Bleeding Disorders

A novel point-of-care assay demonstrated sensitivity to monitor coagulation factor replacement therapy in patients with severe hemophilia A, with and without inhibitors, according to recent study findings.

The ClotChip assay is a novel factor-replacement therapy monitoring tool that uses a dielectric microsensor to assess whole-blood coagulation in patients with severe hemophilia A.

Debnath Maji of Case Western Reserve University, Cleveland, and colleagues evaluated the novel assay in attempt to address the unmet need of reliable monitoring of coagulation factor–replacement therapy. While global haemostasis assays are available to measure the missing function, these tools require expert interpretation, are technically challenging to operate, and may be unavailable at the bedside, they wrote in Haemophilia.

They evaluated the analytical capabilities of the assay in 6 patients with inhibitors and 12 patients without inhibitors. A total of 50 healthy controls were included in the study.

The team collected whole blood samples pre- and postcoagulation factor–replacement therapy. Measurements were also conducted on the thrombin generation assay (TGA), thromboelastography (TEG), and rotational thromboelastometry (ROTEM) global assays for comparison.

After analysis, the researchers found that ClotChip T-peak parameters showed a significant reduction for samples obtained post–factor replacement therapy versus pretherapy among patients with and without inhibitors (P = .028 and P = .0001, respectively).

Additionally, ClotChip T-peak values exhibited strong correlations with factor VIII clotting activity, clotting time parameters of ROTEM, and peak thrombin and endogenous thrombin potential of TGA.

“Taken together, these data suggest that the ClotChip T-peak parameter is sensitive to detection and correction of coagulopathy in children with haemophilia with and without inhibitors, as indicated by T-peak reaching reference‐range values after coagulation factor replacement therapy,” the researchers wrote.

One key limitation of the study was the small sample size, which may limit the generalizability of the findings.

The novel assay may be an appropriate tool for “real-world” decision making around the use of coagulation factor replacement therapy in patients with severe hemophilia A, they added.

The study was funded by the National Institutes of Health, the American Heart Association, and a Veterans Affairs Research Center of Excellence at Case Western Reserve University. The authors reported financial affiliations with Bayer, Bioverativ, Shire, and XaTek.

SOURCE: Maji D et al. Haemophilia. 2019 Jul 7. doi: 10.1111/hae.13799.

A novel point-of-care assay demonstrated sensitivity to monitor coagulation factor replacement therapy in patients with severe hemophilia A, with and without inhibitors, according to recent study findings.

The ClotChip assay is a novel factor-replacement therapy monitoring tool that uses a dielectric microsensor to assess whole-blood coagulation in patients with severe hemophilia A.

Debnath Maji of Case Western Reserve University, Cleveland, and colleagues evaluated the novel assay in attempt to address the unmet need of reliable monitoring of coagulation factor–replacement therapy. While global haemostasis assays are available to measure the missing function, these tools require expert interpretation, are technically challenging to operate, and may be unavailable at the bedside, they wrote in Haemophilia.

They evaluated the analytical capabilities of the assay in 6 patients with inhibitors and 12 patients without inhibitors. A total of 50 healthy controls were included in the study.

The team collected whole blood samples pre- and postcoagulation factor–replacement therapy. Measurements were also conducted on the thrombin generation assay (TGA), thromboelastography (TEG), and rotational thromboelastometry (ROTEM) global assays for comparison.

After analysis, the researchers found that ClotChip T-peak parameters showed a significant reduction for samples obtained post–factor replacement therapy versus pretherapy among patients with and without inhibitors (P = .028 and P = .0001, respectively).

Additionally, ClotChip T-peak values exhibited strong correlations with factor VIII clotting activity, clotting time parameters of ROTEM, and peak thrombin and endogenous thrombin potential of TGA.

“Taken together, these data suggest that the ClotChip T-peak parameter is sensitive to detection and correction of coagulopathy in children with haemophilia with and without inhibitors, as indicated by T-peak reaching reference‐range values after coagulation factor replacement therapy,” the researchers wrote.

One key limitation of the study was the small sample size, which may limit the generalizability of the findings.

The novel assay may be an appropriate tool for “real-world” decision making around the use of coagulation factor replacement therapy in patients with severe hemophilia A, they added.

The study was funded by the National Institutes of Health, the American Heart Association, and a Veterans Affairs Research Center of Excellence at Case Western Reserve University. The authors reported financial affiliations with Bayer, Bioverativ, Shire, and XaTek.

SOURCE: Maji D et al. Haemophilia. 2019 Jul 7. doi: 10.1111/hae.13799.

A novel point-of-care assay demonstrated sensitivity to monitor coagulation factor replacement therapy in patients with severe hemophilia A, with and without inhibitors, according to recent study findings.

The ClotChip assay is a novel factor-replacement therapy monitoring tool that uses a dielectric microsensor to assess whole-blood coagulation in patients with severe hemophilia A.

Debnath Maji of Case Western Reserve University, Cleveland, and colleagues evaluated the novel assay in attempt to address the unmet need of reliable monitoring of coagulation factor–replacement therapy. While global haemostasis assays are available to measure the missing function, these tools require expert interpretation, are technically challenging to operate, and may be unavailable at the bedside, they wrote in Haemophilia.

They evaluated the analytical capabilities of the assay in 6 patients with inhibitors and 12 patients without inhibitors. A total of 50 healthy controls were included in the study.

The team collected whole blood samples pre- and postcoagulation factor–replacement therapy. Measurements were also conducted on the thrombin generation assay (TGA), thromboelastography (TEG), and rotational thromboelastometry (ROTEM) global assays for comparison.

After analysis, the researchers found that ClotChip T-peak parameters showed a significant reduction for samples obtained post–factor replacement therapy versus pretherapy among patients with and without inhibitors (P = .028 and P = .0001, respectively).

Additionally, ClotChip T-peak values exhibited strong correlations with factor VIII clotting activity, clotting time parameters of ROTEM, and peak thrombin and endogenous thrombin potential of TGA.

“Taken together, these data suggest that the ClotChip T-peak parameter is sensitive to detection and correction of coagulopathy in children with haemophilia with and without inhibitors, as indicated by T-peak reaching reference‐range values after coagulation factor replacement therapy,” the researchers wrote.

One key limitation of the study was the small sample size, which may limit the generalizability of the findings.

The novel assay may be an appropriate tool for “real-world” decision making around the use of coagulation factor replacement therapy in patients with severe hemophilia A, they added.

The study was funded by the National Institutes of Health, the American Heart Association, and a Veterans Affairs Research Center of Excellence at Case Western Reserve University. The authors reported financial affiliations with Bayer, Bioverativ, Shire, and XaTek.

SOURCE: Maji D et al. Haemophilia. 2019 Jul 7. doi: 10.1111/hae.13799.

