Neurology

PHILADELPHIA – Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS, and not by patients with secondary progressive disease, researchers reported at the annual meeting of the American Academy of Neurology.

The difference may be related to faster atrophy rates among patients with primary progressive MS who received placebo, compared with those with secondary progressive MS who received placebo.

The finding was surprising, said Andrew Goodman, MD, professor of neurology, chief of the neuroimmunology unit, and director of the multiple sclerosis center at the University of Rochester (N.Y.). “Going into the trial, it was my bias and expectation that both primary and secondary progressive MS would behave more similarly than different.”

The trial, SPRINT-MS, included more than 250 patients with progressive MS at 28 sites. Patients were aged 18-65 years and were followed for 96 weeks. Patients had primary progressive MS (n = 134) or secondary progressive MS (n = 121) and were randomized 1:1 to ibudilast or placebo.

Ibudilast is an orally administered small molecule that has been used in Japan for approximately 30 years for asthma and other indications, Dr. Goodman said. Preclinical models suggested that the drug may have neuroprotective effects.

The trial’s primary result – a 48% slowing in the rate of whole brain atrophy as measured by brain parenchymal fraction with ibudilast – was reported last year (N Engl J Med. 2018 Aug 30;379[9]:846-55).

The present study examined whether the treatment effect of ibudilast was similar by progressive disease type using a linear mixed model analytic approach.

The group with primary progressive MS included a smaller percentage of women. Patients with secondary progressive MS had longer disease duration and more brain atrophy at baseline.

“The overall benefit which we previously reported appears to be driven by subjects with primary progressive rather than secondary progressive MS,” Dr. Goodman said. Accounting for baseline covariates did not affect this result.

Among patients who received placebo, brain atrophy in those with secondary progressive MS was 57% slower than in those with primary progressive MS. The rate of atrophy for untreated patients with primary progressive MS “was roughly twice as fast as that in the secondary progressive MS group, which we think may explain in part the differential in efficacy,” Dr. Goodman said. “These findings may impact future trial design for progressive MS.”

The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

jremaly@mdedge.com

SOURCE: Goodman A et al. AAN 2019, Abstract S12.007.

PHILADELPHIA – Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS, and not by patients with secondary progressive disease, researchers reported at the annual meeting of the American Academy of Neurology.

The difference may be related to faster atrophy rates among patients with primary progressive MS who received placebo, compared with those with secondary progressive MS who received placebo.

The finding was surprising, said Andrew Goodman, MD, professor of neurology, chief of the neuroimmunology unit, and director of the multiple sclerosis center at the University of Rochester (N.Y.). “Going into the trial, it was my bias and expectation that both primary and secondary progressive MS would behave more similarly than different.”

The trial, SPRINT-MS, included more than 250 patients with progressive MS at 28 sites. Patients were aged 18-65 years and were followed for 96 weeks. Patients had primary progressive MS (n = 134) or secondary progressive MS (n = 121) and were randomized 1:1 to ibudilast or placebo.

Ibudilast is an orally administered small molecule that has been used in Japan for approximately 30 years for asthma and other indications, Dr. Goodman said. Preclinical models suggested that the drug may have neuroprotective effects.

The trial’s primary result – a 48% slowing in the rate of whole brain atrophy as measured by brain parenchymal fraction with ibudilast – was reported last year (N Engl J Med. 2018 Aug 30;379[9]:846-55).

The present study examined whether the treatment effect of ibudilast was similar by progressive disease type using a linear mixed model analytic approach.

The group with primary progressive MS included a smaller percentage of women. Patients with secondary progressive MS had longer disease duration and more brain atrophy at baseline.

“The overall benefit which we previously reported appears to be driven by subjects with primary progressive rather than secondary progressive MS,” Dr. Goodman said. Accounting for baseline covariates did not affect this result.

Among patients who received placebo, brain atrophy in those with secondary progressive MS was 57% slower than in those with primary progressive MS. The rate of atrophy for untreated patients with primary progressive MS “was roughly twice as fast as that in the secondary progressive MS group, which we think may explain in part the differential in efficacy,” Dr. Goodman said. “These findings may impact future trial design for progressive MS.”

The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

jremaly@mdedge.com

SOURCE: Goodman A et al. AAN 2019, Abstract S12.007.

PHILADELPHIA – Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS, and not by patients with secondary progressive disease, researchers reported at the annual meeting of the American Academy of Neurology.

The difference may be related to faster atrophy rates among patients with primary progressive MS who received placebo, compared with those with secondary progressive MS who received placebo.

The finding was surprising, said Andrew Goodman, MD, professor of neurology, chief of the neuroimmunology unit, and director of the multiple sclerosis center at the University of Rochester (N.Y.). “Going into the trial, it was my bias and expectation that both primary and secondary progressive MS would behave more similarly than different.”

The trial, SPRINT-MS, included more than 250 patients with progressive MS at 28 sites. Patients were aged 18-65 years and were followed for 96 weeks. Patients had primary progressive MS (n = 134) or secondary progressive MS (n = 121) and were randomized 1:1 to ibudilast or placebo.

Ibudilast is an orally administered small molecule that has been used in Japan for approximately 30 years for asthma and other indications, Dr. Goodman said. Preclinical models suggested that the drug may have neuroprotective effects.

The trial’s primary result – a 48% slowing in the rate of whole brain atrophy as measured by brain parenchymal fraction with ibudilast – was reported last year (N Engl J Med. 2018 Aug 30;379[9]:846-55).

The present study examined whether the treatment effect of ibudilast was similar by progressive disease type using a linear mixed model analytic approach.

