DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

[email protected]

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

[email protected]

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

[email protected]

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – In 2 years of follow-up, about 43% of U.S. patients diagnosed with multiple sclerosis (MS) had not received disease-modifying drug (DMD) therapy, a rate that is consistent with other published studies.

The finding comes from a retrospective analysis of claims data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This rate of DMD treatment merits further exploration given that evidence suggests the importance of early DMD treatment initiation in patients with a confirmed diagnosis of relapsing forms of MS to help optimize the benefits of treatment,” Amy L. Phillips, PharmD, a study author, said in an interview in advance of the meeting.

Little is known about current DMD treatment patterns in U.S. patients with multiple sclerosis following an increase in the number of available DMDs in recent years, according to Dr. Phillips of the department of health economics and outcomes research at EMD Serono.

“Most previous studies have focused on self-injectable DMDs or self-injectable and infusion DMDs,” she said. “Information about the treatment patterns including oral DMDs is scarce, particularly in large population samples. The objective of our study was to describe treatment patterns and sequences of therapy among U.S. patients with MS newly initiating DMD treatment between Jan. 1, 2011 and June 30, 2015.”

Dr. Phillips, lead study author Jacqueline A. Nicholas, MD, MPH, of the OhioHealth Multiple Sclerosis Center, and their colleagues used data from the IQVIA RWD Adjudicated Claims database to identify patients who had at least two medical claims with a MS diagnosis and at least one DMD claim during the study period. Other eligibility criteria included continuous eligibility with commercial insurance 1 year before (baseline period) and 2 years after (follow-up period) initiation of the DMD, no evidence of DMD use during the baseline period, and being aged between 18 and 63 years.

Of 63,946 diagnostically eligible patients, 36,175 (57%) had a claim for a DMD. The researchers reported findings from 8,251 patients who met all of the eligibility criteria. Their mean age was 43 years, 76% were female, and the mean number of DMDs over 2 years among newly treated patients was 1.27.

The most common first-line DMD therapy was glatiramer acetate (GA, 38%), followed by intramuscular interferon beta (IM IFNb-1a, 14%), subcutaneous interferon beta (SC IFNb-1a, 14%), dimethyl fumarate (DMF, 14%), and fingolimod (9%). DMF was the most common second-line therapy (36%), followed by fingolimod (17%), GA (17%), SC IFNb-1a (8%), and IM IFNb-1a (7%).

“Numerous DMD treatment patterns observed in this study highlight the diverse patient and treatment needs,” Dr. Phillips said. “DMD treatment patterns in MS vary due to the heterogeneity of the disease, physician preferences, and patient needs and treatment goals. Patient-centered care and shared decision making has been shown to improve patient satisfaction and to encourage treatment adherence in MS.”

She acknowledged certain limitations of the study, including the fact that the analysis presents only the most common DMD treatment sequences observed in this patient population.

“Future analyses might examine less common DMD treatment sequences,” she said. “Also, more research is needed to understand how DMD treatment patterns and sequences change over time, and the factors that may be associated with DMD switching and treatment discontinuation.”

She also noted that the administrative claims data studied represent mostly patients with commercial health insurance, limiting the generalizability of the findings. Further, ICD-9 and ICD-10 codes do not distinguish between MS types.

Funding for the study was provided by EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the United States and Canada. Dr. Phillips is an employee of the company.

[email protected]

SOURCE: Phillips A et al. ACTRIMS FORUM 2019, Abstract 001.

DALLAS – In 2 years of follow-up, about 43% of U.S. patients diagnosed with multiple sclerosis (MS) had not received disease-modifying drug (DMD) therapy, a rate that is consistent with other published studies.

The finding comes from a retrospective analysis of claims data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This rate of DMD treatment merits further exploration given that evidence suggests the importance of early DMD treatment initiation in patients with a confirmed diagnosis of relapsing forms of MS to help optimize the benefits of treatment,” Amy L. Phillips, PharmD, a study author, said in an interview in advance of the meeting.

Little is known about current DMD treatment patterns in U.S. patients with multiple sclerosis following an increase in the number of available DMDs in recent years, according to Dr. Phillips of the department of health economics and outcomes research at EMD Serono.

“Most previous studies have focused on self-injectable DMDs or self-injectable and infusion DMDs,” she said. “Information about the treatment patterns including oral DMDs is scarce, particularly in large population samples. The objective of our study was to describe treatment patterns and sequences of therapy among U.S. patients with MS newly initiating DMD treatment between Jan. 1, 2011 and June 30, 2015.”

Dr. Phillips, lead study author Jacqueline A. Nicholas, MD, MPH, of the OhioHealth Multiple Sclerosis Center, and their colleagues used data from the IQVIA RWD Adjudicated Claims database to identify patients who had at least two medical claims with a MS diagnosis and at least one DMD claim during the study period. Other eligibility criteria included continuous eligibility with commercial insurance 1 year before (baseline period) and 2 years after (follow-up period) initiation of the DMD, no evidence of DMD use during the baseline period, and being aged between 18 and 63 years.

Of 63,946 diagnostically eligible patients, 36,175 (57%) had a claim for a DMD. The researchers reported findings from 8,251 patients who met all of the eligibility criteria. Their mean age was 43 years, 76% were female, and the mean number of DMDs over 2 years among newly treated patients was 1.27.

The most common first-line DMD therapy was glatiramer acetate (GA, 38%), followed by intramuscular interferon beta (IM IFNb-1a, 14%), subcutaneous interferon beta (SC IFNb-1a, 14%), dimethyl fumarate (DMF, 14%), and fingolimod (9%). DMF was the most common second-line therapy (36%), followed by fingolimod (17%), GA (17%), SC IFNb-1a (8%), and IM IFNb-1a (7%).

“Numerous DMD treatment patterns observed in this study highlight the diverse patient and treatment needs,” Dr. Phillips said. “DMD treatment patterns in MS vary due to the heterogeneity of the disease, physician preferences, and patient needs and treatment goals. Patient-centered care and shared decision making has been shown to improve patient satisfaction and to encourage treatment adherence in MS.”

She acknowledged certain limitations of the study, including the fact that the analysis presents only the most common DMD treatment sequences observed in this patient population.

“Future analyses might examine less common DMD treatment sequences,” she said. “Also, more research is needed to understand how DMD treatment patterns and sequences change over time, and the factors that may be associated with DMD switching and treatment discontinuation.”

She also noted that the administrative claims data studied represent mostly patients with commercial health insurance, limiting the generalizability of the findings. Further, ICD-9 and ICD-10 codes do not distinguish between MS types.

Funding for the study was provided by EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the United States and Canada. Dr. Phillips is an employee of the company.

[email protected]

SOURCE: Phillips A et al. ACTRIMS FORUM 2019, Abstract 001.

DALLAS – In 2 years of follow-up, about 43% of U.S. patients diagnosed with multiple sclerosis (MS) had not received disease-modifying drug (DMD) therapy, a rate that is consistent with other published studies.

The finding comes from a retrospective analysis of claims data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This rate of DMD treatment merits further exploration given that evidence suggests the importance of early DMD treatment initiation in patients with a confirmed diagnosis of relapsing forms of MS to help optimize the benefits of treatment,” Amy L. Phillips, PharmD, a study author, said in an interview in advance of the meeting.

Little is known about current DMD treatment patterns in U.S. patients with multiple sclerosis following an increase in the number of available DMDs in recent years, according to Dr. Phillips of the department of health economics and outcomes research at EMD Serono.

“Most previous studies have focused on self-injectable DMDs or self-injectable and infusion DMDs,” she said. “Information about the treatment patterns including oral DMDs is scarce, particularly in large population samples. The objective of our study was to describe treatment patterns and sequences of therapy among U.S. patients with MS newly initiating DMD treatment between Jan. 1, 2011 and June 30, 2015.”

Dr. Phillips, lead study author Jacqueline A. Nicholas, MD, MPH, of the OhioHealth Multiple Sclerosis Center, and their colleagues used data from the IQVIA RWD Adjudicated Claims database to identify patients who had at least two medical claims with a MS diagnosis and at least one DMD claim during the study period. Other eligibility criteria included continuous eligibility with commercial insurance 1 year before (baseline period) and 2 years after (follow-up period) initiation of the DMD, no evidence of DMD use during the baseline period, and being aged between 18 and 63 years.

