Najibah Galadanci, MBBS

© Todd Buchanan 2016

SAN DIEGO—High rates of recruitment (90%), enrollment (92%), and adherence to study drug and follow-up visits have confirmed the feasibility of conducting a trial of hydroxyurea (HU) for stroke prevention in Nigeria (the SPIN trial), researchers say.

The 235 children with sickle cell anemia (SCA)enrolled on the SPIN trial did not miss any of the scheduled monthly visits, and drug adherence was 84% based on the increase in their mean corpuscular volume (MCV) by 10 fL.

These data provide strong evidence, researchers believe, for patient and family acceptability of the trial and potential safety of a moderate dose of HU to prevent stroke in children with SCA in Nigeria.

Nigeria has the largest burden of sickle cell disease (SCD) in the world, Najibah Galadanci, MBBS, of Bayero University/Aminu Kano Teaching Hospital in Nigeria, said at the 2016 ASH Annual Meeting.

Every year, about 150,000 children in Nigeria are born with SCD. This compares with 2400 children in the United States and 300 children in the United Kingdom.

“And it is estimated that 15,000 children with SCA per year in Nigeria will have strokes,” Dr Galadanci added.

She presented data from the SPIN trial (NCT01801423) at ASH as abstract 122.

At present, she explained, primary stroke prevention consists of regular blood transfusions for patients with transcranial Doppler (TCD) measurements higher than 200 cm/second.

However, distinct challenges with this prevention method exist in sub-Saharan Africa, such as inadequate blood supply, cost, unsafe transfusion practice, and the high probability of blood-borne infections.

HU is the only drug approved by the US Food and Drug administration to treat SCD. It increases total hemoglobin level, which is associated with a decreased risk of strokes.

In addition, HU significantly decreases TCD ultrasound velocity in children with SCD and abnormal TCD and is cost-effective and practical in sub-Saharan Africa.

So investigators at Aminu Kano teaching hospital in Nigeria undertook to study the feasibility of using HU to prevent stroke in children with SCD.

The team based their decision on 3 main components: recruitment rate, retention rate, and adherence to study medication.

SPIN trial

Children ages 5 to 12 were eligible if they had a diagnosis of SCA, either HbSS or HbSb⁰. They had to have 2 independent readings of elevated TCD velocity of 200 to 219 cm/second or 1 reading of 220 cm/second or higher.

Investigators enrolled 25 children on the treatment arm. The children received a moderate dose (20 mg/kg/day) of HU for 3 years.

Investigators also enrolled a comparison group of 210 children with SCA who had a TCD velocity of less than 200 cm/second.

The median follow-up was 2.1 years. The median age was 6.8 years and 8 years in the treatment and comparison groups, respectively.

The treatment group had a total of 603 follow-up visits.

The recruitment rate was 90% (335 of 370 families), the enrollment rate for the treatment arm was 92% (25 of 27 patients), and the adherence rate to monthly visits was 100%. Eighty-four percent of patients (21/25) adhered to the medication regimen, based on their increased MCV.

HU therapy

Investigators observed no laboratory evidence of severe myelosuppression or toxicity.

Of 712 complete blood counts performed on 25 study participants, 2 patients had repeated hemoglobin counts of less than 6 g/dL, and no participant had a repeat platelet count below 80 x 10⁹/L nor a repeat absolute neutrophil count of less than 1.2 x 10⁹/L.

Investigators found no significant difference overall (P=0.37) in the rate of hospitalization between the treatment and comparison groups based on hospitalizations for acute chest syndrome, pain, stroke, transfusion, malaria, and infection.

Investigators also found no significant difference (P=0.67) in rates of severe adverse events between the study and comparison groups.

Twelve deaths occurred during the study period, 2 in the treatment group (2.69/100 patient years) and 10 in the comparison group (1.81/100 patient years).

Deaths in the treatment arm were due to sepsis and progressive renal disease. Deaths in the comparison group were due to severe anemia, infection, and malaria.

“The most interesting finding of our study,” Dr Galadanci indicated, “was the 85% reduction in TCD velocity after starting hydroxyurea therapy.”

Baseline TCD measurements went from 211 cm/second to 165 cm/second at 24 months.

Dr Galadanci said next steps include conducting a phase 3, multicenter, randomized controlled trial (NCT 02560935) comparing low-dose (10 mg/kg/day) and moderate-dose (20 mg/kg/day) HU therapy for preventing primary strokes in children with SCA living in Nigeria (SPRING Trial).

Investigators hypothesize there will be a 66% reduction over 3 years in relative risk of primary strokes in children with SCA and elevated TCD velocity in the moderate-dose group compared to the low-dose group.

Najibah Galadanci, MBBS

© Todd Buchanan 2016

SAN DIEGO—High rates of recruitment (90%), enrollment (92%), and adherence to study drug and follow-up visits have confirmed the feasibility of conducting a trial of hydroxyurea (HU) for stroke prevention in Nigeria (the SPIN trial), researchers say.

The 235 children with sickle cell anemia (SCA)enrolled on the SPIN trial did not miss any of the scheduled monthly visits, and drug adherence was 84% based on the increase in their mean corpuscular volume (MCV) by 10 fL.

These data provide strong evidence, researchers believe, for patient and family acceptability of the trial and potential safety of a moderate dose of HU to prevent stroke in children with SCA in Nigeria.

Nigeria has the largest burden of sickle cell disease (SCD) in the world, Najibah Galadanci, MBBS, of Bayero University/Aminu Kano Teaching Hospital in Nigeria, said at the 2016 ASH Annual Meeting.

Every year, about 150,000 children in Nigeria are born with SCD. This compares with 2400 children in the United States and 300 children in the United Kingdom.

“And it is estimated that 15,000 children with SCA per year in Nigeria will have strokes,” Dr Galadanci added.

She presented data from the SPIN trial (NCT01801423) at ASH as abstract 122.

At present, she explained, primary stroke prevention consists of regular blood transfusions for patients with transcranial Doppler (TCD) measurements higher than 200 cm/second.

However, distinct challenges with this prevention method exist in sub-Saharan Africa, such as inadequate blood supply, cost, unsafe transfusion practice, and the high probability of blood-borne infections.

HU is the only drug approved by the US Food and Drug administration to treat SCD. It increases total hemoglobin level, which is associated with a decreased risk of strokes.

In addition, HU significantly decreases TCD ultrasound velocity in children with SCD and abnormal TCD and is cost-effective and practical in sub-Saharan Africa.

So investigators at Aminu Kano teaching hospital in Nigeria undertook to study the feasibility of using HU to prevent stroke in children with SCD.

The team based their decision on 3 main components: recruitment rate, retention rate, and adherence to study medication.

SPIN trial

Children ages 5 to 12 were eligible if they had a diagnosis of SCA, either HbSS or HbSb⁰. They had to have 2 independent readings of elevated TCD velocity of 200 to 219 cm/second or 1 reading of 220 cm/second or higher.

Investigators enrolled 25 children on the treatment arm. The children received a moderate dose (20 mg/kg/day) of HU for 3 years.

Investigators also enrolled a comparison group of 210 children with SCA who had a TCD velocity of less than 200 cm/second.

The median follow-up was 2.1 years. The median age was 6.8 years and 8 years in the treatment and comparison groups, respectively.

The treatment group had a total of 603 follow-up visits.

The recruitment rate was 90% (335 of 370 families), the enrollment rate for the treatment arm was 92% (25 of 27 patients), and the adherence rate to monthly visits was 100%. Eighty-four percent of patients (21/25) adhered to the medication regimen, based on their increased MCV.

HU therapy

Investigators observed no laboratory evidence of severe myelosuppression or toxicity.

Of 712 complete blood counts performed on 25 study participants, 2 patients had repeated hemoglobin counts of less than 6 g/dL, and no participant had a repeat platelet count below 80 x 10⁹/L nor a repeat absolute neutrophil count of less than 1.2 x 10⁹/L.

Investigators found no significant difference overall (P=0.37) in the rate of hospitalization between the treatment and comparison groups based on hospitalizations for acute chest syndrome, pain, stroke, transfusion, malaria, and infection.

Investigators also found no significant difference (P=0.67) in rates of severe adverse events between the study and comparison groups.

Twelve deaths occurred during the study period, 2 in the treatment group (2.69/100 patient years) and 10 in the comparison group (1.81/100 patient years).

Deaths in the treatment arm were due to sepsis and progressive renal disease. Deaths in the comparison group were due to severe anemia, infection, and malaria.

“The most interesting finding of our study,” Dr Galadanci indicated, “was the 85% reduction in TCD velocity after starting hydroxyurea therapy.”

Baseline TCD measurements went from 211 cm/second to 165 cm/second at 24 months.

Dr Galadanci said next steps include conducting a phase 3, multicenter, randomized controlled trial (NCT 02560935) comparing low-dose (10 mg/kg/day) and moderate-dose (20 mg/kg/day) HU therapy for preventing primary strokes in children with SCA living in Nigeria (SPRING Trial).

Investigators hypothesize there will be a 66% reduction over 3 years in relative risk of primary strokes in children with SCA and elevated TCD velocity in the moderate-dose group compared to the low-dose group.

Najibah Galadanci, MBBS

© Todd Buchanan 2016

SAN DIEGO—High rates of recruitment (90%), enrollment (92%), and adherence to study drug and follow-up visits have confirmed the feasibility of conducting a trial of hydroxyurea (HU) for stroke prevention in Nigeria (the SPIN trial), researchers say.

The 235 children with sickle cell anemia (SCA)enrolled on the SPIN trial did not miss any of the scheduled monthly visits, and drug adherence was 84% based on the increase in their mean corpuscular volume (MCV) by 10 fL.

These data provide strong evidence, researchers believe, for patient and family acceptability of the trial and potential safety of a moderate dose of HU to prevent stroke in children with SCA in Nigeria.