MELBOURNE – Subcutaneous administration of the monoclonal antibody marstacimab (PF-06741086) provides significant reductions in bleeding rates for patients with hemophilia A and B, with reasonably safety and tolerability, according to research presented at the International Society on Thrombosis and Haemostasis congress.

Johnny Mahlangu, MBBCh, of the University of Witwatersrand in Johannesburg, South Africa, presented data from a multicenter, international phase 1B/2 open-label study involving 26 patients with severe hemophilia, who had experienced at least six acute bleeding episodes in the 6 months prior to enrollment. Twenty-three patients had hemophilia A, the remaining three patients had hemophilia B, and all were receiving on-demand treatment.

Patients were divided into one of four cohorts. Cohort 1 received a weekly 300-mg dose subcutaneously for 30 days, cohort 2 received a 300-mg loading dose followed by 150 mg weekly for 30 days, cohort 3 received 450 mg weekly for 30 days, and cohort 4 also received a 300-mg weekly dose for 30 days but consisted of patients with inhibitors.

With the primary outcome being safety, the researchers reported no treatment-related serious adverse events. There were four grade 3/4 adverse events, including two subjects who reported injection site reactions, and some generalized pruritus and erythematous rash.

Two patients discontinued treatment after reaching prespecified dose-limiting toxicity related to decreasing fibrinogen levels, compared with baseline. However, Dr. Mahlangu pointed out that, in one of these patients, the fibrinogen levels were still within normal levels but protocol required removing the patient from the study.

The study did see a significant 85%-97% reduction in annualized bleed rates across the four cohorts, including among patients with inhibitors.

“Most patients who were exposed to marstacimab actually did not bleed at all when they were receiving marstacimab, compared to when they weren’t receiving marstacimab,” Dr. Mahlangu said.

While three patients developed antidrug antibodies, this did not appear to impact the pharmacokinetics, pharmacodynamics, or safety, he said. No patients developed neutralizing antibodies, and the pharmacodynamics showed no difference between patients with hemophilia A and B.

“I would like to believe that the results of this study are fairly promising in terms of the safety, the efficacy, the pharmoacokinetics, and the pharmacodynamics,” Dr. Mahlangu said.

There is an unmet need for therapies that can be used in patients with either hemophilia A or B, and with or without inhibitors, Dr. Mahlangu said in an interview. Another unmet need that marstacimab could potentially address is for subcutaneous treatment options, he added.

“We are particularly pleased by the fact that injection-site reactions are very low, and they seem not to carry on every time the patients have injected,” Dr. Mahlangu said.

Commenting on the presentation, session cochair Julia Phillips, MD, from PathLab in Waikato, New Zealand, said subcutaneous treatments offered a huge advantage to patients with hemophilia and their families.

“Often more than one member of the family is affected. So [for] a family with children, if they have several sons with hemophilia, then doing IV injections before school on a regular basis can be quite a big burden on the family,” she said in an interview.

The study was sponsored by Pfizer. Dr. Mahlangu reported research support from and scientific advisory board and speakers bureau roles with several pharmaceutical companies, including Pfizer.

SOURCE: Mahlangu J et al. 2019. ISTH CONGRESS, Abstract OC 11.2.

MELBOURNE – Subcutaneous administration of the monoclonal antibody marstacimab (PF-06741086) provides significant reductions in bleeding rates for patients with hemophilia A and B, with reasonably safety and tolerability, according to research presented at the International Society on Thrombosis and Haemostasis congress.

Johnny Mahlangu, MBBCh, of the University of Witwatersrand in Johannesburg, South Africa, presented data from a multicenter, international phase 1B/2 open-label study involving 26 patients with severe hemophilia, who had experienced at least six acute bleeding episodes in the 6 months prior to enrollment. Twenty-three patients had hemophilia A, the remaining three patients had hemophilia B, and all were receiving on-demand treatment.

Patients were divided into one of four cohorts. Cohort 1 received a weekly 300-mg dose subcutaneously for 30 days, cohort 2 received a 300-mg loading dose followed by 150 mg weekly for 30 days, cohort 3 received 450 mg weekly for 30 days, and cohort 4 also received a 300-mg weekly dose for 30 days but consisted of patients with inhibitors.

With the primary outcome being safety, the researchers reported no treatment-related serious adverse events. There were four grade 3/4 adverse events, including two subjects who reported injection site reactions, and some generalized pruritus and erythematous rash.

Two patients discontinued treatment after reaching prespecified dose-limiting toxicity related to decreasing fibrinogen levels, compared with baseline. However, Dr. Mahlangu pointed out that, in one of these patients, the fibrinogen levels were still within normal levels but protocol required removing the patient from the study.

The study did see a significant 85%-97% reduction in annualized bleed rates across the four cohorts, including among patients with inhibitors.

“Most patients who were exposed to marstacimab actually did not bleed at all when they were receiving marstacimab, compared to when they weren’t receiving marstacimab,” Dr. Mahlangu said.

While three patients developed antidrug antibodies, this did not appear to impact the pharmacokinetics, pharmacodynamics, or safety, he said. No patients developed neutralizing antibodies, and the pharmacodynamics showed no difference between patients with hemophilia A and B.

“I would like to believe that the results of this study are fairly promising in terms of the safety, the efficacy, the pharmoacokinetics, and the pharmacodynamics,” Dr. Mahlangu said.

There is an unmet need for therapies that can be used in patients with either hemophilia A or B, and with or without inhibitors, Dr. Mahlangu said in an interview. Another unmet need that marstacimab could potentially address is for subcutaneous treatment options, he added.

“We are particularly pleased by the fact that injection-site reactions are very low, and they seem not to carry on every time the patients have injected,” Dr. Mahlangu said.

Commenting on the presentation, session cochair Julia Phillips, MD, from PathLab in Waikato, New Zealand, said subcutaneous treatments offered a huge advantage to patients with hemophilia and their families.

“Often more than one member of the family is affected. So [for] a family with children, if they have several sons with hemophilia, then doing IV injections before school on a regular basis can be quite a big burden on the family,” she said in an interview.

The study was sponsored by Pfizer. Dr. Mahlangu reported research support from and scientific advisory board and speakers bureau roles with several pharmaceutical companies, including Pfizer.

SOURCE: Mahlangu J et al. 2019. ISTH CONGRESS, Abstract OC 11.2.

MELBOURNE – Subcutaneous administration of the monoclonal antibody marstacimab (PF-06741086) provides significant reductions in bleeding rates for patients with hemophilia A and B, with reasonably safety and tolerability, according to research presented at the International Society on Thrombosis and Haemostasis congress.

Johnny Mahlangu, MBBCh, of the University of Witwatersrand in Johannesburg, South Africa, presented data from a multicenter, international phase 1B/2 open-label study involving 26 patients with severe hemophilia, who had experienced at least six acute bleeding episodes in the 6 months prior to enrollment. Twenty-three patients had hemophilia A, the remaining three patients had hemophilia B, and all were receiving on-demand treatment.