The group with primary progressive MS included a smaller percentage of women. Patients with secondary progressive MS had longer disease duration and more brain atrophy at baseline.

“The overall benefit which we previously reported appears to be driven by subjects with primary progressive rather than secondary progressive MS,” Dr. Goodman said. Accounting for baseline covariates did not affect this result.

Among patients who received placebo, brain atrophy in those with secondary progressive MS was 57% slower than in those with primary progressive MS. The rate of atrophy for untreated patients with primary progressive MS “was roughly twice as fast as that in the secondary progressive MS group, which we think may explain in part the differential in efficacy,” Dr. Goodman said. “These findings may impact future trial design for progressive MS.”

The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

jremaly@mdedge.com

SOURCE: Goodman A et al. AAN 2019, Abstract S12.007.

PHILADELPHIA – An orally dissolving tablet formulation of rimegepant has significant effects on pain relief and functional ability at 60 minutes post dose, according to phase 3 trial results presented at the annual meeting of the American Academy of Neurology. The treatment’s efficacy is sustained for 2-48 hours, researchers reported.

Rimegepant is a small molecule calcitonin gene–related peptide receptor antagonist. A 75-mg oral tablet formulation was effective in phase 3 trials. The present study evaluated a novel, orally dissolving tablet formulation that is intended to speed the drug’s onset. The tablet’s time to peak concentration is 1.50 hours, compared with 1.99 hours for the oral tablet.

Formulation preferences

“People with migraine prefer orally dissolving tablets to oral tablets, mainly for their convenience, onset of action, and ability to be taken without drinking liquids,” said first author Richard B. Lipton, MD, of Albert Einstein College of Medicine, New York, and colleagues.

To assess the formulation’s efficacy and safety, the investigators conducted a double-blind, randomized, placebo-controlled, multicenter trial. Participants were aged at least 18 years and had migraine for at least 1 year. They had 2-8 moderate or severe migraine attacks and fewer than 15 headache days per month during the 3 months before the trial. Their preventive migraine medication doses, if any, had been stable for at least 3 months.

Coprimary efficacy endpoints were pain freedom 2 hours post dose and freedom from the most bothersome symptom at 2 hours post dose. The efficacy analyses included randomized subjects who had a qualifying migraine attack, took the study medication, and provided at least one postbaseline efficacy data point.

The investigators included 1,351 patients in their efficacy analysis – 669 who received rimegepant and 682 who received placebo. About 85% were female, and patients’ mean age was 40.2 years. They averaged 4.6 migraine attacks per month, and their most bothersome symptoms included photophobia (57%), nausea (23.5%), and phonophobia (19.3%). About 14% used preventive treatment.

Within 45 days of randomization, patients treated a migraine attack of moderate to severe intensity and completed an electronic diary predose to 48 hours post dose.

Less use of rescue medication

At 2 hours post dose, patients who received 75 mg rimegepant were more likely than patients who received placebo to achieve pain freedom (21.2% vs. 10.9%) and freedom from the most bothersome symptom (35.1% vs. 26.8%).

Numerical differences in the likelihood of pain relief between group began 15 minutes post dose, and the difference was statistically significant at 60 minutes (36.8% vs. 31.2%).

Various secondary endpoints, including ability to function normally at 2 hours post dose (38.1% vs. 25.8%), sustained pain relief from 2-48 hours (42.2% vs. 25.2%), and use of rescue medications within 24 hours (14.2% vs. 29.2%), also were statistically significant.

In the safety analysis, the most common adverse events were nausea (1.6% in the rimegepant group and 0.4% in the placebo group) and urinary tract infection (1.5% in the rimegepant group and 0.6% in the placebo group). There were no serious adverse events. “Safety and tolerability were similar to placebo,” Dr. Lipton and colleagues said.

Biohaven Pharmaceuticals, the developer of the drug, sponsored the study. Dr. Lipton has received honoraria and research support from Biohaven and holds stock in the company. Coauthors are employees of Biohaven.

jremaly@mdedge.com

PHILADELPHIA – An orally dissolving tablet formulation of rimegepant has significant effects on pain relief and functional ability at 60 minutes post dose, according to phase 3 trial results presented at the annual meeting of the American Academy of Neurology. The treatment’s efficacy is sustained for 2-48 hours, researchers reported.

Rimegepant is a small molecule calcitonin gene–related peptide receptor antagonist. A 75-mg oral tablet formulation was effective in phase 3 trials. The present study evaluated a novel, orally dissolving tablet formulation that is intended to speed the drug’s onset. The tablet’s time to peak concentration is 1.50 hours, compared with 1.99 hours for the oral tablet.

Formulation preferences

“People with migraine prefer orally dissolving tablets to oral tablets, mainly for their convenience, onset of action, and ability to be taken without drinking liquids,” said first author Richard B. Lipton, MD, of Albert Einstein College of Medicine, New York, and colleagues.

To assess the formulation’s efficacy and safety, the investigators conducted a double-blind, randomized, placebo-controlled, multicenter trial. Participants were aged at least 18 years and had migraine for at least 1 year. They had 2-8 moderate or severe migraine attacks and fewer than 15 headache days per month during the 3 months before the trial. Their preventive migraine medication doses, if any, had been stable for at least 3 months.

Coprimary efficacy endpoints were pain freedom 2 hours post dose and freedom from the most bothersome symptom at 2 hours post dose. The efficacy analyses included randomized subjects who had a qualifying migraine attack, took the study medication, and provided at least one postbaseline efficacy data point.