Nigeria has the largest burden of sickle cell disease (SCD) in the world, Najibah Galadanci, MBBS, of Bayero University/Aminu Kano Teaching Hospital in Nigeria, said at the 2016 ASH Annual Meeting.

Every year, about 150,000 children in Nigeria are born with SCD. This compares with 2400 children in the United States and 300 children in the United Kingdom.

“And it is estimated that 15,000 children with SCA per year in Nigeria will have strokes,” Dr Galadanci added.

She presented data from the SPIN trial (NCT01801423) at ASH as abstract 122.

At present, she explained, primary stroke prevention consists of regular blood transfusions for patients with transcranial Doppler (TCD) measurements higher than 200 cm/second.

However, distinct challenges with this prevention method exist in sub-Saharan Africa, such as inadequate blood supply, cost, unsafe transfusion practice, and the high probability of blood-borne infections.

HU is the only drug approved by the US Food and Drug administration to treat SCD. It increases total hemoglobin level, which is associated with a decreased risk of strokes.

In addition, HU significantly decreases TCD ultrasound velocity in children with SCD and abnormal TCD and is cost-effective and practical in sub-Saharan Africa.

So investigators at Aminu Kano teaching hospital in Nigeria undertook to study the feasibility of using HU to prevent stroke in children with SCD.

The team based their decision on 3 main components: recruitment rate, retention rate, and adherence to study medication.

SPIN trial

Children ages 5 to 12 were eligible if they had a diagnosis of SCA, either HbSS or HbSb⁰. They had to have 2 independent readings of elevated TCD velocity of 200 to 219 cm/second or 1 reading of 220 cm/second or higher.

Investigators enrolled 25 children on the treatment arm. The children received a moderate dose (20 mg/kg/day) of HU for 3 years.

Investigators also enrolled a comparison group of 210 children with SCA who had a TCD velocity of less than 200 cm/second.

The median follow-up was 2.1 years. The median age was 6.8 years and 8 years in the treatment and comparison groups, respectively.

The treatment group had a total of 603 follow-up visits.

The recruitment rate was 90% (335 of 370 families), the enrollment rate for the treatment arm was 92% (25 of 27 patients), and the adherence rate to monthly visits was 100%. Eighty-four percent of patients (21/25) adhered to the medication regimen, based on their increased MCV.

HU therapy

Investigators observed no laboratory evidence of severe myelosuppression or toxicity.

Of 712 complete blood counts performed on 25 study participants, 2 patients had repeated hemoglobin counts of less than 6 g/dL, and no participant had a repeat platelet count below 80 x 10⁹/L nor a repeat absolute neutrophil count of less than 1.2 x 10⁹/L.

Investigators found no significant difference overall (P=0.37) in the rate of hospitalization between the treatment and comparison groups based on hospitalizations for acute chest syndrome, pain, stroke, transfusion, malaria, and infection.

Investigators also found no significant difference (P=0.67) in rates of severe adverse events between the study and comparison groups.

Twelve deaths occurred during the study period, 2 in the treatment group (2.69/100 patient years) and 10 in the comparison group (1.81/100 patient years).

Deaths in the treatment arm were due to sepsis and progressive renal disease. Deaths in the comparison group were due to severe anemia, infection, and malaria.

“The most interesting finding of our study,” Dr Galadanci indicated, “was the 85% reduction in TCD velocity after starting hydroxyurea therapy.”

Baseline TCD measurements went from 211 cm/second to 165 cm/second at 24 months.

Dr Galadanci said next steps include conducting a phase 3, multicenter, randomized controlled trial (NCT 02560935) comparing low-dose (10 mg/kg/day) and moderate-dose (20 mg/kg/day) HU therapy for preventing primary strokes in children with SCA living in Nigeria (SPRING Trial).

Investigators hypothesize there will be a 66% reduction over 3 years in relative risk of primary strokes in children with SCA and elevated TCD velocity in the moderate-dose group compared to the low-dose group.

Micrograph showing AML

The US Food and Drug Administration (FDA) has placed holds on 3 early stage trials of vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML).

A phase 1/2 trial of vadastuximab talirine monotherapy in pre- and post-allogeneic transplant patients has been placed on full clinical hold.

This means no new subjects can be enrolled on the trial, and there can be no further dosing of subjects who are already enrolled.

Two phase 1 trials of vadastuximab talirine have been placed on partial clinical hold. This means no new subjects can be enrolled, but existing patients may continue treatment with re-consent.

In one of the trials on partial hold, researchers are investigating vadastuximab talirine alone and in combination with hypomethylating agents in AML patients who either relapsed after induction/consolidation or declined treatment with high-dose induction/consolidation.

In the other trial on partial hold, researchers are testing vadastuximab talirine in combination with 7+3 chemotherapy in newly diagnosed AML patients. Results from this trial were presented at the 2016 ASH Annual Meeting.

All 3 clinical holds were initiated to evaluate the potential risk of hepatotoxicity in patients who were treated with vadastuximab talirine and received allogeneic stem cell transplant either before or after treatment.

There have been 6 patients with hepatotoxicity, including several cases of veno-occlusive disease, with 4 fatal events.

Seattle Genetics, Inc., the company developing vadastuximab talirine, said it is working with the FDA to determine whether there is any association between hepatotoxicity and treatment with vadastuximab talirine to identify appropriate protocol amendments for patient safety and to enable continuation of these trials.

No new studies of vadastuximab talirine will be initiated until the clinical holds are lifted.

Seattle Genetics’ other ongoing trials of vadastuximab talirine, including the phase 3 CASCADE trial in older AML patients and phase 1/2 trial in patients with myelodysplastic syndrome (MDS), are proceeding with enrollment.

Overall, more than 300 patients have been treated with vadastuximab talirine in clinical trials across multiple treatment settings.

Vadastuximab talirine is an investigational antibody-drug conjugate (ADC) targeted to CD33, which is expressed on most AML and MDS blast cells. The CD33 engineered cysteine antibody is stably linked to a DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb).

PBD dimers are said to be significantly more potent than systemic chemotherapeutic drugs, and the EC-mAb technology allows uniform drug-loading onto an ADC. The ADC is designed to be stable in the bloodstream and to release its PBD agent upon internalization into CD33-expressing cells.

Micrograph showing AML

The US Food and Drug Administration (FDA) has placed holds on 3 early stage trials of vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML).

A phase 1/2 trial of vadastuximab talirine monotherapy in pre- and post-allogeneic transplant patients has been placed on full clinical hold.

This means no new subjects can be enrolled on the trial, and there can be no further dosing of subjects who are already enrolled.

Two phase 1 trials of vadastuximab talirine have been placed on partial clinical hold. This means no new subjects can be enrolled, but existing patients may continue treatment with re-consent.

In one of the trials on partial hold, researchers are investigating vadastuximab talirine alone and in combination with hypomethylating agents in AML patients who either relapsed after induction/consolidation or declined treatment with high-dose induction/consolidation.

In the other trial on partial hold, researchers are testing vadastuximab talirine in combination with 7+3 chemotherapy in newly diagnosed AML patients. Results from this trial were presented at the 2016 ASH Annual Meeting.

All 3 clinical holds were initiated to evaluate the potential risk of hepatotoxicity in patients who were treated with vadastuximab talirine and received allogeneic stem cell transplant either before or after treatment.

There have been 6 patients with hepatotoxicity, including several cases of veno-occlusive disease, with 4 fatal events.

Seattle Genetics, Inc., the company developing vadastuximab talirine, said it is working with the FDA to determine whether there is any association between hepatotoxicity and treatment with vadastuximab talirine to identify appropriate protocol amendments for patient safety and to enable continuation of these trials.

No new studies of vadastuximab talirine will be initiated until the clinical holds are lifted.

Seattle Genetics’ other ongoing trials of vadastuximab talirine, including the phase 3 CASCADE trial in older AML patients and phase 1/2 trial in patients with myelodysplastic syndrome (MDS), are proceeding with enrollment.

Overall, more than 300 patients have been treated with vadastuximab talirine in clinical trials across multiple treatment settings.

Vadastuximab talirine is an investigational antibody-drug conjugate (ADC) targeted to CD33, which is expressed on most AML and MDS blast cells. The CD33 engineered cysteine antibody is stably linked to a DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb).

PBD dimers are said to be significantly more potent than systemic chemotherapeutic drugs, and the EC-mAb technology allows uniform drug-loading onto an ADC. The ADC is designed to be stable in the bloodstream and to release its PBD agent upon internalization into CD33-expressing cells.

Micrograph showing AML

The US Food and Drug Administration (FDA) has placed holds on 3 early stage trials of vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML).

A phase 1/2 trial of vadastuximab talirine monotherapy in pre- and post-allogeneic transplant patients has been placed on full clinical hold.

This means no new subjects can be enrolled on the trial, and there can be no further dosing of subjects who are already enrolled.

Two phase 1 trials of vadastuximab talirine have been placed on partial clinical hold. This means no new subjects can be enrolled, but existing patients may continue treatment with re-consent.

In one of the trials on partial hold, researchers are investigating vadastuximab talirine alone and in combination with hypomethylating agents in AML patients who either relapsed after induction/consolidation or declined treatment with high-dose induction/consolidation.

In the other trial on partial hold, researchers are testing vadastuximab talirine in combination with 7+3 chemotherapy in newly diagnosed AML patients. Results from this trial were presented at the 2016 ASH Annual Meeting.

All 3 clinical holds were initiated to evaluate the potential risk of hepatotoxicity in patients who were treated with vadastuximab talirine and received allogeneic stem cell transplant either before or after treatment.

There have been 6 patients with hepatotoxicity, including several cases of veno-occlusive disease, with 4 fatal events.

