remained stable throughout. The most common treatment-related adverse event was injection-site reaction (22%), followed distantly by pre-syncope, chills, rash, and erythema, each of which occurred in 2% of patients.
“Overall, the results of HAVEN 4 are consistent with the findings of other HAVEN studies,” the investigators wrote. “The option of treatment with emicizumab every 4 weeks broadens the range of administration frequencies and allows clinicians to tailor treatment to each patient’s needs and preferences.”
F. Hoffman-La Roche and Chugai funded the study. The investigators reported financial relationships with the study sponsors and other companies.
SOURCE: Pipe SW et al. Lancet Haem. 2019 Apr 16. doi: 10.1016/S2352-3026(19)30054-7.
For many patients with hemophilia A, with or without inhibitors, a monthly emicizumab injection is enough to ensure a high level of bleed control, based on results from the ongoing HAVEN 4 trial.
Most patients reported three or fewer treated bleeds, while slightly more than half had no treated bleeds at all, according to lead author Steven W. Pipe, MD, of the University of Michigan, Ann Arbor, and his colleagues. The investigators noted that results from this trial have already led to approval of a monthly dosing schedule in the United States and several other countries.
“This convenient regimen has the potential to improve the care of patients by decreasing their treatment burden, and increasing uptake and adherence to effective prophylaxis, which is known to decrease the development of debilitating secondary complications,” the investigators wrote. The report is in The Lancet Haematology.
The data were collected at 20 centers in 8 countries. Eligibility required that patients have severe congenital hemophilia A (less than 1% normal FVIII activity), or hemophilia A with FVIII inhibitors and concurrent treatment with bypassing agents or FVIII concentrates.
An initial run-in cohort that included seven patients assessed pharmacokinetics and safety. These patients received 6 mg/kg of emicizumab subcutaneously every 4 weeks for at least 24 weeks. After this group showed good responses, 41 additional patients were enrolled in an expansion cohort, which involved an initial loading phase of weekly doses at 3 mg/kg for the first month, followed by monthly dosing at 6 mg/kg for at least 6 months (24 weeks).
The efficacy endpoint of the study was bleed prevention, as measured by treated target joint bleeds, treated joint bleeds, treated spontaneous bleeds, all bleeds (untreated and treated), and annualized bleed rates for treated bleeds.
In the expansion cohort, the median number of bleeds in the 24-week period preceding enrollment was five. In the same group, five patients (12%) had FVIII inhibitors and 61% of patients exhibited at least one target joint.
After a median treatment of 25.6 weeks, the model-based annualized bleed rate for treated bleeds was 2.4, while the median annualized bleed rate was zero.
Slightly more than half of the patients (56.1%) reported no treated bleeds, 90% of patients reported 0-3 treated bleeds, and 85% of patients did not require treatment for targeted joint bleeds.
When untreated bleeds were included, the model-based annualized bleed rate was 4.5, while the median annualized bleed rate was 2.1. Almost one-third of patients (29%) had no bleeding events of any kind and most (80%) had 0-3 treated or untreated bleeds.
Overall, treatment was well tolerated, with no patients withdrawing from the study, discontinuing treatment, or requiring dose modifications. Laboratory parameters remained stable throughout. The most common treatment-related adverse event was injection-site reaction (22%), followed distantly by pre-syncope, chills, rash, and erythema, each of which occurred in 2% of patients.
“Overall, the results of HAVEN 4 are consistent with the findings of other HAVEN studies,” the investigators wrote. “The option of treatment with emicizumab every 4 weeks broadens the range of administration frequencies and allows clinicians to tailor treatment to each patient’s needs and preferences.”
F. Hoffman-La Roche and Chugai funded the study. The investigators reported financial relationships with the study sponsors and other companies.
SOURCE: Pipe SW et al. Lancet Haem. 2019 Apr 16. doi: 10.1016/S2352-3026(19)30054-7.
For many patients with hemophilia A, with or without inhibitors, a monthly emicizumab injection is enough to ensure a high level of bleed control, based on results from the ongoing HAVEN 4 trial.