The investigators included 1,351 patients in their efficacy analysis – 669 who received rimegepant and 682 who received placebo. About 85% were female, and patients’ mean age was 40.2 years. They averaged 4.6 migraine attacks per month, and their most bothersome symptoms included photophobia (57%), nausea (23.5%), and phonophobia (19.3%). About 14% used preventive treatment.

Within 45 days of randomization, patients treated a migraine attack of moderate to severe intensity and completed an electronic diary predose to 48 hours post dose.

Less use of rescue medication

At 2 hours post dose, patients who received 75 mg rimegepant were more likely than patients who received placebo to achieve pain freedom (21.2% vs. 10.9%) and freedom from the most bothersome symptom (35.1% vs. 26.8%).

Numerical differences in the likelihood of pain relief between group began 15 minutes post dose, and the difference was statistically significant at 60 minutes (36.8% vs. 31.2%).

Various secondary endpoints, including ability to function normally at 2 hours post dose (38.1% vs. 25.8%), sustained pain relief from 2-48 hours (42.2% vs. 25.2%), and use of rescue medications within 24 hours (14.2% vs. 29.2%), also were statistically significant.

In the safety analysis, the most common adverse events were nausea (1.6% in the rimegepant group and 0.4% in the placebo group) and urinary tract infection (1.5% in the rimegepant group and 0.6% in the placebo group). There were no serious adverse events. “Safety and tolerability were similar to placebo,” Dr. Lipton and colleagues said.

Biohaven Pharmaceuticals, the developer of the drug, sponsored the study. Dr. Lipton has received honoraria and research support from Biohaven and holds stock in the company. Coauthors are employees of Biohaven.

jremaly@mdedge.com

PHILADELPHIA – An orally dissolving tablet formulation of rimegepant has significant effects on pain relief and functional ability at 60 minutes post dose, according to phase 3 trial results presented at the annual meeting of the American Academy of Neurology. The treatment’s efficacy is sustained for 2-48 hours, researchers reported.

Rimegepant is a small molecule calcitonin gene–related peptide receptor antagonist. A 75-mg oral tablet formulation was effective in phase 3 trials. The present study evaluated a novel, orally dissolving tablet formulation that is intended to speed the drug’s onset. The tablet’s time to peak concentration is 1.50 hours, compared with 1.99 hours for the oral tablet.

Formulation preferences

“People with migraine prefer orally dissolving tablets to oral tablets, mainly for their convenience, onset of action, and ability to be taken without drinking liquids,” said first author Richard B. Lipton, MD, of Albert Einstein College of Medicine, New York, and colleagues.

To assess the formulation’s efficacy and safety, the investigators conducted a double-blind, randomized, placebo-controlled, multicenter trial. Participants were aged at least 18 years and had migraine for at least 1 year. They had 2-8 moderate or severe migraine attacks and fewer than 15 headache days per month during the 3 months before the trial. Their preventive migraine medication doses, if any, had been stable for at least 3 months.

Coprimary efficacy endpoints were pain freedom 2 hours post dose and freedom from the most bothersome symptom at 2 hours post dose. The efficacy analyses included randomized subjects who had a qualifying migraine attack, took the study medication, and provided at least one postbaseline efficacy data point.

The investigators included 1,351 patients in their efficacy analysis – 669 who received rimegepant and 682 who received placebo. About 85% were female, and patients’ mean age was 40.2 years. They averaged 4.6 migraine attacks per month, and their most bothersome symptoms included photophobia (57%), nausea (23.5%), and phonophobia (19.3%). About 14% used preventive treatment.

Within 45 days of randomization, patients treated a migraine attack of moderate to severe intensity and completed an electronic diary predose to 48 hours post dose.

Less use of rescue medication

At 2 hours post dose, patients who received 75 mg rimegepant were more likely than patients who received placebo to achieve pain freedom (21.2% vs. 10.9%) and freedom from the most bothersome symptom (35.1% vs. 26.8%).

Numerical differences in the likelihood of pain relief between group began 15 minutes post dose, and the difference was statistically significant at 60 minutes (36.8% vs. 31.2%).

Various secondary endpoints, including ability to function normally at 2 hours post dose (38.1% vs. 25.8%), sustained pain relief from 2-48 hours (42.2% vs. 25.2%), and use of rescue medications within 24 hours (14.2% vs. 29.2%), also were statistically significant.

In the safety analysis, the most common adverse events were nausea (1.6% in the rimegepant group and 0.4% in the placebo group) and urinary tract infection (1.5% in the rimegepant group and 0.6% in the placebo group). There were no serious adverse events. “Safety and tolerability were similar to placebo,” Dr. Lipton and colleagues said.

Biohaven Pharmaceuticals, the developer of the drug, sponsored the study. Dr. Lipton has received honoraria and research support from Biohaven and holds stock in the company. Coauthors are employees of Biohaven.

jremaly@mdedge.com

Development and use of a specific protocol significantly increased the likelihood of children with elevated blood lead levels receiving standardized care, according to current guidelines, reported Courtney M. Brown, MD, and associates at Cincinnati Children’s Hospital and the University of Cincinnati.

The study protocol, undertaken at Cincinnati Children’s Hospital Medical Center’s pediatric primary care center, consisted of ordering multivitamins with iron and follow-up lead testing, educating families about identifying and reducing sources of lead exposure, and referring to a specialty environmental health clinic when indicated. Quality improvement and a real-time decision support program called Epic SmartPhrase was used to increase provider adherence. Results from patients aged 9-27 months who were seen at the hospital from February 2016 to June 2018 were included, according to the researchers. Their findings were published in Pediatrics.

