11-Year Data From BENEFIT Trial Support Early Treatment of Interferon Beta-1b for CIS

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong