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Interferon treatment does not increase stroke risk in MS
LOS ANGELES – Patients with multiple sclerosis who are treated with subcutaneous interferon beta-1a have no increase in stroke risk, compared with those treated with placebo, according to pooled data from clinical trials and a safety database analysis.
Studies have shown that MS patients have a greater risk of stroke, compared with the general population, but the data with respect to the risk of stroke following interferon treatment are limited, Alan Gillett, PhD, explained in his presentation at the annual meeting of the American Academy of Neurology. He noted that a 2017 report on a series of nested case-control studies showed a 1.8-fold increased risk of stroke in relapsing-remitting MS patients who received interferon.
In the new analysis presented at the meeting, there was a trend toward decreased stroke incidence among patients treated with subcutaneous interferon beta-1a. Stroke incidence was 0.025 per 100 patient-years (25 events) in patients treated with subcutaneous interferon beta-1a vs. 0.051 per 100 patient-years (11 events) in patients who received placebo across 17 phase 2-4 clinical trials. The incidence rate ratio (IRR) and hazard ratio for stroke in interferon- vs. placebo-treated patients were 0.486 and 0.496, respectively, reported Dr. Gillett of EMD Serono, Mississauga, Ont.
Further, no significant difference in stroke incidence was seen between the treatment and placebo groups based on treatment duration, Dr. Gillett said. The IRR in patients treated for less than 2 years was 0.602 vs. 0.469 in those treated for 2 or more years.
“The incidence rate ratio [in both groups] was very comparable to that overall, so this indicates that treatment duration had little impact on the incidence rate of stroke,” he said.
The same was true in an analysis based on dose; the IRRs were similar in those exposed to 44 mcg vs. placebo, and in those receiving any dose vs. placebo, he noted.
The analysis is based on reports of 569 cerebrovascular events occurring over 19 years (2.7 per 10,000 patient-years) in 1,594,414 patient-years of follow-up through May 22, 2017, in the Global Patient Safety Database.
“And according to prescribing information ... this would be classified as rare, with less than 1 in 1,000,” Dr. Gillett said.
“So this led us to our objective to really assess the risk of stroke in patients treated with subcutaneous interferon beta-1a ... and the association with treatment duration and dose,” he said. “What we can conclude from [our] study is that a trend toward decreased risk of stroke for subcutaneous interferon beta-1a, compared to placebo, was observed in 17 clinical trials ... and the safety data from both clinical trials and postmarketing [surveillance] suggests that treatment with subcutaneous interferon beta-1a ... does not increase the risk of stroke in patients with MS.”
This study was supported by Merck KGaA of Darmstadt, Germany. Dr. Gillett is an employee of EMD Serono, the biopharmaceutical division of Merck KGaA.
SOURCE: Sabidó M et al. Neurology. 2018 Apr 90(15 Suppl.):S36.008.
LOS ANGELES – Patients with multiple sclerosis who are treated with subcutaneous interferon beta-1a have no increase in stroke risk, compared with those treated with placebo, according to pooled data from clinical trials and a safety database analysis.
Studies have shown that MS patients have a greater risk of stroke, compared with the general population, but the data with respect to the risk of stroke following interferon treatment are limited, Alan Gillett, PhD, explained in his presentation at the annual meeting of the American Academy of Neurology. He noted that a 2017 report on a series of nested case-control studies showed a 1.8-fold increased risk of stroke in relapsing-remitting MS patients who received interferon.
In the new analysis presented at the meeting, there was a trend toward decreased stroke incidence among patients treated with subcutaneous interferon beta-1a. Stroke incidence was 0.025 per 100 patient-years (25 events) in patients treated with subcutaneous interferon beta-1a vs. 0.051 per 100 patient-years (11 events) in patients who received placebo across 17 phase 2-4 clinical trials. The incidence rate ratio (IRR) and hazard ratio for stroke in interferon- vs. placebo-treated patients were 0.486 and 0.496, respectively, reported Dr. Gillett of EMD Serono, Mississauga, Ont.
Further, no significant difference in stroke incidence was seen between the treatment and placebo groups based on treatment duration, Dr. Gillett said. The IRR in patients treated for less than 2 years was 0.602 vs. 0.469 in those treated for 2 or more years.
“The incidence rate ratio [in both groups] was very comparable to that overall, so this indicates that treatment duration had little impact on the incidence rate of stroke,” he said.
The same was true in an analysis based on dose; the IRRs were similar in those exposed to 44 mcg vs. placebo, and in those receiving any dose vs. placebo, he noted.
The analysis is based on reports of 569 cerebrovascular events occurring over 19 years (2.7 per 10,000 patient-years) in 1,594,414 patient-years of follow-up through May 22, 2017, in the Global Patient Safety Database.
“And according to prescribing information ... this would be classified as rare, with less than 1 in 1,000,” Dr. Gillett said.
“So this led us to our objective to really assess the risk of stroke in patients treated with subcutaneous interferon beta-1a ... and the association with treatment duration and dose,” he said. “What we can conclude from [our] study is that a trend toward decreased risk of stroke for subcutaneous interferon beta-1a, compared to placebo, was observed in 17 clinical trials ... and the safety data from both clinical trials and postmarketing [surveillance] suggests that treatment with subcutaneous interferon beta-1a ... does not increase the risk of stroke in patients with MS.”
This study was supported by Merck KGaA of Darmstadt, Germany. Dr. Gillett is an employee of EMD Serono, the biopharmaceutical division of Merck KGaA.
SOURCE: Sabidó M et al. Neurology. 2018 Apr 90(15 Suppl.):S36.008.
LOS ANGELES – Patients with multiple sclerosis who are treated with subcutaneous interferon beta-1a have no increase in stroke risk, compared with those treated with placebo, according to pooled data from clinical trials and a safety database analysis.
Studies have shown that MS patients have a greater risk of stroke, compared with the general population, but the data with respect to the risk of stroke following interferon treatment are limited, Alan Gillett, PhD, explained in his presentation at the annual meeting of the American Academy of Neurology. He noted that a 2017 report on a series of nested case-control studies showed a 1.8-fold increased risk of stroke in relapsing-remitting MS patients who received interferon.
In the new analysis presented at the meeting, there was a trend toward decreased stroke incidence among patients treated with subcutaneous interferon beta-1a. Stroke incidence was 0.025 per 100 patient-years (25 events) in patients treated with subcutaneous interferon beta-1a vs. 0.051 per 100 patient-years (11 events) in patients who received placebo across 17 phase 2-4 clinical trials. The incidence rate ratio (IRR) and hazard ratio for stroke in interferon- vs. placebo-treated patients were 0.486 and 0.496, respectively, reported Dr. Gillett of EMD Serono, Mississauga, Ont.
Further, no significant difference in stroke incidence was seen between the treatment and placebo groups based on treatment duration, Dr. Gillett said. The IRR in patients treated for less than 2 years was 0.602 vs. 0.469 in those treated for 2 or more years.
“The incidence rate ratio [in both groups] was very comparable to that overall, so this indicates that treatment duration had little impact on the incidence rate of stroke,” he said.
The same was true in an analysis based on dose; the IRRs were similar in those exposed to 44 mcg vs. placebo, and in those receiving any dose vs. placebo, he noted.
The analysis is based on reports of 569 cerebrovascular events occurring over 19 years (2.7 per 10,000 patient-years) in 1,594,414 patient-years of follow-up through May 22, 2017, in the Global Patient Safety Database.
“And according to prescribing information ... this would be classified as rare, with less than 1 in 1,000,” Dr. Gillett said.
“So this led us to our objective to really assess the risk of stroke in patients treated with subcutaneous interferon beta-1a ... and the association with treatment duration and dose,” he said. “What we can conclude from [our] study is that a trend toward decreased risk of stroke for subcutaneous interferon beta-1a, compared to placebo, was observed in 17 clinical trials ... and the safety data from both clinical trials and postmarketing [surveillance] suggests that treatment with subcutaneous interferon beta-1a ... does not increase the risk of stroke in patients with MS.”
This study was supported by Merck KGaA of Darmstadt, Germany. Dr. Gillett is an employee of EMD Serono, the biopharmaceutical division of Merck KGaA.
SOURCE: Sabidó M et al. Neurology. 2018 Apr 90(15 Suppl.):S36.008.
REPORTING FROM AAN 2018
Key clinical point: Pooled data show no increase in stroke risk in MS patients treated with interferon.
Major finding: A trend toward decreased stroke incidence was seen with interferon treatment vs. placebo (IRR, 0.486).
Study details: A review of pooled data from 17 clinical trials and postmarketing surveillance.
Disclosures: This study was supported by Merck KGaA of Darmstadt, Germany. Dr. Gillett is an employee of EMD Serono, the biopharmaceutical division of Merck KGaA.
Source: Sabidó M et al. Neurology. 2018 Apr:90(15 Suppl.):S36.008.
EVOLVE-MS-1 study: ALKS 8700 shows promise for RRMS
LOS ANGELES – ALKS 8700, a novel prodrug of monomethyl fumarate, looks promising as an oral, disease-modifying treatment for relapsing forms of multiple sclerosis, according to interim findings from the phase 3 EVOLVE-MS-1 study.
The annualized relapse rate at a median follow-up of 0.93 patient-years (total, 497.1 patient-years) in 578 patients enrolled to date in the 2-year, open-label study was just 0.16, Robert T. Naismith, MD, reported during an emerging science session at the annual meeting of the American Academy of Neurology.
Further, a statistically significant 80% reduction from baseline was seen in the number of gadolinium-enhancing lesions in 374 patients who completed a 1-year MRI assessment (from a mean of 1.5 to 0.3), said Dr. Naismith of Washington University, St. Louis.
Patients enrolled in the ongoing study are adults aged 18-65 years (mean, 41 years) with confirmed relapsing-remitting MS (RRMS), Expanded Disability Status Scale score of 6.0 or less (mean, 2.7), and no evidence of relapse within 30 days prior to starting ALKS 8700. Those with progressive forms of MS are excluded, as are patients who are pregnant or breastfeeding, patients with a history of other clinically significant conditions, and those with clinically significant abnormal laboratory tests at screening or absolute lymphocyte counts less than 0.9 x 103/mcL.
Of those enrolled so far, 72.5% received prior MS therapies, and their mean time since onset and diagnosis of MS was 9.7 and 7.6 years, respectively. The mean number of relapses in the prior year was 0.8.
ALKS 8700, also known as BIIB098, is given at a dose of 462 mg twice daily for up to 96 weeks; planned enrollment in EVOLVE-MS-1 is approximately 900 patients, Dr. Naismith said.