Most patients reported three or fewer treated bleeds, while slightly more than half had no treated bleeds at all, according to lead author Steven W. Pipe, MD, of the University of Michigan, Ann Arbor, and his colleagues. The investigators noted that results from this trial have already led to approval of a monthly dosing schedule in the United States and several other countries.
“This convenient regimen has the potential to improve the care of patients by decreasing their treatment burden, and increasing uptake and adherence to effective prophylaxis, which is known to decrease the development of debilitating secondary complications,” the investigators wrote. The report is in The Lancet Haematology.
The data were collected at 20 centers in 8 countries. Eligibility required that patients have severe congenital hemophilia A (less than 1% normal FVIII activity), or hemophilia A with FVIII inhibitors and concurrent treatment with bypassing agents or FVIII concentrates.
An initial run-in cohort that included seven patients assessed pharmacokinetics and safety. These patients received 6 mg/kg of emicizumab subcutaneously every 4 weeks for at least 24 weeks. After this group showed good responses, 41 additional patients were enrolled in an expansion cohort, which involved an initial loading phase of weekly doses at 3 mg/kg for the first month, followed by monthly dosing at 6 mg/kg for at least 6 months (24 weeks).
The efficacy endpoint of the study was bleed prevention, as measured by treated target joint bleeds, treated joint bleeds, treated spontaneous bleeds, all bleeds (untreated and treated), and annualized bleed rates for treated bleeds.
In the expansion cohort, the median number of bleeds in the 24-week period preceding enrollment was five. In the same group, five patients (12%) had FVIII inhibitors and 61% of patients exhibited at least one target joint.
After a median treatment of 25.6 weeks, the model-based annualized bleed rate for treated bleeds was 2.4, while the median annualized bleed rate was zero.
Slightly more than half of the patients (56.1%) reported no treated bleeds, 90% of patients reported 0-3 treated bleeds, and 85% of patients did not require treatment for targeted joint bleeds.
When untreated bleeds were included, the model-based annualized bleed rate was 4.5, while the median annualized bleed rate was 2.1. Almost one-third of patients (29%) had no bleeding events of any kind and most (80%) had 0-3 treated or untreated bleeds.
Overall, treatment was well tolerated, with no patients withdrawing from the study, discontinuing treatment, or requiring dose modifications. Laboratory parameters remained stable throughout. The most common treatment-related adverse event was injection-site reaction (22%), followed distantly by pre-syncope, chills, rash, and erythema, each of which occurred in 2% of patients.
“Overall, the results of HAVEN 4 are consistent with the findings of other HAVEN studies,” the investigators wrote. “The option of treatment with emicizumab every 4 weeks broadens the range of administration frequencies and allows clinicians to tailor treatment to each patient’s needs and preferences.”
F. Hoffman-La Roche and Chugai funded the study. The investigators reported financial relationships with the study sponsors and other companies.
SOURCE: Pipe SW et al. Lancet Haem. 2019 Apr 16. doi: 10.1016/S2352-3026(19)30054-7.
FROM THE LANCET HAEMATOLOGY
New consensus recommendations on vaccination in hemophilia
New consensus statements, released by a panel of 11 experts, provide 27 specific recommendations related to the use of vaccines in patients with hemophilia.
The recommendations from the Italian Haemophilia and Vaccinations (HEVA) project were authored by an 11-member committee with expertise in both hemophilia and immunization. The authors reviewed 20 relevant studies published before August 30, 2017.
“Vaccination of patients with severe congenital bleeding disorders remains a challenge, and clinicians are often uncertain about immunization recommendations for these patients,” wrote Elena Santagostino, MD, PhD, of the Centro Emofilia e Trombosi Angelo Bianchi Bonomi in Milan, Italy, and her colleagues. The report is published in Haemophilia.
The statements were also validated by separate groups of clinicians at hemophilia treatment centers across Italy.
The key issues described included vaccination schedule, route of administration, vaccination of patients with antibodies that impede coagulation factor VIII inhibitors, and risk of inhibitor formation with vaccination.
In general, committee members agreed on the majority of statements, with the exception of those related to the possible links between vaccination and inhibitor formation. There were a total of five statements on which no consensus was reached.