Over the study period, 634 elevated blood lead levels (BLLs) were recorded. Between February 2016 – when the protocol was distributed – and May 2017 – when Epic SmartPhrase was introduced – a mean of 5% of cases received protocol-based care. After introduction of Epic Smartphase, the rate of adherence to protocol increased to 90%, which was maintained for the rest of the study.

“A reliable system for responding to BLLs is critical for optimizing outcomes for individuals, as well as activating public health systems to reduce environmental lead sources. Using tools within the EHR, we increased provider adherence with published guidelines. Our Epic SmartPhrase could be easily reproduced by other practices using EHRs. Similar strategies could be applied for standardizing the response to other laboratory tests,” the investigators wrote. “This type of intervention could ensure that screenings of all kinds trigger meaningful interventions.”

The study was supported by the Cincinnati Children’s Hospital Medical Center through the All Children Thrive community health initiative; the study authors had no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Brown CM et al. Pediatrics. 2019 May 9. doi: 10.1542/peds.2018-3085.

Development and use of a specific protocol significantly increased the likelihood of children with elevated blood lead levels receiving standardized care, according to current guidelines, reported Courtney M. Brown, MD, and associates at Cincinnati Children’s Hospital and the University of Cincinnati.

The study protocol, undertaken at Cincinnati Children’s Hospital Medical Center’s pediatric primary care center, consisted of ordering multivitamins with iron and follow-up lead testing, educating families about identifying and reducing sources of lead exposure, and referring to a specialty environmental health clinic when indicated. Quality improvement and a real-time decision support program called Epic SmartPhrase was used to increase provider adherence. Results from patients aged 9-27 months who were seen at the hospital from February 2016 to June 2018 were included, according to the researchers. Their findings were published in Pediatrics.

Over the study period, 634 elevated blood lead levels (BLLs) were recorded. Between February 2016 – when the protocol was distributed – and May 2017 – when Epic SmartPhrase was introduced – a mean of 5% of cases received protocol-based care. After introduction of Epic Smartphase, the rate of adherence to protocol increased to 90%, which was maintained for the rest of the study.

“A reliable system for responding to BLLs is critical for optimizing outcomes for individuals, as well as activating public health systems to reduce environmental lead sources. Using tools within the EHR, we increased provider adherence with published guidelines. Our Epic SmartPhrase could be easily reproduced by other practices using EHRs. Similar strategies could be applied for standardizing the response to other laboratory tests,” the investigators wrote. “This type of intervention could ensure that screenings of all kinds trigger meaningful interventions.”

The study was supported by the Cincinnati Children’s Hospital Medical Center through the All Children Thrive community health initiative; the study authors had no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Brown CM et al. Pediatrics. 2019 May 9. doi: 10.1542/peds.2018-3085.

Development and use of a specific protocol significantly increased the likelihood of children with elevated blood lead levels receiving standardized care, according to current guidelines, reported Courtney M. Brown, MD, and associates at Cincinnati Children’s Hospital and the University of Cincinnati.

The study protocol, undertaken at Cincinnati Children’s Hospital Medical Center’s pediatric primary care center, consisted of ordering multivitamins with iron and follow-up lead testing, educating families about identifying and reducing sources of lead exposure, and referring to a specialty environmental health clinic when indicated. Quality improvement and a real-time decision support program called Epic SmartPhrase was used to increase provider adherence. Results from patients aged 9-27 months who were seen at the hospital from February 2016 to June 2018 were included, according to the researchers. Their findings were published in Pediatrics.

Over the study period, 634 elevated blood lead levels (BLLs) were recorded. Between February 2016 – when the protocol was distributed – and May 2017 – when Epic SmartPhrase was introduced – a mean of 5% of cases received protocol-based care. After introduction of Epic Smartphase, the rate of adherence to protocol increased to 90%, which was maintained for the rest of the study.

“A reliable system for responding to BLLs is critical for optimizing outcomes for individuals, as well as activating public health systems to reduce environmental lead sources. Using tools within the EHR, we increased provider adherence with published guidelines. Our Epic SmartPhrase could be easily reproduced by other practices using EHRs. Similar strategies could be applied for standardizing the response to other laboratory tests,” the investigators wrote. “This type of intervention could ensure that screenings of all kinds trigger meaningful interventions.”

The study was supported by the Cincinnati Children’s Hospital Medical Center through the All Children Thrive community health initiative; the study authors had no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Brown CM et al. Pediatrics. 2019 May 9. doi: 10.1542/peds.2018-3085.

PHILADELPHIA – At the annual meeting of the American Academy of Neurology, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, sat down with Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., to discuss in a video some of the new data presented at the meeting regarding the CGRP monoclonal antibodies, the small molecule receptor antagonists (gepants), and what Dr. Tepper described as “a real shift in paradigm and a watershed moment in migraine.”

The three gepants that are farthest along in clinical trials are ubrogepant, rimegepant, and atogepant. “Reassuring data” was presented, Dr. Tepper said, regarding liver toxicity, which has been a concern with earlier generations of the gepants. The Food and Drug Administration had mandated a close look at liver function with the use of these drugs, which are metabolized in the liver, and, to date, no safety signals have emerged.

The three CGRP monoclonal antibodies that are currently on the market are erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality). Data from numerous open-label extension studies were presented. In general, it seems that “the monoclonal antibodies accumulate greater efficacy over time,” Dr. Tepper said. No safety concerns have emerged from 5 years of clinical trial data. With 250,000 patients on these drugs worldwide, that is “very reassuring,” Dr. Tepper said.