The preliminary findings from EVOLE-MS-1, which is limited by its single-arm, open-label design, “lend credence to ALKS 8700 as an oral treatment for patients with relapsing-remitting MS,” he said.
In addition to continued evaluation for long-term safety and tolerability in the current study, ALKS 8700 is also being evaluated in combination with 240 mg of twice daily dimethyl fumarate (DMF; Tecfidera) in the 5-week, randomized, double-blind EVOLVE-MS-2 study, which is looking at the gastrointestinal tolerability of the combination in patients with RRMS.
Oral DMF is approved for RRMS, and has been shown to significantly reduce clinical and MRI disease activity, but is commonly associated with GI events. Monomethyl fumarate is the active metabolite of DMF, and as a prodrug of monomethyl fumarate, ALKS 8700 is being developed to work in a manner similar to that of DMF, but with improved GI tolerability, Dr. Naismith explained.
EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.
SOURCE: Naismith R et al. AAN 2018 Emerging Science Abstract 006.
LOS ANGELES – ALKS 8700, a novel prodrug of monomethyl fumarate, looks promising as an oral, disease-modifying treatment for relapsing forms of multiple sclerosis, according to interim findings from the phase 3 EVOLVE-MS-1 study.
The annualized relapse rate at a median follow-up of 0.93 patient-years (total, 497.1 patient-years) in 578 patients enrolled to date in the 2-year, open-label study was just 0.16, Robert T. Naismith, MD, reported during an emerging science session at the annual meeting of the American Academy of Neurology.
Further, a statistically significant 80% reduction from baseline was seen in the number of gadolinium-enhancing lesions in 374 patients who completed a 1-year MRI assessment (from a mean of 1.5 to 0.3), said Dr. Naismith of Washington University, St. Louis.
Patients enrolled in the ongoing study are adults aged 18-65 years (mean, 41 years) with confirmed relapsing-remitting MS (RRMS), Expanded Disability Status Scale score of 6.0 or less (mean, 2.7), and no evidence of relapse within 30 days prior to starting ALKS 8700. Those with progressive forms of MS are excluded, as are patients who are pregnant or breastfeeding, patients with a history of other clinically significant conditions, and those with clinically significant abnormal laboratory tests at screening or absolute lymphocyte counts less than 0.9 x 103/mcL.
Of those enrolled so far, 72.5% received prior MS therapies, and their mean time since onset and diagnosis of MS was 9.7 and 7.6 years, respectively. The mean number of relapses in the prior year was 0.8.
ALKS 8700, also known as BIIB098, is given at a dose of 462 mg twice daily for up to 96 weeks; planned enrollment in EVOLVE-MS-1 is approximately 900 patients, Dr. Naismith said.
The preliminary findings from EVOLE-MS-1, which is limited by its single-arm, open-label design, “lend credence to ALKS 8700 as an oral treatment for patients with relapsing-remitting MS,” he said.
In addition to continued evaluation for long-term safety and tolerability in the current study, ALKS 8700 is also being evaluated in combination with 240 mg of twice daily dimethyl fumarate (DMF; Tecfidera) in the 5-week, randomized, double-blind EVOLVE-MS-2 study, which is looking at the gastrointestinal tolerability of the combination in patients with RRMS.
Oral DMF is approved for RRMS, and has been shown to significantly reduce clinical and MRI disease activity, but is commonly associated with GI events. Monomethyl fumarate is the active metabolite of DMF, and as a prodrug of monomethyl fumarate, ALKS 8700 is being developed to work in a manner similar to that of DMF, but with improved GI tolerability, Dr. Naismith explained.
EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.
SOURCE: Naismith R et al. AAN 2018 Emerging Science Abstract 006.
LOS ANGELES – ALKS 8700, a novel prodrug of monomethyl fumarate, looks promising as an oral, disease-modifying treatment for relapsing forms of multiple sclerosis, according to interim findings from the phase 3 EVOLVE-MS-1 study.
The annualized relapse rate at a median follow-up of 0.93 patient-years (total, 497.1 patient-years) in 578 patients enrolled to date in the 2-year, open-label study was just 0.16, Robert T. Naismith, MD, reported during an emerging science session at the annual meeting of the American Academy of Neurology.
Further, a statistically significant 80% reduction from baseline was seen in the number of gadolinium-enhancing lesions in 374 patients who completed a 1-year MRI assessment (from a mean of 1.5 to 0.3), said Dr. Naismith of Washington University, St. Louis.
Patients enrolled in the ongoing study are adults aged 18-65 years (mean, 41 years) with confirmed relapsing-remitting MS (RRMS), Expanded Disability Status Scale score of 6.0 or less (mean, 2.7), and no evidence of relapse within 30 days prior to starting ALKS 8700. Those with progressive forms of MS are excluded, as are patients who are pregnant or breastfeeding, patients with a history of other clinically significant conditions, and those with clinically significant abnormal laboratory tests at screening or absolute lymphocyte counts less than 0.9 x 103/mcL.
Of those enrolled so far, 72.5% received prior MS therapies, and their mean time since onset and diagnosis of MS was 9.7 and 7.6 years, respectively. The mean number of relapses in the prior year was 0.8.
ALKS 8700, also known as BIIB098, is given at a dose of 462 mg twice daily for up to 96 weeks; planned enrollment in EVOLVE-MS-1 is approximately 900 patients, Dr. Naismith said.
The preliminary findings from EVOLE-MS-1, which is limited by its single-arm, open-label design, “lend credence to ALKS 8700 as an oral treatment for patients with relapsing-remitting MS,” he said.
In addition to continued evaluation for long-term safety and tolerability in the current study, ALKS 8700 is also being evaluated in combination with 240 mg of twice daily dimethyl fumarate (DMF; Tecfidera) in the 5-week, randomized, double-blind EVOLVE-MS-2 study, which is looking at the gastrointestinal tolerability of the combination in patients with RRMS.
Oral DMF is approved for RRMS, and has been shown to significantly reduce clinical and MRI disease activity, but is commonly associated with GI events. Monomethyl fumarate is the active metabolite of DMF, and as a prodrug of monomethyl fumarate, ALKS 8700 is being developed to work in a manner similar to that of DMF, but with improved GI tolerability, Dr. Naismith explained.
EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.
SOURCE: Naismith R et al. AAN 2018 Emerging Science Abstract 006.
Key clinical point:
Major finding: The annualized relapse rate at 1 year was just 0.16 vs. 0.8 in the prior year.
Study details: One-year results from 578 patients in an ongoing phase 3, open-label study.
Disclosures: EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.
Source: Naismith R et al. AAN 2018 Emerging Science Abstract 006.
Transient epileptic amnesia: Rare, treatable, and easy to miss
LOS ANGELES – Transient epileptic amnesia is a rare but a treatable memory condition that usually occurs in late life and can be mistaken for neurodegenerative disease among patients presenting to a neurology or memory clinic.
Transient epileptic amnesia (TEA) is thought to be a focal epilepsy whose major clinical feature is the presence of recurrent spells of anterograde or retrograde amnesia lasting under an hour. The spells tend to occur on waking from sleep.
At the annual meeting of the American Academy of Neurology, Vijay Ramanan, MD, PhD, of the Mayo Clinic in Rochester, Minn., presented a retrospective series of 31 TEA cases from a study attempting to characterize the disorder in more demographic, clinical, and neuroimaging detail than has been done in the literature to date.
The cases were seen over a 20-year period (1998-2017) at the Mayo Clinic. All had at least one EEG and at least one MRI result reviewed by a neuroradiologist. Half also underwent fluorodeoxyglucose (FDG)-positron emission tomography (PET). All cases were classed as TEA if they included recurrent amnesia and an epileptic trait (lip smacking, for example), recurrent amnesiac spells and memory complaints between spells, or memory complaints and an epileptic trait.
Of the 31 cases, two-thirds were male, and the mean age was 70. Neuropsychological testing found mild nonspecific abnormalities in 10 individuals and mild cognitive impairment in 2.
The investigators found 20 patients had abnormalities on EEG, usually in the temporal epileptogenic region. On MRI, abnormalities were found in only 6 patients.
FDG-PET, however, revealed focal abnormalities in 11 of the 16 cases that underwent scanning. “Most of them had focal areas of hypometabolism; none of those metabolic patterns fit those of known neurodegenerative disorders, and more rarely they were entirely normal,” Dr. Ramanan said during a presentation of his findings.
The results suggest that FDG-PET “may be a more useful tool than EEG” in distinguishing TEA from other disorders, he said. “I think the fascinating question going forward is whether TEA has an underlying biomarker and if there’s a neuroimaging biomarker for this. From these data, I think FDG-PET could be a very promising avenue for that,” he said.
In most of these cases where there was an abnormality detected on EEG, he noted that the patient “had multiple or prolonged EEGs, so it’s not always an easy thing to catch.”
Dr. Ramanan stressed that it’s important for clinicians “to have your antennae up for this diagnosis, particularly as these patients will come in with chronic memory trouble, because this is something we can fix.” In his study, all of the 22 individuals followed up after treatment with antiepileptic drugs, most commonly lamotrigine or levetiracetam, improved on follow-up.
Dr. Ramanan and his colleagues disclosed no conflicts of interest related to their findings.
SOURCE: Ramanan V et al. Neurology. 2018 Apr 90(15 Suppl.):P3.035.
LOS ANGELES – Transient epileptic amnesia is a rare but a treatable memory condition that usually occurs in late life and can be mistaken for neurodegenerative disease among patients presenting to a neurology or memory clinic.
Transient epileptic amnesia (TEA) is thought to be a focal epilepsy whose major clinical feature is the presence of recurrent spells of anterograde or retrograde amnesia lasting under an hour. The spells tend to occur on waking from sleep.
At the annual meeting of the American Academy of Neurology, Vijay Ramanan, MD, PhD, of the Mayo Clinic in Rochester, Minn., presented a retrospective series of 31 TEA cases from a study attempting to characterize the disorder in more demographic, clinical, and neuroimaging detail than has been done in the literature to date.
The cases were seen over a 20-year period (1998-2017) at the Mayo Clinic. All had at least one EEG and at least one MRI result reviewed by a neuroradiologist. Half also underwent fluorodeoxyglucose (FDG)-positron emission tomography (PET). All cases were classed as TEA if they included recurrent amnesia and an epileptic trait (lip smacking, for example), recurrent amnesiac spells and memory complaints between spells, or memory complaints and an epileptic trait.
Of the 31 cases, two-thirds were male, and the mean age was 70. Neuropsychological testing found mild nonspecific abnormalities in 10 individuals and mild cognitive impairment in 2.
The investigators found 20 patients had abnormalities on EEG, usually in the temporal epileptogenic region. On MRI, abnormalities were found in only 6 patients.