Of 63,946 diagnostically eligible patients, 36,175 (57%) had a claim for a DMD. The researchers reported findings from 8,251 patients who met all of the eligibility criteria. Their mean age was 43 years, 76% were female, and the mean number of DMDs over 2 years among newly treated patients was 1.27.

The most common first-line DMD therapy was glatiramer acetate (GA, 38%), followed by intramuscular interferon beta (IM IFNb-1a, 14%), subcutaneous interferon beta (SC IFNb-1a, 14%), dimethyl fumarate (DMF, 14%), and fingolimod (9%). DMF was the most common second-line therapy (36%), followed by fingolimod (17%), GA (17%), SC IFNb-1a (8%), and IM IFNb-1a (7%).

“Numerous DMD treatment patterns observed in this study highlight the diverse patient and treatment needs,” Dr. Phillips said. “DMD treatment patterns in MS vary due to the heterogeneity of the disease, physician preferences, and patient needs and treatment goals. Patient-centered care and shared decision making has been shown to improve patient satisfaction and to encourage treatment adherence in MS.”

She acknowledged certain limitations of the study, including the fact that the analysis presents only the most common DMD treatment sequences observed in this patient population.

“Future analyses might examine less common DMD treatment sequences,” she said. “Also, more research is needed to understand how DMD treatment patterns and sequences change over time, and the factors that may be associated with DMD switching and treatment discontinuation.”

She also noted that the administrative claims data studied represent mostly patients with commercial health insurance, limiting the generalizability of the findings. Further, ICD-9 and ICD-10 codes do not distinguish between MS types.

Funding for the study was provided by EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the United States and Canada. Dr. Phillips is an employee of the company.

[email protected]

SOURCE: Phillips A et al. ACTRIMS FORUM 2019, Abstract 001.

The 2018-2019 flu season may have peaked as the major nationwide measure of influenza activity held steady for the week ending Feb. 23, according to the Centers for Disease Control and Prevention. The proportion of outpatient visits for influenza-like illness (ILI) was 5.0% for the most recent reporting week, the CDC’s influenza division said in its March 1 report. The previous week’s outpatient visit rate, originally reported as 5.1%, was revised this week to 5.0% as well, suggesting that flu activity is no longer increasing.

Activity at the state level was more mixed. The number of states at level 10 on the CDC’s 1-10 scale of ILI activity stayed at 24 as Indiana and North Dakota replaced Tennessee and Wyoming, but the number of states in the high range (8-10) of the activity scale increased from 30 to 33, CDC data show.

The signs of plateauing ILI activity did not, however, extend to flu-related deaths, with 15 reported among children – the highest weekly number for the 2018-2019 season, although 11 actually occurred in previous weeks – during the week ending Feb. 23 and 289 deaths among all ages for the week ending Feb. 16, which is already more than the 268 listed the week before despite less complete reporting (82% vs. 97%), the CDC reported. Total flu-related deaths in children are now up to 56, compared with 138 at the corresponding point in the 2017-2018 season.

[email protected]

The 2018-2019 flu season may have peaked as the major nationwide measure of influenza activity held steady for the week ending Feb. 23, according to the Centers for Disease Control and Prevention. The proportion of outpatient visits for influenza-like illness (ILI) was 5.0% for the most recent reporting week, the CDC’s influenza division said in its March 1 report. The previous week’s outpatient visit rate, originally reported as 5.1%, was revised this week to 5.0% as well, suggesting that flu activity is no longer increasing.

Activity at the state level was more mixed. The number of states at level 10 on the CDC’s 1-10 scale of ILI activity stayed at 24 as Indiana and North Dakota replaced Tennessee and Wyoming, but the number of states in the high range (8-10) of the activity scale increased from 30 to 33, CDC data show.

The signs of plateauing ILI activity did not, however, extend to flu-related deaths, with 15 reported among children – the highest weekly number for the 2018-2019 season, although 11 actually occurred in previous weeks – during the week ending Feb. 23 and 289 deaths among all ages for the week ending Feb. 16, which is already more than the 268 listed the week before despite less complete reporting (82% vs. 97%), the CDC reported. Total flu-related deaths in children are now up to 56, compared with 138 at the corresponding point in the 2017-2018 season.

[email protected]

The 2018-2019 flu season may have peaked as the major nationwide measure of influenza activity held steady for the week ending Feb. 23, according to the Centers for Disease Control and Prevention. The proportion of outpatient visits for influenza-like illness (ILI) was 5.0% for the most recent reporting week, the CDC’s influenza division said in its March 1 report. The previous week’s outpatient visit rate, originally reported as 5.1%, was revised this week to 5.0% as well, suggesting that flu activity is no longer increasing.

Activity at the state level was more mixed. The number of states at level 10 on the CDC’s 1-10 scale of ILI activity stayed at 24 as Indiana and North Dakota replaced Tennessee and Wyoming, but the number of states in the high range (8-10) of the activity scale increased from 30 to 33, CDC data show.

The signs of plateauing ILI activity did not, however, extend to flu-related deaths, with 15 reported among children – the highest weekly number for the 2018-2019 season, although 11 actually occurred in previous weeks – during the week ending Feb. 23 and 289 deaths among all ages for the week ending Feb. 16, which is already more than the 268 listed the week before despite less complete reporting (82% vs. 97%), the CDC reported. Total flu-related deaths in children are now up to 56, compared with 138 at the corresponding point in the 2017-2018 season.

[email protected]

Among the trajectories of clinical predictors of suicide attempt, depression symptoms were the only ones linked with an increased risk of suicide attempt in young adults whose parents have mood disorders, according to a longitudinal study.

Psychiatric diagnoses are well established as predictors of suicidal behavior; however, symptoms and risk can vary over the course of illness, and it is important to identify symptoms that can change over time, wrote Nadine M. Melhem, PhD, associate professor of psychiatry at the University of Pittsburgh, and her associates. The report is in JAMA Psychiatry.

Between July 15, 1997, and Sept. 6, 2005, 663 adolescents and young adults (mean age, 23.8 years) whose parents have mood disorders were recruited and followed until Jan. 21, 2014. All participants were assessed at baseline and every year for up to 12 years (median follow-up, 8.1 years) for lifetime and current psychiatric disorders as well as suicidal ideation. In addition, participants were assessed at baseline and at each follow-up for the trajectory of depression symptoms, hopelessness, impulsivity, aggression, impulsive aggression, and irritability.

After the study period, participants were analyzed for all trajectories and separated into classes based on mean scores and variability. All trajectories except for depression had two classes, in which participants in class 2 had higher mean scores and variability; for depression, patients were separated into three classes, in which class 3 had the highest mean score and variability.

Over the study period, 71 of the 663 patients attempted suicide (10.7%), with 51 patients attempting suicide for the first time. The mean number of attempts was 1.2, and the median time from the last assessment to the attempt was 45 weeks.

Participants who attempted suicide were more likely to have class 3 depression symptoms (22.9% with vs. 27 without), class 2 impulsivity (38.8% vs. 21.7%), class 2 aggression (29.0% vs. 15.6%), class 2 impulsive aggression (76.5% vs. 52.2%), and class 2 irritability (39.4% vs. 22.7%). However, after adjustment for demographics, parental suicide attempts, and additional clinical characteristics, only class 3 depression remained associated with suicide attempts (odds ratio, 4.72; 95% confidence interval, 1.47-15.21; P = .01).

Other significant predictors of suicide attempts were younger age (OR, 0.82; 95% CI, 0.74-0.90; P less than .001), lifetime history of unipolar disorder (OR, 4.71; 95% CI, 1.63-13.58; P = .004), lifetime history of bipolar disorder (OR, 3.4; 95% CI, 0.96-12.04; P = .06), history of childhood abuse (OR, 2.98; 95% CI, 1.40-6.38; P = .01), and parental suicide attempt (OR, 2.24; 95% CI, 1.06-4.75; P = .04).

The investigators concluded that clinicians should “pay particular attention to the severity of both current and past depression and the variability in these symptoms, and monitor and treat depression symptoms over time to reduce symptom severity and fluctuation, and thus the likelihood for suicide attempt, in high-risk young adults.”

Dr. Melhem reported receiving research support from the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the American Foundation for Suicide Prevention. Several other coauthors also reported conflicts of interest.

[email protected]

SOURCE: Melhem NM et al. JAMA Psychiatry. 2019 Feb 27. doi: 10.1001/jamapsychiatry.2018.4513.

