Movement Disorders

LOS ANGELES—IncobotulinumtoxinA may treat sialorrhea in Parkinson’s disease and other neurologic disorders effectively, according to a trial described at the 70th Annual Meeting of the American Academy of Neurology. The treatment effect may persist for as long as 16 weeks.

Various neurologic disorders, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), may cause troublesome sialorrhea. Olaf Michel, PhD, Vice Chair of the Department of Otorhinolaryngology at the University Hospital Brussels, and colleagues conducted a phase III trial to investigate the safety and efficacy of incobotulinumtoxinA as a treatment for sialorrhea.

LOS ANGELES—IncobotulinumtoxinA may treat sialorrhea in Parkinson’s disease and other neurologic disorders effectively, according to a trial described at the 70th Annual Meeting of the American Academy of Neurology. The treatment effect may persist for as long as 16 weeks.

Various neurologic disorders, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), may cause troublesome sialorrhea. Olaf Michel, PhD, Vice Chair of the Department of Otorhinolaryngology at the University Hospital Brussels, and colleagues conducted a phase III trial to investigate the safety and efficacy of incobotulinumtoxinA as a treatment for sialorrhea.

LOS ANGELES—IncobotulinumtoxinA may treat sialorrhea in Parkinson’s disease and other neurologic disorders effectively, according to a trial described at the 70th Annual Meeting of the American Academy of Neurology. The treatment effect may persist for as long as 16 weeks.

Various neurologic disorders, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), may cause troublesome sialorrhea. Olaf Michel, PhD, Vice Chair of the Department of Otorhinolaryngology at the University Hospital Brussels, and colleagues conducted a phase III trial to investigate the safety and efficacy of incobotulinumtoxinA as a treatment for sialorrhea.

Patients with inflammatory bowel disease were about 22% more likely to develop Parkinson’s disease than were unaffected peers in a population-based cohort study spanning more than 3 decades.

The finding “strengthens the theory of a ‘gut-brain axis,’ in which the intestinal environment influences the functioning of the central nervous system and intestinal imbalance may precede Parkinson’s disease,” wrote Marie Villumsen, PhD, of Bispebjerg and Frederiksberg Hospital in Copenhagen, with her associates.

Thus, clinicians should be vigilant for parkinsonism in patients with inflammatory bowel disease (IBD), the researchers wrote on May 21 in Gut. “Although the absolute risk of Parkinson’s disease [among patients with IBD] remains low, our study points to overlapping pathogenic mechanisms which merit further investigation, as they may represent targets for future therapeutic interventions.”

Gastrointestinal dysfunction can be one of the earliest manifestations of Parkinson’s disease, the researchers noted. Both neurodegenerative disorders and IBD involve chronic inflammation, and both Crohn’s disease and Parkinson’s disease have been linked to aberrations of the LRRK2 gene, which helps regulate inflammation and clearance of alpha-sinuclein, a key component of neuronal Lewy bodies in Parkinson’s disease.

To assess whether IBD directly increases the risk of Parkinson’s disease, the investigators studied individuals from the Danish National Patient Register, which covers all hospitalizations and outpatient visits in Denmark. They matched 76,477 patients with IBD with 7.5 million unaffected individuals of the same sex and age during 1977-2014. Patients with IBD had significantly more comorbidities (P less than .001) than individuals without IBD, so the researchers also controlled for Charlson Comorbidity Index.

In the adjusted analyses, IBD significantly increased the risk of developing Parkinson’s disease among both men (hazard ratio, 1.2) and women (HR, 1.23), irrespective of follow-up time and regardless of whether patients were less than 40 years old (HR, 1.22), 40-65 years old (HR, 1.25), or older than 65 years (HR, 1.30). The association between IBD and Parkinson’s disease also held up after accounting for the possibility that early gut symptoms of Parkinson’s disease were sometimes misdiagnosed as IBD, the researchers wrote.

Interestingly, stratifying by IBD subtype showed that the statistically significant risk factor was ulcerative colitis (HR, 1.35; 95% confidence interval, 1.20-1.52), not Crohn’s disease (HR, 1.12; 95% CI, 0.89-1.40). Prior studies have found that cigarette smoking reduces the risk of both Parkinson’s disease and ulcerative colitis, the investigators noted. They called for additional studies of intestinal inflammation in Parkinson’s disease and the role of the brain-gut axis in the etiology of parkinsonism.

Parkinsonforeningen, Landsforeningen Multipel System Atrofi, and Aage og Johanne Louis-Hansens Fond provided support. The investigators declared no competing interests.

SOURCE: Villumsen M et al. Gut. 2018 May 21. doi: 10.1136/gutjnl-2017-315666.

Patients with inflammatory bowel disease were about 22% more likely to develop Parkinson’s disease than were unaffected peers in a population-based cohort study spanning more than 3 decades.

The finding “strengthens the theory of a ‘gut-brain axis,’ in which the intestinal environment influences the functioning of the central nervous system and intestinal imbalance may precede Parkinson’s disease,” wrote Marie Villumsen, PhD, of Bispebjerg and Frederiksberg Hospital in Copenhagen, with her associates.

Thus, clinicians should be vigilant for parkinsonism in patients with inflammatory bowel disease (IBD), the researchers wrote on May 21 in Gut. “Although the absolute risk of Parkinson’s disease [among patients with IBD] remains low, our study points to overlapping pathogenic mechanisms which merit further investigation, as they may represent targets for future therapeutic interventions.”

Gastrointestinal dysfunction can be one of the earliest manifestations of Parkinson’s disease, the researchers noted. Both neurodegenerative disorders and IBD involve chronic inflammation, and both Crohn’s disease and Parkinson’s disease have been linked to aberrations of the LRRK2 gene, which helps regulate inflammation and clearance of alpha-sinuclein, a key component of neuronal Lewy bodies in Parkinson’s disease.

To assess whether IBD directly increases the risk of Parkinson’s disease, the investigators studied individuals from the Danish National Patient Register, which covers all hospitalizations and outpatient visits in Denmark. They matched 76,477 patients with IBD with 7.5 million unaffected individuals of the same sex and age during 1977-2014. Patients with IBD had significantly more comorbidities (P less than .001) than individuals without IBD, so the researchers also controlled for Charlson Comorbidity Index.