Patients were divided into one of four cohorts. Cohort 1 received a weekly 300-mg dose subcutaneously for 30 days, cohort 2 received a 300-mg loading dose followed by 150 mg weekly for 30 days, cohort 3 received 450 mg weekly for 30 days, and cohort 4 also received a 300-mg weekly dose for 30 days but consisted of patients with inhibitors.

With the primary outcome being safety, the researchers reported no treatment-related serious adverse events. There were four grade 3/4 adverse events, including two subjects who reported injection site reactions, and some generalized pruritus and erythematous rash.

Two patients discontinued treatment after reaching prespecified dose-limiting toxicity related to decreasing fibrinogen levels, compared with baseline. However, Dr. Mahlangu pointed out that, in one of these patients, the fibrinogen levels were still within normal levels but protocol required removing the patient from the study.

The study did see a significant 85%-97% reduction in annualized bleed rates across the four cohorts, including among patients with inhibitors.

“Most patients who were exposed to marstacimab actually did not bleed at all when they were receiving marstacimab, compared to when they weren’t receiving marstacimab,” Dr. Mahlangu said.

While three patients developed antidrug antibodies, this did not appear to impact the pharmacokinetics, pharmacodynamics, or safety, he said. No patients developed neutralizing antibodies, and the pharmacodynamics showed no difference between patients with hemophilia A and B.

“I would like to believe that the results of this study are fairly promising in terms of the safety, the efficacy, the pharmoacokinetics, and the pharmacodynamics,” Dr. Mahlangu said.

There is an unmet need for therapies that can be used in patients with either hemophilia A or B, and with or without inhibitors, Dr. Mahlangu said in an interview. Another unmet need that marstacimab could potentially address is for subcutaneous treatment options, he added.

“We are particularly pleased by the fact that injection-site reactions are very low, and they seem not to carry on every time the patients have injected,” Dr. Mahlangu said.

Commenting on the presentation, session cochair Julia Phillips, MD, from PathLab in Waikato, New Zealand, said subcutaneous treatments offered a huge advantage to patients with hemophilia and their families.

“Often more than one member of the family is affected. So [for] a family with children, if they have several sons with hemophilia, then doing IV injections before school on a regular basis can be quite a big burden on the family,” she said in an interview.

The study was sponsored by Pfizer. Dr. Mahlangu reported research support from and scientific advisory board and speakers bureau roles with several pharmaceutical companies, including Pfizer.

SOURCE: Mahlangu J et al. 2019. ISTH CONGRESS, Abstract OC 11.2.

MELBOURNE – The treatment of cancer-associated thrombosis may be complicated by increased bleeding risk in patients with gastrointestinal cancer, in whom direct oral anticoagulants may not be the ideal first choice, one expert reported at the International Society on Thrombosis and Haemostasis congress.

Agnes Y.Y. Lee, MD, medical director of the Thrombosis Program at Vancouver General Hospital and the University of British Columbia, spoke about the challenges and necessity of treating cancer-associated thrombosis, pointing out that about 20% of all cases of venous thromboembolism (VTE) are associated with cancer.

“In those with cancer, thrombosis can also interfere with cancer treatment, increases health care costs, and is extraordinarily burdensome to patients and their families,” she said. “Fortunately the most effective way to reduce this burden is to use anticoagulant therapy for prevention and treatment.”

While direct oral anticoagulants have been shown in several studies to be comparable to warfarin in treating most patients with thrombosis, Dr. Lee said there has been a question of how they compare in safety and efficacy to low-molecular-weight heparin in individuals with cancer.

Data from the Hokusai VTE Cancer trial, which compared oral edoxaban with subcutaneous dalteparin in patients with cancer, showed that the two treatments were comparable in time to first occurrence of thrombosis. However, the study did show a fourfold higher risk of bleeding with edoxaban, compared with that of dalteparin, among individuals with gastrointestinal cancers, a difference in bleeding rate that was not seen in patients with nongastrointestinal cancers, Dr. Lee said.

Dr. Lee pointed out that this study also showed a higher bleeding risk in patients with other bleeding risk factors, including those with primary or metastatic brain cancer.

“This study also showed that, when patients developed major bleeding, 60%-80% of them required hospitalization or an ICU stay, so major bleeding is a serious complication and certainly will increase the cost of therapy for these patients,” she said.

In the SELECT-D pilot study, which compared rivaroxaban with dalteparin in patients with cancer, there was a higher risk of bleeding for patients with esophageal or gastroesophageal cancers.

Bleeding risk is generally not well addressed in current guidelines on managing hemostasis in patients with malignancies, partly because it is difficult to quantify bleeding in these patients whose hemoglobin levels would be affected by their disease and their chemotherapy, Dr. Lee said in an interview.

“The bleeding events in cancer patients do get more complicated because there’s all this other noise in the background,” she said.

Commenting on her personal approach to treatment, Dr. Lee said she favors starting patients on low-molecular-weight heparin because it gives her time to understand patients, their disease, and their needs.

“A lot of patients arrive, and they can’t really tell me what their cancer is doing, they can’t really tell me what cancer therapy they’re going through,” she says. “And if they’re on a long list of drugs, then I have to talk to my pharmacist about whether there are drug-drug interactions.”

If patients were well managed on low-molecular-weight heparin without any bleeding, then Dr. Lee said she would consider switching them to direct oral anticoagulants.

Cochair of the session, Ingrid Pabinger, MD, from the Medical University of Vienna commented that vitamin K antagonists should not be forgotten because some patients are unable to afford low-molecular-weight heparin.

However Dr. Lee said these were last on the list for her because of the risk of drug-drug interactions, drug-food interactions, and the issues faced by patients experiencing vomiting or diarrhea with their chemotherapy.

Dr. Lee reported research funding, consultancies, and honoraria from the pharmaceutical sector.

MELBOURNE – The treatment of cancer-associated thrombosis may be complicated by increased bleeding risk in patients with gastrointestinal cancer, in whom direct oral anticoagulants may not be the ideal first choice, one expert reported at the International Society on Thrombosis and Haemostasis congress.

Agnes Y.Y. Lee, MD, medical director of the Thrombosis Program at Vancouver General Hospital and the University of British Columbia, spoke about the challenges and necessity of treating cancer-associated thrombosis, pointing out that about 20% of all cases of venous thromboembolism (VTE) are associated with cancer.

“In those with cancer, thrombosis can also interfere with cancer treatment, increases health care costs, and is extraordinarily burdensome to patients and their families,” she said. “Fortunately the most effective way to reduce this burden is to use anticoagulant therapy for prevention and treatment.”

While direct oral anticoagulants have been shown in several studies to be comparable to warfarin in treating most patients with thrombosis, Dr. Lee said there has been a question of how they compare in safety and efficacy to low-molecular-weight heparin in individuals with cancer.