Seattle Genetics, Inc., the company developing vadastuximab talirine, said it is working with the FDA to determine whether there is any association between hepatotoxicity and treatment with vadastuximab talirine to identify appropriate protocol amendments for patient safety and to enable continuation of these trials.

No new studies of vadastuximab talirine will be initiated until the clinical holds are lifted.

Seattle Genetics’ other ongoing trials of vadastuximab talirine, including the phase 3 CASCADE trial in older AML patients and phase 1/2 trial in patients with myelodysplastic syndrome (MDS), are proceeding with enrollment.

Overall, more than 300 patients have been treated with vadastuximab talirine in clinical trials across multiple treatment settings.

Vadastuximab talirine is an investigational antibody-drug conjugate (ADC) targeted to CD33, which is expressed on most AML and MDS blast cells. The CD33 engineered cysteine antibody is stably linked to a DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb).

PBD dimers are said to be significantly more potent than systemic chemotherapeutic drugs, and the EC-mAb technology allows uniform drug-loading onto an ADC. The ADC is designed to be stable in the bloodstream and to release its PBD agent upon internalization into CD33-expressing cells.

Vial of Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has expanded the approved use of Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

Adynovate was previously approved as routine prophylaxis and for on-demand treatment of bleeding episodes in patients age 12 and older.

Now, Adynovate is approved for the same indications in patients younger than 12 and for perioperative management in patients of all ages.

Adynovate is built on the full-length Advate molecule, which was approved by the FDA in 2003. Adynovate leverages proprietary pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Adynovate and Advate are registered trademarks of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

For more details on Adynovate, see the full prescribing information.

Trials of Adynovate

The FDA’s approval of Adynovate in children is based on data from a phase 3 trial, which were presented at the World Federation of Hemophilia 2016 World Congress.

The study enrolled previously treated children younger than 12 with no history of FVIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

Sixty-six patients were evaluable. None of them developed inhibitory antibodies, and there were no adverse events related to Adynovate.

The median annualized bleeding rate was 2.0, and 38% of patients did not have any bleeding episodes.

The FDA’s approval of Adynovate for perioperative management was based on interim results of an ongoing phase 3 study in 15 patients with severe hemophilia A undergoing surgical procedures. The interim results were presented at the 2015 ASH Annual Meeting.

The patients underwent 11 major surgical procedures (3 knee replacements, 2 arthroscopic synovectomies, 1 cyst extirpation, 1 port placement, 1 gastric band placement, and 3 multiple tooth extractions including 1 radicular cyst removal) and 4 minor surgeries (1 synoviorthesis, 1 radiosynovectomy, 1 tooth extraction, and 1 dermatological surgery).

Perioperative hemostatic efficacy was rated as “excellent” for most procedures. Excellent hemostatic efficacy was defined as blood loss less than or equal to that expected for the same type of procedure performed in a non-hemophilic patient and requiring blood components for transfusions less than or similar to that expected in the non-hemophilic population.

The median observed intraoperative blood loss (n=10) was 10.0 mL, compared to the predicted average blood loss (n=11) of 50.0 mL for major surgeries.

Vial of Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has expanded the approved use of Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

Adynovate was previously approved as routine prophylaxis and for on-demand treatment of bleeding episodes in patients age 12 and older.

Now, Adynovate is approved for the same indications in patients younger than 12 and for perioperative management in patients of all ages.

Adynovate is built on the full-length Advate molecule, which was approved by the FDA in 2003. Adynovate leverages proprietary pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Adynovate and Advate are registered trademarks of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

For more details on Adynovate, see the full prescribing information.

Trials of Adynovate

The FDA’s approval of Adynovate in children is based on data from a phase 3 trial, which were presented at the World Federation of Hemophilia 2016 World Congress.

The study enrolled previously treated children younger than 12 with no history of FVIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

Sixty-six patients were evaluable. None of them developed inhibitory antibodies, and there were no adverse events related to Adynovate.

The median annualized bleeding rate was 2.0, and 38% of patients did not have any bleeding episodes.

The FDA’s approval of Adynovate for perioperative management was based on interim results of an ongoing phase 3 study in 15 patients with severe hemophilia A undergoing surgical procedures. The interim results were presented at the 2015 ASH Annual Meeting.

The patients underwent 11 major surgical procedures (3 knee replacements, 2 arthroscopic synovectomies, 1 cyst extirpation, 1 port placement, 1 gastric band placement, and 3 multiple tooth extractions including 1 radicular cyst removal) and 4 minor surgeries (1 synoviorthesis, 1 radiosynovectomy, 1 tooth extraction, and 1 dermatological surgery).

Perioperative hemostatic efficacy was rated as “excellent” for most procedures. Excellent hemostatic efficacy was defined as blood loss less than or equal to that expected for the same type of procedure performed in a non-hemophilic patient and requiring blood components for transfusions less than or similar to that expected in the non-hemophilic population.

The median observed intraoperative blood loss (n=10) was 10.0 mL, compared to the predicted average blood loss (n=11) of 50.0 mL for major surgeries.

Vial of Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has expanded the approved use of Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

Adynovate was previously approved as routine prophylaxis and for on-demand treatment of bleeding episodes in patients age 12 and older.

Now, Adynovate is approved for the same indications in patients younger than 12 and for perioperative management in patients of all ages.

Adynovate is built on the full-length Advate molecule, which was approved by the FDA in 2003. Adynovate leverages proprietary pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Adynovate and Advate are registered trademarks of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

For more details on Adynovate, see the full prescribing information.

Trials of Adynovate

The FDA’s approval of Adynovate in children is based on data from a phase 3 trial, which were presented at the World Federation of Hemophilia 2016 World Congress.

The study enrolled previously treated children younger than 12 with no history of FVIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

Sixty-six patients were evaluable. None of them developed inhibitory antibodies, and there were no adverse events related to Adynovate.

The median annualized bleeding rate was 2.0, and 38% of patients did not have any bleeding episodes.

The FDA’s approval of Adynovate for perioperative management was based on interim results of an ongoing phase 3 study in 15 patients with severe hemophilia A undergoing surgical procedures. The interim results were presented at the 2015 ASH Annual Meeting.

The patients underwent 11 major surgical procedures (3 knee replacements, 2 arthroscopic synovectomies, 1 cyst extirpation, 1 port placement, 1 gastric band placement, and 3 multiple tooth extractions including 1 radicular cyst removal) and 4 minor surgeries (1 synoviorthesis, 1 radiosynovectomy, 1 tooth extraction, and 1 dermatological surgery).

Perioperative hemostatic efficacy was rated as “excellent” for most procedures. Excellent hemostatic efficacy was defined as blood loss less than or equal to that expected for the same type of procedure performed in a non-hemophilic patient and requiring blood components for transfusions less than or similar to that expected in the non-hemophilic population.

The median observed intraoperative blood loss (n=10) was 10.0 mL, compared to the predicted average blood loss (n=11) of 50.0 mL for major surgeries.

Apoptosis

Preclinical research appears to explain why certain tissues in very young children are more sensitive to collateral damage from cancer treatment than tissues in older individuals.

Researchers found evidence to suggest that, early in life, cells in the brain, heart, and kidney are primed for apoptosis.

On the other hand, cells in the healthy adult brain, heart, and kidneys are apoptosis-refractory.

Kristopher A. Sarosiek, PhD, of the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and his colleagues reported these findings in Cancer Cell.

The researchers used BH3 profiling to measure the relative dominance of pro-survival or pro-death signals inside cells.

A cancer cell in which apoptotic signals are dominant is said to be “highly primed” for self-destruction and therefore easily killed by therapy, while a cell with low priming is more resistant to death or damage.

Dr Sarosiek and his colleagues measured the priming of cells in tissues from adult mice and young mice.

In the adult mice, cells of the hematopoietic lineage from the periphery, thymus, spleen, and bone marrow were the most primed for apoptosis. Cells from the large intestine, small intestine, lungs, and liver were relatively unprimed. And cells in brain, heart, and kidney tissues were far less primed.

However, in embryonic and very young mice, cells in the brain, heart, and kidney were extremely primed for apoptosis.

The researchers found that, in the adult brains, hearts, and kidneys, the molecular machinery needed to perform apoptosis was nearly completely absent.

In contrast, this machinery was abundant in the brains, hearts, and kidneys of young mice. As a result, brain, heart, and kidney cells were much more vulnerable to cell death when exposed to chemotherapy or radiation.

After determining in mouse models that certain cells grew more resistant to treatment toxicity with age, the researchers tested human cells. The team obtained fresh samples of tissue that had been removed from brains of children and adults to prevent intractable epileptic seizures.

As in the mice, the youngest human brain cells were more highly primed with apoptotic machinery and vulnerable to chemotherapy and radiation damage.

The researchers said there was a period of higher heterogeneity in apoptotic priming among patients between 2 and 6 years of age. After that, the brain transitions to full apoptotic resistance.

The team also found that, in young tissues, expression of the apoptotic protein machinery is driven by c-Myc. This transcription factor drives an apoptotically primed state by directly activating transcription of the pro-apoptotic genes Bax, Bim, and Bid.

“[This research] has uncovered some opportunities to selectively block apoptosis in our healthy tissues and prevent toxicity from radiation or chemotherapy while still maintaining sensitivity within cancer cells,” Dr Sarosiek said. “We are actively pursuing the identification of new medicines that can be used exactly for this purpose.”

Apoptosis

Preclinical research appears to explain why certain tissues in very young children are more sensitive to collateral damage from cancer treatment than tissues in older individuals.

Researchers found evidence to suggest that, early in life, cells in the brain, heart, and kidney are primed for apoptosis.

On the other hand, cells in the healthy adult brain, heart, and kidneys are apoptosis-refractory.

Kristopher A. Sarosiek, PhD, of the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and his colleagues reported these findings in Cancer Cell.

The researchers used BH3 profiling to measure the relative dominance of pro-survival or pro-death signals inside cells.