In the adjusted analyses, IBD significantly increased the risk of developing Parkinson’s disease among both men (hazard ratio, 1.2) and women (HR, 1.23), irrespective of follow-up time and regardless of whether patients were less than 40 years old (HR, 1.22), 40-65 years old (HR, 1.25), or older than 65 years (HR, 1.30). The association between IBD and Parkinson’s disease also held up after accounting for the possibility that early gut symptoms of Parkinson’s disease were sometimes misdiagnosed as IBD, the researchers wrote.

Interestingly, stratifying by IBD subtype showed that the statistically significant risk factor was ulcerative colitis (HR, 1.35; 95% confidence interval, 1.20-1.52), not Crohn’s disease (HR, 1.12; 95% CI, 0.89-1.40). Prior studies have found that cigarette smoking reduces the risk of both Parkinson’s disease and ulcerative colitis, the investigators noted. They called for additional studies of intestinal inflammation in Parkinson’s disease and the role of the brain-gut axis in the etiology of parkinsonism.

Parkinsonforeningen, Landsforeningen Multipel System Atrofi, and Aage og Johanne Louis-Hansens Fond provided support. The investigators declared no competing interests.

SOURCE: Villumsen M et al. Gut. 2018 May 21. doi: 10.1136/gutjnl-2017-315666.

Patients with inflammatory bowel disease were about 22% more likely to develop Parkinson’s disease than were unaffected peers in a population-based cohort study spanning more than 3 decades.

The finding “strengthens the theory of a ‘gut-brain axis,’ in which the intestinal environment influences the functioning of the central nervous system and intestinal imbalance may precede Parkinson’s disease,” wrote Marie Villumsen, PhD, of Bispebjerg and Frederiksberg Hospital in Copenhagen, with her associates.

Thus, clinicians should be vigilant for parkinsonism in patients with inflammatory bowel disease (IBD), the researchers wrote on May 21 in Gut. “Although the absolute risk of Parkinson’s disease [among patients with IBD] remains low, our study points to overlapping pathogenic mechanisms which merit further investigation, as they may represent targets for future therapeutic interventions.”

Gastrointestinal dysfunction can be one of the earliest manifestations of Parkinson’s disease, the researchers noted. Both neurodegenerative disorders and IBD involve chronic inflammation, and both Crohn’s disease and Parkinson’s disease have been linked to aberrations of the LRRK2 gene, which helps regulate inflammation and clearance of alpha-sinuclein, a key component of neuronal Lewy bodies in Parkinson’s disease.

To assess whether IBD directly increases the risk of Parkinson’s disease, the investigators studied individuals from the Danish National Patient Register, which covers all hospitalizations and outpatient visits in Denmark. They matched 76,477 patients with IBD with 7.5 million unaffected individuals of the same sex and age during 1977-2014. Patients with IBD had significantly more comorbidities (P less than .001) than individuals without IBD, so the researchers also controlled for Charlson Comorbidity Index.

In the adjusted analyses, IBD significantly increased the risk of developing Parkinson’s disease among both men (hazard ratio, 1.2) and women (HR, 1.23), irrespective of follow-up time and regardless of whether patients were less than 40 years old (HR, 1.22), 40-65 years old (HR, 1.25), or older than 65 years (HR, 1.30). The association between IBD and Parkinson’s disease also held up after accounting for the possibility that early gut symptoms of Parkinson’s disease were sometimes misdiagnosed as IBD, the researchers wrote.

Interestingly, stratifying by IBD subtype showed that the statistically significant risk factor was ulcerative colitis (HR, 1.35; 95% confidence interval, 1.20-1.52), not Crohn’s disease (HR, 1.12; 95% CI, 0.89-1.40). Prior studies have found that cigarette smoking reduces the risk of both Parkinson’s disease and ulcerative colitis, the investigators noted. They called for additional studies of intestinal inflammation in Parkinson’s disease and the role of the brain-gut axis in the etiology of parkinsonism.

Parkinsonforeningen, Landsforeningen Multipel System Atrofi, and Aage og Johanne Louis-Hansens Fond provided support. The investigators declared no competing interests.

SOURCE: Villumsen M et al. Gut. 2018 May 21. doi: 10.1136/gutjnl-2017-315666.

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

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.

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.

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.

SOURCE: Pahwa R et al. AAN 2018, Abstract P4.474.

Antidepressant, urologic, and antiparkinson drugs with definite anticholinergic activity were associated with an increased risk of dementia as long as 20 years after exposure in a large observational study published in The BMJ.

Kathryn Richardson, PhD, of the University of East Anglia, Norwich, England, and her colleagues said that while the associations were “moderate” given the high incidence of dementia observed in the study, they nevertheless reflected an “appreciable risk” for patients.

MarkRyanDesigns/getty images

Overall, 14,453 cases (35%) and 86,403 controls (30%) were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. People prescribed greater dosage quantities over time of probable (ACB category 2) and definite (ACB category 3) anticholinergics had a higher risk of dementia, the researchers reported.

For example, anticholinergic use consistent with the highest dose category (more than 1,460 defined daily doses) was associated with an adjusted odds ratio for dementia of 1.57 (95% confidence interval, 1.18-2.09) for probable and 1.31 (95% CI, 1.22-1.41) for definite anticholinergics.

However, no increased risk was found for anticholinergics used to treat gastrointestinal, cardiovascular, or respiratory conditions. The research team also found no evidence for a cumulative harm of drugs considered “possibly” anticholinergic.

“A typical patient aged 65-70 might normally expect a period incidence of dementia of around 10% over the next 15 years, so this odds ratio would be consistent with an absolute risk increase of 2% (1% to 3%) over that period, corresponding to a number needed to harm of 50 (33 to 100),” they wrote.

They suggested that their findings could be explained by the drugs being markers of prodromal symptoms or dementia risk factors. The class effect observed might also reflect differences in the way anticholinergics crossed the blood-brain barrier.

The Alzheimer’s Society supported the research. Several of the authors reported receiving personal fees from Astellas. One author declared personal fees from Thame Pharmaceuticals.