Data from the Hokusai VTE Cancer trial, which compared oral edoxaban with subcutaneous dalteparin in patients with cancer, showed that the two treatments were comparable in time to first occurrence of thrombosis. However, the study did show a fourfold higher risk of bleeding with edoxaban, compared with that of dalteparin, among individuals with gastrointestinal cancers, a difference in bleeding rate that was not seen in patients with nongastrointestinal cancers, Dr. Lee said.

Dr. Lee pointed out that this study also showed a higher bleeding risk in patients with other bleeding risk factors, including those with primary or metastatic brain cancer.

“This study also showed that, when patients developed major bleeding, 60%-80% of them required hospitalization or an ICU stay, so major bleeding is a serious complication and certainly will increase the cost of therapy for these patients,” she said.

In the SELECT-D pilot study, which compared rivaroxaban with dalteparin in patients with cancer, there was a higher risk of bleeding for patients with esophageal or gastroesophageal cancers.

Bleeding risk is generally not well addressed in current guidelines on managing hemostasis in patients with malignancies, partly because it is difficult to quantify bleeding in these patients whose hemoglobin levels would be affected by their disease and their chemotherapy, Dr. Lee said in an interview.

“The bleeding events in cancer patients do get more complicated because there’s all this other noise in the background,” she said.

Commenting on her personal approach to treatment, Dr. Lee said she favors starting patients on low-molecular-weight heparin because it gives her time to understand patients, their disease, and their needs.

“A lot of patients arrive, and they can’t really tell me what their cancer is doing, they can’t really tell me what cancer therapy they’re going through,” she says. “And if they’re on a long list of drugs, then I have to talk to my pharmacist about whether there are drug-drug interactions.”

If patients were well managed on low-molecular-weight heparin without any bleeding, then Dr. Lee said she would consider switching them to direct oral anticoagulants.

Cochair of the session, Ingrid Pabinger, MD, from the Medical University of Vienna commented that vitamin K antagonists should not be forgotten because some patients are unable to afford low-molecular-weight heparin.

However Dr. Lee said these were last on the list for her because of the risk of drug-drug interactions, drug-food interactions, and the issues faced by patients experiencing vomiting or diarrhea with their chemotherapy.

Dr. Lee reported research funding, consultancies, and honoraria from the pharmaceutical sector.

MELBOURNE – The treatment of cancer-associated thrombosis may be complicated by increased bleeding risk in patients with gastrointestinal cancer, in whom direct oral anticoagulants may not be the ideal first choice, one expert reported at the International Society on Thrombosis and Haemostasis congress.

Agnes Y.Y. Lee, MD, medical director of the Thrombosis Program at Vancouver General Hospital and the University of British Columbia, spoke about the challenges and necessity of treating cancer-associated thrombosis, pointing out that about 20% of all cases of venous thromboembolism (VTE) are associated with cancer.

“In those with cancer, thrombosis can also interfere with cancer treatment, increases health care costs, and is extraordinarily burdensome to patients and their families,” she said. “Fortunately the most effective way to reduce this burden is to use anticoagulant therapy for prevention and treatment.”

While direct oral anticoagulants have been shown in several studies to be comparable to warfarin in treating most patients with thrombosis, Dr. Lee said there has been a question of how they compare in safety and efficacy to low-molecular-weight heparin in individuals with cancer.

Data from the Hokusai VTE Cancer trial, which compared oral edoxaban with subcutaneous dalteparin in patients with cancer, showed that the two treatments were comparable in time to first occurrence of thrombosis. However, the study did show a fourfold higher risk of bleeding with edoxaban, compared with that of dalteparin, among individuals with gastrointestinal cancers, a difference in bleeding rate that was not seen in patients with nongastrointestinal cancers, Dr. Lee said.

Dr. Lee pointed out that this study also showed a higher bleeding risk in patients with other bleeding risk factors, including those with primary or metastatic brain cancer.

“This study also showed that, when patients developed major bleeding, 60%-80% of them required hospitalization or an ICU stay, so major bleeding is a serious complication and certainly will increase the cost of therapy for these patients,” she said.

In the SELECT-D pilot study, which compared rivaroxaban with dalteparin in patients with cancer, there was a higher risk of bleeding for patients with esophageal or gastroesophageal cancers.

Bleeding risk is generally not well addressed in current guidelines on managing hemostasis in patients with malignancies, partly because it is difficult to quantify bleeding in these patients whose hemoglobin levels would be affected by their disease and their chemotherapy, Dr. Lee said in an interview.

“The bleeding events in cancer patients do get more complicated because there’s all this other noise in the background,” she said.

Commenting on her personal approach to treatment, Dr. Lee said she favors starting patients on low-molecular-weight heparin because it gives her time to understand patients, their disease, and their needs.

“A lot of patients arrive, and they can’t really tell me what their cancer is doing, they can’t really tell me what cancer therapy they’re going through,” she says. “And if they’re on a long list of drugs, then I have to talk to my pharmacist about whether there are drug-drug interactions.”

If patients were well managed on low-molecular-weight heparin without any bleeding, then Dr. Lee said she would consider switching them to direct oral anticoagulants.

Cochair of the session, Ingrid Pabinger, MD, from the Medical University of Vienna commented that vitamin K antagonists should not be forgotten because some patients are unable to afford low-molecular-weight heparin.

However Dr. Lee said these were last on the list for her because of the risk of drug-drug interactions, drug-food interactions, and the issues faced by patients experiencing vomiting or diarrhea with their chemotherapy.

Dr. Lee reported research funding, consultancies, and honoraria from the pharmaceutical sector.

The recombinant factor VIII (rFVIII) product BAY 94‐9027 had a better pharmacokinetic (PK) profile than a recombinant factor VIII-Fc fusion protein (rFVIIIFc) in patients with hemophilia A, according to a recent report.

“The objective of the current study was to directly compare the PK profiles of BAY 94-9027 and rFVIIIFc,” wrote Anita Shah, lead author and an employee of Bayer, and colleagues. The findings were published in the Annals of Hematology.

In a two-way PK crossover study, adults (aged 18-65 years) with severe hemophilia A were randomized to receive a single intravenous dose (60 IU/kg) of BAY 94-9027 or rFVIIIFc. These infusions were followed by a crossover to a single infusion of the other product.

The maximum wash-out period between infusions was 28 days, with a greater than or equal to 7-day wash-out between doses. FVIII activity was analyzed using a single one-stage clotting assay.

After population PK modeling, the median time to achieve FVIII threshold levels (1 IU/dL) was found to be 13 hours longer for BAY 94-9027 than it was for rFVIIIFc following a single intravenous dose of 60 IU/kg.

In addition, the team reported that the geometric mean area under the curve from baseline to the last data point was significantly greater for BAY 94-9027 than it was for rFVIIIFc (coefficient of variation, 2,940 vs. 2,360 IU h/dL; P = .0001)

“This increase in the time above threshold may thereby provide improved bleeding protection,” the authors explained.