FDG-PET, however, revealed focal abnormalities in 11 of the 16 cases that underwent scanning. “Most of them had focal areas of hypometabolism; none of those metabolic patterns fit those of known neurodegenerative disorders, and more rarely they were entirely normal,” Dr. Ramanan said during a presentation of his findings.
The results suggest that FDG-PET “may be a more useful tool than EEG” in distinguishing TEA from other disorders, he said. “I think the fascinating question going forward is whether TEA has an underlying biomarker and if there’s a neuroimaging biomarker for this. From these data, I think FDG-PET could be a very promising avenue for that,” he said.
In most of these cases where there was an abnormality detected on EEG, he noted that the patient “had multiple or prolonged EEGs, so it’s not always an easy thing to catch.”
Dr. Ramanan stressed that it’s important for clinicians “to have your antennae up for this diagnosis, particularly as these patients will come in with chronic memory trouble, because this is something we can fix.” In his study, all of the 22 individuals followed up after treatment with antiepileptic drugs, most commonly lamotrigine or levetiracetam, improved on follow-up.
Dr. Ramanan and his colleagues disclosed no conflicts of interest related to their findings.
SOURCE: Ramanan V et al. Neurology. 2018 Apr 90(15 Suppl.):P3.035.
LOS ANGELES – Transient epileptic amnesia is a rare but a treatable memory condition that usually occurs in late life and can be mistaken for neurodegenerative disease among patients presenting to a neurology or memory clinic.
Transient epileptic amnesia (TEA) is thought to be a focal epilepsy whose major clinical feature is the presence of recurrent spells of anterograde or retrograde amnesia lasting under an hour. The spells tend to occur on waking from sleep.
At the annual meeting of the American Academy of Neurology, Vijay Ramanan, MD, PhD, of the Mayo Clinic in Rochester, Minn., presented a retrospective series of 31 TEA cases from a study attempting to characterize the disorder in more demographic, clinical, and neuroimaging detail than has been done in the literature to date.
The cases were seen over a 20-year period (1998-2017) at the Mayo Clinic. All had at least one EEG and at least one MRI result reviewed by a neuroradiologist. Half also underwent fluorodeoxyglucose (FDG)-positron emission tomography (PET). All cases were classed as TEA if they included recurrent amnesia and an epileptic trait (lip smacking, for example), recurrent amnesiac spells and memory complaints between spells, or memory complaints and an epileptic trait.
Of the 31 cases, two-thirds were male, and the mean age was 70. Neuropsychological testing found mild nonspecific abnormalities in 10 individuals and mild cognitive impairment in 2.
The investigators found 20 patients had abnormalities on EEG, usually in the temporal epileptogenic region. On MRI, abnormalities were found in only 6 patients.
FDG-PET, however, revealed focal abnormalities in 11 of the 16 cases that underwent scanning. “Most of them had focal areas of hypometabolism; none of those metabolic patterns fit those of known neurodegenerative disorders, and more rarely they were entirely normal,” Dr. Ramanan said during a presentation of his findings.
The results suggest that FDG-PET “may be a more useful tool than EEG” in distinguishing TEA from other disorders, he said. “I think the fascinating question going forward is whether TEA has an underlying biomarker and if there’s a neuroimaging biomarker for this. From these data, I think FDG-PET could be a very promising avenue for that,” he said.
In most of these cases where there was an abnormality detected on EEG, he noted that the patient “had multiple or prolonged EEGs, so it’s not always an easy thing to catch.”
Dr. Ramanan stressed that it’s important for clinicians “to have your antennae up for this diagnosis, particularly as these patients will come in with chronic memory trouble, because this is something we can fix.” In his study, all of the 22 individuals followed up after treatment with antiepileptic drugs, most commonly lamotrigine or levetiracetam, improved on follow-up.
Dr. Ramanan and his colleagues disclosed no conflicts of interest related to their findings.
SOURCE: Ramanan V et al. Neurology. 2018 Apr 90(15 Suppl.):P3.035.
Key clinical point:
Major finding: Brain FDG-PET revealed focal abnormalities in 69% of subjects with suspected TEA.
Study details: A retrospective analysis of 31 suspected TEA cases treated from 1998-2017 at one clinic.
Disclosures: Dr. Ramanan and his colleagues disclosed no conflicts of interest.
Source: Ramanan V et al. Neurology. 2018 Apr 90(15 Suppl.):P3.035.
Peripheral nerve stimulation can reduce tremor symptoms
LOS ANGELES – A noninvasive peripheral nerve stimulation device has been shown to reduce symptoms of hand tremor among people with essential tremor, offering a possible alternative to invasive treatments such as deep-brain stimulation.
The neuromodulation device is worn on the wrist and uses electrodes to stimulate the radial and median nerves at a frequency that interrupts tremor. It contains sensors that measure tremor and adjust stimulation accordingly.
In two small, randomized, controlled studies presented at the annual meeting of the at the American Academy of Neurology, investigator Rajesh Pahwa, MD, of the University of Kansas in Kansas City, said that treatment with the device significantly reduced tremor symptoms, compared with sham treatment.
On April 26, the device’s manufacturer, Cala Health, announced in a news release that the U.S. Food and Drug Administration had granted marketing clearance for the device, based on this evidence.
For the first study, conducted in-clinic, 77 patients were randomized to either treatment (n = 40) or sham stimulation (n = 37) of the tremor-dominant hand. Tremor was measured before and immediately after a single 40-minute session of stimulation, and patients were asked to perform tasks in accordance with the Essential Tremor Rating Assessment Scale or TETRAS, a severity measure.
Subjects in the intervention group had about a 65% improvement in their upper-limb TETRAS scores, compared with those receiving sham treatment (P less than .01) and in total TETRAS performance (P less than .05).
Subjects also were tested in-clinic with props simulating common daily tasks such as unlocking a door with a key, holding a cup of tea, picking up loose change, or dialing a phone. Patients in the treatment group self-reported greater ease with all of these tasks after treatment, compared with the sham-treated group. Differences for some tasks reached statistical significance.
For the second study, conducted for 4 weeks, 61 patients were randomized to at-home treatment sessions with the neuromodulator or sham treatment for 40 minutes at least twice daily. Those receiving treatment (n = 31) saw greater reduction in tremor measured by the devices’ built-in sensors, compared with those assigned sham treatment (n = 15) or no treatment (n = 15). Nearly all sessions completed resulted in a measurable reduction of tremor.
In an interview at AAN, Manish Gupta of Cala Health, the device manufacturer, said that further studies are underway to assess the durability of the treatment.
“What we seem to be looking at is an on-demand therapy that delivers a transient relief,” Mr. Gupta said, adding that the devices could be used by patients at times when their tremor is most bothersome, or in anticipation of a task – such as dressing oneself or eating – that a tremor would affect the ability to perform.
“One thing we’re learning from clinicians is that tremor is variable within the patient, and it’s variable across patients,” Mr. Gupta said. “The same patient may find that they have less tremor a certain day or at certain times of the day. We don’t think this would replace deep-brain stimulation, which is a constant treatment effect, but it could serve for some patients as a step before it.”
Cala Health, the manufacturer, sponsored the study. One coauthor is an employee of Cala Health.
SOURCE: Pahwa R et al. AAN 2018, Abstract P4.474.
LOS ANGELES – A noninvasive peripheral nerve stimulation device has been shown to reduce symptoms of hand tremor among people with essential tremor, offering a possible alternative to invasive treatments such as deep-brain stimulation.
The neuromodulation device is worn on the wrist and uses electrodes to stimulate the radial and median nerves at a frequency that interrupts tremor. It contains sensors that measure tremor and adjust stimulation accordingly.
In two small, randomized, controlled studies presented at the annual meeting of the at the American Academy of Neurology, investigator Rajesh Pahwa, MD, of the University of Kansas in Kansas City, said that treatment with the device significantly reduced tremor symptoms, compared with sham treatment.
On April 26, the device’s manufacturer, Cala Health, announced in a news release that the U.S. Food and Drug Administration had granted marketing clearance for the device, based on this evidence.
For the first study, conducted in-clinic, 77 patients were randomized to either treatment (n = 40) or sham stimulation (n = 37) of the tremor-dominant hand. Tremor was measured before and immediately after a single 40-minute session of stimulation, and patients were asked to perform tasks in accordance with the Essential Tremor Rating Assessment Scale or TETRAS, a severity measure.
Subjects in the intervention group had about a 65% improvement in their upper-limb TETRAS scores, compared with those receiving sham treatment (P less than .01) and in total TETRAS performance (P less than .05).
Subjects also were tested in-clinic with props simulating common daily tasks such as unlocking a door with a key, holding a cup of tea, picking up loose change, or dialing a phone. Patients in the treatment group self-reported greater ease with all of these tasks after treatment, compared with the sham-treated group. Differences for some tasks reached statistical significance.
For the second study, conducted for 4 weeks, 61 patients were randomized to at-home treatment sessions with the neuromodulator or sham treatment for 40 minutes at least twice daily. Those receiving treatment (n = 31) saw greater reduction in tremor measured by the devices’ built-in sensors, compared with those assigned sham treatment (n = 15) or no treatment (n = 15). Nearly all sessions completed resulted in a measurable reduction of tremor.
In an interview at AAN, Manish Gupta of Cala Health, the device manufacturer, said that further studies are underway to assess the durability of the treatment.
“What we seem to be looking at is an on-demand therapy that delivers a transient relief,” Mr. Gupta said, adding that the devices could be used by patients at times when their tremor is most bothersome, or in anticipation of a task – such as dressing oneself or eating – that a tremor would affect the ability to perform.
“One thing we’re learning from clinicians is that tremor is variable within the patient, and it’s variable across patients,” Mr. Gupta said. “The same patient may find that they have less tremor a certain day or at certain times of the day. We don’t think this would replace deep-brain stimulation, which is a constant treatment effect, but it could serve for some patients as a step before it.”
Cala Health, the manufacturer, sponsored the study. One coauthor is an employee of Cala Health.
SOURCE: Pahwa R et al. AAN 2018, Abstract P4.474.
LOS ANGELES – A noninvasive peripheral nerve stimulation device has been shown to reduce symptoms of hand tremor among people with essential tremor, offering a possible alternative to invasive treatments such as deep-brain stimulation.
The neuromodulation device is worn on the wrist and uses electrodes to stimulate the radial and median nerves at a frequency that interrupts tremor. It contains sensors that measure tremor and adjust stimulation accordingly.
In two small, randomized, controlled studies presented at the annual meeting of the at the American Academy of Neurology, investigator Rajesh Pahwa, MD, of the University of Kansas in Kansas City, said that treatment with the device significantly reduced tremor symptoms, compared with sham treatment.