SOURCE: Richardson K et al. BMJ. 2018;360:k1315. doi: 10.1136/bmj.k1315.

Antidepressant, urologic, and antiparkinson drugs with definite anticholinergic activity were associated with an increased risk of dementia as long as 20 years after exposure in a large observational study published in The BMJ.

Kathryn Richardson, PhD, of the University of East Anglia, Norwich, England, and her colleagues said that while the associations were “moderate” given the high incidence of dementia observed in the study, they nevertheless reflected an “appreciable risk” for patients.

MarkRyanDesigns/getty images

Overall, 14,453 cases (35%) and 86,403 controls (30%) were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. People prescribed greater dosage quantities over time of probable (ACB category 2) and definite (ACB category 3) anticholinergics had a higher risk of dementia, the researchers reported.

For example, anticholinergic use consistent with the highest dose category (more than 1,460 defined daily doses) was associated with an adjusted odds ratio for dementia of 1.57 (95% confidence interval, 1.18-2.09) for probable and 1.31 (95% CI, 1.22-1.41) for definite anticholinergics.

However, no increased risk was found for anticholinergics used to treat gastrointestinal, cardiovascular, or respiratory conditions. The research team also found no evidence for a cumulative harm of drugs considered “possibly” anticholinergic.

“A typical patient aged 65-70 might normally expect a period incidence of dementia of around 10% over the next 15 years, so this odds ratio would be consistent with an absolute risk increase of 2% (1% to 3%) over that period, corresponding to a number needed to harm of 50 (33 to 100),” they wrote.

They suggested that their findings could be explained by the drugs being markers of prodromal symptoms or dementia risk factors. The class effect observed might also reflect differences in the way anticholinergics crossed the blood-brain barrier.

The Alzheimer’s Society supported the research. Several of the authors reported receiving personal fees from Astellas. One author declared personal fees from Thame Pharmaceuticals.

SOURCE: Richardson K et al. BMJ. 2018;360:k1315. doi: 10.1136/bmj.k1315.

Antidepressant, urologic, and antiparkinson drugs with definite anticholinergic activity were associated with an increased risk of dementia as long as 20 years after exposure in a large observational study published in The BMJ.

Kathryn Richardson, PhD, of the University of East Anglia, Norwich, England, and her colleagues said that while the associations were “moderate” given the high incidence of dementia observed in the study, they nevertheless reflected an “appreciable risk” for patients.

MarkRyanDesigns/getty images

Overall, 14,453 cases (35%) and 86,403 controls (30%) were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. People prescribed greater dosage quantities over time of probable (ACB category 2) and definite (ACB category 3) anticholinergics had a higher risk of dementia, the researchers reported.

For example, anticholinergic use consistent with the highest dose category (more than 1,460 defined daily doses) was associated with an adjusted odds ratio for dementia of 1.57 (95% confidence interval, 1.18-2.09) for probable and 1.31 (95% CI, 1.22-1.41) for definite anticholinergics.

However, no increased risk was found for anticholinergics used to treat gastrointestinal, cardiovascular, or respiratory conditions. The research team also found no evidence for a cumulative harm of drugs considered “possibly” anticholinergic.

“A typical patient aged 65-70 might normally expect a period incidence of dementia of around 10% over the next 15 years, so this odds ratio would be consistent with an absolute risk increase of 2% (1% to 3%) over that period, corresponding to a number needed to harm of 50 (33 to 100),” they wrote.

They suggested that their findings could be explained by the drugs being markers of prodromal symptoms or dementia risk factors. The class effect observed might also reflect differences in the way anticholinergics crossed the blood-brain barrier.

The Alzheimer’s Society supported the research. Several of the authors reported receiving personal fees from Astellas. One author declared personal fees from Thame Pharmaceuticals.

SOURCE: Richardson K et al. BMJ. 2018;360:k1315. doi: 10.1136/bmj.k1315.

LOS ANGELES—Once-daily treatment with valbenazine for 48 weeks provides substantial improvements on clinician- and patient-reported outcomes in adults with tardive dyskinesia, according to data described at the 70th Annual Meeting of the American Academy of Neurology. The results are consistent with those of previous trials, said the researchers. Valbenazine is well-tolerated and does not raise significant safety concerns.

Valbenazine was approved as a treatment for tardive dyskinesia on the basis of several short-term placebo-controlled trials, a blinded extension study, and the long-term KINECT 4 study. Stewart Factor, DO, Professor of Neurology at Emory University School of Medicine in Atlanta, and colleagues conducted a study to evaluate the long-term effects of once-daily valbenazine on tardive dyskinesia.

Eligible participants were adults with de novo tardive dyskinesia and those who had participated in prior trials of valbenazine. All participants received 48 weeks of open-label treatment with valbenazine. The initial dose was 40 mg. If an investigator judged that a patient had inadequate clinical response at week four, the dose was increased to 80 mg, based on tolerability. For patients who could not tolerate the 80-mg dose, the dose was decreased to 40 mg.

Dr. Factor and colleagues used the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score to assess changes in tardive dyskinesia. Other efficacy assessments included the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) scales. The investigators applied standard safety methods, including treatment-emergent adverse event reporting.

The safety population included 163 participants. Of this group, 107 participants received and tolerated the 80-mg dose, 45 did not require escalation from the 40-mg dose, and 11 were escalated to 80-mg dose, but later required reduction to the 40-mg dose. The mean change from baseline to week 48 in AIMS total score indicated improvements in tardive dyskinesia in all dose groups. The 80-mg group had a decrease of 11.0 points, the 40-mg group had a decrease of 10.2 points, and the group whose dose was decreased from 80 mg to 40 mg had a decrease of 7.2 points.

At week 48, more than 75% of participants in each study arm had a PGIC score of 2 or lower (ie, much improved or very much improved). This outcome was achieved in 89.2% of the 80-mg group, 90.0% of the 40-mg group, and 77.8% of the group whose dose was decreased from 80 mg to 40 mg. Mean CGI-TD scores at week 48 were 1.6 for the 80-mg group, 1.7 for the 40-mg group, and 2.3 for the group whose dose was reduced from 80 mg to 40 mg. These scores indicated clinically meaningful long-term improvement for all dose groups.