With respect to safety, no adverse events were reported among study participants.

The researchers acknowledged a key limitation of the study was the nonexistence of a two-stage chromogenic assay to measure FVIII activity of both products. As a result, a one-stage clotting assay was used to analyze FVIII activity for both treatments.

“Real-world data may provide an insight into whether these PK advantages provide additional bleeding protection,” they concluded.

The study was funded by Bayer AG. The authors reported financial affiliations with Bayer, LFB, Octapharma, Pfizer, Roche, Shire, and several others.

SOURCE: Shah A et al. Ann Hematol. 2019 Jun 24. doi: 10.1007/s00277-019-03747-2.

The recombinant factor VIII (rFVIII) product BAY 94‐9027 had a better pharmacokinetic (PK) profile than a recombinant factor VIII-Fc fusion protein (rFVIIIFc) in patients with hemophilia A, according to a recent report.

“The objective of the current study was to directly compare the PK profiles of BAY 94-9027 and rFVIIIFc,” wrote Anita Shah, lead author and an employee of Bayer, and colleagues. The findings were published in the Annals of Hematology.

In a two-way PK crossover study, adults (aged 18-65 years) with severe hemophilia A were randomized to receive a single intravenous dose (60 IU/kg) of BAY 94-9027 or rFVIIIFc. These infusions were followed by a crossover to a single infusion of the other product.

The maximum wash-out period between infusions was 28 days, with a greater than or equal to 7-day wash-out between doses. FVIII activity was analyzed using a single one-stage clotting assay.

After population PK modeling, the median time to achieve FVIII threshold levels (1 IU/dL) was found to be 13 hours longer for BAY 94-9027 than it was for rFVIIIFc following a single intravenous dose of 60 IU/kg.

In addition, the team reported that the geometric mean area under the curve from baseline to the last data point was significantly greater for BAY 94-9027 than it was for rFVIIIFc (coefficient of variation, 2,940 vs. 2,360 IU h/dL; P = .0001)

“This increase in the time above threshold may thereby provide improved bleeding protection,” the authors explained.

With respect to safety, no adverse events were reported among study participants.

The researchers acknowledged a key limitation of the study was the nonexistence of a two-stage chromogenic assay to measure FVIII activity of both products. As a result, a one-stage clotting assay was used to analyze FVIII activity for both treatments.

“Real-world data may provide an insight into whether these PK advantages provide additional bleeding protection,” they concluded.

The study was funded by Bayer AG. The authors reported financial affiliations with Bayer, LFB, Octapharma, Pfizer, Roche, Shire, and several others.

SOURCE: Shah A et al. Ann Hematol. 2019 Jun 24. doi: 10.1007/s00277-019-03747-2.

The recombinant factor VIII (rFVIII) product BAY 94‐9027 had a better pharmacokinetic (PK) profile than a recombinant factor VIII-Fc fusion protein (rFVIIIFc) in patients with hemophilia A, according to a recent report.

“The objective of the current study was to directly compare the PK profiles of BAY 94-9027 and rFVIIIFc,” wrote Anita Shah, lead author and an employee of Bayer, and colleagues. The findings were published in the Annals of Hematology.

In a two-way PK crossover study, adults (aged 18-65 years) with severe hemophilia A were randomized to receive a single intravenous dose (60 IU/kg) of BAY 94-9027 or rFVIIIFc. These infusions were followed by a crossover to a single infusion of the other product.

The maximum wash-out period between infusions was 28 days, with a greater than or equal to 7-day wash-out between doses. FVIII activity was analyzed using a single one-stage clotting assay.

After population PK modeling, the median time to achieve FVIII threshold levels (1 IU/dL) was found to be 13 hours longer for BAY 94-9027 than it was for rFVIIIFc following a single intravenous dose of 60 IU/kg.

In addition, the team reported that the geometric mean area under the curve from baseline to the last data point was significantly greater for BAY 94-9027 than it was for rFVIIIFc (coefficient of variation, 2,940 vs. 2,360 IU h/dL; P = .0001)

“This increase in the time above threshold may thereby provide improved bleeding protection,” the authors explained.

With respect to safety, no adverse events were reported among study participants.

The researchers acknowledged a key limitation of the study was the nonexistence of a two-stage chromogenic assay to measure FVIII activity of both products. As a result, a one-stage clotting assay was used to analyze FVIII activity for both treatments.

“Real-world data may provide an insight into whether these PK advantages provide additional bleeding protection,” they concluded.

The study was funded by Bayer AG. The authors reported financial affiliations with Bayer, LFB, Octapharma, Pfizer, Roche, Shire, and several others.

SOURCE: Shah A et al. Ann Hematol. 2019 Jun 24. doi: 10.1007/s00277-019-03747-2.

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

[email protected]

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

[email protected]

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

[email protected]

For previously untreated patients with severe hemophilia A, the risk of developing factor VIII (FVIII) inhibitors becomes marginal after 75 exposure days, according to an observational study of more than 1,000 infants on prophylaxis.

“Most inhibitors develop during the first 50 exposure days to FVIII, with 50% of inhibitors already present after 14-15 exposure days,” wrote H. Marijke van den Berg, MD, PhD, of the PedNet Haemophilia Research Foundation, Baarn, the Netherlands. The findings were published in Blood.

Dr. van den Berg and her colleagues aimed to characterize the risk of inhibitor development beyond 50 exposure days and to calculate the age when patients reach near-zero risk. The researchers followed 1,038 previously untreated patients with severe hemophilia A from first exposure to FVIII until inhibitor development, up to a maximum of 1,000 exposure days. Data was obtained from the PedNet Haemophilia Registry.

From the initial cohort, 943 patients (91%) were followed until 50 exposure days, and 899 (87%) were followed until 75 exposure days. Inhibitor development was defined by a minimum of two positive inhibitor titers in conjunction with reduced in-vivo FVIII recovery. The team also conducted a survival analysis to measure inhibitor incidence and reported median ages at initial exposure and at exposure day 75.

After analysis, the researchers found that 298 of 300 (99.3%) occurrences of inhibitor development ensued within 75 exposure days. No inhibitor development occurred between exposure day 75 and 150. The final two occurrences developed at exposure day 249 and 262, each with a low titer. The median age at first exposure was 1.1 years versus 2.3 years at exposure day 75.

“Our study shows that children on prophylaxis reach a near-zero risk plateau of inhibitor development at 75 [exposure days] only 1.2 years after the first [exposure day],” they wrote.

The researchers explained that these findings could impact the design of future clinical studies for previously untreated patients with severe hemophilia A. And they noted that these data are applicable to patients administered early prophylaxis, since the majority of study participants began prophylaxis early in life. “Frequent testing for inhibitors until 75 instead of 50 exposure days, therefore, is feasible and should be recommended for all [previously untreated patients],” they concluded.