On April 26, the device’s manufacturer, Cala Health, announced in a news release that the U.S. Food and Drug Administration had granted marketing clearance for the device, based on this evidence.
For the first study, conducted in-clinic, 77 patients were randomized to either treatment (n = 40) or sham stimulation (n = 37) of the tremor-dominant hand. Tremor was measured before and immediately after a single 40-minute session of stimulation, and patients were asked to perform tasks in accordance with the Essential Tremor Rating Assessment Scale or TETRAS, a severity measure.
Subjects in the intervention group had about a 65% improvement in their upper-limb TETRAS scores, compared with those receiving sham treatment (P less than .01) and in total TETRAS performance (P less than .05).
Subjects also were tested in-clinic with props simulating common daily tasks such as unlocking a door with a key, holding a cup of tea, picking up loose change, or dialing a phone. Patients in the treatment group self-reported greater ease with all of these tasks after treatment, compared with the sham-treated group. Differences for some tasks reached statistical significance.
For the second study, conducted for 4 weeks, 61 patients were randomized to at-home treatment sessions with the neuromodulator or sham treatment for 40 minutes at least twice daily. Those receiving treatment (n = 31) saw greater reduction in tremor measured by the devices’ built-in sensors, compared with those assigned sham treatment (n = 15) or no treatment (n = 15). Nearly all sessions completed resulted in a measurable reduction of tremor.
In an interview at AAN, Manish Gupta of Cala Health, the device manufacturer, said that further studies are underway to assess the durability of the treatment.
“What we seem to be looking at is an on-demand therapy that delivers a transient relief,” Mr. Gupta said, adding that the devices could be used by patients at times when their tremor is most bothersome, or in anticipation of a task – such as dressing oneself or eating – that a tremor would affect the ability to perform.
“One thing we’re learning from clinicians is that tremor is variable within the patient, and it’s variable across patients,” Mr. Gupta said. “The same patient may find that they have less tremor a certain day or at certain times of the day. We don’t think this would replace deep-brain stimulation, which is a constant treatment effect, but it could serve for some patients as a step before it.”
Cala Health, the manufacturer, sponsored the study. One coauthor is an employee of Cala Health.
SOURCE: Pahwa R et al. AAN 2018, Abstract P4.474.
REPORTING FROM AAN 2018
Key clinical point:
Major finding: Subjects using the devices saw improvement in their upper-limb tremor scores, compared with those receiving sham treatment (P less than .01)
Study details: Two randomized studies (n = 77 and n = 61) comparing in-home or in-office treatment with stimulation or sham treatment.
Disclosures: The device manufacturer sponsored the study. One employee is a coauthor.
Source: Pahwa R et al. AAN 2018, Abstract P4.474.
REM sleep behavior disorder predicts impending synucleinopathy
LOS ANGELES – , according to a years-long, multicenter investigation of 1,280 patients – the largest study of the issue to date.
REM sleep behavior disorder (RBD) has been known for years to increase the risk for synucleinopathies, namely Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. However, previous studies have mostly been conducted at single institutions, so the exact extent to which RBD increases the risk wasn’t clear.
These findings have important implications for the field. Now that it’s known who’s at risk, “we have a chance to do neuroprotective therapy. It’s time to move forward and start preventing disease,” Dr. Postuma said at the American Academy of Neurology annual meeting. He estimated that it would take only a few hundred patients to do a 2-year trial of neuroprotective therapy.
The 1,280 study subjects were culled from 24 sleep centers on four continents, all participants in the international RBD study group. The patients needed for a trial “are sitting right now” in the study group, “so maybe we can get on with this,” he said.
REM sleep – the dream state – normally paralyzes people, but something breaks down in RBD, and people act out their dreams, sometimes to disturbing effects. It occurs in about 1% of the population, usually in older people and in slightly more men than women.
The risk of neurodegenerative disease in RBD increases even more if patients test positive at baseline for movement declines, cognitive issues, olfactory problems, constipation, color vision loss, erectile dysfunction, or abnormal dopamine transporter scans. Dr. Postuma and his team found no predictive value for somnolence, insomnia, urinary problems, depression, or anxiety. These negative findings were surprising, he said, because mood disorders and sleep troubles are known to increase the risk in the general population.
The subjects all had polysomnographic-proven RBD at baseline, without neurodegenerative disease. Most of them were men and were about 70 years old, on average. Subjects were tested for synucleinopathies and risk variables annually. The mean disease-free follow-up was about 4 years, but ranged out to 19 years. Risks were adjusted for age, sex, and study center.
Cognition deficits were the only thing that distinguished future dementia patients from those destined for movement disorders. “Everything [else] is really the same between who gets dementia and who gets Parkinsonism,” Dr. Postuma said.
The study was funded by the Canadian Institute of Health Research and the Fonds de la Recherche Sante Quebec. Dr. Postuma disclosed consulting, speaking, and other fees from Biotie, Roche/Prothena, Teva Neurosciences, Novartis Canada, Theranexus, Jazz Pharmaceuticals, and GE HealthCare.
SOURCE: Postuma R et al. AAN 2018, plenary session.
LOS ANGELES – , according to a years-long, multicenter investigation of 1,280 patients – the largest study of the issue to date.
REM sleep behavior disorder (RBD) has been known for years to increase the risk for synucleinopathies, namely Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. However, previous studies have mostly been conducted at single institutions, so the exact extent to which RBD increases the risk wasn’t clear.
These findings have important implications for the field. Now that it’s known who’s at risk, “we have a chance to do neuroprotective therapy. It’s time to move forward and start preventing disease,” Dr. Postuma said at the American Academy of Neurology annual meeting. He estimated that it would take only a few hundred patients to do a 2-year trial of neuroprotective therapy.
The 1,280 study subjects were culled from 24 sleep centers on four continents, all participants in the international RBD study group. The patients needed for a trial “are sitting right now” in the study group, “so maybe we can get on with this,” he said.
REM sleep – the dream state – normally paralyzes people, but something breaks down in RBD, and people act out their dreams, sometimes to disturbing effects. It occurs in about 1% of the population, usually in older people and in slightly more men than women.
The risk of neurodegenerative disease in RBD increases even more if patients test positive at baseline for movement declines, cognitive issues, olfactory problems, constipation, color vision loss, erectile dysfunction, or abnormal dopamine transporter scans. Dr. Postuma and his team found no predictive value for somnolence, insomnia, urinary problems, depression, or anxiety. These negative findings were surprising, he said, because mood disorders and sleep troubles are known to increase the risk in the general population.
The subjects all had polysomnographic-proven RBD at baseline, without neurodegenerative disease. Most of them were men and were about 70 years old, on average. Subjects were tested for synucleinopathies and risk variables annually. The mean disease-free follow-up was about 4 years, but ranged out to 19 years. Risks were adjusted for age, sex, and study center.
Cognition deficits were the only thing that distinguished future dementia patients from those destined for movement disorders. “Everything [else] is really the same between who gets dementia and who gets Parkinsonism,” Dr. Postuma said.
The study was funded by the Canadian Institute of Health Research and the Fonds de la Recherche Sante Quebec. Dr. Postuma disclosed consulting, speaking, and other fees from Biotie, Roche/Prothena, Teva Neurosciences, Novartis Canada, Theranexus, Jazz Pharmaceuticals, and GE HealthCare.
SOURCE: Postuma R et al. AAN 2018, plenary session.
LOS ANGELES – , according to a years-long, multicenter investigation of 1,280 patients – the largest study of the issue to date.
REM sleep behavior disorder (RBD) has been known for years to increase the risk for synucleinopathies, namely Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. However, previous studies have mostly been conducted at single institutions, so the exact extent to which RBD increases the risk wasn’t clear.
These findings have important implications for the field. Now that it’s known who’s at risk, “we have a chance to do neuroprotective therapy. It’s time to move forward and start preventing disease,” Dr. Postuma said at the American Academy of Neurology annual meeting. He estimated that it would take only a few hundred patients to do a 2-year trial of neuroprotective therapy.
The 1,280 study subjects were culled from 24 sleep centers on four continents, all participants in the international RBD study group. The patients needed for a trial “are sitting right now” in the study group, “so maybe we can get on with this,” he said.
REM sleep – the dream state – normally paralyzes people, but something breaks down in RBD, and people act out their dreams, sometimes to disturbing effects. It occurs in about 1% of the population, usually in older people and in slightly more men than women.
The risk of neurodegenerative disease in RBD increases even more if patients test positive at baseline for movement declines, cognitive issues, olfactory problems, constipation, color vision loss, erectile dysfunction, or abnormal dopamine transporter scans. Dr. Postuma and his team found no predictive value for somnolence, insomnia, urinary problems, depression, or anxiety. These negative findings were surprising, he said, because mood disorders and sleep troubles are known to increase the risk in the general population.
The subjects all had polysomnographic-proven RBD at baseline, without neurodegenerative disease. Most of them were men and were about 70 years old, on average. Subjects were tested for synucleinopathies and risk variables annually. The mean disease-free follow-up was about 4 years, but ranged out to 19 years. Risks were adjusted for age, sex, and study center.
Cognition deficits were the only thing that distinguished future dementia patients from those destined for movement disorders. “Everything [else] is really the same between who gets dementia and who gets Parkinsonism,” Dr. Postuma said.
The study was funded by the Canadian Institute of Health Research and the Fonds de la Recherche Sante Quebec. Dr. Postuma disclosed consulting, speaking, and other fees from Biotie, Roche/Prothena, Teva Neurosciences, Novartis Canada, Theranexus, Jazz Pharmaceuticals, and GE HealthCare.
SOURCE: Postuma R et al. AAN 2018, plenary session.
REPORTING FROM AAN 2018
Key clinical point: Idiopathic REM sleep behavior disorder patients need neuroprotection.
Major finding: At least 70% of patients with idiopathic REM sleep behavior disorder (RBD) will develop a neurodegenerative disease within about a decade.
Study details: An observational study of 1,280 RBD patients from 24 asleep centers on four continents.
Disclosures: The study was funded by the Canadian Institute of Health Research and the Fonds de la Recherche Sante Quebec. Dr. Postuma disclosed consulting, speaking, and other fees from Biotie, Roche/Prothena, Teva Neurosciences, Novartis Canada, Theranexus, Jazz Pharmaceuticals, and GE HealthCare.
Source: Postuma R et al. AAN 2018, plenary session.
Cluster headache presents differently in never-smokers, survey finds
Los Angeles – Cluster headache, a severe, one-sided headache that occurs in cyclical patterns or clusters, is highly associated with smoking, but when it presents in people without any lifetime tobacco exposure, there are key differences – possibly due to a different underlying pathology.