Among the trajectories of clinical predictors of suicide attempt, depression symptoms were the only ones linked with an increased risk of suicide attempt in young adults whose parents have mood disorders, according to a longitudinal study.

Psychiatric diagnoses are well established as predictors of suicidal behavior; however, symptoms and risk can vary over the course of illness, and it is important to identify symptoms that can change over time, wrote Nadine M. Melhem, PhD, associate professor of psychiatry at the University of Pittsburgh, and her associates. The report is in JAMA Psychiatry.

Between July 15, 1997, and Sept. 6, 2005, 663 adolescents and young adults (mean age, 23.8 years) whose parents have mood disorders were recruited and followed until Jan. 21, 2014. All participants were assessed at baseline and every year for up to 12 years (median follow-up, 8.1 years) for lifetime and current psychiatric disorders as well as suicidal ideation. In addition, participants were assessed at baseline and at each follow-up for the trajectory of depression symptoms, hopelessness, impulsivity, aggression, impulsive aggression, and irritability.

After the study period, participants were analyzed for all trajectories and separated into classes based on mean scores and variability. All trajectories except for depression had two classes, in which participants in class 2 had higher mean scores and variability; for depression, patients were separated into three classes, in which class 3 had the highest mean score and variability.

Over the study period, 71 of the 663 patients attempted suicide (10.7%), with 51 patients attempting suicide for the first time. The mean number of attempts was 1.2, and the median time from the last assessment to the attempt was 45 weeks.

Participants who attempted suicide were more likely to have class 3 depression symptoms (22.9% with vs. 27 without), class 2 impulsivity (38.8% vs. 21.7%), class 2 aggression (29.0% vs. 15.6%), class 2 impulsive aggression (76.5% vs. 52.2%), and class 2 irritability (39.4% vs. 22.7%). However, after adjustment for demographics, parental suicide attempts, and additional clinical characteristics, only class 3 depression remained associated with suicide attempts (odds ratio, 4.72; 95% confidence interval, 1.47-15.21; P = .01).

Other significant predictors of suicide attempts were younger age (OR, 0.82; 95% CI, 0.74-0.90; P less than .001), lifetime history of unipolar disorder (OR, 4.71; 95% CI, 1.63-13.58; P = .004), lifetime history of bipolar disorder (OR, 3.4; 95% CI, 0.96-12.04; P = .06), history of childhood abuse (OR, 2.98; 95% CI, 1.40-6.38; P = .01), and parental suicide attempt (OR, 2.24; 95% CI, 1.06-4.75; P = .04).

The investigators concluded that clinicians should “pay particular attention to the severity of both current and past depression and the variability in these symptoms, and monitor and treat depression symptoms over time to reduce symptom severity and fluctuation, and thus the likelihood for suicide attempt, in high-risk young adults.”

Dr. Melhem reported receiving research support from the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the American Foundation for Suicide Prevention. Several other coauthors also reported conflicts of interest.

[email protected]

SOURCE: Melhem NM et al. JAMA Psychiatry. 2019 Feb 27. doi: 10.1001/jamapsychiatry.2018.4513.

Among the trajectories of clinical predictors of suicide attempt, depression symptoms were the only ones linked with an increased risk of suicide attempt in young adults whose parents have mood disorders, according to a longitudinal study.

Psychiatric diagnoses are well established as predictors of suicidal behavior; however, symptoms and risk can vary over the course of illness, and it is important to identify symptoms that can change over time, wrote Nadine M. Melhem, PhD, associate professor of psychiatry at the University of Pittsburgh, and her associates. The report is in JAMA Psychiatry.

Between July 15, 1997, and Sept. 6, 2005, 663 adolescents and young adults (mean age, 23.8 years) whose parents have mood disorders were recruited and followed until Jan. 21, 2014. All participants were assessed at baseline and every year for up to 12 years (median follow-up, 8.1 years) for lifetime and current psychiatric disorders as well as suicidal ideation. In addition, participants were assessed at baseline and at each follow-up for the trajectory of depression symptoms, hopelessness, impulsivity, aggression, impulsive aggression, and irritability.

After the study period, participants were analyzed for all trajectories and separated into classes based on mean scores and variability. All trajectories except for depression had two classes, in which participants in class 2 had higher mean scores and variability; for depression, patients were separated into three classes, in which class 3 had the highest mean score and variability.

Over the study period, 71 of the 663 patients attempted suicide (10.7%), with 51 patients attempting suicide for the first time. The mean number of attempts was 1.2, and the median time from the last assessment to the attempt was 45 weeks.

Participants who attempted suicide were more likely to have class 3 depression symptoms (22.9% with vs. 27 without), class 2 impulsivity (38.8% vs. 21.7%), class 2 aggression (29.0% vs. 15.6%), class 2 impulsive aggression (76.5% vs. 52.2%), and class 2 irritability (39.4% vs. 22.7%). However, after adjustment for demographics, parental suicide attempts, and additional clinical characteristics, only class 3 depression remained associated with suicide attempts (odds ratio, 4.72; 95% confidence interval, 1.47-15.21; P = .01).

Other significant predictors of suicide attempts were younger age (OR, 0.82; 95% CI, 0.74-0.90; P less than .001), lifetime history of unipolar disorder (OR, 4.71; 95% CI, 1.63-13.58; P = .004), lifetime history of bipolar disorder (OR, 3.4; 95% CI, 0.96-12.04; P = .06), history of childhood abuse (OR, 2.98; 95% CI, 1.40-6.38; P = .01), and parental suicide attempt (OR, 2.24; 95% CI, 1.06-4.75; P = .04).

The investigators concluded that clinicians should “pay particular attention to the severity of both current and past depression and the variability in these symptoms, and monitor and treat depression symptoms over time to reduce symptom severity and fluctuation, and thus the likelihood for suicide attempt, in high-risk young adults.”

Dr. Melhem reported receiving research support from the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the American Foundation for Suicide Prevention. Several other coauthors also reported conflicts of interest.

[email protected]

SOURCE: Melhem NM et al. JAMA Psychiatry. 2019 Feb 27. doi: 10.1001/jamapsychiatry.2018.4513.

DALLAS – Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

[email protected]

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

DALLAS – Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

[email protected]

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

DALLAS – Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

[email protected]

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

DALLAS – The theme for ACTRIMS Forum 2019 revolves around precision medicine for patients with multiple sclerosis. In an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, the conference’s cochair, Tanuja Chitnis, MD, explained why this is the right time to take a deep dive into what precision medicine means in MS, for patients and physicians alike.

“We chose the topic of precision medicine for this forum because it’s a really timely issue,” said Dr. Chitnis, noting that there are now over 16 approved treatments for MS, and an increasing recognition that “not every patient has the same disease course.”

“It’s the right time to think about individualized treatment, and not a one-size-fits-all approach,” she said, noting that clinicians and patients stand to benefit from guidance about treatment choices.

“In addition, we are aided by the number of biomarkers that are becoming available,” including quantitative MRI and serum biomarkers. “I think we – as a field – need to understand how to use these in clinical settings in order to guide treatment decisions,” said Dr. Chitnis, professor of neurology at Harvard Medical School, Boston.

Advances in data science are allowing the connection of disparate kinds of data for discovery and hypothesis testing and validation, said Dr. Chitnis, who serves as medical director for the large longitudinal CLIMB study. The study follows about 2,000 patients who have yearly neurologic examinations and brain MRI; serum biomarkers and self-report data are also acquired annually.

“Network science can help in the precision medicine approach to multiple sclerosis, because we have a very clear understanding that MS is a complex disease. It is not one gene; it is not one modality,” she said.

Dr. Chitnis reported that she has received research funding from multiple pharmaceutical companies.
 

[email protected]

DALLAS – The theme for ACTRIMS Forum 2019 revolves around precision medicine for patients with multiple sclerosis. In an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, the conference’s cochair, Tanuja Chitnis, MD, explained why this is the right time to take a deep dive into what precision medicine means in MS, for patients and physicians alike.

“We chose the topic of precision medicine for this forum because it’s a really timely issue,” said Dr. Chitnis, noting that there are now over 16 approved treatments for MS, and an increasing recognition that “not every patient has the same disease course.”

“It’s the right time to think about individualized treatment, and not a one-size-fits-all approach,” she said, noting that clinicians and patients stand to benefit from guidance about treatment choices.