A cancer cell in which apoptotic signals are dominant is said to be “highly primed” for self-destruction and therefore easily killed by therapy, while a cell with low priming is more resistant to death or damage.

Dr Sarosiek and his colleagues measured the priming of cells in tissues from adult mice and young mice.

In the adult mice, cells of the hematopoietic lineage from the periphery, thymus, spleen, and bone marrow were the most primed for apoptosis. Cells from the large intestine, small intestine, lungs, and liver were relatively unprimed. And cells in brain, heart, and kidney tissues were far less primed.

However, in embryonic and very young mice, cells in the brain, heart, and kidney were extremely primed for apoptosis.

The researchers found that, in the adult brains, hearts, and kidneys, the molecular machinery needed to perform apoptosis was nearly completely absent.

In contrast, this machinery was abundant in the brains, hearts, and kidneys of young mice. As a result, brain, heart, and kidney cells were much more vulnerable to cell death when exposed to chemotherapy or radiation.

After determining in mouse models that certain cells grew more resistant to treatment toxicity with age, the researchers tested human cells. The team obtained fresh samples of tissue that had been removed from brains of children and adults to prevent intractable epileptic seizures.

As in the mice, the youngest human brain cells were more highly primed with apoptotic machinery and vulnerable to chemotherapy and radiation damage.

The researchers said there was a period of higher heterogeneity in apoptotic priming among patients between 2 and 6 years of age. After that, the brain transitions to full apoptotic resistance.

The team also found that, in young tissues, expression of the apoptotic protein machinery is driven by c-Myc. This transcription factor drives an apoptotically primed state by directly activating transcription of the pro-apoptotic genes Bax, Bim, and Bid.

“[This research] has uncovered some opportunities to selectively block apoptosis in our healthy tissues and prevent toxicity from radiation or chemotherapy while still maintaining sensitivity within cancer cells,” Dr Sarosiek said. “We are actively pursuing the identification of new medicines that can be used exactly for this purpose.”

Apoptosis

Preclinical research appears to explain why certain tissues in very young children are more sensitive to collateral damage from cancer treatment than tissues in older individuals.

Researchers found evidence to suggest that, early in life, cells in the brain, heart, and kidney are primed for apoptosis.

On the other hand, cells in the healthy adult brain, heart, and kidneys are apoptosis-refractory.

Kristopher A. Sarosiek, PhD, of the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and his colleagues reported these findings in Cancer Cell.

The researchers used BH3 profiling to measure the relative dominance of pro-survival or pro-death signals inside cells.

A cancer cell in which apoptotic signals are dominant is said to be “highly primed” for self-destruction and therefore easily killed by therapy, while a cell with low priming is more resistant to death or damage.

Dr Sarosiek and his colleagues measured the priming of cells in tissues from adult mice and young mice.

In the adult mice, cells of the hematopoietic lineage from the periphery, thymus, spleen, and bone marrow were the most primed for apoptosis. Cells from the large intestine, small intestine, lungs, and liver were relatively unprimed. And cells in brain, heart, and kidney tissues were far less primed.

However, in embryonic and very young mice, cells in the brain, heart, and kidney were extremely primed for apoptosis.

The researchers found that, in the adult brains, hearts, and kidneys, the molecular machinery needed to perform apoptosis was nearly completely absent.

In contrast, this machinery was abundant in the brains, hearts, and kidneys of young mice. As a result, brain, heart, and kidney cells were much more vulnerable to cell death when exposed to chemotherapy or radiation.

After determining in mouse models that certain cells grew more resistant to treatment toxicity with age, the researchers tested human cells. The team obtained fresh samples of tissue that had been removed from brains of children and adults to prevent intractable epileptic seizures.

As in the mice, the youngest human brain cells were more highly primed with apoptotic machinery and vulnerable to chemotherapy and radiation damage.

The researchers said there was a period of higher heterogeneity in apoptotic priming among patients between 2 and 6 years of age. After that, the brain transitions to full apoptotic resistance.

The team also found that, in young tissues, expression of the apoptotic protein machinery is driven by c-Myc. This transcription factor drives an apoptotically primed state by directly activating transcription of the pro-apoptotic genes Bax, Bim, and Bid.

“[This research] has uncovered some opportunities to selectively block apoptosis in our healthy tissues and prevent toxicity from radiation or chemotherapy while still maintaining sensitivity within cancer cells,” Dr Sarosiek said. “We are actively pursuing the identification of new medicines that can be used exactly for this purpose.”

After a traumatic brain injury (TBI), people also experience major sleep problems, including changes in their sleep–wake cycle. A new study published online ahead of print December 21, 2016, in Neurology showed that recovering from these two conditions occurs in parallel.

“These results suggest that monitoring a person’s sleep–wake cycle may be a useful tool for assessing their recovery after TBI,” said study author Nadia Gosselin, PhD, an Assistant Professor in the Department of Psychology at the University of Montréal in Québec. “We found that when someone sustained a brain injury and had not recovered a certain level of consciousness to keep them awake and aware of their surroundings, they were not able to generate a good sleep–wake cycle. But as they recovered, their quality of sleep improved.”

The study involved 30 people, ages 17 to 58, who had been hospitalized for moderate to severe TBI. Most of the patients were in a coma when they were admitted to the hospital, and all initially received care in an ICU. The injuries were caused by motor vehicle accidents for 20 people, falls for seven people, recreational or sports activities for two people and a blow to the head for one person. They were hospitalized for an average of 45 days, with monitoring for the study beginning an average of 21 days into the patient’s stay.

Each person was monitored daily for an average of 11 days for level of consciousness and thinking abilities using the Rancho Los Amigos scale, which ranges from 1 to 8. Each person also wore an activity monitor on the wrist so researchers could measure their sleep.

Researchers found that consciousness and thinking abilities improved hand in hand with measures of quality of sleep, showing a linear relationship.

One measure, the daytime activity ratio, reflects the percentage of activity that occurs during the day. Immediately after the injury, activity occurs throughout the day and night. The study showed that participants reached an acceptable sleep–wake cycle, with a daytime activity ratio of at least 80%, at the same point when they emerged from a minimally conscious state.

The participants still had inadequate sleep–wake cycles, at a score of 5 on the Rancho Los Amigos scale, where people are confused and give inappropriate responses to stimuli, but are able to follow simple commands. Sleep–wake cycles reached adequate levels at the same time that people reached a score of 6 on the Rancho Los Amigos scale, which is when people can give appropriate responses while still depending on outside input for direction. At that level, they can remember relearned tasks, but cannot remember new tasks.

The results were the same when researchers adjusted for the amount of time that had passed since the injury and the amount of medications they had received while they were in the ICU.

“It is possible that there are common underlying brain mechanisms involved in both recovery from TBI and improvement in sleep,” said Dr. Gosselin. “Still, more study needs to be done, and future research may want to examine how hospital lighting and noise also affect quality of sleep for those with TBI.”

Suggested Reading

Duclos C, Dumont M, Arbour C, et al. Parallel recovery of consciousness and sleep in acute traumatic brain injury. Neurology. 2016 Dec 21 [Epub ahead of print].

Soddu A, Bassetti CL. A good sleep for a fresh mind in patients with acute tramatic brain injury. Neurology. 2016 Dec 21 [Epub ahead of print].

After a traumatic brain injury (TBI), people also experience major sleep problems, including changes in their sleep–wake cycle. A new study published online ahead of print December 21, 2016, in Neurology showed that recovering from these two conditions occurs in parallel.

“These results suggest that monitoring a person’s sleep–wake cycle may be a useful tool for assessing their recovery after TBI,” said study author Nadia Gosselin, PhD, an Assistant Professor in the Department of Psychology at the University of Montréal in Québec. “We found that when someone sustained a brain injury and had not recovered a certain level of consciousness to keep them awake and aware of their surroundings, they were not able to generate a good sleep–wake cycle. But as they recovered, their quality of sleep improved.”

The study involved 30 people, ages 17 to 58, who had been hospitalized for moderate to severe TBI. Most of the patients were in a coma when they were admitted to the hospital, and all initially received care in an ICU. The injuries were caused by motor vehicle accidents for 20 people, falls for seven people, recreational or sports activities for two people and a blow to the head for one person. They were hospitalized for an average of 45 days, with monitoring for the study beginning an average of 21 days into the patient’s stay.

Each person was monitored daily for an average of 11 days for level of consciousness and thinking abilities using the Rancho Los Amigos scale, which ranges from 1 to 8. Each person also wore an activity monitor on the wrist so researchers could measure their sleep.

Researchers found that consciousness and thinking abilities improved hand in hand with measures of quality of sleep, showing a linear relationship.

One measure, the daytime activity ratio, reflects the percentage of activity that occurs during the day. Immediately after the injury, activity occurs throughout the day and night. The study showed that participants reached an acceptable sleep–wake cycle, with a daytime activity ratio of at least 80%, at the same point when they emerged from a minimally conscious state.

The participants still had inadequate sleep–wake cycles, at a score of 5 on the Rancho Los Amigos scale, where people are confused and give inappropriate responses to stimuli, but are able to follow simple commands. Sleep–wake cycles reached adequate levels at the same time that people reached a score of 6 on the Rancho Los Amigos scale, which is when people can give appropriate responses while still depending on outside input for direction. At that level, they can remember relearned tasks, but cannot remember new tasks.

The results were the same when researchers adjusted for the amount of time that had passed since the injury and the amount of medications they had received while they were in the ICU.

“It is possible that there are common underlying brain mechanisms involved in both recovery from TBI and improvement in sleep,” said Dr. Gosselin. “Still, more study needs to be done, and future research may want to examine how hospital lighting and noise also affect quality of sleep for those with TBI.”

Suggested Reading

Duclos C, Dumont M, Arbour C, et al. Parallel recovery of consciousness and sleep in acute traumatic brain injury. Neurology. 2016 Dec 21 [Epub ahead of print].