At the American Academy of Neurology annual meeting, Todd D. Rozen, MD, of the Mayo Clinic in Jacksonville, Fla., presented a new analysis from the United States Cluster Headache Survey, an online survey of 1,134 patients with cluster headache, of whom only 12% reported neither personal tobacco use nor a parent who smoked. Dr. Rozen is a coauthor on the original survey, which collected data for a two-month period in late 2008, and has published several analyses using the survey’s data (Headache. 2012 Jan;52[1]:99-113).
Patients not exposed to tobacco developed cluster headache at a younger age than exposed subjects, with a significantly higher percentage reporting onset in their 20s and 30s, while tobacco-exposed people were more likely to see onset at aged 40 years or older.
And there were other important differences. The tobacco-naïve were more likely to have a family history of migraine (65% vs. 50%, P equal to .002). They were significantly more likely to have headache cycles that varied throughout the year rather than being concentrated during specific months or seasons (52% vs. 40%, P equal to .02), which is a hallmark of cluster headache.
Tobacco-exposed patients were more likely to transition from episodic to chronic cluster headaches (23% vs. 14%, P equal to .02) and to have cycles lasting 7 weeks or more (54% vs. 35%, P equal to .0003) compared with those who were tobacco-naïve. They also reported significantly more frequent attacks per day, and were more likely to develop cluster headache during the night (12 pm to 6 am).
“With cluster headache, the majority of patients smoke, and started smoking before they ever developed cluster headache,” Dr. Rozen said. Among the tobacco-exposed patients in the survey, 85% had what he described as a “double hit” – a parent who smoked and a personal history of smoking. “And that may be what’s necessary to develop cluster headache of this classic type,” he said.
Dr. Rozen said he suspects that tobacco-exposed people with cluster headache may have abnormal hypothalamic entrainment related to injury from toxins, though the exact mechanisms are unknown.
“So in times of hypothalamic stress – whether clock change or solstice, the hypothalamus has to work more, it doesn’t work correctly, and headache develops,” he said, noting the highly cyclical nature of the classic cluster phenotype.
As to what causes cluster headache in the non-exposed, Dr. Rozen said it’s possible that genetic factors may be more relevant – a possibility underscored by the higher rate of familial migraine reported among the tobacco-naïve in the cohort.
Dr. Rozen reported no financial conflicts of interest related to his findings.
SOURCE: Rozen TD, et al. AAN2018, P3 122.
Los Angeles – Cluster headache, a severe, one-sided headache that occurs in cyclical patterns or clusters, is highly associated with smoking, but when it presents in people without any lifetime tobacco exposure, there are key differences – possibly due to a different underlying pathology.
At the American Academy of Neurology annual meeting, Todd D. Rozen, MD, of the Mayo Clinic in Jacksonville, Fla., presented a new analysis from the United States Cluster Headache Survey, an online survey of 1,134 patients with cluster headache, of whom only 12% reported neither personal tobacco use nor a parent who smoked. Dr. Rozen is a coauthor on the original survey, which collected data for a two-month period in late 2008, and has published several analyses using the survey’s data (Headache. 2012 Jan;52[1]:99-113).
Patients not exposed to tobacco developed cluster headache at a younger age than exposed subjects, with a significantly higher percentage reporting onset in their 20s and 30s, while tobacco-exposed people were more likely to see onset at aged 40 years or older.
And there were other important differences. The tobacco-naïve were more likely to have a family history of migraine (65% vs. 50%, P equal to .002). They were significantly more likely to have headache cycles that varied throughout the year rather than being concentrated during specific months or seasons (52% vs. 40%, P equal to .02), which is a hallmark of cluster headache.
Tobacco-exposed patients were more likely to transition from episodic to chronic cluster headaches (23% vs. 14%, P equal to .02) and to have cycles lasting 7 weeks or more (54% vs. 35%, P equal to .0003) compared with those who were tobacco-naïve. They also reported significantly more frequent attacks per day, and were more likely to develop cluster headache during the night (12 pm to 6 am).
“With cluster headache, the majority of patients smoke, and started smoking before they ever developed cluster headache,” Dr. Rozen said. Among the tobacco-exposed patients in the survey, 85% had what he described as a “double hit” – a parent who smoked and a personal history of smoking. “And that may be what’s necessary to develop cluster headache of this classic type,” he said.
Dr. Rozen said he suspects that tobacco-exposed people with cluster headache may have abnormal hypothalamic entrainment related to injury from toxins, though the exact mechanisms are unknown.
“So in times of hypothalamic stress – whether clock change or solstice, the hypothalamus has to work more, it doesn’t work correctly, and headache develops,” he said, noting the highly cyclical nature of the classic cluster phenotype.
As to what causes cluster headache in the non-exposed, Dr. Rozen said it’s possible that genetic factors may be more relevant – a possibility underscored by the higher rate of familial migraine reported among the tobacco-naïve in the cohort.
Dr. Rozen reported no financial conflicts of interest related to his findings.
SOURCE: Rozen TD, et al. AAN2018, P3 122.
Los Angeles – Cluster headache, a severe, one-sided headache that occurs in cyclical patterns or clusters, is highly associated with smoking, but when it presents in people without any lifetime tobacco exposure, there are key differences – possibly due to a different underlying pathology.
At the American Academy of Neurology annual meeting, Todd D. Rozen, MD, of the Mayo Clinic in Jacksonville, Fla., presented a new analysis from the United States Cluster Headache Survey, an online survey of 1,134 patients with cluster headache, of whom only 12% reported neither personal tobacco use nor a parent who smoked. Dr. Rozen is a coauthor on the original survey, which collected data for a two-month period in late 2008, and has published several analyses using the survey’s data (Headache. 2012 Jan;52[1]:99-113).
Patients not exposed to tobacco developed cluster headache at a younger age than exposed subjects, with a significantly higher percentage reporting onset in their 20s and 30s, while tobacco-exposed people were more likely to see onset at aged 40 years or older.
And there were other important differences. The tobacco-naïve were more likely to have a family history of migraine (65% vs. 50%, P equal to .002). They were significantly more likely to have headache cycles that varied throughout the year rather than being concentrated during specific months or seasons (52% vs. 40%, P equal to .02), which is a hallmark of cluster headache.
Tobacco-exposed patients were more likely to transition from episodic to chronic cluster headaches (23% vs. 14%, P equal to .02) and to have cycles lasting 7 weeks or more (54% vs. 35%, P equal to .0003) compared with those who were tobacco-naïve. They also reported significantly more frequent attacks per day, and were more likely to develop cluster headache during the night (12 pm to 6 am).
“With cluster headache, the majority of patients smoke, and started smoking before they ever developed cluster headache,” Dr. Rozen said. Among the tobacco-exposed patients in the survey, 85% had what he described as a “double hit” – a parent who smoked and a personal history of smoking. “And that may be what’s necessary to develop cluster headache of this classic type,” he said.
Dr. Rozen said he suspects that tobacco-exposed people with cluster headache may have abnormal hypothalamic entrainment related to injury from toxins, though the exact mechanisms are unknown.
“So in times of hypothalamic stress – whether clock change or solstice, the hypothalamus has to work more, it doesn’t work correctly, and headache develops,” he said, noting the highly cyclical nature of the classic cluster phenotype.
As to what causes cluster headache in the non-exposed, Dr. Rozen said it’s possible that genetic factors may be more relevant – a possibility underscored by the higher rate of familial migraine reported among the tobacco-naïve in the cohort.
Dr. Rozen reported no financial conflicts of interest related to his findings.
SOURCE: Rozen TD, et al. AAN2018, P3 122.
REPORTING FROM AAN 2018
Key clinical point: Tobacco-naïve people with cluster headache have significant differences in symptomology compared with the tobacco-exposed
Major finding: Family history of migraine, earlier age of onset and episodic pattern were seen in non-tobacco exposed patients vs. smokers
Study details: Data came from more than 1,000 cluster headache patients surveyed in the U.S. Cluster Headache Survey.
Disclosures: The authors had no disclosures.
Source: Rozen TD, et al. AAN2018, P3 122.
MS drugs in Medicare Part D: Higher tiers, less coverage, more prior authorizations
LOS ANGELES – Under Medicare Part D, private prescription drug plans and those bundled with Medicare Advantage plans have steadily raised injectable and oral disease-modifying therapies for multiple sclerosis to higher tiers with higher cost sharing, reduced coverage of particular drugs, and increased prior authorizations during the 10-year period of 2007-2016, according to an analysis conducted by Oregon State University researchers.
At the annual meeting of the American Academy of Neurology, Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues reported that the proportion of plans with disease-modifying therapies (DMTs) in the highest tiers, generally tier 5 and above, rose from 11% in 2007 to 95% in 2016.
The scope of drugs covered by the plans declined marginally. Over the 10-year period, plans covering at least three DMTs declined from 98% to 95%, but plans that covered interferon beta-1b, intramuscular or subcutaneous interferon beta-1a, or glatiramer acetate declined from 85%-100% of plans to 60%-81%.
Plans with prior authorizations for DMTs rose across the board. The percentage of plans with at least one DMT not needing prior authorization dropped from 40% to 27%, while plans that covered interferon beta-1b, intramuscular or subcutaneous interferon beta-1a, or glatiramer acetate rose from 62%-65% to 77%-80%.
Based on 2016 coverage characteristics, Dr. Hartung and his associates estimated that the expected annual out-of-pocket costs for patients in 2019 would be over $5,000 for all drugs in the analysis, after accounting for the Bipartisan Budget Act’s closing the Part D coverage gap in 2019.
Part D covers noninfusible DMTs, which in this analysis included glatiramer acetate 20 and 40 mg (Copaxone 20 and Copaxone 40), generic glatiramer acetate 20 mg (Glatopa), interferon beta-1a intramuscular (Avonex), interferon beta-1a subcutaneous (Rebif), interferon beta-1b (Extavia and Betaseron), peginterferon beta-1a (Plegridy), fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera). The infusible drugs natalizumab (Tysabri), alemtuzumab (Lemtrada), and ocrelizumab (Ocrevus) fall under Medicare Part B.
The study was supported by the National Multiple Sclerosis Society. None of the authors had anything to disclose.
SOURCE: Hartung D et al. AAN 2018. Abstract P3.161
LOS ANGELES – Under Medicare Part D, private prescription drug plans and those bundled with Medicare Advantage plans have steadily raised injectable and oral disease-modifying therapies for multiple sclerosis to higher tiers with higher cost sharing, reduced coverage of particular drugs, and increased prior authorizations during the 10-year period of 2007-2016, according to an analysis conducted by Oregon State University researchers.
At the annual meeting of the American Academy of Neurology, Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues reported that the proportion of plans with disease-modifying therapies (DMTs) in the highest tiers, generally tier 5 and above, rose from 11% in 2007 to 95% in 2016.