New data also show that the majority of patients with chronic migraine who are taking monoclonal antibodies convert from chronic migraine to episodic migraine. Additionally, new data show that use of monoclonal antibodies “dramatically reduce all migraine medication use,” Dr. Tepper said.

gwilliams@mdedge.com

PHILADELPHIA – At the annual meeting of the American Academy of Neurology, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, sat down with Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., to discuss in a video some of the new data presented at the meeting regarding the CGRP monoclonal antibodies, the small molecule receptor antagonists (gepants), and what Dr. Tepper described as “a real shift in paradigm and a watershed moment in migraine.”

The three gepants that are farthest along in clinical trials are ubrogepant, rimegepant, and atogepant. “Reassuring data” was presented, Dr. Tepper said, regarding liver toxicity, which has been a concern with earlier generations of the gepants. The Food and Drug Administration had mandated a close look at liver function with the use of these drugs, which are metabolized in the liver, and, to date, no safety signals have emerged.

The three CGRP monoclonal antibodies that are currently on the market are erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality). Data from numerous open-label extension studies were presented. In general, it seems that “the monoclonal antibodies accumulate greater efficacy over time,” Dr. Tepper said. No safety concerns have emerged from 5 years of clinical trial data. With 250,000 patients on these drugs worldwide, that is “very reassuring,” Dr. Tepper said.

New data also show that the majority of patients with chronic migraine who are taking monoclonal antibodies convert from chronic migraine to episodic migraine. Additionally, new data show that use of monoclonal antibodies “dramatically reduce all migraine medication use,” Dr. Tepper said.

gwilliams@mdedge.com

PHILADELPHIA – At the annual meeting of the American Academy of Neurology, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, sat down with Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., to discuss in a video some of the new data presented at the meeting regarding the CGRP monoclonal antibodies, the small molecule receptor antagonists (gepants), and what Dr. Tepper described as “a real shift in paradigm and a watershed moment in migraine.”

The three gepants that are farthest along in clinical trials are ubrogepant, rimegepant, and atogepant. “Reassuring data” was presented, Dr. Tepper said, regarding liver toxicity, which has been a concern with earlier generations of the gepants. The Food and Drug Administration had mandated a close look at liver function with the use of these drugs, which are metabolized in the liver, and, to date, no safety signals have emerged.

The three CGRP monoclonal antibodies that are currently on the market are erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality). Data from numerous open-label extension studies were presented. In general, it seems that “the monoclonal antibodies accumulate greater efficacy over time,” Dr. Tepper said. No safety concerns have emerged from 5 years of clinical trial data. With 250,000 patients on these drugs worldwide, that is “very reassuring,” Dr. Tepper said.

New data also show that the majority of patients with chronic migraine who are taking monoclonal antibodies convert from chronic migraine to episodic migraine. Additionally, new data show that use of monoclonal antibodies “dramatically reduce all migraine medication use,” Dr. Tepper said.

gwilliams@mdedge.com

Patients who undergo appendectomy face an increased risk of Parkinson’s disease, especially those aged 18-64 years, results from a large population-based study demonstrated.

“One of the factors that’s seen in the brains of patients with Parkinson’s disease is accumulation of an abnormal protein known as alpha-synuclein,” one of the study authors, Gregory S. Cooper, MD, said during a media briefing in advance of the annual Digestive Disease Week. “It’s released by damaged nerve cells in the brain. Not only is alpha-synuclein found in the brain of patients with Parkinson’s disease; it’s also found in the GI tract. It’s thought that its accumulation in the GI tract occurs prior to the development of its accumulation in the brain.”

This has prompted scientists around the world to evaluate the GI tract, including the appendix, for evidence about the pathophysiology and onset of Parkinson’s disease, said Dr. Cooper, professor of medicine, oncology, and population and quantitative health sciences at Case Western Reserve University, Cleveland. “It’s thought that, potentially, in the presence of inflammation, [molecules] of this protein are released from damaged nerves in the gut and then are transported to the brain, where they accumulate,” he said. “Or, it could be that the appendix is a storage place for this protein and gets released at the time of appendectomy.”

To investigate if appendectomy increases the risk of Parkinson’s disease, Dr. Cooper and colleagues drew from the Explorys database, which contains EHRs from 26 integrated U.S. health care systems. They limited their search to patients who underwent appendectomies and those who were diagnosed with Parkinson’s disease based on Systematized Nomenclature of Medicine–Clinical Terms. The researchers chose a washout period of 6 months to the development of Parkinson’s disease after appendectomy, and compared the prevalence of Parkinson’s disease in the general population to those with appendectomies.

Of the 62,218,050 records in the database, Dr. Cooper and colleagues identified 488,190 patients who underwent appendectomies. In all, 4,470 cases of Parkinson’s disease were observed in patients with appendectomies, and 177,230 cases of Parkinson’s disease in patients without appendectomies. The overall relative risk of developing Parkinson’s disease in patients after appendectomies was 3.19 (95% confidence interval, 3.10-3.28; P less than .0001), compared with those who did not undergo the procedure. The relative risk was higher in patients aged 18-64 years (RR, 4.27; 95% CI, 3.99-4.57; P less than .0001), compared with those 65 years and older (RR, 2.20; 95% CI, 2.13-2.27; P less than .0001). “We know that Parkinson’s disease is more common in the elderly,” Dr. Cooper said. “But at virtually all ages, the prevalence of Parkinson’s disease was higher in patients who had an appendectomy, compared to those without an appendectomy.”