Less than 15% of all participants had a serious treatment-emergent adverse event (12.9%) or treatment-emergent adverse event leading to discontinuation (14.7%).

The study was funded by Neurocrine Biosciences, the manufacturer of valbenazine.

LOS ANGELES—Once-daily treatment with valbenazine for 48 weeks provides substantial improvements on clinician- and patient-reported outcomes in adults with tardive dyskinesia, according to data described at the 70th Annual Meeting of the American Academy of Neurology. The results are consistent with those of previous trials, said the researchers. Valbenazine is well-tolerated and does not raise significant safety concerns.

Valbenazine was approved as a treatment for tardive dyskinesia on the basis of several short-term placebo-controlled trials, a blinded extension study, and the long-term KINECT 4 study. Stewart Factor, DO, Professor of Neurology at Emory University School of Medicine in Atlanta, and colleagues conducted a study to evaluate the long-term effects of once-daily valbenazine on tardive dyskinesia.

Eligible participants were adults with de novo tardive dyskinesia and those who had participated in prior trials of valbenazine. All participants received 48 weeks of open-label treatment with valbenazine. The initial dose was 40 mg. If an investigator judged that a patient had inadequate clinical response at week four, the dose was increased to 80 mg, based on tolerability. For patients who could not tolerate the 80-mg dose, the dose was decreased to 40 mg.

Dr. Factor and colleagues used the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score to assess changes in tardive dyskinesia. Other efficacy assessments included the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) scales. The investigators applied standard safety methods, including treatment-emergent adverse event reporting.

The safety population included 163 participants. Of this group, 107 participants received and tolerated the 80-mg dose, 45 did not require escalation from the 40-mg dose, and 11 were escalated to 80-mg dose, but later required reduction to the 40-mg dose. The mean change from baseline to week 48 in AIMS total score indicated improvements in tardive dyskinesia in all dose groups. The 80-mg group had a decrease of 11.0 points, the 40-mg group had a decrease of 10.2 points, and the group whose dose was decreased from 80 mg to 40 mg had a decrease of 7.2 points.

At week 48, more than 75% of participants in each study arm had a PGIC score of 2 or lower (ie, much improved or very much improved). This outcome was achieved in 89.2% of the 80-mg group, 90.0% of the 40-mg group, and 77.8% of the group whose dose was decreased from 80 mg to 40 mg. Mean CGI-TD scores at week 48 were 1.6 for the 80-mg group, 1.7 for the 40-mg group, and 2.3 for the group whose dose was reduced from 80 mg to 40 mg. These scores indicated clinically meaningful long-term improvement for all dose groups.

Less than 15% of all participants had a serious treatment-emergent adverse event (12.9%) or treatment-emergent adverse event leading to discontinuation (14.7%).

The study was funded by Neurocrine Biosciences, the manufacturer of valbenazine.

LOS ANGELES—Once-daily treatment with valbenazine for 48 weeks provides substantial improvements on clinician- and patient-reported outcomes in adults with tardive dyskinesia, according to data described at the 70th Annual Meeting of the American Academy of Neurology. The results are consistent with those of previous trials, said the researchers. Valbenazine is well-tolerated and does not raise significant safety concerns.

Valbenazine was approved as a treatment for tardive dyskinesia on the basis of several short-term placebo-controlled trials, a blinded extension study, and the long-term KINECT 4 study. Stewart Factor, DO, Professor of Neurology at Emory University School of Medicine in Atlanta, and colleagues conducted a study to evaluate the long-term effects of once-daily valbenazine on tardive dyskinesia.

Eligible participants were adults with de novo tardive dyskinesia and those who had participated in prior trials of valbenazine. All participants received 48 weeks of open-label treatment with valbenazine. The initial dose was 40 mg. If an investigator judged that a patient had inadequate clinical response at week four, the dose was increased to 80 mg, based on tolerability. For patients who could not tolerate the 80-mg dose, the dose was decreased to 40 mg.

Dr. Factor and colleagues used the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score to assess changes in tardive dyskinesia. Other efficacy assessments included the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) scales. The investigators applied standard safety methods, including treatment-emergent adverse event reporting.

The safety population included 163 participants. Of this group, 107 participants received and tolerated the 80-mg dose, 45 did not require escalation from the 40-mg dose, and 11 were escalated to 80-mg dose, but later required reduction to the 40-mg dose. The mean change from baseline to week 48 in AIMS total score indicated improvements in tardive dyskinesia in all dose groups. The 80-mg group had a decrease of 11.0 points, the 40-mg group had a decrease of 10.2 points, and the group whose dose was decreased from 80 mg to 40 mg had a decrease of 7.2 points.

At week 48, more than 75% of participants in each study arm had a PGIC score of 2 or lower (ie, much improved or very much improved). This outcome was achieved in 89.2% of the 80-mg group, 90.0% of the 40-mg group, and 77.8% of the group whose dose was decreased from 80 mg to 40 mg. Mean CGI-TD scores at week 48 were 1.6 for the 80-mg group, 1.7 for the 40-mg group, and 2.3 for the group whose dose was reduced from 80 mg to 40 mg. These scores indicated clinically meaningful long-term improvement for all dose groups.

Less than 15% of all participants had a serious treatment-emergent adverse event (12.9%) or treatment-emergent adverse event leading to discontinuation (14.7%).

The study was funded by Neurocrine Biosciences, the manufacturer of valbenazine.

LOS ANGELES – Two studies of real-world use of pimavanserin after its approval in March 2016 for the treatment of Parkinson’s disease–associated psychosis indicate its effectiveness, tolerability, and safety in line with clinical trial results, according to reports presented at the annual meeting of the American Academy of Neurology.

In the first study, 102 patients were prescribed pimavanserin (Nuplazid) during May 2016-March 2018. Of the 88 patients who actually took the drug, 83% had Parkinson’s, and 78% were men. Participants’ mean age was 79 years. Nearly a third had deep brain stimulation.