The scope of drugs covered by the plans declined marginally. Over the 10-year period, plans covering at least three DMTs declined from 98% to 95%, but plans that covered interferon beta-1b, intramuscular or subcutaneous interferon beta-1a, or glatiramer acetate declined from 85%-100% of plans to 60%-81%.
Plans with prior authorizations for DMTs rose across the board. The percentage of plans with at least one DMT not needing prior authorization dropped from 40% to 27%, while plans that covered interferon beta-1b, intramuscular or subcutaneous interferon beta-1a, or glatiramer acetate rose from 62%-65% to 77%-80%.
Based on 2016 coverage characteristics, Dr. Hartung and his associates estimated that the expected annual out-of-pocket costs for patients in 2019 would be over $5,000 for all drugs in the analysis, after accounting for the Bipartisan Budget Act’s closing the Part D coverage gap in 2019.
Part D covers noninfusible DMTs, which in this analysis included glatiramer acetate 20 and 40 mg (Copaxone 20 and Copaxone 40), generic glatiramer acetate 20 mg (Glatopa), interferon beta-1a intramuscular (Avonex), interferon beta-1a subcutaneous (Rebif), interferon beta-1b (Extavia and Betaseron), peginterferon beta-1a (Plegridy), fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera). The infusible drugs natalizumab (Tysabri), alemtuzumab (Lemtrada), and ocrelizumab (Ocrevus) fall under Medicare Part B.
The study was supported by the National Multiple Sclerosis Society. None of the authors had anything to disclose.
SOURCE: Hartung D et al. AAN 2018. Abstract P3.161
LOS ANGELES – Under Medicare Part D, private prescription drug plans and those bundled with Medicare Advantage plans have steadily raised injectable and oral disease-modifying therapies for multiple sclerosis to higher tiers with higher cost sharing, reduced coverage of particular drugs, and increased prior authorizations during the 10-year period of 2007-2016, according to an analysis conducted by Oregon State University researchers.
At the annual meeting of the American Academy of Neurology, Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues reported that the proportion of plans with disease-modifying therapies (DMTs) in the highest tiers, generally tier 5 and above, rose from 11% in 2007 to 95% in 2016.
The scope of drugs covered by the plans declined marginally. Over the 10-year period, plans covering at least three DMTs declined from 98% to 95%, but plans that covered interferon beta-1b, intramuscular or subcutaneous interferon beta-1a, or glatiramer acetate declined from 85%-100% of plans to 60%-81%.
Plans with prior authorizations for DMTs rose across the board. The percentage of plans with at least one DMT not needing prior authorization dropped from 40% to 27%, while plans that covered interferon beta-1b, intramuscular or subcutaneous interferon beta-1a, or glatiramer acetate rose from 62%-65% to 77%-80%.
Based on 2016 coverage characteristics, Dr. Hartung and his associates estimated that the expected annual out-of-pocket costs for patients in 2019 would be over $5,000 for all drugs in the analysis, after accounting for the Bipartisan Budget Act’s closing the Part D coverage gap in 2019.
Part D covers noninfusible DMTs, which in this analysis included glatiramer acetate 20 and 40 mg (Copaxone 20 and Copaxone 40), generic glatiramer acetate 20 mg (Glatopa), interferon beta-1a intramuscular (Avonex), interferon beta-1a subcutaneous (Rebif), interferon beta-1b (Extavia and Betaseron), peginterferon beta-1a (Plegridy), fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera). The infusible drugs natalizumab (Tysabri), alemtuzumab (Lemtrada), and ocrelizumab (Ocrevus) fall under Medicare Part B.
The study was supported by the National Multiple Sclerosis Society. None of the authors had anything to disclose.
SOURCE: Hartung D et al. AAN 2018. Abstract P3.161
REPORTING FROM AAN 2018
VIDEO: Meeting stroke screening demand will require systems’ reorganization
In a video interview at the annual meeting of the American Academy of Neurology, Dr. Wechsler described steps being taken at the University of Pittsburgh Medical Center’s comprehensive stroke center to handle the additional workload.
UPMC conducts telemedicine acute stroke evaluations of patients at community hospitals’ primary stroke centers in the greater Pittsburgh area to make sure that only the cases that require mechanical thrombectomy are transferred to them for specialized care, while also continuing to see nontransferred patients via telemedicine for follow-up, said Dr. Wechsler, chair of the department of neurology at UPMC and founder of its Stroke Institute and telestroke network.
This sort of solution may be more feasible and practical for comprehensive stroke centers to implement in order to manage the number of cases, instead of expanding neurology residencies, capping stroke services, adding a nonteaching service, adding advanced practice providers, or increasing the case loads of vascular neurology fellows and attending neurologists, he said.
In just the short time since the DAWN trial results were released in November 2017 and set the new standard for treating eligible patients with large-vessel occlusions with mechanical thrombectomy within 6-24 hours, stroke admissions and transfers to the comprehensive stroke center at UPMC from November 2017 to February 2018 rose 18% from the same time period a year before, including a 5% rise in telemedicine transfers, Dr. Wechsler said in a presentation at the meeting. These additional cases led to a 35% increase in thrombectomy cases.
Putting the matter into additional perspective, in the time period from November 2014 to February 2017, 30% of all 2,667 acute ischemic stroke patients seen at UPMC would have met DAWN trial inclusion criteria with a 6- to 24-hour window, but less than 3% of all the strokes seen at UPMC would have qualified for thrombectomy under criteria from the DAWN and DEFUSE-3 trials. That makes it imperative for comprehensive stroke centers to triage cases and receive only those that require endovascular treatment, he said.
Meeting the already-rising needs for triaging acute ischemic stroke patients arriving in the window of 6-24 hours will be difficult, considering that there are about 800,000 new strokes per year in the United States but only 1,100 vascular neurologists, nearly 1,100 primary stroke centers, and only 110 comprehensive stroke centers at which endovascular thrombectomy treatment may be offered. As of 2016, he noted that there also were only 74 U.S. stroke fellowship programs with 123 positions offered, of which 34% went unfilled.
In a video interview at the annual meeting of the American Academy of Neurology, Dr. Wechsler described steps being taken at the University of Pittsburgh Medical Center’s comprehensive stroke center to handle the additional workload.
UPMC conducts telemedicine acute stroke evaluations of patients at community hospitals’ primary stroke centers in the greater Pittsburgh area to make sure that only the cases that require mechanical thrombectomy are transferred to them for specialized care, while also continuing to see nontransferred patients via telemedicine for follow-up, said Dr. Wechsler, chair of the department of neurology at UPMC and founder of its Stroke Institute and telestroke network.
This sort of solution may be more feasible and practical for comprehensive stroke centers to implement in order to manage the number of cases, instead of expanding neurology residencies, capping stroke services, adding a nonteaching service, adding advanced practice providers, or increasing the case loads of vascular neurology fellows and attending neurologists, he said.
In just the short time since the DAWN trial results were released in November 2017 and set the new standard for treating eligible patients with large-vessel occlusions with mechanical thrombectomy within 6-24 hours, stroke admissions and transfers to the comprehensive stroke center at UPMC from November 2017 to February 2018 rose 18% from the same time period a year before, including a 5% rise in telemedicine transfers, Dr. Wechsler said in a presentation at the meeting. These additional cases led to a 35% increase in thrombectomy cases.
Putting the matter into additional perspective, in the time period from November 2014 to February 2017, 30% of all 2,667 acute ischemic stroke patients seen at UPMC would have met DAWN trial inclusion criteria with a 6- to 24-hour window, but less than 3% of all the strokes seen at UPMC would have qualified for thrombectomy under criteria from the DAWN and DEFUSE-3 trials. That makes it imperative for comprehensive stroke centers to triage cases and receive only those that require endovascular treatment, he said.
Meeting the already-rising needs for triaging acute ischemic stroke patients arriving in the window of 6-24 hours will be difficult, considering that there are about 800,000 new strokes per year in the United States but only 1,100 vascular neurologists, nearly 1,100 primary stroke centers, and only 110 comprehensive stroke centers at which endovascular thrombectomy treatment may be offered. As of 2016, he noted that there also were only 74 U.S. stroke fellowship programs with 123 positions offered, of which 34% went unfilled.
In a video interview at the annual meeting of the American Academy of Neurology, Dr. Wechsler described steps being taken at the University of Pittsburgh Medical Center’s comprehensive stroke center to handle the additional workload.
UPMC conducts telemedicine acute stroke evaluations of patients at community hospitals’ primary stroke centers in the greater Pittsburgh area to make sure that only the cases that require mechanical thrombectomy are transferred to them for specialized care, while also continuing to see nontransferred patients via telemedicine for follow-up, said Dr. Wechsler, chair of the department of neurology at UPMC and founder of its Stroke Institute and telestroke network.
This sort of solution may be more feasible and practical for comprehensive stroke centers to implement in order to manage the number of cases, instead of expanding neurology residencies, capping stroke services, adding a nonteaching service, adding advanced practice providers, or increasing the case loads of vascular neurology fellows and attending neurologists, he said.
In just the short time since the DAWN trial results were released in November 2017 and set the new standard for treating eligible patients with large-vessel occlusions with mechanical thrombectomy within 6-24 hours, stroke admissions and transfers to the comprehensive stroke center at UPMC from November 2017 to February 2018 rose 18% from the same time period a year before, including a 5% rise in telemedicine transfers, Dr. Wechsler said in a presentation at the meeting. These additional cases led to a 35% increase in thrombectomy cases.
Putting the matter into additional perspective, in the time period from November 2014 to February 2017, 30% of all 2,667 acute ischemic stroke patients seen at UPMC would have met DAWN trial inclusion criteria with a 6- to 24-hour window, but less than 3% of all the strokes seen at UPMC would have qualified for thrombectomy under criteria from the DAWN and DEFUSE-3 trials. That makes it imperative for comprehensive stroke centers to triage cases and receive only those that require endovascular treatment, he said.
Meeting the already-rising needs for triaging acute ischemic stroke patients arriving in the window of 6-24 hours will be difficult, considering that there are about 800,000 new strokes per year in the United States but only 1,100 vascular neurologists, nearly 1,100 primary stroke centers, and only 110 comprehensive stroke centers at which endovascular thrombectomy treatment may be offered. As of 2016, he noted that there also were only 74 U.S. stroke fellowship programs with 123 positions offered, of which 34% went unfilled.
REPORTING FROM AAN 2018
VIDEO: Eptinezumab shows efficacy in episodic and chronic migraine trials
LOS ANGELES – New results from phase 3 randomized trials of the prophylactic migraine treatment eptinezumab show significant reductions in the number of monthly migraine headache days experienced by patients with chronic or frequent episodic migraines.