Soddu A, Bassetti CL. A good sleep for a fresh mind in patients with acute tramatic brain injury. Neurology. 2016 Dec 21 [Epub ahead of print].

After a traumatic brain injury (TBI), people also experience major sleep problems, including changes in their sleep–wake cycle. A new study published online ahead of print December 21, 2016, in Neurology showed that recovering from these two conditions occurs in parallel.

“These results suggest that monitoring a person’s sleep–wake cycle may be a useful tool for assessing their recovery after TBI,” said study author Nadia Gosselin, PhD, an Assistant Professor in the Department of Psychology at the University of Montréal in Québec. “We found that when someone sustained a brain injury and had not recovered a certain level of consciousness to keep them awake and aware of their surroundings, they were not able to generate a good sleep–wake cycle. But as they recovered, their quality of sleep improved.”

The study involved 30 people, ages 17 to 58, who had been hospitalized for moderate to severe TBI. Most of the patients were in a coma when they were admitted to the hospital, and all initially received care in an ICU. The injuries were caused by motor vehicle accidents for 20 people, falls for seven people, recreational or sports activities for two people and a blow to the head for one person. They were hospitalized for an average of 45 days, with monitoring for the study beginning an average of 21 days into the patient’s stay.

Each person was monitored daily for an average of 11 days for level of consciousness and thinking abilities using the Rancho Los Amigos scale, which ranges from 1 to 8. Each person also wore an activity monitor on the wrist so researchers could measure their sleep.

Researchers found that consciousness and thinking abilities improved hand in hand with measures of quality of sleep, showing a linear relationship.

One measure, the daytime activity ratio, reflects the percentage of activity that occurs during the day. Immediately after the injury, activity occurs throughout the day and night. The study showed that participants reached an acceptable sleep–wake cycle, with a daytime activity ratio of at least 80%, at the same point when they emerged from a minimally conscious state.

The participants still had inadequate sleep–wake cycles, at a score of 5 on the Rancho Los Amigos scale, where people are confused and give inappropriate responses to stimuli, but are able to follow simple commands. Sleep–wake cycles reached adequate levels at the same time that people reached a score of 6 on the Rancho Los Amigos scale, which is when people can give appropriate responses while still depending on outside input for direction. At that level, they can remember relearned tasks, but cannot remember new tasks.

The results were the same when researchers adjusted for the amount of time that had passed since the injury and the amount of medications they had received while they were in the ICU.

“It is possible that there are common underlying brain mechanisms involved in both recovery from TBI and improvement in sleep,” said Dr. Gosselin. “Still, more study needs to be done, and future research may want to examine how hospital lighting and noise also affect quality of sleep for those with TBI.”

Suggested Reading

Duclos C, Dumont M, Arbour C, et al. Parallel recovery of consciousness and sleep in acute traumatic brain injury. Neurology. 2016 Dec 21 [Epub ahead of print].

Soddu A, Bassetti CL. A good sleep for a fresh mind in patients with acute tramatic brain injury. Neurology. 2016 Dec 21 [Epub ahead of print].

Click here to download the PDF. 

Click here to download the PDF. 

Click here to download the PDF. 

HOUSTON—Adults with epilepsy report cardiovascular disease more often than adults without epilepsy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

In the 2013 US National Health Interview Survey, women with epilepsy reported significantly more hypertension, stroke, and angina pectoris than women without epilepsy. Men with epilepsy reported significantly more stroke than men without epilepsy, said Matthew Zack, MD, MPH, an epidemiologist in the Division of Population Health in the National Center for Chronic Disease Prevention and Health Promotion at the CDC, and colleagues.

Recommending that patients with epilepsy practice healthier behaviors to reduce cardiovascular risk (eg, quitting cigarette smoking, increasing aerobic activity, and eating a healthy diet) “will reduce the burden from these outcomes,” the researchers said. Among patients with cardiovascular disease, adherence to treatments and self-management also will reduce risk, they said.

Cardiovascular diseases are among the most common potentially preventable comorbidities. To compare how often adults with and without epilepsy in the general United States population report common cardiovascular diseases, Dr. Zack and his research colleagues analyzed data from the US National Health Interview Survey, a cross-sectional survey of the civilian noninstitutionalized population.

Participants were age 18 or older and answered questions about epilepsy and cardiovascular disease. In all, 587 adults reported ever having been told by a health professional that they had a seizure disorder or epilepsy, and 33,946 adults did not report a history of epilepsy. Participants also reported whether they had been told by a health professional that they had hypertension, coronary heart disease, angina pectoris, heart attack, other heart condition, or stroke. The investigators adjusted results for age, race/ethnicity, marital status, educational attainment, the ratio of family income to the poverty level, and geographic region.

Compared with people without epilepsy, people with epilepsy reported significantly more hypertension (36.4% vs 30.2%), angina pectoris (3.9% vs 2.0%), heart attack (5.2% vs 3.3%), other heart condition (11.8% vs 7.4%), and stroke (12.2% vs 2.6%). Women with epilepsy reported significantly more hypertension (36.4% vs 29.6%), angina pectoris (3.9% vs 1.7%), and stroke (14.1% vs 2.6%) than women without epilepsy. Men with epilepsy reported significantly more stroke (10.1% vs 2.7%) than men without epilepsy.

People with epilepsy may report more cardiovascular disease than people without epilepsy because of behavioral risk factors, genetic predisposition, seizure-related damage to the heart, or medication effects, the researchers said. The sex-specific differences require further study. The investigators noted that the study’s reliance on self-report increases the likelihood of misclassification of epilepsy status and cardiovascular disease outcomes. In addition, researchers do not know whether cardiovascular outcomes occurred before or after the onset of epilepsy.

—Jake Remaly

Suggested Reading

Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44:121-126.

Kadima NT, Kobau R, Zack MM, Helmers S. Comorbidity in adults with epilepsy—United States, 2010. MMWR Morb Mortal Wkly Rep. 2013;62(43):849-853.

HOUSTON—Adults with epilepsy report cardiovascular disease more often than adults without epilepsy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

In the 2013 US National Health Interview Survey, women with epilepsy reported significantly more hypertension, stroke, and angina pectoris than women without epilepsy. Men with epilepsy reported significantly more stroke than men without epilepsy, said Matthew Zack, MD, MPH, an epidemiologist in the Division of Population Health in the National Center for Chronic Disease Prevention and Health Promotion at the CDC, and colleagues.

Recommending that patients with epilepsy practice healthier behaviors to reduce cardiovascular risk (eg, quitting cigarette smoking, increasing aerobic activity, and eating a healthy diet) “will reduce the burden from these outcomes,” the researchers said. Among patients with cardiovascular disease, adherence to treatments and self-management also will reduce risk, they said.

Cardiovascular diseases are among the most common potentially preventable comorbidities. To compare how often adults with and without epilepsy in the general United States population report common cardiovascular diseases, Dr. Zack and his research colleagues analyzed data from the US National Health Interview Survey, a cross-sectional survey of the civilian noninstitutionalized population.

Participants were age 18 or older and answered questions about epilepsy and cardiovascular disease. In all, 587 adults reported ever having been told by a health professional that they had a seizure disorder or epilepsy, and 33,946 adults did not report a history of epilepsy. Participants also reported whether they had been told by a health professional that they had hypertension, coronary heart disease, angina pectoris, heart attack, other heart condition, or stroke. The investigators adjusted results for age, race/ethnicity, marital status, educational attainment, the ratio of family income to the poverty level, and geographic region.

Compared with people without epilepsy, people with epilepsy reported significantly more hypertension (36.4% vs 30.2%), angina pectoris (3.9% vs 2.0%), heart attack (5.2% vs 3.3%), other heart condition (11.8% vs 7.4%), and stroke (12.2% vs 2.6%). Women with epilepsy reported significantly more hypertension (36.4% vs 29.6%), angina pectoris (3.9% vs 1.7%), and stroke (14.1% vs 2.6%) than women without epilepsy. Men with epilepsy reported significantly more stroke (10.1% vs 2.7%) than men without epilepsy.

People with epilepsy may report more cardiovascular disease than people without epilepsy because of behavioral risk factors, genetic predisposition, seizure-related damage to the heart, or medication effects, the researchers said. The sex-specific differences require further study. The investigators noted that the study’s reliance on self-report increases the likelihood of misclassification of epilepsy status and cardiovascular disease outcomes. In addition, researchers do not know whether cardiovascular outcomes occurred before or after the onset of epilepsy.

—Jake Remaly

Suggested Reading

Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44:121-126.

Kadima NT, Kobau R, Zack MM, Helmers S. Comorbidity in adults with epilepsy—United States, 2010. MMWR Morb Mortal Wkly Rep. 2013;62(43):849-853.

HOUSTON—Adults with epilepsy report cardiovascular disease more often than adults without epilepsy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

In the 2013 US National Health Interview Survey, women with epilepsy reported significantly more hypertension, stroke, and angina pectoris than women without epilepsy. Men with epilepsy reported significantly more stroke than men without epilepsy, said Matthew Zack, MD, MPH, an epidemiologist in the Division of Population Health in the National Center for Chronic Disease Prevention and Health Promotion at the CDC, and colleagues.

Recommending that patients with epilepsy practice healthier behaviors to reduce cardiovascular risk (eg, quitting cigarette smoking, increasing aerobic activity, and eating a healthy diet) “will reduce the burden from these outcomes,” the researchers said. Among patients with cardiovascular disease, adherence to treatments and self-management also will reduce risk, they said.

Cardiovascular diseases are among the most common potentially preventable comorbidities. To compare how often adults with and without epilepsy in the general United States population report common cardiovascular diseases, Dr. Zack and his research colleagues analyzed data from the US National Health Interview Survey, a cross-sectional survey of the civilian noninstitutionalized population.

Participants were age 18 or older and answered questions about epilepsy and cardiovascular disease. In all, 587 adults reported ever having been told by a health professional that they had a seizure disorder or epilepsy, and 33,946 adults did not report a history of epilepsy. Participants also reported whether they had been told by a health professional that they had hypertension, coronary heart disease, angina pectoris, heart attack, other heart condition, or stroke. The investigators adjusted results for age, race/ethnicity, marital status, educational attainment, the ratio of family income to the poverty level, and geographic region.

Compared with people without epilepsy, people with epilepsy reported significantly more hypertension (36.4% vs 30.2%), angina pectoris (3.9% vs 2.0%), heart attack (5.2% vs 3.3%), other heart condition (11.8% vs 7.4%), and stroke (12.2% vs 2.6%). Women with epilepsy reported significantly more hypertension (36.4% vs 29.6%), angina pectoris (3.9% vs 1.7%), and stroke (14.1% vs 2.6%) than women without epilepsy. Men with epilepsy reported significantly more stroke (10.1% vs 2.7%) than men without epilepsy.

People with epilepsy may report more cardiovascular disease than people without epilepsy because of behavioral risk factors, genetic predisposition, seizure-related damage to the heart, or medication effects, the researchers said. The sex-specific differences require further study. The investigators noted that the study’s reliance on self-report increases the likelihood of misclassification of epilepsy status and cardiovascular disease outcomes. In addition, researchers do not know whether cardiovascular outcomes occurred before or after the onset of epilepsy.

—Jake Remaly

Suggested Reading

Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44:121-126.

Kadima NT, Kobau R, Zack MM, Helmers S. Comorbidity in adults with epilepsy—United States, 2010. MMWR Morb Mortal Wkly Rep. 2013;62(43):849-853.

LAS VEGAS—An oral extended-release agent composed of carbidopa–levodopa microbeads that was shown, in clinical studies, to improve symptoms in patients with early or advanced Parkinson’s disease is one of several promising new therapies for this neurodegenerative disorder, according to a presentation at the American Academy of Neurology’s Fall 2016 Conference.

In addition to extended-release carbidopa–levodopa (Rytary), these therapies include drugs recently approved by the FDA for orthostatic hypotension (droxidopa) and psychosis (pimavanserin) in Parkinson’s disease and investigational agents such as an inhaled levodopa (CVT-301) and a leukemia drug (nilotinib) currently in clinical trials for use in patients with Parkinson’s disease. “These are things that patients are going to be talking to you about and that you all can use in taking care of patients with Parkinson’s disease,” said Jeff A. Kraakevik, MD, Associate Professor of Neurology at Oregon Health & Science University in Portland.

Expanding the Armamentarium

Dr. Kraakevik presented data on two new deep brain stimulation systems—Vercise from Boston Scientific, which has not yet been approved by the FDA, and Infinity from St. Jude Medical, which has been FDA approved—and a third surgical device from Medtronic, which is not new, but now has new FDA labeling regarding broader MRI compatibility for limited body scans. He also reported on a randomized trial of focused ultrasound for essential tremor that has led to FDA approval and touched on a clinical trial of a specific gene therapy for Huntington’s disease that is now enrolling patients. However, the bulk of his presentation focused on pharmacologic therapy.

Extended-Release Carbidopa–Levodopa (Rytary)

Citing a 2016 review of cumulative data by Dhall and Kreitzman that included five randomized controlled trials, Dr. Kraakevik indicated that Rytary is a superior formulation of carbidopa–levodopa, compared with a prior controlled-release formulation—largely owing to factors related to gut absorption, such as the slow rate at which the extended-release component of the latter formulation goes through the stomach. “Parkinson’s patients are often constipated, so there is a variable gut transport, as well as a protein competing with the carbidopa–levodopa as it [gets absorbed],” he said. “All those things led to this being a fairly unpredictable [process]. If you talk to patients about it, they usually are rather unhappy with the controlled-release formulation, especially as the disease progresses.”

The extended-release formulation of Rytary can entail what essentially amounts to a dosing-related trial period for some patients started on it; but, in Dr. Kraakevik’s experience, patients who stick it out usually are glad that they did. For one, the combination of immediate-release and sustained-release beads in each capsule makes the formulation much more predictable than controlled release. “The patients I’ve been able to get through the transition period have really, really liked it,” he said. “We tell people we are going to have … maybe at least a couple of weeks to a month of trying to figure out what the best dose of Rytary is.”

He also commented on the high cost of the drug. “The company has a support desk that patients can call; but, even with that, every time I’ve had to do a dose adjustment and change the pill I’ve had to do another prior authorization, which then sets it back,” said Dr. Kraakevik. “That also has been a barrier for some of my patients to get started on Rytary. That being said, especially for later-onset … motor fluctuations, it is a very good formulation.”

Droxidopa (Northera)

In terms of treating orthostatic hypotension in Parkinson’s disease, prior agents include midodrine, fludrocortisone, and pyridostigmine. They all work relatively well, according to Dr. Kraakevik; however, if one looks at the studies on midodrine, for example, the data are somewhat equivocal. “It is nice that we have this additional therapeutic in our armamentarium,” he said of droxidopa (Northera). “It is a precursor to norepinephrine, so it has a different mechanism of action than [any] of the medications we have to treat orthostasis.”

Symptom and symptom-impact composite scores from the trial that resulted in FDA approval for droxidopa show a statistically significant difference versus placebo. In his practice, Dr. Kraakevik talks to his patients a lot more about whether they are fainting or feeling lightheaded and a lot less about listing all their orthostatic blood pressure readings over the previous several weeks. Most of his patients have been seeing primary care physicians who, for years, have been telling them that their blood pressure should not exceed 140/90 and that, if it does, they should call their doctor and, if it is more than 180 or 185, they should go to the emergency room.

“I get a lot of phone calls because these medications are going to make these people have blood pressures that are going to be above those ranges,” said Dr. Kraakevik. “It is probably going to be up there for only about five, 10 minutes, and then it is going to come back down. So that is why I do not tell people to focus on the numbers, but more on symptoms. You can see [in the aforementioned trial] that for dizziness/lightheadedness, visual disturbances … [droxidopa] has a nice effect. Looking at symptoms [such as] when they are standing for a long time, standing for a short time, all these things—except for walking for a long time—symptoms were significantly reduced with use of droxidopa.”

Pimavanserin (Nuplazid)

Pimavanserin (Nuplazid) has recently been FDA approved for treatment of hallucinations in Parkinson’s disease. It is a 5-HT2A inverse agonist. Pimavanserin blocks the serotonergic receptor and reduces the stimulation effect, causing a decrease in the ability to create hallucinations to the striatal limit. In a 2014 trial, pimavanserin was shown to significantly decrease hallucinations over 43 days. “It is an effective medication … not much in the way of side effects at this point,” said Dr. Kraakevik. “It does have that QT prolongation possibility, so you need to be a little careful in patients who have some cardiac abnormalities or rhythm abnormalities when you use this medication. But otherwise it is relatively well tolerated.”

Therapeutics on the Horizon

Medications in the pipeline include an inhaled carbidopa–levodopa agent (CVT-301). In a randomized controlled trial of 86 subjects, investigators found it to be effective in rapidly reversing “off” symptoms, Dr. Kraakevik reported. “Most of the patients who were in this trial had reversal of their symptoms within about 10 minutes,” he said, adding that CVT-301 should be in phase III studies soon and coming up for approval within the next two years.

Nilotinib was approved by the FDA in 2010 as a treatment for adult patients with a form of chronic myeloid leukemia. Given its mechanism of action as a tyrosine kinase inhibitor, researchers hypothesize that it could be applicable to Parkinson’s disease. In a phase I study involving 12 subjects, investigators found that all of the patients who received nilotinib had a reversible decrease in their Unified Parkinson’s Disease Rating Scale score while also scoring “much better on their Mini-Mental State Examination,” according to Dr. Kraakevik.

“It reversed when the medication was taken away,” he emphasized. “This led to a lot of press and a lot of questions in my clinic, where we are asked … why is not every [therapy] able to do this? And my response to patients is, ‘Right now we have 12 people in an open-label study. We need more data.’”

Such data could come from a double-blind, placebo-controlled clinical trial currently in the planning stages, “but there have allegedly been some disagreements between the key entities about the best way to proceed, and this has slowed the process significantly.”

—Fred Balzac

Suggested Reading

Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014;383(9916):533-540.

Dhall R, Kreitzman DL. Advances in levodopa therapy for Parkinson disease: review of RYTARY (carbidopa and levodopa) clinical efficacy and safety. Neurology. 2016;86(14 suppl 1):S13-S24.

Fox SH. Pimavanserin as treatment for Parkinson’s disease psychosis. Lancet. 2014;383(9916):494-496.

Kaufmann H, Freeman R, Biaggioni I, et al for the NOH301 Investigators. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328-335.

LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord. 2016;31(9):1356-1365.

Pagan F, Hebron M, Valadez EH, et al. Nilotinib effects in Parkinson’s disease and dementia with Lewy bodies. J Parkinsons Dis. 2016;6(3):503-517.

LAS VEGAS—An oral extended-release agent composed of carbidopa–levodopa microbeads that was shown, in clinical studies, to improve symptoms in patients with early or advanced Parkinson’s disease is one of several promising new therapies for this neurodegenerative disorder, according to a presentation at the American Academy of Neurology’s Fall 2016 Conference.

In addition to extended-release carbidopa–levodopa (Rytary), these therapies include drugs recently approved by the FDA for orthostatic hypotension (droxidopa) and psychosis (pimavanserin) in Parkinson’s disease and investigational agents such as an inhaled levodopa (CVT-301) and a leukemia drug (nilotinib) currently in clinical trials for use in patients with Parkinson’s disease. “These are things that patients are going to be talking to you about and that you all can use in taking care of patients with Parkinson’s disease,” said Jeff A. Kraakevik, MD, Associate Professor of Neurology at Oregon Health & Science University in Portland.