Jeff Evans/MDedge News

There was no consistent strategy implemented for starting pimavanserin: 17 stopped or were advised to stop their other antipsychotic before starting pimavanserin, 15 were told to taper off their other antipsychotic for 1 week or for up to 3 months, and 22 were told to keep taking their other antipsychotic after starting pimavanserin.

The mean treatment duration has been nearly 11 months for the two-thirds of patients who remain on pimavanserin, including 38 who take it alone and another 20 who take it with another antipsychotic.

A total of 10 patients were unable to tolerate pimavanserin because of adverse events, 5 of whom had generalized weakness/gait instability. This adverse event was the only difference in adverse events that was seen from the clinical trials, said lead author Jessie Sellers, a nurse practitioner at Vanderbilt University Medical Center in Nashville, Tenn.

“But overall the drug was really well tolerated and was effective,” she said.

There also was no increase in mortality detected in users, providing evidence against an association with mortality in older people with dementia-related psychosis that previously led to a boxed warning for atypical antipsychotics, noted senior author Daniel O. Claassen, MD. A total of 6 of the 88 patients died, compared with 5 of the 14 patients who never started the drug.

Patients who stopped pimavanserin and started another antipsychotic had only limited success. Of 11 patients who stopped pimavanserin and started another antipsychotic, only 5 were successful. Another six who stopped pimavanserin did not take another antipsychotic drug, primarily because of the resolution of their symptoms.

The pimavanserin status was unknown for four patients, and another three patients who stopped the drug had not returned for follow-up.

Abhimanyu Mahajan, MD, and other researchers from Henry Ford Hospital in Detroit reported similar results with pimavanserin at the AAN annual meeting in a separate, smaller, retrospective chart review of 16 patients with Parkinson’s disease–associated psychosis and 1 with Lewy body dementia.

These patients had a mean duration of parkinsonism of nearly 12 years and more than 2 years of psychotic symptoms, which consisted of daily or continuous hallucinations in all but one patient.

Telephone interviews with patients and caregivers revealed that 10 of 14 had improvement in hallucinations, and 3 had stopped taking it because of either no benefit or remission. Of six patients who took pimavanserin monotherapy, half improved from severe to mild hallucination severity (less than one episode per week), two had no change, and one improved from severe to moderate. For the other eight patients who took pimavanserin with another antipsychotic, two had no change in hallucination severity, two went from severe to mild, three improved from severe to moderate, and one went from moderate to mild. The patients reported no major adverse events.

Ms. Sellers and another author had no disclosures. Dr. Claassen disclosed personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with several companies, including Acadia, which markets pimavanserin.

Two of the authors of Dr. Mahajan’s study reported financial ties to Acadia and other companies.

[email protected]

SOURCE: Sellers J et al. AAN 2018, abstract P1.040 and Mahajan A et al. AAN 2018, abstract P5.065

LOS ANGELES – Two studies of real-world use of pimavanserin after its approval in March 2016 for the treatment of Parkinson’s disease–associated psychosis indicate its effectiveness, tolerability, and safety in line with clinical trial results, according to reports presented at the annual meeting of the American Academy of Neurology.

In the first study, 102 patients were prescribed pimavanserin (Nuplazid) during May 2016-March 2018. Of the 88 patients who actually took the drug, 83% had Parkinson’s, and 78% were men. Participants’ mean age was 79 years. Nearly a third had deep brain stimulation.

Jeff Evans/MDedge News

There was no consistent strategy implemented for starting pimavanserin: 17 stopped or were advised to stop their other antipsychotic before starting pimavanserin, 15 were told to taper off their other antipsychotic for 1 week or for up to 3 months, and 22 were told to keep taking their other antipsychotic after starting pimavanserin.

The mean treatment duration has been nearly 11 months for the two-thirds of patients who remain on pimavanserin, including 38 who take it alone and another 20 who take it with another antipsychotic.

A total of 10 patients were unable to tolerate pimavanserin because of adverse events, 5 of whom had generalized weakness/gait instability. This adverse event was the only difference in adverse events that was seen from the clinical trials, said lead author Jessie Sellers, a nurse practitioner at Vanderbilt University Medical Center in Nashville, Tenn.

“But overall the drug was really well tolerated and was effective,” she said.

There also was no increase in mortality detected in users, providing evidence against an association with mortality in older people with dementia-related psychosis that previously led to a boxed warning for atypical antipsychotics, noted senior author Daniel O. Claassen, MD. A total of 6 of the 88 patients died, compared with 5 of the 14 patients who never started the drug.

Patients who stopped pimavanserin and started another antipsychotic had only limited success. Of 11 patients who stopped pimavanserin and started another antipsychotic, only 5 were successful. Another six who stopped pimavanserin did not take another antipsychotic drug, primarily because of the resolution of their symptoms.

The pimavanserin status was unknown for four patients, and another three patients who stopped the drug had not returned for follow-up.

Abhimanyu Mahajan, MD, and other researchers from Henry Ford Hospital in Detroit reported similar results with pimavanserin at the AAN annual meeting in a separate, smaller, retrospective chart review of 16 patients with Parkinson’s disease–associated psychosis and 1 with Lewy body dementia.

These patients had a mean duration of parkinsonism of nearly 12 years and more than 2 years of psychotic symptoms, which consisted of daily or continuous hallucinations in all but one patient.

Telephone interviews with patients and caregivers revealed that 10 of 14 had improvement in hallucinations, and 3 had stopped taking it because of either no benefit or remission. Of six patients who took pimavanserin monotherapy, half improved from severe to mild hallucination severity (less than one episode per week), two had no change, and one improved from severe to moderate. For the other eight patients who took pimavanserin with another antipsychotic, two had no change in hallucination severity, two went from severe to mild, three improved from severe to moderate, and one went from moderate to mild. The patients reported no major adverse events.

Ms. Sellers and another author had no disclosures. Dr. Claassen disclosed personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with several companies, including Acadia, which markets pimavanserin.

Two of the authors of Dr. Mahajan’s study reported financial ties to Acadia and other companies.

[email protected]

SOURCE: Sellers J et al. AAN 2018, abstract P1.040 and Mahajan A et al. AAN 2018, abstract P5.065

LOS ANGELES – Two studies of real-world use of pimavanserin after its approval in March 2016 for the treatment of Parkinson’s disease–associated psychosis indicate its effectiveness, tolerability, and safety in line with clinical trial results, according to reports presented at the annual meeting of the American Academy of Neurology.