Vaccinations in both adults and children with hemophilia should be provided in accordance with the institutional schedule for those without bleeding disorders, according to the recommendations.
“The only difference is that vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk,” the experts wrote.
The panel also reported that current data suggest that vaccination timing is not affected by the timing of factor VIII replacement.
The authors acknowledged that the recommendations were formed by a group of experts from Italy using a specific consensus framework. As a result, they may not be applicable to all patient populations.
The manuscript was supported by Sobi. The authors reported financial relationships with Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Pfizer, and other companies.
SOURCE: Santagostino E et al. Haemophilia. 2019 Apr 16. doi: 10.1111/hae.13756.
New consensus statements, released by a panel of 11 experts, provide 27 specific recommendations related to the use of vaccines in patients with hemophilia.
The recommendations from the Italian Haemophilia and Vaccinations (HEVA) project were authored by an 11-member committee with expertise in both hemophilia and immunization. The authors reviewed 20 relevant studies published before August 30, 2017.
“Vaccination of patients with severe congenital bleeding disorders remains a challenge, and clinicians are often uncertain about immunization recommendations for these patients,” wrote Elena Santagostino, MD, PhD, of the Centro Emofilia e Trombosi Angelo Bianchi Bonomi in Milan, Italy, and her colleagues. The report is published in Haemophilia.
The statements were also validated by separate groups of clinicians at hemophilia treatment centers across Italy.
The key issues described included vaccination schedule, route of administration, vaccination of patients with antibodies that impede coagulation factor VIII inhibitors, and risk of inhibitor formation with vaccination.
In general, committee members agreed on the majority of statements, with the exception of those related to the possible links between vaccination and inhibitor formation. There were a total of five statements on which no consensus was reached.
Vaccinations in both adults and children with hemophilia should be provided in accordance with the institutional schedule for those without bleeding disorders, according to the recommendations.
“The only difference is that vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk,” the experts wrote.
The panel also reported that current data suggest that vaccination timing is not affected by the timing of factor VIII replacement.
The authors acknowledged that the recommendations were formed by a group of experts from Italy using a specific consensus framework. As a result, they may not be applicable to all patient populations.
The manuscript was supported by Sobi. The authors reported financial relationships with Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Pfizer, and other companies.
SOURCE: Santagostino E et al. Haemophilia. 2019 Apr 16. doi: 10.1111/hae.13756.
New consensus statements, released by a panel of 11 experts, provide 27 specific recommendations related to the use of vaccines in patients with hemophilia.
The recommendations from the Italian Haemophilia and Vaccinations (HEVA) project were authored by an 11-member committee with expertise in both hemophilia and immunization. The authors reviewed 20 relevant studies published before August 30, 2017.
“Vaccination of patients with severe congenital bleeding disorders remains a challenge, and clinicians are often uncertain about immunization recommendations for these patients,” wrote Elena Santagostino, MD, PhD, of the Centro Emofilia e Trombosi Angelo Bianchi Bonomi in Milan, Italy, and her colleagues. The report is published in Haemophilia.
The statements were also validated by separate groups of clinicians at hemophilia treatment centers across Italy.
The key issues described included vaccination schedule, route of administration, vaccination of patients with antibodies that impede coagulation factor VIII inhibitors, and risk of inhibitor formation with vaccination.
In general, committee members agreed on the majority of statements, with the exception of those related to the possible links between vaccination and inhibitor formation. There were a total of five statements on which no consensus was reached.
Vaccinations in both adults and children with hemophilia should be provided in accordance with the institutional schedule for those without bleeding disorders, according to the recommendations.
“The only difference is that vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk,” the experts wrote.
The panel also reported that current data suggest that vaccination timing is not affected by the timing of factor VIII replacement.
The authors acknowledged that the recommendations were formed by a group of experts from Italy using a specific consensus framework. As a result, they may not be applicable to all patient populations.
The manuscript was supported by Sobi. The authors reported financial relationships with Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Pfizer, and other companies.
SOURCE: Santagostino E et al. Haemophilia. 2019 Apr 16. doi: 10.1111/hae.13756.
FROM HAEMOPHILIA