Expanding the Armamentarium

Dr. Kraakevik presented data on two new deep brain stimulation systems—Vercise from Boston Scientific, which has not yet been approved by the FDA, and Infinity from St. Jude Medical, which has been FDA approved—and a third surgical device from Medtronic, which is not new, but now has new FDA labeling regarding broader MRI compatibility for limited body scans. He also reported on a randomized trial of focused ultrasound for essential tremor that has led to FDA approval and touched on a clinical trial of a specific gene therapy for Huntington’s disease that is now enrolling patients. However, the bulk of his presentation focused on pharmacologic therapy.

Extended-Release Carbidopa–Levodopa (Rytary)

Citing a 2016 review of cumulative data by Dhall and Kreitzman that included five randomized controlled trials, Dr. Kraakevik indicated that Rytary is a superior formulation of carbidopa–levodopa, compared with a prior controlled-release formulation—largely owing to factors related to gut absorption, such as the slow rate at which the extended-release component of the latter formulation goes through the stomach. “Parkinson’s patients are often constipated, so there is a variable gut transport, as well as a protein competing with the carbidopa–levodopa as it [gets absorbed],” he said. “All those things led to this being a fairly unpredictable [process]. If you talk to patients about it, they usually are rather unhappy with the controlled-release formulation, especially as the disease progresses.”

The extended-release formulation of Rytary can entail what essentially amounts to a dosing-related trial period for some patients started on it; but, in Dr. Kraakevik’s experience, patients who stick it out usually are glad that they did. For one, the combination of immediate-release and sustained-release beads in each capsule makes the formulation much more predictable than controlled release. “The patients I’ve been able to get through the transition period have really, really liked it,” he said. “We tell people we are going to have … maybe at least a couple of weeks to a month of trying to figure out what the best dose of Rytary is.”

He also commented on the high cost of the drug. “The company has a support desk that patients can call; but, even with that, every time I’ve had to do a dose adjustment and change the pill I’ve had to do another prior authorization, which then sets it back,” said Dr. Kraakevik. “That also has been a barrier for some of my patients to get started on Rytary. That being said, especially for later-onset … motor fluctuations, it is a very good formulation.”

Droxidopa (Northera)

In terms of treating orthostatic hypotension in Parkinson’s disease, prior agents include midodrine, fludrocortisone, and pyridostigmine. They all work relatively well, according to Dr. Kraakevik; however, if one looks at the studies on midodrine, for example, the data are somewhat equivocal. “It is nice that we have this additional therapeutic in our armamentarium,” he said of droxidopa (Northera). “It is a precursor to norepinephrine, so it has a different mechanism of action than [any] of the medications we have to treat orthostasis.”

Symptom and symptom-impact composite scores from the trial that resulted in FDA approval for droxidopa show a statistically significant difference versus placebo. In his practice, Dr. Kraakevik talks to his patients a lot more about whether they are fainting or feeling lightheaded and a lot less about listing all their orthostatic blood pressure readings over the previous several weeks. Most of his patients have been seeing primary care physicians who, for years, have been telling them that their blood pressure should not exceed 140/90 and that, if it does, they should call their doctor and, if it is more than 180 or 185, they should go to the emergency room.

“I get a lot of phone calls because these medications are going to make these people have blood pressures that are going to be above those ranges,” said Dr. Kraakevik. “It is probably going to be up there for only about five, 10 minutes, and then it is going to come back down. So that is why I do not tell people to focus on the numbers, but more on symptoms. You can see [in the aforementioned trial] that for dizziness/lightheadedness, visual disturbances … [droxidopa] has a nice effect. Looking at symptoms [such as] when they are standing for a long time, standing for a short time, all these things—except for walking for a long time—symptoms were significantly reduced with use of droxidopa.”

Pimavanserin (Nuplazid)

Pimavanserin (Nuplazid) has recently been FDA approved for treatment of hallucinations in Parkinson’s disease. It is a 5-HT2A inverse agonist. Pimavanserin blocks the serotonergic receptor and reduces the stimulation effect, causing a decrease in the ability to create hallucinations to the striatal limit. In a 2014 trial, pimavanserin was shown to significantly decrease hallucinations over 43 days. “It is an effective medication … not much in the way of side effects at this point,” said Dr. Kraakevik. “It does have that QT prolongation possibility, so you need to be a little careful in patients who have some cardiac abnormalities or rhythm abnormalities when you use this medication. But otherwise it is relatively well tolerated.”

Therapeutics on the Horizon

Medications in the pipeline include an inhaled carbidopa–levodopa agent (CVT-301). In a randomized controlled trial of 86 subjects, investigators found it to be effective in rapidly reversing “off” symptoms, Dr. Kraakevik reported. “Most of the patients who were in this trial had reversal of their symptoms within about 10 minutes,” he said, adding that CVT-301 should be in phase III studies soon and coming up for approval within the next two years.

Nilotinib was approved by the FDA in 2010 as a treatment for adult patients with a form of chronic myeloid leukemia. Given its mechanism of action as a tyrosine kinase inhibitor, researchers hypothesize that it could be applicable to Parkinson’s disease. In a phase I study involving 12 subjects, investigators found that all of the patients who received nilotinib had a reversible decrease in their Unified Parkinson’s Disease Rating Scale score while also scoring “much better on their Mini-Mental State Examination,” according to Dr. Kraakevik.

“It reversed when the medication was taken away,” he emphasized. “This led to a lot of press and a lot of questions in my clinic, where we are asked … why is not every [therapy] able to do this? And my response to patients is, ‘Right now we have 12 people in an open-label study. We need more data.’”

Such data could come from a double-blind, placebo-controlled clinical trial currently in the planning stages, “but there have allegedly been some disagreements between the key entities about the best way to proceed, and this has slowed the process significantly.”

—Fred Balzac

Suggested Reading

Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014;383(9916):533-540.

Dhall R, Kreitzman DL. Advances in levodopa therapy for Parkinson disease: review of RYTARY (carbidopa and levodopa) clinical efficacy and safety. Neurology. 2016;86(14 suppl 1):S13-S24.

Fox SH. Pimavanserin as treatment for Parkinson’s disease psychosis. Lancet. 2014;383(9916):494-496.

Kaufmann H, Freeman R, Biaggioni I, et al for the NOH301 Investigators. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328-335.

LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord. 2016;31(9):1356-1365.

Pagan F, Hebron M, Valadez EH, et al. Nilotinib effects in Parkinson’s disease and dementia with Lewy bodies. J Parkinsons Dis. 2016;6(3):503-517.

LAS VEGAS—An oral extended-release agent composed of carbidopa–levodopa microbeads that was shown, in clinical studies, to improve symptoms in patients with early or advanced Parkinson’s disease is one of several promising new therapies for this neurodegenerative disorder, according to a presentation at the American Academy of Neurology’s Fall 2016 Conference.

In addition to extended-release carbidopa–levodopa (Rytary), these therapies include drugs recently approved by the FDA for orthostatic hypotension (droxidopa) and psychosis (pimavanserin) in Parkinson’s disease and investigational agents such as an inhaled levodopa (CVT-301) and a leukemia drug (nilotinib) currently in clinical trials for use in patients with Parkinson’s disease. “These are things that patients are going to be talking to you about and that you all can use in taking care of patients with Parkinson’s disease,” said Jeff A. Kraakevik, MD, Associate Professor of Neurology at Oregon Health & Science University in Portland.

Expanding the Armamentarium

Dr. Kraakevik presented data on two new deep brain stimulation systems—Vercise from Boston Scientific, which has not yet been approved by the FDA, and Infinity from St. Jude Medical, which has been FDA approved—and a third surgical device from Medtronic, which is not new, but now has new FDA labeling regarding broader MRI compatibility for limited body scans. He also reported on a randomized trial of focused ultrasound for essential tremor that has led to FDA approval and touched on a clinical trial of a specific gene therapy for Huntington’s disease that is now enrolling patients. However, the bulk of his presentation focused on pharmacologic therapy.

Extended-Release Carbidopa–Levodopa (Rytary)

Citing a 2016 review of cumulative data by Dhall and Kreitzman that included five randomized controlled trials, Dr. Kraakevik indicated that Rytary is a superior formulation of carbidopa–levodopa, compared with a prior controlled-release formulation—largely owing to factors related to gut absorption, such as the slow rate at which the extended-release component of the latter formulation goes through the stomach. “Parkinson’s patients are often constipated, so there is a variable gut transport, as well as a protein competing with the carbidopa–levodopa as it [gets absorbed],” he said. “All those things led to this being a fairly unpredictable [process]. If you talk to patients about it, they usually are rather unhappy with the controlled-release formulation, especially as the disease progresses.”

The extended-release formulation of Rytary can entail what essentially amounts to a dosing-related trial period for some patients started on it; but, in Dr. Kraakevik’s experience, patients who stick it out usually are glad that they did. For one, the combination of immediate-release and sustained-release beads in each capsule makes the formulation much more predictable than controlled release. “The patients I’ve been able to get through the transition period have really, really liked it,” he said. “We tell people we are going to have … maybe at least a couple of weeks to a month of trying to figure out what the best dose of Rytary is.”

He also commented on the high cost of the drug. “The company has a support desk that patients can call; but, even with that, every time I’ve had to do a dose adjustment and change the pill I’ve had to do another prior authorization, which then sets it back,” said Dr. Kraakevik. “That also has been a barrier for some of my patients to get started on Rytary. That being said, especially for later-onset … motor fluctuations, it is a very good formulation.”