“In addition, we are aided by the number of biomarkers that are becoming available,” including quantitative MRI and serum biomarkers. “I think we – as a field – need to understand how to use these in clinical settings in order to guide treatment decisions,” said Dr. Chitnis, professor of neurology at Harvard Medical School, Boston.

Advances in data science are allowing the connection of disparate kinds of data for discovery and hypothesis testing and validation, said Dr. Chitnis, who serves as medical director for the large longitudinal CLIMB study. The study follows about 2,000 patients who have yearly neurologic examinations and brain MRI; serum biomarkers and self-report data are also acquired annually.

“Network science can help in the precision medicine approach to multiple sclerosis, because we have a very clear understanding that MS is a complex disease. It is not one gene; it is not one modality,” she said.

Dr. Chitnis reported that she has received research funding from multiple pharmaceutical companies.
 

[email protected]

DALLAS – The theme for ACTRIMS Forum 2019 revolves around precision medicine for patients with multiple sclerosis. In an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, the conference’s cochair, Tanuja Chitnis, MD, explained why this is the right time to take a deep dive into what precision medicine means in MS, for patients and physicians alike.

“We chose the topic of precision medicine for this forum because it’s a really timely issue,” said Dr. Chitnis, noting that there are now over 16 approved treatments for MS, and an increasing recognition that “not every patient has the same disease course.”

“It’s the right time to think about individualized treatment, and not a one-size-fits-all approach,” she said, noting that clinicians and patients stand to benefit from guidance about treatment choices.

“In addition, we are aided by the number of biomarkers that are becoming available,” including quantitative MRI and serum biomarkers. “I think we – as a field – need to understand how to use these in clinical settings in order to guide treatment decisions,” said Dr. Chitnis, professor of neurology at Harvard Medical School, Boston.

Advances in data science are allowing the connection of disparate kinds of data for discovery and hypothesis testing and validation, said Dr. Chitnis, who serves as medical director for the large longitudinal CLIMB study. The study follows about 2,000 patients who have yearly neurologic examinations and brain MRI; serum biomarkers and self-report data are also acquired annually.

“Network science can help in the precision medicine approach to multiple sclerosis, because we have a very clear understanding that MS is a complex disease. It is not one gene; it is not one modality,” she said.

Dr. Chitnis reported that she has received research funding from multiple pharmaceutical companies.
 

[email protected]

For adults with chronic hepatitis B virus infection, treatment with a novel investigational capsid assembly modulator was well tolerated and showed antiviral activity against HBV, according to the results of a phase 1 study of 73 patients.

CDC/Dr. Erskine Palmer

“Substantial and correlated reductions in serum HBV DNA and HBV RNA levels were observed consistently with the higher-dose cohorts and were notably greatest for combination treatment with NVR 3-778 and pegIFN [pegylated interferon],” Man Fung Yuen, MD, of the University of Hong Kong, and his associates wrote in a report published in Gastroenterology. Hence, this first-in-class capsid assembly modulator might help prolong treatment responses, “most likely as a component of new combination treatment regimens for HBV-infected patients.” However, one patient developed severe rash immediately after completing treatment that took 6 months of intensive outpatient treatment to resolve, they noted.

Chronic viral hepatitis due to HBV is a major cause of early death worldwide, and new therapies are needed to help prevent severe liver disease and liver death from this infection. Current treatments for HBV infection consist of nucleoside or nucleotide analogs or pegylated interferon. These suppress HBV replication in many patients, but most patients do not achieve durable responses. Consequently, most patients require long-term treatment with HBV nucleosides and nucleotide analogs, which they may find difficult to tolerate or adhere to and to which their infections can become resistant, the researchers said.

The HBV virion contains a viral core protein (HBc) that is required to encapsidate viral polymerase and pregenomic HBV RNA into a nucleocapsid. To target this process, researchers developed NVR 3-778, a first-in-class, orally bioavailable small molecule that binds HBc so that HBc forms a defective capsid that lacks nuclear material. Hence, NVR 3-778 is intended to stop the production of HBV nucleocapsids and keep infected cells from releasing the enveloped infectious viral particles that perpetuate HBV infection.

To assess the safety, pharmacokinetics, and antiviral activity of NVR 3-778, the researchers conducted a phase 1 study of 73 patients with chronic HBV infection who tested positive for hepatitis B e-antigen (HBeAg) and had no detectable cirrhosis. Patients were randomly assigned to receive oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1,000 mg twice daily ) or placebo for 28 days. Some patients received combination therapy with pegylated interferon plus either NVR 3-778 (600 mg twice daily) or placebo. Treatment was generally well tolerated, and adverse events were usually mild and deemed unrelated to therapy. No patient stopped treatment for adverse effects.

The only serious adverse event in the study consisted of grade 3 rash that developed in a 42-year-old male after 22 days of treatment at the lowest dose of NVR 3-778 (100 mg per day). This patient completed treatment and ultimately developed a severe papulovesicular rash with a predominantly acral distribution over the hands, arm, side of neck, and one leg (palmar plantar erythrodysesthesia), the researchers said. “There were no perioral or mucosal lesions, no ecchymotic skin involvement, no bullae, and no systemic manifestations or hematological abnormalities,” they wrote. “The rash was subsequently managed with a psoriasis-like treatment regimen of psoralen, ultraviolet light, and topical steroid ointment during outpatient follow-up and resolved after approximately 6 months.”

Another three cases of “minor” skin rash were considered probably related to treatment in the cohort that received 600 mg NVR 3-778 b.i.d. plus pegylated interferon, the investigators said. Two additional cases of mild rash were deemed unrelated to treatment.

“The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778,” the researchers concluded. “This class of compounds can also inhibit replenishment of intranuclear covalently closed circular DNA over time and may have immunomodulatory properties.” Longer treatment periods would be needed to study these mechanisms and to quantify reductions in serum HBsAg and HBeAG, they noted.

Novira Therapeutics developed NVR 3-778 and is a Janssen Pharmaceutical Company. Janssen provided funding for editorial support. Dr. Yuen disclosed relationships with AbbVie, Biocartis, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Ionis, Roche, Vir Biotechnology, and several other pharmaceutical companies. Other coinvestigators disclosed ties to pharmaceutical companies; eight reported employment by Novira or a Janssen company.

SOURCE: Yuen MF et al. Gastroenterology. 2019 Jan 5. doi: 10.1053/j.gastro.2018.12.023.

For adults with chronic hepatitis B virus infection, treatment with a novel investigational capsid assembly modulator was well tolerated and showed antiviral activity against HBV, according to the results of a phase 1 study of 73 patients.

CDC/Dr. Erskine Palmer

“Substantial and correlated reductions in serum HBV DNA and HBV RNA levels were observed consistently with the higher-dose cohorts and were notably greatest for combination treatment with NVR 3-778 and pegIFN [pegylated interferon],” Man Fung Yuen, MD, of the University of Hong Kong, and his associates wrote in a report published in Gastroenterology. Hence, this first-in-class capsid assembly modulator might help prolong treatment responses, “most likely as a component of new combination treatment regimens for HBV-infected patients.” However, one patient developed severe rash immediately after completing treatment that took 6 months of intensive outpatient treatment to resolve, they noted.

Chronic viral hepatitis due to HBV is a major cause of early death worldwide, and new therapies are needed to help prevent severe liver disease and liver death from this infection. Current treatments for HBV infection consist of nucleoside or nucleotide analogs or pegylated interferon. These suppress HBV replication in many patients, but most patients do not achieve durable responses. Consequently, most patients require long-term treatment with HBV nucleosides and nucleotide analogs, which they may find difficult to tolerate or adhere to and to which their infections can become resistant, the researchers said.

The HBV virion contains a viral core protein (HBc) that is required to encapsidate viral polymerase and pregenomic HBV RNA into a nucleocapsid. To target this process, researchers developed NVR 3-778, a first-in-class, orally bioavailable small molecule that binds HBc so that HBc forms a defective capsid that lacks nuclear material. Hence, NVR 3-778 is intended to stop the production of HBV nucleocapsids and keep infected cells from releasing the enveloped infectious viral particles that perpetuate HBV infection.