In the first study, 102 patients were prescribed pimavanserin (Nuplazid) during May 2016-March 2018. Of the 88 patients who actually took the drug, 83% had Parkinson’s, and 78% were men. Participants’ mean age was 79 years. Nearly a third had deep brain stimulation.

Jeff Evans/MDedge News

There was no consistent strategy implemented for starting pimavanserin: 17 stopped or were advised to stop their other antipsychotic before starting pimavanserin, 15 were told to taper off their other antipsychotic for 1 week or for up to 3 months, and 22 were told to keep taking their other antipsychotic after starting pimavanserin.

The mean treatment duration has been nearly 11 months for the two-thirds of patients who remain on pimavanserin, including 38 who take it alone and another 20 who take it with another antipsychotic.

A total of 10 patients were unable to tolerate pimavanserin because of adverse events, 5 of whom had generalized weakness/gait instability. This adverse event was the only difference in adverse events that was seen from the clinical trials, said lead author Jessie Sellers, a nurse practitioner at Vanderbilt University Medical Center in Nashville, Tenn.

“But overall the drug was really well tolerated and was effective,” she said.

There also was no increase in mortality detected in users, providing evidence against an association with mortality in older people with dementia-related psychosis that previously led to a boxed warning for atypical antipsychotics, noted senior author Daniel O. Claassen, MD. A total of 6 of the 88 patients died, compared with 5 of the 14 patients who never started the drug.

Patients who stopped pimavanserin and started another antipsychotic had only limited success. Of 11 patients who stopped pimavanserin and started another antipsychotic, only 5 were successful. Another six who stopped pimavanserin did not take another antipsychotic drug, primarily because of the resolution of their symptoms.

The pimavanserin status was unknown for four patients, and another three patients who stopped the drug had not returned for follow-up.

Abhimanyu Mahajan, MD, and other researchers from Henry Ford Hospital in Detroit reported similar results with pimavanserin at the AAN annual meeting in a separate, smaller, retrospective chart review of 16 patients with Parkinson’s disease–associated psychosis and 1 with Lewy body dementia.

These patients had a mean duration of parkinsonism of nearly 12 years and more than 2 years of psychotic symptoms, which consisted of daily or continuous hallucinations in all but one patient.

Telephone interviews with patients and caregivers revealed that 10 of 14 had improvement in hallucinations, and 3 had stopped taking it because of either no benefit or remission. Of six patients who took pimavanserin monotherapy, half improved from severe to mild hallucination severity (less than one episode per week), two had no change, and one improved from severe to moderate. For the other eight patients who took pimavanserin with another antipsychotic, two had no change in hallucination severity, two went from severe to mild, three improved from severe to moderate, and one went from moderate to mild. The patients reported no major adverse events.

Ms. Sellers and another author had no disclosures. Dr. Claassen disclosed personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with several companies, including Acadia, which markets pimavanserin.

Two of the authors of Dr. Mahajan’s study reported financial ties to Acadia and other companies.

[email protected]

SOURCE: Sellers J et al. AAN 2018, abstract P1.040 and Mahajan A et al. AAN 2018, abstract P5.065

Patients with inflammatory bowel disease had about a 28% higher risk of Parkinson’s disease (PD) than that of matched controls in a large retrospective analysis of administrative health care claims.

But tumor necrosis factor (TNF) inhibitor therapy appeared to attenuate this risk, wrote Inga Peter, PhD, of Icahn School of Medicine at Mount Sinai, New York, and her associates. Patients with inflammatory bowel disease (IBD) who received TNF inhibitors were 78% less likely to develop PD than were those who did not (P = .03). “Reducing systemic inflammation in at-risk individuals may decrease the incidence of PD [Parkinson disease],” the researchers wrote. The study was published online April 23 in JAMA Neurology.

The researchers queried the Truven Health MarketScan database and the Medicare Supplemental Database for patients with IBD from 2000 through 2016. The databases included more than 170 million patients, of whom 144,018 had at least two IBD-related claims, at least 6 months of follow-up, and no baseline PD diagnosis. These patients were matched by age, sex, and treatment year with 720,090 individuals without IBD from the same databases.

A total of 1,796 patients had at least two recorded PD diagnoses and had filled at least one associated prescription, said the researchers. Based on this PD definition, patients with IBD developed PD at a 28% higher rate than that of matched controls (adjusted IRR, 1.28; 95% CI, 1.14 to 1.44; P less than .001).

Among the IBD patients, those receiving anti-TNF therapy developed about 0.08 cases of PD for every 1,000 person-years, versus 0.76 PD cases per 1,000 person-years in the group not receiving anti-TNF therapy. After adjustment for age, sex, and time at risk, anti-TNF therapy was associated with a 78% reduction in the incidence of PD among IBD patients (adjusted incidence rate ratio, 0.22; 95% confidence interval, 0.05-0.88; P = .03).

“In summary, we showed a potential clinical link between IBD and PD, supporting shared mechanisms involved in the pathogenesis of these diseases,” the researchers wrote. “Moreover, our data suggest that early exposure to anti-TNF therapy may reduce the risk of PD among patients with IBD, potentially owing to a reduction in systemic inflammation. These findings should be further assessed and confirmed by other studies.”

Dr. Peter received support from the Leona M. and Harry B. Helmsley Charitable Trust. AbbVie employed three coinvestigators. Two coinvestigators had other ties to Abbvie and Amgen.

SOURCE: Peter I et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0605.

Patients with inflammatory bowel disease had about a 28% higher risk of Parkinson’s disease (PD) than that of matched controls in a large retrospective analysis of administrative health care claims.

But tumor necrosis factor (TNF) inhibitor therapy appeared to attenuate this risk, wrote Inga Peter, PhD, of Icahn School of Medicine at Mount Sinai, New York, and her associates. Patients with inflammatory bowel disease (IBD) who received TNF inhibitors were 78% less likely to develop PD than were those who did not (P = .03). “Reducing systemic inflammation in at-risk individuals may decrease the incidence of PD [Parkinson disease],” the researchers wrote. The study was published online April 23 in JAMA Neurology.