The overall relative risk of developing Parkinson’s disease in patients after appendectomies was slightly higher in females (RR, 3.86; 95% CI, 3.71-4.02; P less than .0001), compared with males (RR, 2.67; 95% CI, 2.56-2.79; P less than .0001). The researchers also observed a similar effect of appendectomy by race. The overall relative risk of developing Parkinson’s disease in patients after appendectomy was slightly higher in African Americans (RR, 3.11; 95% CI, 2.69-3.58; P less than .0001), compared with Asians (RR, 2.73; 95% CI, 2.19-3.41; P less than .0001), and whites (RR, 2.55; 95% CI, 2.48-2.63; P less than .0001).

“If these data get borne out, it may question the role of doing a discretionary appendectomy in a patient who’s having surgery for another reason,” Dr. Cooper said. “Our research does show a clear relationship between appendectomy and Parkinson’s disease. However, at this point, it’s only an association. As a next step, we’d like to conduct additional research to confirm this connection and better understand the mechanisms involved.”

He pointed out that, because of the nature of the Explorys database, he and his colleagues were unable to determine the length of time following appendectomy to the development of Parkinson’s disease.

The study’s lead author was Mohammed Z. Sheriff, MD, also of Case Western Reserve University, Cleveland. The researchers reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Sheriff MZ et al. DDW 2019, Abstract 739.

Patients who undergo appendectomy face an increased risk of Parkinson’s disease, especially those aged 18-64 years, results from a large population-based study demonstrated.

“One of the factors that’s seen in the brains of patients with Parkinson’s disease is accumulation of an abnormal protein known as alpha-synuclein,” one of the study authors, Gregory S. Cooper, MD, said during a media briefing in advance of the annual Digestive Disease Week. “It’s released by damaged nerve cells in the brain. Not only is alpha-synuclein found in the brain of patients with Parkinson’s disease; it’s also found in the GI tract. It’s thought that its accumulation in the GI tract occurs prior to the development of its accumulation in the brain.”

This has prompted scientists around the world to evaluate the GI tract, including the appendix, for evidence about the pathophysiology and onset of Parkinson’s disease, said Dr. Cooper, professor of medicine, oncology, and population and quantitative health sciences at Case Western Reserve University, Cleveland. “It’s thought that, potentially, in the presence of inflammation, [molecules] of this protein are released from damaged nerves in the gut and then are transported to the brain, where they accumulate,” he said. “Or, it could be that the appendix is a storage place for this protein and gets released at the time of appendectomy.”

To investigate if appendectomy increases the risk of Parkinson’s disease, Dr. Cooper and colleagues drew from the Explorys database, which contains EHRs from 26 integrated U.S. health care systems. They limited their search to patients who underwent appendectomies and those who were diagnosed with Parkinson’s disease based on Systematized Nomenclature of Medicine–Clinical Terms. The researchers chose a washout period of 6 months to the development of Parkinson’s disease after appendectomy, and compared the prevalence of Parkinson’s disease in the general population to those with appendectomies.

Of the 62,218,050 records in the database, Dr. Cooper and colleagues identified 488,190 patients who underwent appendectomies. In all, 4,470 cases of Parkinson’s disease were observed in patients with appendectomies, and 177,230 cases of Parkinson’s disease in patients without appendectomies. The overall relative risk of developing Parkinson’s disease in patients after appendectomies was 3.19 (95% confidence interval, 3.10-3.28; P less than .0001), compared with those who did not undergo the procedure. The relative risk was higher in patients aged 18-64 years (RR, 4.27; 95% CI, 3.99-4.57; P less than .0001), compared with those 65 years and older (RR, 2.20; 95% CI, 2.13-2.27; P less than .0001). “We know that Parkinson’s disease is more common in the elderly,” Dr. Cooper said. “But at virtually all ages, the prevalence of Parkinson’s disease was higher in patients who had an appendectomy, compared to those without an appendectomy.”

The overall relative risk of developing Parkinson’s disease in patients after appendectomies was slightly higher in females (RR, 3.86; 95% CI, 3.71-4.02; P less than .0001), compared with males (RR, 2.67; 95% CI, 2.56-2.79; P less than .0001). The researchers also observed a similar effect of appendectomy by race. The overall relative risk of developing Parkinson’s disease in patients after appendectomy was slightly higher in African Americans (RR, 3.11; 95% CI, 2.69-3.58; P less than .0001), compared with Asians (RR, 2.73; 95% CI, 2.19-3.41; P less than .0001), and whites (RR, 2.55; 95% CI, 2.48-2.63; P less than .0001).

“If these data get borne out, it may question the role of doing a discretionary appendectomy in a patient who’s having surgery for another reason,” Dr. Cooper said. “Our research does show a clear relationship between appendectomy and Parkinson’s disease. However, at this point, it’s only an association. As a next step, we’d like to conduct additional research to confirm this connection and better understand the mechanisms involved.”

He pointed out that, because of the nature of the Explorys database, he and his colleagues were unable to determine the length of time following appendectomy to the development of Parkinson’s disease.

The study’s lead author was Mohammed Z. Sheriff, MD, also of Case Western Reserve University, Cleveland. The researchers reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Sheriff MZ et al. DDW 2019, Abstract 739.

Patients who undergo appendectomy face an increased risk of Parkinson’s disease, especially those aged 18-64 years, results from a large population-based study demonstrated.