To assess the safety, pharmacokinetics, and antiviral activity of NVR 3-778, the researchers conducted a phase 1 study of 73 patients with chronic HBV infection who tested positive for hepatitis B e-antigen (HBeAg) and had no detectable cirrhosis. Patients were randomly assigned to receive oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1,000 mg twice daily ) or placebo for 28 days. Some patients received combination therapy with pegylated interferon plus either NVR 3-778 (600 mg twice daily) or placebo. Treatment was generally well tolerated, and adverse events were usually mild and deemed unrelated to therapy. No patient stopped treatment for adverse effects.

The only serious adverse event in the study consisted of grade 3 rash that developed in a 42-year-old male after 22 days of treatment at the lowest dose of NVR 3-778 (100 mg per day). This patient completed treatment and ultimately developed a severe papulovesicular rash with a predominantly acral distribution over the hands, arm, side of neck, and one leg (palmar plantar erythrodysesthesia), the researchers said. “There were no perioral or mucosal lesions, no ecchymotic skin involvement, no bullae, and no systemic manifestations or hematological abnormalities,” they wrote. “The rash was subsequently managed with a psoriasis-like treatment regimen of psoralen, ultraviolet light, and topical steroid ointment during outpatient follow-up and resolved after approximately 6 months.”

Another three cases of “minor” skin rash were considered probably related to treatment in the cohort that received 600 mg NVR 3-778 b.i.d. plus pegylated interferon, the investigators said. Two additional cases of mild rash were deemed unrelated to treatment.

“The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778,” the researchers concluded. “This class of compounds can also inhibit replenishment of intranuclear covalently closed circular DNA over time and may have immunomodulatory properties.” Longer treatment periods would be needed to study these mechanisms and to quantify reductions in serum HBsAg and HBeAG, they noted.

Novira Therapeutics developed NVR 3-778 and is a Janssen Pharmaceutical Company. Janssen provided funding for editorial support. Dr. Yuen disclosed relationships with AbbVie, Biocartis, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Ionis, Roche, Vir Biotechnology, and several other pharmaceutical companies. Other coinvestigators disclosed ties to pharmaceutical companies; eight reported employment by Novira or a Janssen company.

SOURCE: Yuen MF et al. Gastroenterology. 2019 Jan 5. doi: 10.1053/j.gastro.2018.12.023.

For adults with chronic hepatitis B virus infection, treatment with a novel investigational capsid assembly modulator was well tolerated and showed antiviral activity against HBV, according to the results of a phase 1 study of 73 patients.

CDC/Dr. Erskine Palmer

“Substantial and correlated reductions in serum HBV DNA and HBV RNA levels were observed consistently with the higher-dose cohorts and were notably greatest for combination treatment with NVR 3-778 and pegIFN [pegylated interferon],” Man Fung Yuen, MD, of the University of Hong Kong, and his associates wrote in a report published in Gastroenterology. Hence, this first-in-class capsid assembly modulator might help prolong treatment responses, “most likely as a component of new combination treatment regimens for HBV-infected patients.” However, one patient developed severe rash immediately after completing treatment that took 6 months of intensive outpatient treatment to resolve, they noted.

Chronic viral hepatitis due to HBV is a major cause of early death worldwide, and new therapies are needed to help prevent severe liver disease and liver death from this infection. Current treatments for HBV infection consist of nucleoside or nucleotide analogs or pegylated interferon. These suppress HBV replication in many patients, but most patients do not achieve durable responses. Consequently, most patients require long-term treatment with HBV nucleosides and nucleotide analogs, which they may find difficult to tolerate or adhere to and to which their infections can become resistant, the researchers said.

The HBV virion contains a viral core protein (HBc) that is required to encapsidate viral polymerase and pregenomic HBV RNA into a nucleocapsid. To target this process, researchers developed NVR 3-778, a first-in-class, orally bioavailable small molecule that binds HBc so that HBc forms a defective capsid that lacks nuclear material. Hence, NVR 3-778 is intended to stop the production of HBV nucleocapsids and keep infected cells from releasing the enveloped infectious viral particles that perpetuate HBV infection.

To assess the safety, pharmacokinetics, and antiviral activity of NVR 3-778, the researchers conducted a phase 1 study of 73 patients with chronic HBV infection who tested positive for hepatitis B e-antigen (HBeAg) and had no detectable cirrhosis. Patients were randomly assigned to receive oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1,000 mg twice daily ) or placebo for 28 days. Some patients received combination therapy with pegylated interferon plus either NVR 3-778 (600 mg twice daily) or placebo. Treatment was generally well tolerated, and adverse events were usually mild and deemed unrelated to therapy. No patient stopped treatment for adverse effects.

The only serious adverse event in the study consisted of grade 3 rash that developed in a 42-year-old male after 22 days of treatment at the lowest dose of NVR 3-778 (100 mg per day). This patient completed treatment and ultimately developed a severe papulovesicular rash with a predominantly acral distribution over the hands, arm, side of neck, and one leg (palmar plantar erythrodysesthesia), the researchers said. “There were no perioral or mucosal lesions, no ecchymotic skin involvement, no bullae, and no systemic manifestations or hematological abnormalities,” they wrote. “The rash was subsequently managed with a psoriasis-like treatment regimen of psoralen, ultraviolet light, and topical steroid ointment during outpatient follow-up and resolved after approximately 6 months.”

Another three cases of “minor” skin rash were considered probably related to treatment in the cohort that received 600 mg NVR 3-778 b.i.d. plus pegylated interferon, the investigators said. Two additional cases of mild rash were deemed unrelated to treatment.

“The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778,” the researchers concluded. “This class of compounds can also inhibit replenishment of intranuclear covalently closed circular DNA over time and may have immunomodulatory properties.” Longer treatment periods would be needed to study these mechanisms and to quantify reductions in serum HBsAg and HBeAG, they noted.

Novira Therapeutics developed NVR 3-778 and is a Janssen Pharmaceutical Company. Janssen provided funding for editorial support. Dr. Yuen disclosed relationships with AbbVie, Biocartis, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Ionis, Roche, Vir Biotechnology, and several other pharmaceutical companies. Other coinvestigators disclosed ties to pharmaceutical companies; eight reported employment by Novira or a Janssen company.

SOURCE: Yuen MF et al. Gastroenterology. 2019 Jan 5. doi: 10.1053/j.gastro.2018.12.023.

PRAGUE – Adeno-associated virus (AAV)–based gene therapy is probably not the “endgame” in gene therapy for hemophilia, according to John Pasi, MD, PhD, director of the Haemophilia Centre at the Royal London Hospital.

Will Pass/MDedge News

“Gene therapy today is essentially gene therapy version 1.0,” Dr. Pasi said, kicking off the third day at the annual congress of the European Association for Haemophilia and Allied Disorders.

Interwoven with a summary of recent research and upcoming trends, Dr. Pasi reflected upon the medical community’s expectations for gene therapy, both past and present.

“For years,” Dr. Pasi said, “gene therapy has been regarded, essentially, as the Holy Grail of treatment for hemophilia.” This sentiment has been supported by the fact that hemophilia “is a single-gene disorder with a cause and effect relationship that is extremely clear and straightforward for us to recognize.”

A small increase in clotting factor can significantly reduce bleeding while providing a measurable efficacy outcome, making it a strong research candidate.


Looking back, however, when gene therapy research began in the early 1990s, it “really did go through a peak of inflated expectations,” Dr. Pasi said. “We thought for years it was just around the corner. But there were abject failures; there were learning curves we had to go through to understand many of the issues that gene therapy threw up, which we didn’t understand at the beginning.”

When this early excitement was met with tough realities, a period of disillusionment began and persisted through the early 2000s. Dr. Pasi suggested that this period of disillusionment may be reaching an end because of a “huge amount of steady work” that has ushered in a new period of productivity.

Dr. Pasi cited two 2017 studies published in the New England Journal of Medicine by Savita Rangarajan, MBBS, and colleagues and Lindsey A. George, MD, and colleagues for hemophilia A and B, respectively (N Engl J Med. 2017; 377:2519-30; N Engl J Med. 2017; 377:2215-27).

In contrast with previous studies showing factor levels in the single digits, recent studies have achieved normal-range values. Seeing such improvements in hemophilia A, is a particular source of optimism; historically, gene therapy for hemophilia A has lagged behind hemophilia B because of a larger gene that is more difficult to work with.

“This has stepped up the game hugely,” Dr. Pasi said.

The elements of gene therapy for hemophilia may change over time. For instance, lentiviruses could be used instead of AAV-based methods, and ex vivo techniques could make a comeback, potentially using different tissue sources. These changes are likely on the distant horizon, however.

Gene modification is also not coming anytime soon.

“Gene replacement, gene editing, and gene repair are something that we hear a lot about in the general field of gene therapy,” Dr. Pasi said, “But in practical terms for our patients, we probably are a significant way off from this at the moment, and this is because we know and we all recognize that there are a wide range of mutations causing hemophilia, and many of these are highly specific; we will need specific gene therapies to address specific mutations.”

Dr. Pasi likened the current state of gene therapy to that of the self-driving car, suggesting that “we still have strides to make, and there are still things we can improve on beyond what we have today.

“The biggest question for gene therapy today is durability,” Dr. Pasi said. “How long are these things going to last?”

Patients from earlier studies are now crossing the half-decade mark, albeit with relatively low factor levels, compared with recent techniques. One such study, presented at the 2018 annual meeting of the American Society of Hematology by Amit C. Nathwani, MD, PhD, and colleagues, is “very critical to our understanding,” Dr. Pasi said, referring to patients who are now 6-8 years post treatment. “What we see is … continued, stable expression of factor IX,” he said.

Alongside questions of durability, safety remains paramount in the quest for better methods of gene therapy.

“We are seeing liver function abnormalities,” Dr. Pasi said, noting that these tend to be transient elevations of ALT. “We know that many patients now have to receive steroid treatment, which very effectively reduces the immune response, but it is something that we are increasingly having to bear in mind.”

The latest techniques are using liver-specific promoters in novel synthetic capsids, and more capsids are under development.

Dr. Pasi also emphasized safety and caution. “We must never forget that gene therapy is a completely new approach to treatment, and we’ve got to think about safety. It is the number one priority when we are investigating new treatments.”

Safety remains untested in several key patient subpopulations, including children and those with comorbidities or inhibitors.

“For gene therapy in 2019,” he said, “we’ve made massive strides, but we’re not quite there yet.”

PRAGUE – Adeno-associated virus (AAV)–based gene therapy is probably not the “endgame” in gene therapy for hemophilia, according to John Pasi, MD, PhD, director of the Haemophilia Centre at the Royal London Hospital.

Will Pass/MDedge News

“Gene therapy today is essentially gene therapy version 1.0,” Dr. Pasi said, kicking off the third day at the annual congress of the European Association for Haemophilia and Allied Disorders.

Interwoven with a summary of recent research and upcoming trends, Dr. Pasi reflected upon the medical community’s expectations for gene therapy, both past and present.

“For years,” Dr. Pasi said, “gene therapy has been regarded, essentially, as the Holy Grail of treatment for hemophilia.” This sentiment has been supported by the fact that hemophilia “is a single-gene disorder with a cause and effect relationship that is extremely clear and straightforward for us to recognize.”

A small increase in clotting factor can significantly reduce bleeding while providing a measurable efficacy outcome, making it a strong research candidate.


Looking back, however, when gene therapy research began in the early 1990s, it “really did go through a peak of inflated expectations,” Dr. Pasi said. “We thought for years it was just around the corner. But there were abject failures; there were learning curves we had to go through to understand many of the issues that gene therapy threw up, which we didn’t understand at the beginning.”

When this early excitement was met with tough realities, a period of disillusionment began and persisted through the early 2000s. Dr. Pasi suggested that this period of disillusionment may be reaching an end because of a “huge amount of steady work” that has ushered in a new period of productivity.

Dr. Pasi cited two 2017 studies published in the New England Journal of Medicine by Savita Rangarajan, MBBS, and colleagues and Lindsey A. George, MD, and colleagues for hemophilia A and B, respectively (N Engl J Med. 2017; 377:2519-30; N Engl J Med. 2017; 377:2215-27).

In contrast with previous studies showing factor levels in the single digits, recent studies have achieved normal-range values. Seeing such improvements in hemophilia A, is a particular source of optimism; historically, gene therapy for hemophilia A has lagged behind hemophilia B because of a larger gene that is more difficult to work with.

“This has stepped up the game hugely,” Dr. Pasi said.

The elements of gene therapy for hemophilia may change over time. For instance, lentiviruses could be used instead of AAV-based methods, and ex vivo techniques could make a comeback, potentially using different tissue sources. These changes are likely on the distant horizon, however.

Gene modification is also not coming anytime soon.

“Gene replacement, gene editing, and gene repair are something that we hear a lot about in the general field of gene therapy,” Dr. Pasi said, “But in practical terms for our patients, we probably are a significant way off from this at the moment, and this is because we know and we all recognize that there are a wide range of mutations causing hemophilia, and many of these are highly specific; we will need specific gene therapies to address specific mutations.”

Dr. Pasi likened the current state of gene therapy to that of the self-driving car, suggesting that “we still have strides to make, and there are still things we can improve on beyond what we have today.

“The biggest question for gene therapy today is durability,” Dr. Pasi said. “How long are these things going to last?”

Patients from earlier studies are now crossing the half-decade mark, albeit with relatively low factor levels, compared with recent techniques. One such study, presented at the 2018 annual meeting of the American Society of Hematology by Amit C. Nathwani, MD, PhD, and colleagues, is “very critical to our understanding,” Dr. Pasi said, referring to patients who are now 6-8 years post treatment. “What we see is … continued, stable expression of factor IX,” he said.

Alongside questions of durability, safety remains paramount in the quest for better methods of gene therapy.

“We are seeing liver function abnormalities,” Dr. Pasi said, noting that these tend to be transient elevations of ALT. “We know that many patients now have to receive steroid treatment, which very effectively reduces the immune response, but it is something that we are increasingly having to bear in mind.”

The latest techniques are using liver-specific promoters in novel synthetic capsids, and more capsids are under development.

Dr. Pasi also emphasized safety and caution. “We must never forget that gene therapy is a completely new approach to treatment, and we’ve got to think about safety. It is the number one priority when we are investigating new treatments.”

Safety remains untested in several key patient subpopulations, including children and those with comorbidities or inhibitors.

“For gene therapy in 2019,” he said, “we’ve made massive strides, but we’re not quite there yet.”

PRAGUE – Adeno-associated virus (AAV)–based gene therapy is probably not the “endgame” in gene therapy for hemophilia, according to John Pasi, MD, PhD, director of the Haemophilia Centre at the Royal London Hospital.

Will Pass/MDedge News

“Gene therapy today is essentially gene therapy version 1.0,” Dr. Pasi said, kicking off the third day at the annual congress of the European Association for Haemophilia and Allied Disorders.

Interwoven with a summary of recent research and upcoming trends, Dr. Pasi reflected upon the medical community’s expectations for gene therapy, both past and present.

“For years,” Dr. Pasi said, “gene therapy has been regarded, essentially, as the Holy Grail of treatment for hemophilia.” This sentiment has been supported by the fact that hemophilia “is a single-gene disorder with a cause and effect relationship that is extremely clear and straightforward for us to recognize.”

A small increase in clotting factor can significantly reduce bleeding while providing a measurable efficacy outcome, making it a strong research candidate.


Looking back, however, when gene therapy research began in the early 1990s, it “really did go through a peak of inflated expectations,” Dr. Pasi said. “We thought for years it was just around the corner. But there were abject failures; there were learning curves we had to go through to understand many of the issues that gene therapy threw up, which we didn’t understand at the beginning.”

When this early excitement was met with tough realities, a period of disillusionment began and persisted through the early 2000s. Dr. Pasi suggested that this period of disillusionment may be reaching an end because of a “huge amount of steady work” that has ushered in a new period of productivity.

Dr. Pasi cited two 2017 studies published in the New England Journal of Medicine by Savita Rangarajan, MBBS, and colleagues and Lindsey A. George, MD, and colleagues for hemophilia A and B, respectively (N Engl J Med. 2017; 377:2519-30; N Engl J Med. 2017; 377:2215-27).

In contrast with previous studies showing factor levels in the single digits, recent studies have achieved normal-range values. Seeing such improvements in hemophilia A, is a particular source of optimism; historically, gene therapy for hemophilia A has lagged behind hemophilia B because of a larger gene that is more difficult to work with.

“This has stepped up the game hugely,” Dr. Pasi said.

The elements of gene therapy for hemophilia may change over time. For instance, lentiviruses could be used instead of AAV-based methods, and ex vivo techniques could make a comeback, potentially using different tissue sources. These changes are likely on the distant horizon, however.