The researchers queried the Truven Health MarketScan database and the Medicare Supplemental Database for patients with IBD from 2000 through 2016. The databases included more than 170 million patients, of whom 144,018 had at least two IBD-related claims, at least 6 months of follow-up, and no baseline PD diagnosis. These patients were matched by age, sex, and treatment year with 720,090 individuals without IBD from the same databases.

A total of 1,796 patients had at least two recorded PD diagnoses and had filled at least one associated prescription, said the researchers. Based on this PD definition, patients with IBD developed PD at a 28% higher rate than that of matched controls (adjusted IRR, 1.28; 95% CI, 1.14 to 1.44; P less than .001).

Among the IBD patients, those receiving anti-TNF therapy developed about 0.08 cases of PD for every 1,000 person-years, versus 0.76 PD cases per 1,000 person-years in the group not receiving anti-TNF therapy. After adjustment for age, sex, and time at risk, anti-TNF therapy was associated with a 78% reduction in the incidence of PD among IBD patients (adjusted incidence rate ratio, 0.22; 95% confidence interval, 0.05-0.88; P = .03).

“In summary, we showed a potential clinical link between IBD and PD, supporting shared mechanisms involved in the pathogenesis of these diseases,” the researchers wrote. “Moreover, our data suggest that early exposure to anti-TNF therapy may reduce the risk of PD among patients with IBD, potentially owing to a reduction in systemic inflammation. These findings should be further assessed and confirmed by other studies.”

Dr. Peter received support from the Leona M. and Harry B. Helmsley Charitable Trust. AbbVie employed three coinvestigators. Two coinvestigators had other ties to Abbvie and Amgen.

SOURCE: Peter I et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0605.

Patients with inflammatory bowel disease had about a 28% higher risk of Parkinson’s disease (PD) than that of matched controls in a large retrospective analysis of administrative health care claims.

But tumor necrosis factor (TNF) inhibitor therapy appeared to attenuate this risk, wrote Inga Peter, PhD, of Icahn School of Medicine at Mount Sinai, New York, and her associates. Patients with inflammatory bowel disease (IBD) who received TNF inhibitors were 78% less likely to develop PD than were those who did not (P = .03). “Reducing systemic inflammation in at-risk individuals may decrease the incidence of PD [Parkinson disease],” the researchers wrote. The study was published online April 23 in JAMA Neurology.

The researchers queried the Truven Health MarketScan database and the Medicare Supplemental Database for patients with IBD from 2000 through 2016. The databases included more than 170 million patients, of whom 144,018 had at least two IBD-related claims, at least 6 months of follow-up, and no baseline PD diagnosis. These patients were matched by age, sex, and treatment year with 720,090 individuals without IBD from the same databases.

A total of 1,796 patients had at least two recorded PD diagnoses and had filled at least one associated prescription, said the researchers. Based on this PD definition, patients with IBD developed PD at a 28% higher rate than that of matched controls (adjusted IRR, 1.28; 95% CI, 1.14 to 1.44; P less than .001).

Among the IBD patients, those receiving anti-TNF therapy developed about 0.08 cases of PD for every 1,000 person-years, versus 0.76 PD cases per 1,000 person-years in the group not receiving anti-TNF therapy. After adjustment for age, sex, and time at risk, anti-TNF therapy was associated with a 78% reduction in the incidence of PD among IBD patients (adjusted incidence rate ratio, 0.22; 95% confidence interval, 0.05-0.88; P = .03).

“In summary, we showed a potential clinical link between IBD and PD, supporting shared mechanisms involved in the pathogenesis of these diseases,” the researchers wrote. “Moreover, our data suggest that early exposure to anti-TNF therapy may reduce the risk of PD among patients with IBD, potentially owing to a reduction in systemic inflammation. These findings should be further assessed and confirmed by other studies.”

Dr. Peter received support from the Leona M. and Harry B. Helmsley Charitable Trust. AbbVie employed three coinvestigators. Two coinvestigators had other ties to Abbvie and Amgen.

SOURCE: Peter I et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0605.

LOS ANGELES – Results from the first-in-human trial of the investigational antisense oligonucleotide therapy IONIS-HTTRx showed strong dose-dependent reductions in the toxic huntingtin protein in Huntington’s disease patients’ cerebrospinal fluid when compared with placebo.

An exploratory analysis also showed signals of clinical improvement among patients receiving the therapy, the study’s lead author, Sarah Tabrizi, MD, PhD, of University College London, reported at the annual meeting of the American Academy of Neurology.

The findings represent a potential breakthrough in the way Huntington’s – and possibly other neurodegenerative diseases – are treated, said Dr. Tabrizi of University College London. The intrathecally-delivered drug binds to mutant huntingtin protein mRNA to reduce the level of the toxic protein being made.

In the phase 1/2a trial, Dr. Tabrizi and her colleagues enrolled 46 patients with early-stage Huntington’s disease and randomized them to four doses of IONIS-HTTRx or placebo. Patients received four monthly injections of the study drug into the cerebrospinal fluid followed by a 4-month untreated follow-up period. IONIS-HTTRx was delivered in five ascending-dose cohorts.

IONIS-HTTRx was safe and well tolerated and all patients completed the study, Dr. Tabrizi reported. “Our results show that we had significant lowering of the toxic mutant huntingtin protein in the spinal fluid of the patients,” she said, noting that patients receiving the highest doses saw 40%-60% lowering of the protein, which preclinical work suggests correlates to reductions of the protein in the brain.

Dr. Tabrizi stressed that the main outcome measures in the study were reduction of the mutant protein in the CSF and safety and tolerance of the study drug. The investigators did not expect to see clinical measures to change in such a short, small study, she said.

“But then when we looked more carefully at the data with exploratory analysis we found a link between lowering of CSF mutant huntingtin and improvement in total motor score, which is a measure of neurological function, and also, improvement in the Symbol Digit Modalities Test.”

The clinical results are exploratory and require confirmation in larger studies, Dr. Tabrizi stressed.

The study was supported by Ionis Pharmaceuticals. Roche will develop the drug in further clinical trials.

SOURCE: Tabrizi S et al. AAN 2018 abstract CT.002.

LOS ANGELES – Results from the first-in-human trial of the investigational antisense oligonucleotide therapy IONIS-HTTRx showed strong dose-dependent reductions in the toxic huntingtin protein in Huntington’s disease patients’ cerebrospinal fluid when compared with placebo.

An exploratory analysis also showed signals of clinical improvement among patients receiving the therapy, the study’s lead author, Sarah Tabrizi, MD, PhD, of University College London, reported at the annual meeting of the American Academy of Neurology.

The findings represent a potential breakthrough in the way Huntington’s – and possibly other neurodegenerative diseases – are treated, said Dr. Tabrizi of University College London. The intrathecally-delivered drug binds to mutant huntingtin protein mRNA to reduce the level of the toxic protein being made.

In the phase 1/2a trial, Dr. Tabrizi and her colleagues enrolled 46 patients with early-stage Huntington’s disease and randomized them to four doses of IONIS-HTTRx or placebo. Patients received four monthly injections of the study drug into the cerebrospinal fluid followed by a 4-month untreated follow-up period. IONIS-HTTRx was delivered in five ascending-dose cohorts.

IONIS-HTTRx was safe and well tolerated and all patients completed the study, Dr. Tabrizi reported. “Our results show that we had significant lowering of the toxic mutant huntingtin protein in the spinal fluid of the patients,” she said, noting that patients receiving the highest doses saw 40%-60% lowering of the protein, which preclinical work suggests correlates to reductions of the protein in the brain.

Dr. Tabrizi stressed that the main outcome measures in the study were reduction of the mutant protein in the CSF and safety and tolerance of the study drug. The investigators did not expect to see clinical measures to change in such a short, small study, she said.

“But then when we looked more carefully at the data with exploratory analysis we found a link between lowering of CSF mutant huntingtin and improvement in total motor score, which is a measure of neurological function, and also, improvement in the Symbol Digit Modalities Test.”

The clinical results are exploratory and require confirmation in larger studies, Dr. Tabrizi stressed.

The study was supported by Ionis Pharmaceuticals. Roche will develop the drug in further clinical trials.

SOURCE: Tabrizi S et al. AAN 2018 abstract CT.002.

LOS ANGELES – Results from the first-in-human trial of the investigational antisense oligonucleotide therapy IONIS-HTTRx showed strong dose-dependent reductions in the toxic huntingtin protein in Huntington’s disease patients’ cerebrospinal fluid when compared with placebo.

An exploratory analysis also showed signals of clinical improvement among patients receiving the therapy, the study’s lead author, Sarah Tabrizi, MD, PhD, of University College London, reported at the annual meeting of the American Academy of Neurology.

The findings represent a potential breakthrough in the way Huntington’s – and possibly other neurodegenerative diseases – are treated, said Dr. Tabrizi of University College London. The intrathecally-delivered drug binds to mutant huntingtin protein mRNA to reduce the level of the toxic protein being made.

In the phase 1/2a trial, Dr. Tabrizi and her colleagues enrolled 46 patients with early-stage Huntington’s disease and randomized them to four doses of IONIS-HTTRx or placebo. Patients received four monthly injections of the study drug into the cerebrospinal fluid followed by a 4-month untreated follow-up period. IONIS-HTTRx was delivered in five ascending-dose cohorts.

IONIS-HTTRx was safe and well tolerated and all patients completed the study, Dr. Tabrizi reported. “Our results show that we had significant lowering of the toxic mutant huntingtin protein in the spinal fluid of the patients,” she said, noting that patients receiving the highest doses saw 40%-60% lowering of the protein, which preclinical work suggests correlates to reductions of the protein in the brain.

Dr. Tabrizi stressed that the main outcome measures in the study were reduction of the mutant protein in the CSF and safety and tolerance of the study drug. The investigators did not expect to see clinical measures to change in such a short, small study, she said.

“But then when we looked more carefully at the data with exploratory analysis we found a link between lowering of CSF mutant huntingtin and improvement in total motor score, which is a measure of neurological function, and also, improvement in the Symbol Digit Modalities Test.”

The clinical results are exploratory and require confirmation in larger studies, Dr. Tabrizi stressed.

The study was supported by Ionis Pharmaceuticals. Roche will develop the drug in further clinical trials.

SOURCE: Tabrizi S et al. AAN 2018 abstract CT.002.

Constantine G. Lyketsos, MD, remembers when the Academy of Psychosomatic Medicine held annual meetings that attracted 200. Now, the subspecialty organization’s meeting attracts about 1,000 people, and is getting a new name to reflect that growth.

“The field has grown substantially, and I think it will grow further with this name change,” said Dr. Lyketsos, who along with James L. Levenson, MD, spearheaded the effort to have the subspecialty recognized almost 20 years ago. “The field is the same. [But the] name change is going to change the way we are perceived by our primary customers – the patients. It will probably be a positive development for our trainees.”

[email protected]

Constantine G. Lyketsos, MD, remembers when the Academy of Psychosomatic Medicine held annual meetings that attracted 200. Now, the subspecialty organization’s meeting attracts about 1,000 people, and is getting a new name to reflect that growth.

“The field has grown substantially, and I think it will grow further with this name change,” said Dr. Lyketsos, who along with James L. Levenson, MD, spearheaded the effort to have the subspecialty recognized almost 20 years ago. “The field is the same. [But the] name change is going to change the way we are perceived by our primary customers – the patients. It will probably be a positive development for our trainees.”

[email protected]

Constantine G. Lyketsos, MD, remembers when the Academy of Psychosomatic Medicine held annual meetings that attracted 200. Now, the subspecialty organization’s meeting attracts about 1,000 people, and is getting a new name to reflect that growth.

“The field has grown substantially, and I think it will grow further with this name change,” said Dr. Lyketsos, who along with James L. Levenson, MD, spearheaded the effort to have the subspecialty recognized almost 20 years ago. “The field is the same. [But the] name change is going to change the way we are perceived by our primary customers – the patients. It will probably be a positive development for our trainees.”

[email protected]