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

SOURCE: van den Berg HM et al. Blood. 2019 Jun 11. doi: 10.1182/blood.2019000658.

For previously untreated patients with severe hemophilia A, the risk of developing factor VIII (FVIII) inhibitors becomes marginal after 75 exposure days, according to an observational study of more than 1,000 infants on prophylaxis.

“Most inhibitors develop during the first 50 exposure days to FVIII, with 50% of inhibitors already present after 14-15 exposure days,” wrote H. Marijke van den Berg, MD, PhD, of the PedNet Haemophilia Research Foundation, Baarn, the Netherlands. The findings were published in Blood.

Dr. van den Berg and her colleagues aimed to characterize the risk of inhibitor development beyond 50 exposure days and to calculate the age when patients reach near-zero risk. The researchers followed 1,038 previously untreated patients with severe hemophilia A from first exposure to FVIII until inhibitor development, up to a maximum of 1,000 exposure days. Data was obtained from the PedNet Haemophilia Registry.

From the initial cohort, 943 patients (91%) were followed until 50 exposure days, and 899 (87%) were followed until 75 exposure days. Inhibitor development was defined by a minimum of two positive inhibitor titers in conjunction with reduced in-vivo FVIII recovery. The team also conducted a survival analysis to measure inhibitor incidence and reported median ages at initial exposure and at exposure day 75.

After analysis, the researchers found that 298 of 300 (99.3%) occurrences of inhibitor development ensued within 75 exposure days. No inhibitor development occurred between exposure day 75 and 150. The final two occurrences developed at exposure day 249 and 262, each with a low titer. The median age at first exposure was 1.1 years versus 2.3 years at exposure day 75.

“Our study shows that children on prophylaxis reach a near-zero risk plateau of inhibitor development at 75 [exposure days] only 1.2 years after the first [exposure day],” they wrote.

The researchers explained that these findings could impact the design of future clinical studies for previously untreated patients with severe hemophilia A. And they noted that these data are applicable to patients administered early prophylaxis, since the majority of study participants began prophylaxis early in life. “Frequent testing for inhibitors until 75 instead of 50 exposure days, therefore, is feasible and should be recommended for all [previously untreated patients],” they concluded.

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

SOURCE: van den Berg HM et al. Blood. 2019 Jun 11. doi: 10.1182/blood.2019000658.

For previously untreated patients with severe hemophilia A, the risk of developing factor VIII (FVIII) inhibitors becomes marginal after 75 exposure days, according to an observational study of more than 1,000 infants on prophylaxis.

“Most inhibitors develop during the first 50 exposure days to FVIII, with 50% of inhibitors already present after 14-15 exposure days,” wrote H. Marijke van den Berg, MD, PhD, of the PedNet Haemophilia Research Foundation, Baarn, the Netherlands. The findings were published in Blood.

Dr. van den Berg and her colleagues aimed to characterize the risk of inhibitor development beyond 50 exposure days and to calculate the age when patients reach near-zero risk. The researchers followed 1,038 previously untreated patients with severe hemophilia A from first exposure to FVIII until inhibitor development, up to a maximum of 1,000 exposure days. Data was obtained from the PedNet Haemophilia Registry.

From the initial cohort, 943 patients (91%) were followed until 50 exposure days, and 899 (87%) were followed until 75 exposure days. Inhibitor development was defined by a minimum of two positive inhibitor titers in conjunction with reduced in-vivo FVIII recovery. The team also conducted a survival analysis to measure inhibitor incidence and reported median ages at initial exposure and at exposure day 75.

After analysis, the researchers found that 298 of 300 (99.3%) occurrences of inhibitor development ensued within 75 exposure days. No inhibitor development occurred between exposure day 75 and 150. The final two occurrences developed at exposure day 249 and 262, each with a low titer. The median age at first exposure was 1.1 years versus 2.3 years at exposure day 75.

“Our study shows that children on prophylaxis reach a near-zero risk plateau of inhibitor development at 75 [exposure days] only 1.2 years after the first [exposure day],” they wrote.

The researchers explained that these findings could impact the design of future clinical studies for previously untreated patients with severe hemophilia A. And they noted that these data are applicable to patients administered early prophylaxis, since the majority of study participants began prophylaxis early in life. “Frequent testing for inhibitors until 75 instead of 50 exposure days, therefore, is feasible and should be recommended for all [previously untreated patients],” they concluded.

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

SOURCE: van den Berg HM et al. Blood. 2019 Jun 11. doi: 10.1182/blood.2019000658.

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – For patients with immune thrombocytopenia (ITP), platelet glycoprotein genotypes may predict effectiveness of specific therapies, according to investigators.

Will Pass/MDedge News

Significant relationships were detected between allelic polymorphisms of glycoprotein genes and durable responses to corticosteroids, thrombopoietin receptor agonists (aTPOr), and splenectomy, reported lead author Irina Zotova, MD, of the Russian Research Institute of Hematology and Transfusiology, Federal Biomedical Agency, in Saint Petersburg and colleagues.

These findings could guide clinical decision making in ITP, according to Dr. Zotova.

“Currently, the choice of therapeutic approach to ITP treatment, especially the second-line, is empirical, and often based on the experience of the clinician,” Dr. Zotova said during her presentation at the annual congress of the European Hematology Association. “Recent studies have shown that ... genes coding for glycoprotein are involved in platelet function and are associated with different responses to ITP treatment. This provides an opportunity for an individual approach and personalization of ITP therapy in accordance with the genetic status of the patient.”

In the present study, the investigators used PCR-RFLP (polymerase chain reaction–restriction fragment length polymorphism) to determine GPIa A1648G and GPIIb 2622TG gene status in 81 patients with primary ITP and compared these genotypes with clinical responses.

All patients received first-line corticosteroid therapy. If necessary, second-line treatment was delivered. In total, 37 patients (46%) received aTPOr, while 22 patients (27%) underwent splenectomy. Responses were classified as durable response, nondurable response, or no response.

Analysis showed that a significantly greater proportion of patients who had durable responses to corticosteroid therapy exhibited a heterozygous GPIIb 2622TG genotype, compared with patients who had nondurable responses (72.2% vs. 30.9%; odds ratio, 5.8; P = .005).

For second-line responses, patients who had durable response to aTPOr were much more likely to be homozygous for the GPIa A1648G than nonresponders (87.5% vs. 20.0%; OR, 28.0; P = .005). More strikingly, all patients who achieved durable responses to splenectomy had the GPIa A1648G genotype, compared with just 44% of nonresponders (OR, 33.0; P = .005).

“Gentoyping for the GPIIb T2622G and GPIa A1648G polymorphisms allows [clinicians] to predict the response to first-line and second-line treatment, giving the possibility to stratify patients to groups with favorable and unfavorable courses of the disease,” Dr. Zotova concluded.