Gene modification is also not coming anytime soon.

“Gene replacement, gene editing, and gene repair are something that we hear a lot about in the general field of gene therapy,” Dr. Pasi said, “But in practical terms for our patients, we probably are a significant way off from this at the moment, and this is because we know and we all recognize that there are a wide range of mutations causing hemophilia, and many of these are highly specific; we will need specific gene therapies to address specific mutations.”

Dr. Pasi likened the current state of gene therapy to that of the self-driving car, suggesting that “we still have strides to make, and there are still things we can improve on beyond what we have today.

“The biggest question for gene therapy today is durability,” Dr. Pasi said. “How long are these things going to last?”

Patients from earlier studies are now crossing the half-decade mark, albeit with relatively low factor levels, compared with recent techniques. One such study, presented at the 2018 annual meeting of the American Society of Hematology by Amit C. Nathwani, MD, PhD, and colleagues, is “very critical to our understanding,” Dr. Pasi said, referring to patients who are now 6-8 years post treatment. “What we see is … continued, stable expression of factor IX,” he said.

Alongside questions of durability, safety remains paramount in the quest for better methods of gene therapy.

“We are seeing liver function abnormalities,” Dr. Pasi said, noting that these tend to be transient elevations of ALT. “We know that many patients now have to receive steroid treatment, which very effectively reduces the immune response, but it is something that we are increasingly having to bear in mind.”

The latest techniques are using liver-specific promoters in novel synthetic capsids, and more capsids are under development.

Dr. Pasi also emphasized safety and caution. “We must never forget that gene therapy is a completely new approach to treatment, and we’ve got to think about safety. It is the number one priority when we are investigating new treatments.”

Safety remains untested in several key patient subpopulations, including children and those with comorbidities or inhibitors.

“For gene therapy in 2019,” he said, “we’ve made massive strides, but we’re not quite there yet.”

DALLAS – A number of sociodemographic factors may influence health and disability insurance access by individuals with multiple sclerosis, including employment, age, gender, disease duration, marital status, and ethnicity, results from a large survey suggest.

“The last similar work was conducted over 10 years ago and so much has happened in the meantime, including the Great Recession and the introduction of the Affordable Care Act, that offers protection for health care but not for other important types of insurance (short- and long-term disability, long-term care, and life),” lead study author Sarah Planchon, PhD, said in an interview in advance of the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “MS is one of the most costly chronic diseases today. That is not only because of the cost of disease-modifying therapies but also because of lost employment and income. We wanted to better understand the insurance landscape so that we could in turn educate patients and professionals about the protection these insurances offer and advise them on how to obtain these policies.”

In an effort to evaluate factors that affect insurance access in MS, Dr. Planchon, a project scientist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio, and her colleagues used the North American Research Committee on MS (NARCOMS), iConquerMS, and the National Multiple Sclerosis Society to survey 2,507 individuals with the disease regarding insurance, demographic, health, disability, and employment status. They used covariate-adjusted nominal logistic regression to estimate odds ratios for the likelihood of having or not having a type of insurance. The majority of respondents (83%) were female, their mean age was 54 years, 91% were white, 65% were currently married, and their mean disease duration at the time of the survey was 16 years. In addition, 43% were employed full/part-time, and 29% were not employed or retired because of disability. Nearly all respondents (96%) reported having health insurance, while 59% had life insurance, 29% had private long-term disability insurance, 18% had short-term disability insurance, and 10% had long-term care insurance.

The researchers found that employment status had the greatest impact on insurance coverage. Of those with health insurance, 33% were employed full-time, compared with 89% of those with short-term disability insurance, 42% of those with private long-term disability insurance, 44% of those with long-term care insurance, and 41% of those with life insurance. Logistic regression analyses indicated that respondents employed part time were significantly more likely to have short-term disability insurance if they were currently married (odds ratio, 4.4). Short-term disability insurance was significantly more likely among fully employed patients with disease duration of 5-10 years vs. more than 20 years (OR, 2.0). Private long-term disability insurance was significantly associated with female gender (OR, 1.6), age 50-59 years vs. younger than 40 (OR, 1.6), full-time vs. part-time employment (OR, 2.3), and shorter disease duration (ORs, 1.4-1.6 for 6-10, 11-15, and 16-20 years’ duration). Long-term care insurance was associated with older age (ORs, 2.5 and 4.3 for those aged 50-59 and 60-65 vs. younger than 40), and having excellent or good general health status vs. fair or poor (OR, 1.8). Life insurance was associated with non-Hispanic ethnicity (OR, 1.6), full-time vs. part-time employment (OR, 2.4), older age (ORs, 1.6-1.7 for ages 40-49 and 50-59 vs. younger than 40), and marital status (currently/previously married, ORs, 1.6-2.6). Considering the high rate of survey respondents with health insurance, covariate-adjusted modeling was not applicable.

“The number of people with MS who do not have long-term care insurance was surprisingly high,” Dr. Planchon said. “Although the improved treatment climate recently may decrease the long-term disability levels, we do not yet know this with certainty. A large number of people with MS are likely to need long-term care in the future, which often is a significant financial burden to families.” The findings suggest that clinical care teams “need to initiate early discussions of possible long-term needs with their patients,” she continued. “Incorporation of social work teams, who are familiar with the needs of people with MS and insurance options available to them, within MS specialty practices will bolster the comprehensive care of patients and their families.”

She acknowledged certain limitations of the study, including the low proportion of respondents who were Hispanic/Latino and African American (about 4% each). “The insurance landscape may differ in these groups compared to the majority Caucasian population who responded to this survey,” Dr. Planchon said.

The National Multiple Sclerosis Society funded the study. Dr. Planchon reported having no relevant financial disclosures.

[email protected]

SOURCE: Planchon S et al. ACTRIMS Forum 2019, Abstract P295.

DALLAS – A number of sociodemographic factors may influence health and disability insurance access by individuals with multiple sclerosis, including employment, age, gender, disease duration, marital status, and ethnicity, results from a large survey suggest.

“The last similar work was conducted over 10 years ago and so much has happened in the meantime, including the Great Recession and the introduction of the Affordable Care Act, that offers protection for health care but not for other important types of insurance (short- and long-term disability, long-term care, and life),” lead study author Sarah Planchon, PhD, said in an interview in advance of the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “MS is one of the most costly chronic diseases today. That is not only because of the cost of disease-modifying therapies but also because of lost employment and income. We wanted to better understand the insurance landscape so that we could in turn educate patients and professionals about the protection these insurances offer and advise them on how to obtain these policies.”

In an effort to evaluate factors that affect insurance access in MS, Dr. Planchon, a project scientist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio, and her colleagues used the North American Research Committee on MS (NARCOMS), iConquerMS, and the National Multiple Sclerosis Society to survey 2,507 individuals with the disease regarding insurance, demographic, health, disability, and employment status. They used covariate-adjusted nominal logistic regression to estimate odds ratios for the likelihood of having or not having a type of insurance. The majority of respondents (83%) were female, their mean age was 54 years, 91% were white, 65% were currently married, and their mean disease duration at the time of the survey was 16 years. In addition, 43% were employed full/part-time, and 29% were not employed or retired because of disability. Nearly all respondents (96%) reported having health insurance, while 59% had life insurance, 29% had private long-term disability insurance, 18% had short-term disability insurance, and 10% had long-term care insurance.

The researchers found that employment status had the greatest impact on insurance coverage. Of those with health insurance, 33% were employed full-time, compared with 89% of those with short-term disability insurance, 42% of those with private long-term disability insurance, 44% of those with long-term care insurance, and 41% of those with life insurance. Logistic regression analyses indicated that respondents employed part time were significantly more likely to have short-term disability insurance if they were currently married (odds ratio, 4.4). Short-term disability insurance was significantly more likely among fully employed patients with disease duration of 5-10 years vs. more than 20 years (OR, 2.0). Private long-term disability insurance was significantly associated with female gender (OR, 1.6), age 50-59 years vs. younger than 40 (OR, 1.6), full-time vs. part-time employment (OR, 2.3), and shorter disease duration (ORs, 1.4-1.6 for 6-10, 11-15, and 16-20 years’ duration). Long-term care insurance was associated with older age (ORs, 2.5 and 4.3 for those aged 50-59 and 60-65 vs. younger than 40), and having excellent or good general health status vs. fair or poor (OR, 1.8). Life insurance was associated with non-Hispanic ethnicity (OR, 1.6), full-time vs. part-time employment (OR, 2.4), older age (ORs, 1.6-1.7 for ages 40-49 and 50-59 vs. younger than 40), and marital status (currently/previously married, ORs, 1.6-2.6). Considering the high rate of survey respondents with health insurance, covariate-adjusted modeling was not applicable.