“One of the factors that’s seen in the brains of patients with Parkinson’s disease is accumulation of an abnormal protein known as alpha-synuclein,” one of the study authors, Gregory S. Cooper, MD, said during a media briefing in advance of the annual Digestive Disease Week. “It’s released by damaged nerve cells in the brain. Not only is alpha-synuclein found in the brain of patients with Parkinson’s disease; it’s also found in the GI tract. It’s thought that its accumulation in the GI tract occurs prior to the development of its accumulation in the brain.”

This has prompted scientists around the world to evaluate the GI tract, including the appendix, for evidence about the pathophysiology and onset of Parkinson’s disease, said Dr. Cooper, professor of medicine, oncology, and population and quantitative health sciences at Case Western Reserve University, Cleveland. “It’s thought that, potentially, in the presence of inflammation, [molecules] of this protein are released from damaged nerves in the gut and then are transported to the brain, where they accumulate,” he said. “Or, it could be that the appendix is a storage place for this protein and gets released at the time of appendectomy.”

To investigate if appendectomy increases the risk of Parkinson’s disease, Dr. Cooper and colleagues drew from the Explorys database, which contains EHRs from 26 integrated U.S. health care systems. They limited their search to patients who underwent appendectomies and those who were diagnosed with Parkinson’s disease based on Systematized Nomenclature of Medicine–Clinical Terms. The researchers chose a washout period of 6 months to the development of Parkinson’s disease after appendectomy, and compared the prevalence of Parkinson’s disease in the general population to those with appendectomies.

Of the 62,218,050 records in the database, Dr. Cooper and colleagues identified 488,190 patients who underwent appendectomies. In all, 4,470 cases of Parkinson’s disease were observed in patients with appendectomies, and 177,230 cases of Parkinson’s disease in patients without appendectomies. The overall relative risk of developing Parkinson’s disease in patients after appendectomies was 3.19 (95% confidence interval, 3.10-3.28; P less than .0001), compared with those who did not undergo the procedure. The relative risk was higher in patients aged 18-64 years (RR, 4.27; 95% CI, 3.99-4.57; P less than .0001), compared with those 65 years and older (RR, 2.20; 95% CI, 2.13-2.27; P less than .0001). “We know that Parkinson’s disease is more common in the elderly,” Dr. Cooper said. “But at virtually all ages, the prevalence of Parkinson’s disease was higher in patients who had an appendectomy, compared to those without an appendectomy.”

The overall relative risk of developing Parkinson’s disease in patients after appendectomies was slightly higher in females (RR, 3.86; 95% CI, 3.71-4.02; P less than .0001), compared with males (RR, 2.67; 95% CI, 2.56-2.79; P less than .0001). The researchers also observed a similar effect of appendectomy by race. The overall relative risk of developing Parkinson’s disease in patients after appendectomy was slightly higher in African Americans (RR, 3.11; 95% CI, 2.69-3.58; P less than .0001), compared with Asians (RR, 2.73; 95% CI, 2.19-3.41; P less than .0001), and whites (RR, 2.55; 95% CI, 2.48-2.63; P less than .0001).

“If these data get borne out, it may question the role of doing a discretionary appendectomy in a patient who’s having surgery for another reason,” Dr. Cooper said. “Our research does show a clear relationship between appendectomy and Parkinson’s disease. However, at this point, it’s only an association. As a next step, we’d like to conduct additional research to confirm this connection and better understand the mechanisms involved.”

He pointed out that, because of the nature of the Explorys database, he and his colleagues were unable to determine the length of time following appendectomy to the development of Parkinson’s disease.

The study’s lead author was Mohammed Z. Sheriff, MD, also of Case Western Reserve University, Cleveland. The researchers reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Sheriff MZ et al. DDW 2019, Abstract 739.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

egreb@mdedge.com

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

egreb@mdedge.com

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

egreb@mdedge.com

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

The Food and Drug Administration will now require that certain medications prescribed for insomnia carry a boxed warning because of associated complex sleep behaviors.

cpalmer@mdedge.com

The Food and Drug Administration will now require that certain medications prescribed for insomnia carry a boxed warning because of associated complex sleep behaviors.

cpalmer@mdedge.com

The Food and Drug Administration will now require that certain medications prescribed for insomnia carry a boxed warning because of associated complex sleep behaviors.

cpalmer@mdedge.com

Buprenorphine for opioid use disorder is much less likely to be prescribed to patients who are black or who do not have health insurance, an analysis of two national surveys shows.

Researchers analyzed data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2004 to 2015, including 13.4 million visits in which buprenorphine was prescribed. The analysis was published as a research letter in JAMA Psychiatry.

From 2012 to 2015, the number of ambulatory visits involving buprenorphine rose from 0.04% to 0.36%. Black patients were 77% less likely to receive a prescription for buprenorphine at their visit – even after adjustment for payment method, sex, and age – while the number of prescription received by white patients was considerably higher than for patients of any other ethnicity, wrote Pooja A. Lagisetty, MD, and coauthors.

Men were also more than twice as likely to be prescribed buprenorphine than were women, and the age group with the highest incidence of buprenorphine prescriptions was 30-50 years.

Self-pay and private health insurance were the most common payment methods, but the number of self-paying patients receiving buprenorphine prescriptions dramatically increased from 585,568 in 2004-2007 to 5.3 million in 2012-2015.

“This finding in nationally representative data builds on a previous study that reported buprenorphine treatment disparities on the basis of race/ethnicity and income in New York City,” said Dr. Lagisetty of the department of medicine at the University of Michigan, Ann Arbor, and coauthors.