Eptinezumab, an experimental monoclonal antibody delivered by intravenous infusion, is one of several antimigraine agents in development that targets calcitonin gene-related peptide (CGRP), a key mediator of migraine.
At the annual meeting of the American Academy of Neurology, Richard Lipton, MD, of Albert Einstein College of Medicine in New York, presented results from PROMISE 2, a phase 3 randomized, placebo-controlled trial of eptinezumab in patients with chronic migraine, or 15 or more days with migraine per month.
The investigators randomized 1,072 patients to quarterly IV infusions of eptinezumab 100 or 300 mg or placebo.
The vast majority of patients in the study were women, (86%-90% across groups) with a mean age of about 40 years. Patients reported 11-12 years of chronic migraine and about 16 migraine days per month at baseline, Dr. Lipton told the conference, reflecting a high level of disability in the cohort.
The primary endpoint of the study was mean change in monthly migraine days from baseline through week 12. Dr. Lipton reported that the placebo group saw a 5.6-day reduction in migraine, while the 100-mg group saw a 7.7-day reduction, and patients receiving the 300-mg dose saw an 8.2-day reduction during the first 12 weeks after injection (P less than .0001 for both).
One-third of patients receiving the highest dose saw a 75% or greater reduction in monthly migraine days by week 12, “a relatively high bar” to meet, Dr. Lipton said. Some 61% of patients on the high dose saw a reduction of 50% or more in the same time period.
A unique secondary endpoint of the study was the proportion of patients who experienced migraine on day 1 after the initial dose. The treatment groups saw a 52% reduction 1 day after receiving the study drug, while the placebo group saw a 27% reduction in the expected prevalence of migraine in the cohort for any single day, and the decrease was sustained through day 28. The results suggest a rapid onset of action for eptinezumab, followed by a sustained benefit, Dr. Lipton said.
Also at AAN, Stephen D. Silberstein, MD, of Thomas Jefferson University in Philadelphia, presented new 12-month results from the PROMISE 1 trial, a randomized clinical trial to evaluate quarterly IV infusions of eptinezumab 30 mg, 100 mg, 300 mg, or placebo, in 888 patients with episodic migraines, defined as 14 or fewer days per month with migraine.
The researchers, who last year published 6-month results showing significant reductions in monthly migraine days associated with eptinezumab treatment over placebo, described further reductions from patients’ baseline frequency of migraines with longer duration of treatment.
After their third and fourth quarterly injections, 70.7% of eptinezumab-treated patients achieved a 50% reduction of monthly migraine days from baseline, compared with 58.7% for placebo, the investigators reported. These findings represent an 8.9% improvement over the reductions experienced during the first two quarterly doses of eptinezumab in this cohort.
More than half of patients in the treatment arms achieved on average a 75% reduction or greater of monthly migraine days from baseline, compared with 38.7% for placebo, a 12.8% improvement from the reductions experienced with the first two doses of eptinezumab.
Adverse effects seen in the trials were upper respiratory infection, nasopharyngitis, sinusitis, and nausea.
Both trials were sponsored by eptinezumab’s manufacturer, Alder. Dr. Lipton, Dr. Silberstein, and several of their coauthors disclosed support from Alder and other manufacturers, while some coauthors on the studies are employees of Alder.
SOURCE: Saper J et al. AAN 2018, Abstract S20.001 and Lipton R et al. AAN 2018, Clinical Trials Plenary Session Abstract.
LOS ANGELES – New results from phase 3 randomized trials of the prophylactic migraine treatment eptinezumab show significant reductions in the number of monthly migraine headache days experienced by patients with chronic or frequent episodic migraines.
Eptinezumab, an experimental monoclonal antibody delivered by intravenous infusion, is one of several antimigraine agents in development that targets calcitonin gene-related peptide (CGRP), a key mediator of migraine.
At the annual meeting of the American Academy of Neurology, Richard Lipton, MD, of Albert Einstein College of Medicine in New York, presented results from PROMISE 2, a phase 3 randomized, placebo-controlled trial of eptinezumab in patients with chronic migraine, or 15 or more days with migraine per month.
The investigators randomized 1,072 patients to quarterly IV infusions of eptinezumab 100 or 300 mg or placebo.
The vast majority of patients in the study were women, (86%-90% across groups) with a mean age of about 40 years. Patients reported 11-12 years of chronic migraine and about 16 migraine days per month at baseline, Dr. Lipton told the conference, reflecting a high level of disability in the cohort.
The primary endpoint of the study was mean change in monthly migraine days from baseline through week 12. Dr. Lipton reported that the placebo group saw a 5.6-day reduction in migraine, while the 100-mg group saw a 7.7-day reduction, and patients receiving the 300-mg dose saw an 8.2-day reduction during the first 12 weeks after injection (P less than .0001 for both).
One-third of patients receiving the highest dose saw a 75% or greater reduction in monthly migraine days by week 12, “a relatively high bar” to meet, Dr. Lipton said. Some 61% of patients on the high dose saw a reduction of 50% or more in the same time period.
A unique secondary endpoint of the study was the proportion of patients who experienced migraine on day 1 after the initial dose. The treatment groups saw a 52% reduction 1 day after receiving the study drug, while the placebo group saw a 27% reduction in the expected prevalence of migraine in the cohort for any single day, and the decrease was sustained through day 28. The results suggest a rapid onset of action for eptinezumab, followed by a sustained benefit, Dr. Lipton said.
Also at AAN, Stephen D. Silberstein, MD, of Thomas Jefferson University in Philadelphia, presented new 12-month results from the PROMISE 1 trial, a randomized clinical trial to evaluate quarterly IV infusions of eptinezumab 30 mg, 100 mg, 300 mg, or placebo, in 888 patients with episodic migraines, defined as 14 or fewer days per month with migraine.
The researchers, who last year published 6-month results showing significant reductions in monthly migraine days associated with eptinezumab treatment over placebo, described further reductions from patients’ baseline frequency of migraines with longer duration of treatment.
After their third and fourth quarterly injections, 70.7% of eptinezumab-treated patients achieved a 50% reduction of monthly migraine days from baseline, compared with 58.7% for placebo, the investigators reported. These findings represent an 8.9% improvement over the reductions experienced during the first two quarterly doses of eptinezumab in this cohort.
More than half of patients in the treatment arms achieved on average a 75% reduction or greater of monthly migraine days from baseline, compared with 38.7% for placebo, a 12.8% improvement from the reductions experienced with the first two doses of eptinezumab.
Adverse effects seen in the trials were upper respiratory infection, nasopharyngitis, sinusitis, and nausea.
Both trials were sponsored by eptinezumab’s manufacturer, Alder. Dr. Lipton, Dr. Silberstein, and several of their coauthors disclosed support from Alder and other manufacturers, while some coauthors on the studies are employees of Alder.
SOURCE: Saper J et al. AAN 2018, Abstract S20.001 and Lipton R et al. AAN 2018, Clinical Trials Plenary Session Abstract.
LOS ANGELES – New results from phase 3 randomized trials of the prophylactic migraine treatment eptinezumab show significant reductions in the number of monthly migraine headache days experienced by patients with chronic or frequent episodic migraines.
Eptinezumab, an experimental monoclonal antibody delivered by intravenous infusion, is one of several antimigraine agents in development that targets calcitonin gene-related peptide (CGRP), a key mediator of migraine.
At the annual meeting of the American Academy of Neurology, Richard Lipton, MD, of Albert Einstein College of Medicine in New York, presented results from PROMISE 2, a phase 3 randomized, placebo-controlled trial of eptinezumab in patients with chronic migraine, or 15 or more days with migraine per month.
The investigators randomized 1,072 patients to quarterly IV infusions of eptinezumab 100 or 300 mg or placebo.
The vast majority of patients in the study were women, (86%-90% across groups) with a mean age of about 40 years. Patients reported 11-12 years of chronic migraine and about 16 migraine days per month at baseline, Dr. Lipton told the conference, reflecting a high level of disability in the cohort.
The primary endpoint of the study was mean change in monthly migraine days from baseline through week 12. Dr. Lipton reported that the placebo group saw a 5.6-day reduction in migraine, while the 100-mg group saw a 7.7-day reduction, and patients receiving the 300-mg dose saw an 8.2-day reduction during the first 12 weeks after injection (P less than .0001 for both).
One-third of patients receiving the highest dose saw a 75% or greater reduction in monthly migraine days by week 12, “a relatively high bar” to meet, Dr. Lipton said. Some 61% of patients on the high dose saw a reduction of 50% or more in the same time period.
A unique secondary endpoint of the study was the proportion of patients who experienced migraine on day 1 after the initial dose. The treatment groups saw a 52% reduction 1 day after receiving the study drug, while the placebo group saw a 27% reduction in the expected prevalence of migraine in the cohort for any single day, and the decrease was sustained through day 28. The results suggest a rapid onset of action for eptinezumab, followed by a sustained benefit, Dr. Lipton said.
Also at AAN, Stephen D. Silberstein, MD, of Thomas Jefferson University in Philadelphia, presented new 12-month results from the PROMISE 1 trial, a randomized clinical trial to evaluate quarterly IV infusions of eptinezumab 30 mg, 100 mg, 300 mg, or placebo, in 888 patients with episodic migraines, defined as 14 or fewer days per month with migraine.
The researchers, who last year published 6-month results showing significant reductions in monthly migraine days associated with eptinezumab treatment over placebo, described further reductions from patients’ baseline frequency of migraines with longer duration of treatment.
After their third and fourth quarterly injections, 70.7% of eptinezumab-treated patients achieved a 50% reduction of monthly migraine days from baseline, compared with 58.7% for placebo, the investigators reported. These findings represent an 8.9% improvement over the reductions experienced during the first two quarterly doses of eptinezumab in this cohort.
More than half of patients in the treatment arms achieved on average a 75% reduction or greater of monthly migraine days from baseline, compared with 38.7% for placebo, a 12.8% improvement from the reductions experienced with the first two doses of eptinezumab.
Adverse effects seen in the trials were upper respiratory infection, nasopharyngitis, sinusitis, and nausea.
Both trials were sponsored by eptinezumab’s manufacturer, Alder. Dr. Lipton, Dr. Silberstein, and several of their coauthors disclosed support from Alder and other manufacturers, while some coauthors on the studies are employees of Alder.
SOURCE: Saper J et al. AAN 2018, Abstract S20.001 and Lipton R et al. AAN 2018, Clinical Trials Plenary Session Abstract.