Will Pass/MDedge News

Session moderator János Kappelmayer, MD, of the University of Debrecen (Hungary) highlighted a key opportunity presented by the study. “I think that one important aspect of these findings could be that splenectomy is an irreversible procedure, so one can exclude those patients who will not benefit from splenectomy,” he said. “I think this is a real advantage.”

The investigators reported no study funding or conflicts of interest.

SOURCE: Zotova I et al. EHA Congress, Abstract S848.

AMSTERDAM – For patients with immune thrombocytopenia (ITP), platelet glycoprotein genotypes may predict effectiveness of specific therapies, according to investigators.

Will Pass/MDedge News

Significant relationships were detected between allelic polymorphisms of glycoprotein genes and durable responses to corticosteroids, thrombopoietin receptor agonists (aTPOr), and splenectomy, reported lead author Irina Zotova, MD, of the Russian Research Institute of Hematology and Transfusiology, Federal Biomedical Agency, in Saint Petersburg and colleagues.

These findings could guide clinical decision making in ITP, according to Dr. Zotova.

“Currently, the choice of therapeutic approach to ITP treatment, especially the second-line, is empirical, and often based on the experience of the clinician,” Dr. Zotova said during her presentation at the annual congress of the European Hematology Association. “Recent studies have shown that ... genes coding for glycoprotein are involved in platelet function and are associated with different responses to ITP treatment. This provides an opportunity for an individual approach and personalization of ITP therapy in accordance with the genetic status of the patient.”

In the present study, the investigators used PCR-RFLP (polymerase chain reaction–restriction fragment length polymorphism) to determine GPIa A1648G and GPIIb 2622TG gene status in 81 patients with primary ITP and compared these genotypes with clinical responses.

All patients received first-line corticosteroid therapy. If necessary, second-line treatment was delivered. In total, 37 patients (46%) received aTPOr, while 22 patients (27%) underwent splenectomy. Responses were classified as durable response, nondurable response, or no response.

Analysis showed that a significantly greater proportion of patients who had durable responses to corticosteroid therapy exhibited a heterozygous GPIIb 2622TG genotype, compared with patients who had nondurable responses (72.2% vs. 30.9%; odds ratio, 5.8; P = .005).

For second-line responses, patients who had durable response to aTPOr were much more likely to be homozygous for the GPIa A1648G than nonresponders (87.5% vs. 20.0%; OR, 28.0; P = .005). More strikingly, all patients who achieved durable responses to splenectomy had the GPIa A1648G genotype, compared with just 44% of nonresponders (OR, 33.0; P = .005).

“Gentoyping for the GPIIb T2622G and GPIa A1648G polymorphisms allows [clinicians] to predict the response to first-line and second-line treatment, giving the possibility to stratify patients to groups with favorable and unfavorable courses of the disease,” Dr. Zotova concluded.

Will Pass/MDedge News

Session moderator János Kappelmayer, MD, of the University of Debrecen (Hungary) highlighted a key opportunity presented by the study. “I think that one important aspect of these findings could be that splenectomy is an irreversible procedure, so one can exclude those patients who will not benefit from splenectomy,” he said. “I think this is a real advantage.”

The investigators reported no study funding or conflicts of interest.

SOURCE: Zotova I et al. EHA Congress, Abstract S848.

AMSTERDAM – For patients with immune thrombocytopenia (ITP), platelet glycoprotein genotypes may predict effectiveness of specific therapies, according to investigators.

Will Pass/MDedge News

Significant relationships were detected between allelic polymorphisms of glycoprotein genes and durable responses to corticosteroids, thrombopoietin receptor agonists (aTPOr), and splenectomy, reported lead author Irina Zotova, MD, of the Russian Research Institute of Hematology and Transfusiology, Federal Biomedical Agency, in Saint Petersburg and colleagues.

These findings could guide clinical decision making in ITP, according to Dr. Zotova.

“Currently, the choice of therapeutic approach to ITP treatment, especially the second-line, is empirical, and often based on the experience of the clinician,” Dr. Zotova said during her presentation at the annual congress of the European Hematology Association. “Recent studies have shown that ... genes coding for glycoprotein are involved in platelet function and are associated with different responses to ITP treatment. This provides an opportunity for an individual approach and personalization of ITP therapy in accordance with the genetic status of the patient.”

In the present study, the investigators used PCR-RFLP (polymerase chain reaction–restriction fragment length polymorphism) to determine GPIa A1648G and GPIIb 2622TG gene status in 81 patients with primary ITP and compared these genotypes with clinical responses.

All patients received first-line corticosteroid therapy. If necessary, second-line treatment was delivered. In total, 37 patients (46%) received aTPOr, while 22 patients (27%) underwent splenectomy. Responses were classified as durable response, nondurable response, or no response.

Analysis showed that a significantly greater proportion of patients who had durable responses to corticosteroid therapy exhibited a heterozygous GPIIb 2622TG genotype, compared with patients who had nondurable responses (72.2% vs. 30.9%; odds ratio, 5.8; P = .005).

For second-line responses, patients who had durable response to aTPOr were much more likely to be homozygous for the GPIa A1648G than nonresponders (87.5% vs. 20.0%; OR, 28.0; P = .005). More strikingly, all patients who achieved durable responses to splenectomy had the GPIa A1648G genotype, compared with just 44% of nonresponders (OR, 33.0; P = .005).

“Gentoyping for the GPIIb T2622G and GPIa A1648G polymorphisms allows [clinicians] to predict the response to first-line and second-line treatment, giving the possibility to stratify patients to groups with favorable and unfavorable courses of the disease,” Dr. Zotova concluded.

Will Pass/MDedge News

Session moderator János Kappelmayer, MD, of the University of Debrecen (Hungary) highlighted a key opportunity presented by the study. “I think that one important aspect of these findings could be that splenectomy is an irreversible procedure, so one can exclude those patients who will not benefit from splenectomy,” he said. “I think this is a real advantage.”

The investigators reported no study funding or conflicts of interest.

SOURCE: Zotova I et al. EHA Congress, Abstract S848.

The recombinant factor IX product nonacog alfa appears safe and effective for patients with hemophilia B, according to results from a recent postmarketing study in Japan.

While nonacog alfa was approved in the United States and Europe in 1997, the product wasn’t approved in Japan until 2009. Since it was the first recombinant factor IX product available there, and only a small number of patients were enrolled in domestic clinical trials, the Japanese government required additional real-world studies.

“In the last couple of years, several extended half‐life blood coagulation factor products gained regulatory approval for the treatment of hemophilia B. However, access to this most advanced treatment option remains limited to developed countries, and the need for standard half‐life recombinant or plasma‐derived FIX products is still high,” wrote Katsuyuki Fukutake, MD, PhD, of Tokyo Medical University, Japan, and colleagues.