However, they acknowledged that it was unclear whether the treatment disparity might in fact reflect a difference in the prevalence of opioid use disorder across ethnicities.

Commenting on the differences in payment methods, the authors noted that, despite the enactment of mental health parity legislation and the expansion of Medicaid, the proportion of self-pay visits remained relatively unchanged across the study period.

“A recent study demonstrated that half of the physicians prescribing buprenorphine in Ohio accepted cash alone, and our findings suggest that this practice may be widespread and may be associated with additional financial barriers for low-income populations,” the researchers wrote. “With rising rates of opioid overdoses, it is imperative that policy and research efforts specifically address racial/ethnic and economic differences in treatment access and engagement.”

No conflicts of interest were declared.

SOURCE: Lagisetty P et al. JAMA Psychiatry. 2019 May 8. doi: 10.1001/jamapsychiatry.2019.0876.

Buprenorphine for opioid use disorder is much less likely to be prescribed to patients who are black or who do not have health insurance, an analysis of two national surveys shows.

Researchers analyzed data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2004 to 2015, including 13.4 million visits in which buprenorphine was prescribed. The analysis was published as a research letter in JAMA Psychiatry.

From 2012 to 2015, the number of ambulatory visits involving buprenorphine rose from 0.04% to 0.36%. Black patients were 77% less likely to receive a prescription for buprenorphine at their visit – even after adjustment for payment method, sex, and age – while the number of prescription received by white patients was considerably higher than for patients of any other ethnicity, wrote Pooja A. Lagisetty, MD, and coauthors.

Men were also more than twice as likely to be prescribed buprenorphine than were women, and the age group with the highest incidence of buprenorphine prescriptions was 30-50 years.

Self-pay and private health insurance were the most common payment methods, but the number of self-paying patients receiving buprenorphine prescriptions dramatically increased from 585,568 in 2004-2007 to 5.3 million in 2012-2015.

“This finding in nationally representative data builds on a previous study that reported buprenorphine treatment disparities on the basis of race/ethnicity and income in New York City,” said Dr. Lagisetty of the department of medicine at the University of Michigan, Ann Arbor, and coauthors.

However, they acknowledged that it was unclear whether the treatment disparity might in fact reflect a difference in the prevalence of opioid use disorder across ethnicities.

Commenting on the differences in payment methods, the authors noted that, despite the enactment of mental health parity legislation and the expansion of Medicaid, the proportion of self-pay visits remained relatively unchanged across the study period.

“A recent study demonstrated that half of the physicians prescribing buprenorphine in Ohio accepted cash alone, and our findings suggest that this practice may be widespread and may be associated with additional financial barriers for low-income populations,” the researchers wrote. “With rising rates of opioid overdoses, it is imperative that policy and research efforts specifically address racial/ethnic and economic differences in treatment access and engagement.”

No conflicts of interest were declared.

SOURCE: Lagisetty P et al. JAMA Psychiatry. 2019 May 8. doi: 10.1001/jamapsychiatry.2019.0876.

Buprenorphine for opioid use disorder is much less likely to be prescribed to patients who are black or who do not have health insurance, an analysis of two national surveys shows.

Researchers analyzed data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2004 to 2015, including 13.4 million visits in which buprenorphine was prescribed. The analysis was published as a research letter in JAMA Psychiatry.

From 2012 to 2015, the number of ambulatory visits involving buprenorphine rose from 0.04% to 0.36%. Black patients were 77% less likely to receive a prescription for buprenorphine at their visit – even after adjustment for payment method, sex, and age – while the number of prescription received by white patients was considerably higher than for patients of any other ethnicity, wrote Pooja A. Lagisetty, MD, and coauthors.

Men were also more than twice as likely to be prescribed buprenorphine than were women, and the age group with the highest incidence of buprenorphine prescriptions was 30-50 years.

Self-pay and private health insurance were the most common payment methods, but the number of self-paying patients receiving buprenorphine prescriptions dramatically increased from 585,568 in 2004-2007 to 5.3 million in 2012-2015.

“This finding in nationally representative data builds on a previous study that reported buprenorphine treatment disparities on the basis of race/ethnicity and income in New York City,” said Dr. Lagisetty of the department of medicine at the University of Michigan, Ann Arbor, and coauthors.

However, they acknowledged that it was unclear whether the treatment disparity might in fact reflect a difference in the prevalence of opioid use disorder across ethnicities.

Commenting on the differences in payment methods, the authors noted that, despite the enactment of mental health parity legislation and the expansion of Medicaid, the proportion of self-pay visits remained relatively unchanged across the study period.

“A recent study demonstrated that half of the physicians prescribing buprenorphine in Ohio accepted cash alone, and our findings suggest that this practice may be widespread and may be associated with additional financial barriers for low-income populations,” the researchers wrote. “With rising rates of opioid overdoses, it is imperative that policy and research efforts specifically address racial/ethnic and economic differences in treatment access and engagement.”

No conflicts of interest were declared.

SOURCE: Lagisetty P et al. JAMA Psychiatry. 2019 May 8. doi: 10.1001/jamapsychiatry.2019.0876.

Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is the first for a LEMS treatment specifically for pediatric patients.

“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.

Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.

A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.

The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.

The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.

mdales@mdedge.com

Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is the first for a LEMS treatment specifically for pediatric patients.

“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.

Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.

A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.

The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.

The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.

mdales@mdedge.com

Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is the first for a LEMS treatment specifically for pediatric patients.

“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.

Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.

A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.

The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.

The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.

mdales@mdedge.com