REPORTING FROM AAN 2018
Intraventricular enzyme replacement slows CLN2 disease progression
LOS ANGELES – Intraventricular administration of cerliponase alfa seemed to slow the rate of motor and language decline in an open-label trial of 23 children with neuronal ceroid lipofuscinosis type 2 disease.
Neuronal ceroid lipofuscinosis type 2 disease (CLN2), a form of Batten’s disease, is a rare lysosomal storage disorder that causes progressive dementia in children. Patients have pathogenic variants in the gene encoding lysosomal enzyme tripeptidyl peptidase 1 (TPP1). Without functioning enzyme, lysosomal storage material accumulates in neurons throughout the CNS and retina.
Symptoms start at 2-4 years with seizures and language delays, followed by rapid motor, language, and cognitive declines, and blindness. Children die in early adolescence. Treatment is symptomatic; there are no approved therapies.
The idea of the study was to replace the enzyme in the CNS with cerliponase alfa, a recombinant form of TPP1. Twenty-four children aged 3-16 years received 30 mg, 100 mg, or 300 mg intraventricular infusions every 2 weeks during the dose-finding phase of the open-label trial; they were then switched to 300 mg infused over 4 hours every 14 days for at least 96 weeks. One child dropped out after the first dose in the study, but the others continued.
The investigators used Ommaya or Rickham ventricular reservoirs to deliver the enzyme, which were more convenient than intrathecal administration, said investigator Emily de Los Reyes, MD, a pediatric neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
The primary outcome was the time until a 2-point decline on the motor and language scores of the CLN2 Clinical Rating Scale, with 0 representing no function and 6 representing normal function in both domains. The mean unadjusted rate of decline in the motor-language score per 48-week period was 0.27 points in treated patients, versus 2.12 points in 42 historical controls (P less than .001). The treatment difference at 96 weeks was about 3.3 points. There was also a decrease in seizure severity and frequency.
All but one child experienced convulsions, over two-thirds pyrexia, and almost two-thirds vomiting and hypersensitivity. About half developed upper respiratory tract infections, and about half had increased CSF white-cell counts. There were also cases of device leakage, and two children developed infections detected by CSF monitoring, without symptoms of meningitis. Both continued treatment after removal of the intraventricular device, followed by antibiotics, and device replacement.
Fourteen patients (58%) had at least one grade 3 adverse event, and there was one grade 4 event: status epilepticus deemed unrelated to the study. Side effects resolved on their own or responded to medical management. There were no deaths, study discontinuations, or dose reductions.
The mean age in the study was 60 months, about two-thirds of the patients were girls, and CLN2 diagnosis was confirmed by genotyping. Almost all the children had seizure histories. The majority were moderately advanced at baseline, with motor-language scores of 3 out of 6 in 11 patients.
An audience member asked Dr. de Los Reyes if there would be even more benefit by starting treatment before children became symptomatic. “I think all the neurologists in this group, we know that the earlier the treatment for rare diseases, the better the response,” she said.
The results were published simultaneously in the New England Journal of Medicine.
BioMarin Pharmaceutical funded the work, along with grants from the German Federal Ministry of Education and Research, the European Union’s Horizon 2020 Research and Innovation Program, and the National Institute for Health Research. Several authors were BioMarin employees. Dr. de Los Reyes is a consultant and reported a grant from the company.
SOURCE: Schulz A et al. N Engl J Med. 2018 Apr 24. doi: 10.1056/NEJMoa1712649.
LOS ANGELES – Intraventricular administration of cerliponase alfa seemed to slow the rate of motor and language decline in an open-label trial of 23 children with neuronal ceroid lipofuscinosis type 2 disease.
Neuronal ceroid lipofuscinosis type 2 disease (CLN2), a form of Batten’s disease, is a rare lysosomal storage disorder that causes progressive dementia in children. Patients have pathogenic variants in the gene encoding lysosomal enzyme tripeptidyl peptidase 1 (TPP1). Without functioning enzyme, lysosomal storage material accumulates in neurons throughout the CNS and retina.
Symptoms start at 2-4 years with seizures and language delays, followed by rapid motor, language, and cognitive declines, and blindness. Children die in early adolescence. Treatment is symptomatic; there are no approved therapies.
The idea of the study was to replace the enzyme in the CNS with cerliponase alfa, a recombinant form of TPP1. Twenty-four children aged 3-16 years received 30 mg, 100 mg, or 300 mg intraventricular infusions every 2 weeks during the dose-finding phase of the open-label trial; they were then switched to 300 mg infused over 4 hours every 14 days for at least 96 weeks. One child dropped out after the first dose in the study, but the others continued.
The investigators used Ommaya or Rickham ventricular reservoirs to deliver the enzyme, which were more convenient than intrathecal administration, said investigator Emily de Los Reyes, MD, a pediatric neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
The primary outcome was the time until a 2-point decline on the motor and language scores of the CLN2 Clinical Rating Scale, with 0 representing no function and 6 representing normal function in both domains. The mean unadjusted rate of decline in the motor-language score per 48-week period was 0.27 points in treated patients, versus 2.12 points in 42 historical controls (P less than .001). The treatment difference at 96 weeks was about 3.3 points. There was also a decrease in seizure severity and frequency.
All but one child experienced convulsions, over two-thirds pyrexia, and almost two-thirds vomiting and hypersensitivity. About half developed upper respiratory tract infections, and about half had increased CSF white-cell counts. There were also cases of device leakage, and two children developed infections detected by CSF monitoring, without symptoms of meningitis. Both continued treatment after removal of the intraventricular device, followed by antibiotics, and device replacement.
Fourteen patients (58%) had at least one grade 3 adverse event, and there was one grade 4 event: status epilepticus deemed unrelated to the study. Side effects resolved on their own or responded to medical management. There were no deaths, study discontinuations, or dose reductions.
The mean age in the study was 60 months, about two-thirds of the patients were girls, and CLN2 diagnosis was confirmed by genotyping. Almost all the children had seizure histories. The majority were moderately advanced at baseline, with motor-language scores of 3 out of 6 in 11 patients.
An audience member asked Dr. de Los Reyes if there would be even more benefit by starting treatment before children became symptomatic. “I think all the neurologists in this group, we know that the earlier the treatment for rare diseases, the better the response,” she said.
The results were published simultaneously in the New England Journal of Medicine.
BioMarin Pharmaceutical funded the work, along with grants from the German Federal Ministry of Education and Research, the European Union’s Horizon 2020 Research and Innovation Program, and the National Institute for Health Research. Several authors were BioMarin employees. Dr. de Los Reyes is a consultant and reported a grant from the company.
SOURCE: Schulz A et al. N Engl J Med. 2018 Apr 24. doi: 10.1056/NEJMoa1712649.
LOS ANGELES – Intraventricular administration of cerliponase alfa seemed to slow the rate of motor and language decline in an open-label trial of 23 children with neuronal ceroid lipofuscinosis type 2 disease.
Neuronal ceroid lipofuscinosis type 2 disease (CLN2), a form of Batten’s disease, is a rare lysosomal storage disorder that causes progressive dementia in children. Patients have pathogenic variants in the gene encoding lysosomal enzyme tripeptidyl peptidase 1 (TPP1). Without functioning enzyme, lysosomal storage material accumulates in neurons throughout the CNS and retina.
Symptoms start at 2-4 years with seizures and language delays, followed by rapid motor, language, and cognitive declines, and blindness. Children die in early adolescence. Treatment is symptomatic; there are no approved therapies.
The idea of the study was to replace the enzyme in the CNS with cerliponase alfa, a recombinant form of TPP1. Twenty-four children aged 3-16 years received 30 mg, 100 mg, or 300 mg intraventricular infusions every 2 weeks during the dose-finding phase of the open-label trial; they were then switched to 300 mg infused over 4 hours every 14 days for at least 96 weeks. One child dropped out after the first dose in the study, but the others continued.
The investigators used Ommaya or Rickham ventricular reservoirs to deliver the enzyme, which were more convenient than intrathecal administration, said investigator Emily de Los Reyes, MD, a pediatric neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
The primary outcome was the time until a 2-point decline on the motor and language scores of the CLN2 Clinical Rating Scale, with 0 representing no function and 6 representing normal function in both domains. The mean unadjusted rate of decline in the motor-language score per 48-week period was 0.27 points in treated patients, versus 2.12 points in 42 historical controls (P less than .001). The treatment difference at 96 weeks was about 3.3 points. There was also a decrease in seizure severity and frequency.
All but one child experienced convulsions, over two-thirds pyrexia, and almost two-thirds vomiting and hypersensitivity. About half developed upper respiratory tract infections, and about half had increased CSF white-cell counts. There were also cases of device leakage, and two children developed infections detected by CSF monitoring, without symptoms of meningitis. Both continued treatment after removal of the intraventricular device, followed by antibiotics, and device replacement.
Fourteen patients (58%) had at least one grade 3 adverse event, and there was one grade 4 event: status epilepticus deemed unrelated to the study. Side effects resolved on their own or responded to medical management. There were no deaths, study discontinuations, or dose reductions.
The mean age in the study was 60 months, about two-thirds of the patients were girls, and CLN2 diagnosis was confirmed by genotyping. Almost all the children had seizure histories. The majority were moderately advanced at baseline, with motor-language scores of 3 out of 6 in 11 patients.
An audience member asked Dr. de Los Reyes if there would be even more benefit by starting treatment before children became symptomatic. “I think all the neurologists in this group, we know that the earlier the treatment for rare diseases, the better the response,” she said.
The results were published simultaneously in the New England Journal of Medicine.
BioMarin Pharmaceutical funded the work, along with grants from the German Federal Ministry of Education and Research, the European Union’s Horizon 2020 Research and Innovation Program, and the National Institute for Health Research. Several authors were BioMarin employees. Dr. de Los Reyes is a consultant and reported a grant from the company.
SOURCE: Schulz A et al. N Engl J Med. 2018 Apr 24. doi: 10.1056/NEJMoa1712649.
REPORTING FROM AAN 2018
Key clinical point: Intraventricular administration of cerliponase alfa seemed to slow the rate of motor and language decline in 23 children with neuronal ceroid lipofuscinosis type 2 disease.
Major finding: The mean unadjusted rate of decline in the motor-language score per 48-week period was 0.27 points in treated patients, versus 2.12 points in 42 historical controls (P less than .001).
Study details: Open-label trial of 23 children.
Disclosures: BioMarin Pharmaceutical funded the work, along with grants from the German Federal Ministry of Education and Research, the European Union’s Horizon 2020 Research and Innovation Program, and the National Institute for Health Research. Several authors were BioMarin employees. The presenter is a consultant to BioMarin and reported a grant from the company.
Source: Schulz A et al. N Engl J Med. 2018 Apr 24. doi: 10.1056/NEJMoa1712649.