Droxidopa (Northera)

In terms of treating orthostatic hypotension in Parkinson’s disease, prior agents include midodrine, fludrocortisone, and pyridostigmine. They all work relatively well, according to Dr. Kraakevik; however, if one looks at the studies on midodrine, for example, the data are somewhat equivocal. “It is nice that we have this additional therapeutic in our armamentarium,” he said of droxidopa (Northera). “It is a precursor to norepinephrine, so it has a different mechanism of action than [any] of the medications we have to treat orthostasis.”

Symptom and symptom-impact composite scores from the trial that resulted in FDA approval for droxidopa show a statistically significant difference versus placebo. In his practice, Dr. Kraakevik talks to his patients a lot more about whether they are fainting or feeling lightheaded and a lot less about listing all their orthostatic blood pressure readings over the previous several weeks. Most of his patients have been seeing primary care physicians who, for years, have been telling them that their blood pressure should not exceed 140/90 and that, if it does, they should call their doctor and, if it is more than 180 or 185, they should go to the emergency room.

“I get a lot of phone calls because these medications are going to make these people have blood pressures that are going to be above those ranges,” said Dr. Kraakevik. “It is probably going to be up there for only about five, 10 minutes, and then it is going to come back down. So that is why I do not tell people to focus on the numbers, but more on symptoms. You can see [in the aforementioned trial] that for dizziness/lightheadedness, visual disturbances … [droxidopa] has a nice effect. Looking at symptoms [such as] when they are standing for a long time, standing for a short time, all these things—except for walking for a long time—symptoms were significantly reduced with use of droxidopa.”

Pimavanserin (Nuplazid)

Pimavanserin (Nuplazid) has recently been FDA approved for treatment of hallucinations in Parkinson’s disease. It is a 5-HT2A inverse agonist. Pimavanserin blocks the serotonergic receptor and reduces the stimulation effect, causing a decrease in the ability to create hallucinations to the striatal limit. In a 2014 trial, pimavanserin was shown to significantly decrease hallucinations over 43 days. “It is an effective medication … not much in the way of side effects at this point,” said Dr. Kraakevik. “It does have that QT prolongation possibility, so you need to be a little careful in patients who have some cardiac abnormalities or rhythm abnormalities when you use this medication. But otherwise it is relatively well tolerated.”

Therapeutics on the Horizon

Medications in the pipeline include an inhaled carbidopa–levodopa agent (CVT-301). In a randomized controlled trial of 86 subjects, investigators found it to be effective in rapidly reversing “off” symptoms, Dr. Kraakevik reported. “Most of the patients who were in this trial had reversal of their symptoms within about 10 minutes,” he said, adding that CVT-301 should be in phase III studies soon and coming up for approval within the next two years.

Nilotinib was approved by the FDA in 2010 as a treatment for adult patients with a form of chronic myeloid leukemia. Given its mechanism of action as a tyrosine kinase inhibitor, researchers hypothesize that it could be applicable to Parkinson’s disease. In a phase I study involving 12 subjects, investigators found that all of the patients who received nilotinib had a reversible decrease in their Unified Parkinson’s Disease Rating Scale score while also scoring “much better on their Mini-Mental State Examination,” according to Dr. Kraakevik.

“It reversed when the medication was taken away,” he emphasized. “This led to a lot of press and a lot of questions in my clinic, where we are asked … why is not every [therapy] able to do this? And my response to patients is, ‘Right now we have 12 people in an open-label study. We need more data.’”

Such data could come from a double-blind, placebo-controlled clinical trial currently in the planning stages, “but there have allegedly been some disagreements between the key entities about the best way to proceed, and this has slowed the process significantly.”

—Fred Balzac

Suggested Reading

Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014;383(9916):533-540.

Dhall R, Kreitzman DL. Advances in levodopa therapy for Parkinson disease: review of RYTARY (carbidopa and levodopa) clinical efficacy and safety. Neurology. 2016;86(14 suppl 1):S13-S24.

Fox SH. Pimavanserin as treatment for Parkinson’s disease psychosis. Lancet. 2014;383(9916):494-496.

Kaufmann H, Freeman R, Biaggioni I, et al for the NOH301 Investigators. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328-335.

LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord. 2016;31(9):1356-1365.

Pagan F, Hebron M, Valadez EH, et al. Nilotinib effects in Parkinson’s disease and dementia with Lewy bodies. J Parkinsons Dis. 2016;6(3):503-517.

HOUSTON—Younger age and greater stroke volume are risk factors for the development of poststroke epilepsy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

Beate Diehl, MD, PhD, neurologist and clinical neurophysiologist at University College London, and colleagues examined information from the Predicting Language Outcome and Recovery After Stroke (PLORAS) database to ascertain the frequency of poststroke epilepsy and compare lesion characteristics between people with and without poststroke epilepsy. The database includes T1-weighted whole brain MRIs acquired with a 3-T scanner.

The investigators identified 369 patients with left-hemisphere strokes, and 42 of them (11.4%) had poststroke epilepsy. Of 81 patients with right-hemisphere strokes, nine (11.1%) had poststroke epilepsy. Gender, handedness, and stroke etiology were similar between patients with and without poststroke epilepsy.

Patients with poststroke epilepsy were significantly younger than those without poststroke epilepsy, however (44 vs 56). In addition, patients with poststroke epilepsy had significantly larger lesions than patients without poststroke epilepsy (148 cm³ vs 73 cm³). Large lesions are more likely to damage deep white matter, said Dr. Diehl.

The most consistent lesion sites among all patients with poststroke epilepsy included the basal ganglia (ie, globus pallidus and caudate nucleus) and most nuclei of the thalamus (ie, anterior and ventral nuclei and posterior regions, including pulvinar). Damage to these regions occurred in 27 (64%) of patients with left-hemisphere stroke and poststroke epilepsy. Furthermore, 55 (17%) patients with left-hemisphere stroke without poststroke epilepsy also had damage in the same regions. Damage to these regions thus was associated with poststroke epilepsy in 27 of 82 (33%) patients.

“Many physicians treating stroke patients do not realize that falls, episodes of confusion, and loss of consciousness may be signs of poststroke epilepsy,” said Dr. Diehl. “Poststroke epileptic seizures can negatively affect stroke recovery and rehabilitation.”

—Erik Greb

HOUSTON—Younger age and greater stroke volume are risk factors for the development of poststroke epilepsy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

Beate Diehl, MD, PhD, neurologist and clinical neurophysiologist at University College London, and colleagues examined information from the Predicting Language Outcome and Recovery After Stroke (PLORAS) database to ascertain the frequency of poststroke epilepsy and compare lesion characteristics between people with and without poststroke epilepsy. The database includes T1-weighted whole brain MRIs acquired with a 3-T scanner.

The investigators identified 369 patients with left-hemisphere strokes, and 42 of them (11.4%) had poststroke epilepsy. Of 81 patients with right-hemisphere strokes, nine (11.1%) had poststroke epilepsy. Gender, handedness, and stroke etiology were similar between patients with and without poststroke epilepsy.

Patients with poststroke epilepsy were significantly younger than those without poststroke epilepsy, however (44 vs 56). In addition, patients with poststroke epilepsy had significantly larger lesions than patients without poststroke epilepsy (148 cm³ vs 73 cm³). Large lesions are more likely to damage deep white matter, said Dr. Diehl.

The most consistent lesion sites among all patients with poststroke epilepsy included the basal ganglia (ie, globus pallidus and caudate nucleus) and most nuclei of the thalamus (ie, anterior and ventral nuclei and posterior regions, including pulvinar). Damage to these regions occurred in 27 (64%) of patients with left-hemisphere stroke and poststroke epilepsy. Furthermore, 55 (17%) patients with left-hemisphere stroke without poststroke epilepsy also had damage in the same regions. Damage to these regions thus was associated with poststroke epilepsy in 27 of 82 (33%) patients.

“Many physicians treating stroke patients do not realize that falls, episodes of confusion, and loss of consciousness may be signs of poststroke epilepsy,” said Dr. Diehl. “Poststroke epileptic seizures can negatively affect stroke recovery and rehabilitation.”

—Erik Greb

HOUSTON—Younger age and greater stroke volume are risk factors for the development of poststroke epilepsy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

Beate Diehl, MD, PhD, neurologist and clinical neurophysiologist at University College London, and colleagues examined information from the Predicting Language Outcome and Recovery After Stroke (PLORAS) database to ascertain the frequency of poststroke epilepsy and compare lesion characteristics between people with and without poststroke epilepsy. The database includes T1-weighted whole brain MRIs acquired with a 3-T scanner.

The investigators identified 369 patients with left-hemisphere strokes, and 42 of them (11.4%) had poststroke epilepsy. Of 81 patients with right-hemisphere strokes, nine (11.1%) had poststroke epilepsy. Gender, handedness, and stroke etiology were similar between patients with and without poststroke epilepsy.

Patients with poststroke epilepsy were significantly younger than those without poststroke epilepsy, however (44 vs 56). In addition, patients with poststroke epilepsy had significantly larger lesions than patients without poststroke epilepsy (148 cm³ vs 73 cm³). Large lesions are more likely to damage deep white matter, said Dr. Diehl.

The most consistent lesion sites among all patients with poststroke epilepsy included the basal ganglia (ie, globus pallidus and caudate nucleus) and most nuclei of the thalamus (ie, anterior and ventral nuclei and posterior regions, including pulvinar). Damage to these regions occurred in 27 (64%) of patients with left-hemisphere stroke and poststroke epilepsy. Furthermore, 55 (17%) patients with left-hemisphere stroke without poststroke epilepsy also had damage in the same regions. Damage to these regions thus was associated with poststroke epilepsy in 27 of 82 (33%) patients.

“Many physicians treating stroke patients do not realize that falls, episodes of confusion, and loss of consciousness may be signs of poststroke epilepsy,” said Dr. Diehl. “Poststroke epileptic seizures can negatively affect stroke recovery and rehabilitation.”

—Erik Greb