“The number of people with MS who do not have long-term care insurance was surprisingly high,” Dr. Planchon said. “Although the improved treatment climate recently may decrease the long-term disability levels, we do not yet know this with certainty. A large number of people with MS are likely to need long-term care in the future, which often is a significant financial burden to families.” The findings suggest that clinical care teams “need to initiate early discussions of possible long-term needs with their patients,” she continued. “Incorporation of social work teams, who are familiar with the needs of people with MS and insurance options available to them, within MS specialty practices will bolster the comprehensive care of patients and their families.”

She acknowledged certain limitations of the study, including the low proportion of respondents who were Hispanic/Latino and African American (about 4% each). “The insurance landscape may differ in these groups compared to the majority Caucasian population who responded to this survey,” Dr. Planchon said.

The National Multiple Sclerosis Society funded the study. Dr. Planchon reported having no relevant financial disclosures.

[email protected]

SOURCE: Planchon S et al. ACTRIMS Forum 2019, Abstract P295.

DALLAS – A number of sociodemographic factors may influence health and disability insurance access by individuals with multiple sclerosis, including employment, age, gender, disease duration, marital status, and ethnicity, results from a large survey suggest.

“The last similar work was conducted over 10 years ago and so much has happened in the meantime, including the Great Recession and the introduction of the Affordable Care Act, that offers protection for health care but not for other important types of insurance (short- and long-term disability, long-term care, and life),” lead study author Sarah Planchon, PhD, said in an interview in advance of the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “MS is one of the most costly chronic diseases today. That is not only because of the cost of disease-modifying therapies but also because of lost employment and income. We wanted to better understand the insurance landscape so that we could in turn educate patients and professionals about the protection these insurances offer and advise them on how to obtain these policies.”

In an effort to evaluate factors that affect insurance access in MS, Dr. Planchon, a project scientist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio, and her colleagues used the North American Research Committee on MS (NARCOMS), iConquerMS, and the National Multiple Sclerosis Society to survey 2,507 individuals with the disease regarding insurance, demographic, health, disability, and employment status. They used covariate-adjusted nominal logistic regression to estimate odds ratios for the likelihood of having or not having a type of insurance. The majority of respondents (83%) were female, their mean age was 54 years, 91% were white, 65% were currently married, and their mean disease duration at the time of the survey was 16 years. In addition, 43% were employed full/part-time, and 29% were not employed or retired because of disability. Nearly all respondents (96%) reported having health insurance, while 59% had life insurance, 29% had private long-term disability insurance, 18% had short-term disability insurance, and 10% had long-term care insurance.

The researchers found that employment status had the greatest impact on insurance coverage. Of those with health insurance, 33% were employed full-time, compared with 89% of those with short-term disability insurance, 42% of those with private long-term disability insurance, 44% of those with long-term care insurance, and 41% of those with life insurance. Logistic regression analyses indicated that respondents employed part time were significantly more likely to have short-term disability insurance if they were currently married (odds ratio, 4.4). Short-term disability insurance was significantly more likely among fully employed patients with disease duration of 5-10 years vs. more than 20 years (OR, 2.0). Private long-term disability insurance was significantly associated with female gender (OR, 1.6), age 50-59 years vs. younger than 40 (OR, 1.6), full-time vs. part-time employment (OR, 2.3), and shorter disease duration (ORs, 1.4-1.6 for 6-10, 11-15, and 16-20 years’ duration). Long-term care insurance was associated with older age (ORs, 2.5 and 4.3 for those aged 50-59 and 60-65 vs. younger than 40), and having excellent or good general health status vs. fair or poor (OR, 1.8). Life insurance was associated with non-Hispanic ethnicity (OR, 1.6), full-time vs. part-time employment (OR, 2.4), older age (ORs, 1.6-1.7 for ages 40-49 and 50-59 vs. younger than 40), and marital status (currently/previously married, ORs, 1.6-2.6). Considering the high rate of survey respondents with health insurance, covariate-adjusted modeling was not applicable.

“The number of people with MS who do not have long-term care insurance was surprisingly high,” Dr. Planchon said. “Although the improved treatment climate recently may decrease the long-term disability levels, we do not yet know this with certainty. A large number of people with MS are likely to need long-term care in the future, which often is a significant financial burden to families.” The findings suggest that clinical care teams “need to initiate early discussions of possible long-term needs with their patients,” she continued. “Incorporation of social work teams, who are familiar with the needs of people with MS and insurance options available to them, within MS specialty practices will bolster the comprehensive care of patients and their families.”

She acknowledged certain limitations of the study, including the low proportion of respondents who were Hispanic/Latino and African American (about 4% each). “The insurance landscape may differ in these groups compared to the majority Caucasian population who responded to this survey,” Dr. Planchon said.

The National Multiple Sclerosis Society funded the study. Dr. Planchon reported having no relevant financial disclosures.

[email protected]

SOURCE: Planchon S et al. ACTRIMS Forum 2019, Abstract P295.

DALLAS – A battery of smartphone-based tests has been developed to help detect visual pathway disturbances in MS patients and to follow them over time.

“One of the ideas is, can you design something that’s so easy to use and quick that it’s not a burden on the patient?” Randy H. Kardon, MD, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other was to test a couple of different modalities. By that I mean we test visual acuity, contrast sensitivity, and critical flicker fusion, which is a way of measuring the speed of conduction of nerves in the visual system.”

Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City, worked with colleagues from Aalborg University, Denmark, to study these tests and a novel measure known as the vanishing optotype on 117 patients with MS and 103 age-matched controls. They found that the tests “very nicely discriminated between normal eyes from patients that had MS,” said Dr. Kardon, director of the Iowa City VA Center for Prevention and Treatment of Visual Loss. “Furthermore, we could determine which eyes from the MS patients had previous optic neuritis and which eyes hadn’t. We’re now looking for partners to go forward with larger studies to validate it further and refine these tests even more.”

Dr. Kardon disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

[email protected]

DALLAS – A battery of smartphone-based tests has been developed to help detect visual pathway disturbances in MS patients and to follow them over time.

“One of the ideas is, can you design something that’s so easy to use and quick that it’s not a burden on the patient?” Randy H. Kardon, MD, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other was to test a couple of different modalities. By that I mean we test visual acuity, contrast sensitivity, and critical flicker fusion, which is a way of measuring the speed of conduction of nerves in the visual system.”

Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City, worked with colleagues from Aalborg University, Denmark, to study these tests and a novel measure known as the vanishing optotype on 117 patients with MS and 103 age-matched controls. They found that the tests “very nicely discriminated between normal eyes from patients that had MS,” said Dr. Kardon, director of the Iowa City VA Center for Prevention and Treatment of Visual Loss. “Furthermore, we could determine which eyes from the MS patients had previous optic neuritis and which eyes hadn’t. We’re now looking for partners to go forward with larger studies to validate it further and refine these tests even more.”

Dr. Kardon disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

[email protected]

DALLAS – A battery of smartphone-based tests has been developed to help detect visual pathway disturbances in MS patients and to follow them over time.

“One of the ideas is, can you design something that’s so easy to use and quick that it’s not a burden on the patient?” Randy H. Kardon, MD, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other was to test a couple of different modalities. By that I mean we test visual acuity, contrast sensitivity, and critical flicker fusion, which is a way of measuring the speed of conduction of nerves in the visual system.”

Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City, worked with colleagues from Aalborg University, Denmark, to study these tests and a novel measure known as the vanishing optotype on 117 patients with MS and 103 age-matched controls. They found that the tests “very nicely discriminated between normal eyes from patients that had MS,” said Dr. Kardon, director of the Iowa City VA Center for Prevention and Treatment of Visual Loss. “Furthermore, we could determine which eyes from the MS patients had previous optic neuritis and which eyes hadn’t. We’re now looking for partners to go forward with larger studies to validate it further and refine these tests even more.”

Dr. Kardon disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

[email protected]