The researchers conducted an observational postmarketing surveillance study of 312 patients with hemophilia B who received nonacog alfa therapy from 2010 to 2014. The team evaluated the real-world safety, including the incidence of inhibitors and adverse events, and effectiveness of the recombinant product in Japan.

The findings were published in Haemophilia.

The study included both previously treated and untreated participants who were followed for 1 and 2 years, respectively, after starting recombinant factor IX therapy.

The primary safety outcome was the incidence and number of adverse drug reactions. Effectiveness was measured using clinical effectiveness rates and annualized bleeding rates (ABR).

After analysis, the researchers found that the effectiveness rates were 95.5% and 93.7% for patients who received routine prophylaxis and on-demand treatment, respectively.

The median ABR was lower during routine prophylaxis – 2.0 – versus the rest of the observation period – 8.3. “This difference was prominent among patients with severe haemophilia B or haemophilic arthropathy,” the researchers wrote.

With respect to safety, 11 adverse drug reactions were seen in seven previously treated patients. New inhibitor development was not observed in any participants, but recurrence was seen in one patient.

“Our results are consistent with those of previous studies where the incidence of inhibitor antibody development in hemophilia B has been reported as 1%-5%,” Dr. Fukutake and colleagues wrote.

The researchers acknowledged that one key limitation of the study was the observational design.

“The results suggest that nonacog alfa was well tolerated and appropriately used under routine clinical practice,” the authors concluded.

The study was funded and conducted by Pfizer Japan. The authors reported financial relationships with Pfizer and several other companies. One coauthor is an employee of Pfizer Japan.

SOURCE: Fukutake K et al. Haemophilia. 2019 Jun 6. doi: 10.1111/hae.13783.
 

The recombinant factor IX product nonacog alfa appears safe and effective for patients with hemophilia B, according to results from a recent postmarketing study in Japan.

While nonacog alfa was approved in the United States and Europe in 1997, the product wasn’t approved in Japan until 2009. Since it was the first recombinant factor IX product available there, and only a small number of patients were enrolled in domestic clinical trials, the Japanese government required additional real-world studies.

“In the last couple of years, several extended half‐life blood coagulation factor products gained regulatory approval for the treatment of hemophilia B. However, access to this most advanced treatment option remains limited to developed countries, and the need for standard half‐life recombinant or plasma‐derived FIX products is still high,” wrote Katsuyuki Fukutake, MD, PhD, of Tokyo Medical University, Japan, and colleagues.

The researchers conducted an observational postmarketing surveillance study of 312 patients with hemophilia B who received nonacog alfa therapy from 2010 to 2014. The team evaluated the real-world safety, including the incidence of inhibitors and adverse events, and effectiveness of the recombinant product in Japan.

The findings were published in Haemophilia.

The study included both previously treated and untreated participants who were followed for 1 and 2 years, respectively, after starting recombinant factor IX therapy.

The primary safety outcome was the incidence and number of adverse drug reactions. Effectiveness was measured using clinical effectiveness rates and annualized bleeding rates (ABR).

After analysis, the researchers found that the effectiveness rates were 95.5% and 93.7% for patients who received routine prophylaxis and on-demand treatment, respectively.

The median ABR was lower during routine prophylaxis – 2.0 – versus the rest of the observation period – 8.3. “This difference was prominent among patients with severe haemophilia B or haemophilic arthropathy,” the researchers wrote.

With respect to safety, 11 adverse drug reactions were seen in seven previously treated patients. New inhibitor development was not observed in any participants, but recurrence was seen in one patient.

“Our results are consistent with those of previous studies where the incidence of inhibitor antibody development in hemophilia B has been reported as 1%-5%,” Dr. Fukutake and colleagues wrote.

The researchers acknowledged that one key limitation of the study was the observational design.

“The results suggest that nonacog alfa was well tolerated and appropriately used under routine clinical practice,” the authors concluded.

The study was funded and conducted by Pfizer Japan. The authors reported financial relationships with Pfizer and several other companies. One coauthor is an employee of Pfizer Japan.

SOURCE: Fukutake K et al. Haemophilia. 2019 Jun 6. doi: 10.1111/hae.13783.
 

The recombinant factor IX product nonacog alfa appears safe and effective for patients with hemophilia B, according to results from a recent postmarketing study in Japan.

While nonacog alfa was approved in the United States and Europe in 1997, the product wasn’t approved in Japan until 2009. Since it was the first recombinant factor IX product available there, and only a small number of patients were enrolled in domestic clinical trials, the Japanese government required additional real-world studies.

“In the last couple of years, several extended half‐life blood coagulation factor products gained regulatory approval for the treatment of hemophilia B. However, access to this most advanced treatment option remains limited to developed countries, and the need for standard half‐life recombinant or plasma‐derived FIX products is still high,” wrote Katsuyuki Fukutake, MD, PhD, of Tokyo Medical University, Japan, and colleagues.

The researchers conducted an observational postmarketing surveillance study of 312 patients with hemophilia B who received nonacog alfa therapy from 2010 to 2014. The team evaluated the real-world safety, including the incidence of inhibitors and adverse events, and effectiveness of the recombinant product in Japan.

The findings were published in Haemophilia.

The study included both previously treated and untreated participants who were followed for 1 and 2 years, respectively, after starting recombinant factor IX therapy.

The primary safety outcome was the incidence and number of adverse drug reactions. Effectiveness was measured using clinical effectiveness rates and annualized bleeding rates (ABR).

After analysis, the researchers found that the effectiveness rates were 95.5% and 93.7% for patients who received routine prophylaxis and on-demand treatment, respectively.

The median ABR was lower during routine prophylaxis – 2.0 – versus the rest of the observation period – 8.3. “This difference was prominent among patients with severe haemophilia B or haemophilic arthropathy,” the researchers wrote.

With respect to safety, 11 adverse drug reactions were seen in seven previously treated patients. New inhibitor development was not observed in any participants, but recurrence was seen in one patient.

“Our results are consistent with those of previous studies where the incidence of inhibitor antibody development in hemophilia B has been reported as 1%-5%,” Dr. Fukutake and colleagues wrote.

The researchers acknowledged that one key limitation of the study was the observational design.

“The results suggest that nonacog alfa was well tolerated and appropriately used under routine clinical practice,” the authors concluded.

The study was funded and conducted by Pfizer Japan. The authors reported financial relationships with Pfizer and several other companies. One coauthor is an employee of Pfizer Japan.

SOURCE: Fukutake K et al. Haemophilia. 2019 Jun 6. doi: 10.1111/hae.13783.
 

SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.

Doug Brunk/MDedge News

“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”

Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.

Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.

During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).

Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).

When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.

Doug Brunk/MDedge News

“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”

Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.

Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.

During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).

Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).

When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.

Doug Brunk/MDedge News

“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”

Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.

Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.

During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).

Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).

When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.

[email protected]