ICYMI Multiple Sclerosis

INDIANAPOLIS—A standardized MRI is important for the diagnosis and follow-up of patients with multiple sclerosis (MS). However, acquisition and interpretation of MRI scans may be complicated due to differences in pulse sequence (eg, FLAIR vs PD/T2), the use of contiguous and thinner (eg, 3 mm vs 5 mm) slices, as well as different patient positioning. Therefore, the Consortium of Multiple Sclerosis Centers (CMSC) convened a task force to develop and periodically revise indications and guidelines for a standardized MRI protocol in the diagnosis and follow-up of patients with MS. The panel’s most recent recommendations were presented at the 2015 CMSC Annual Meeting and will be published in an upcoming issue of American Journal of Neuroradiology.

Lead author Anthony Traboulsee, MD, Associate Professor at the University of British Columbia in Vancouver, and colleagues reported that a standardized brain MRI protocol with gadolinium is recommended for the diagnosis of MS. A spinal cord MRI is additionally recommended if the brain MRI is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MRI with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline prior to starting or modifying therapy. A routine brain MRI should be considered every six months to two years for all patients with relapsing MS. The standardized brain MRI protocol includes 3D T1-weighted, 3D T2-FLAIR (fluid-attenuated inversion recovery), 3D T2-weighted, post single-dose gadolinium-enhanced T1-weighted, and a diffusion-weighted sequence.

According to the 2015 Revised CMSC MRI Protocol, a simplified progressive multifocal leukoencephalopathy (PML) surveillance protocol includes FLAIR and diffusion-weighted imaging sequences only.

The spinal cord MRI protocol includes sagittal T1-weighted and proton density, short-time inversion recovery (STIR) or phase-sensitive inversion recovery (PSIR), axial T2- or T2*-weighted through suspicious lesions, and, in some cases, post-contrast gadolinium-enhanced T1-weighted imaging.

The task force’s revised guideline specifies that the clinical question being addressed should be provided in the requisition for the MRI. The radiology report should be descriptive with results referenced to previous studies. MRI studies should be permanently retained and available.

The 2015 revision incorporates new information and practice recommendations, and modification as modern imaging techniques (eg, 3D) have become more robust and available.

Key changes to the MRI protocol since the last revision in 2006 include an emphasis on 3D sequences for brain MRI, a PML-specific monitoring protocol, and an optional orbit MRI protocol for severe optic neuritis.

Key changes to the clinical guidelines since the 2006 revision include more specific guidance on timing of brain MRI for patients on disease-modifying therapy, timing of brain MRI for PML surveillance, updated evidence on the value of MRI changes in determining treatment effectiveness, and inclusion of radiologically isolated syndrome.

INDIANAPOLIS—A standardized MRI is important for the diagnosis and follow-up of patients with multiple sclerosis (MS). However, acquisition and interpretation of MRI scans may be complicated due to differences in pulse sequence (eg, FLAIR vs PD/T2), the use of contiguous and thinner (eg, 3 mm vs 5 mm) slices, as well as different patient positioning. Therefore, the Consortium of Multiple Sclerosis Centers (CMSC) convened a task force to develop and periodically revise indications and guidelines for a standardized MRI protocol in the diagnosis and follow-up of patients with MS. The panel’s most recent recommendations were presented at the 2015 CMSC Annual Meeting and will be published in an upcoming issue of American Journal of Neuroradiology.

Lead author Anthony Traboulsee, MD, Associate Professor at the University of British Columbia in Vancouver, and colleagues reported that a standardized brain MRI protocol with gadolinium is recommended for the diagnosis of MS. A spinal cord MRI is additionally recommended if the brain MRI is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MRI with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline prior to starting or modifying therapy. A routine brain MRI should be considered every six months to two years for all patients with relapsing MS. The standardized brain MRI protocol includes 3D T1-weighted, 3D T2-FLAIR (fluid-attenuated inversion recovery), 3D T2-weighted, post single-dose gadolinium-enhanced T1-weighted, and a diffusion-weighted sequence.

According to the 2015 Revised CMSC MRI Protocol, a simplified progressive multifocal leukoencephalopathy (PML) surveillance protocol includes FLAIR and diffusion-weighted imaging sequences only.

The spinal cord MRI protocol includes sagittal T1-weighted and proton density, short-time inversion recovery (STIR) or phase-sensitive inversion recovery (PSIR), axial T2- or T2*-weighted through suspicious lesions, and, in some cases, post-contrast gadolinium-enhanced T1-weighted imaging.

The task force’s revised guideline specifies that the clinical question being addressed should be provided in the requisition for the MRI. The radiology report should be descriptive with results referenced to previous studies. MRI studies should be permanently retained and available.

The 2015 revision incorporates new information and practice recommendations, and modification as modern imaging techniques (eg, 3D) have become more robust and available.

Key changes to the MRI protocol since the last revision in 2006 include an emphasis on 3D sequences for brain MRI, a PML-specific monitoring protocol, and an optional orbit MRI protocol for severe optic neuritis.

Key changes to the clinical guidelines since the 2006 revision include more specific guidance on timing of brain MRI for patients on disease-modifying therapy, timing of brain MRI for PML surveillance, updated evidence on the value of MRI changes in determining treatment effectiveness, and inclusion of radiologically isolated syndrome.

INDIANAPOLIS—A standardized MRI is important for the diagnosis and follow-up of patients with multiple sclerosis (MS). However, acquisition and interpretation of MRI scans may be complicated due to differences in pulse sequence (eg, FLAIR vs PD/T2), the use of contiguous and thinner (eg, 3 mm vs 5 mm) slices, as well as different patient positioning. Therefore, the Consortium of Multiple Sclerosis Centers (CMSC) convened a task force to develop and periodically revise indications and guidelines for a standardized MRI protocol in the diagnosis and follow-up of patients with MS. The panel’s most recent recommendations were presented at the 2015 CMSC Annual Meeting and will be published in an upcoming issue of American Journal of Neuroradiology.

Lead author Anthony Traboulsee, MD, Associate Professor at the University of British Columbia in Vancouver, and colleagues reported that a standardized brain MRI protocol with gadolinium is recommended for the diagnosis of MS. A spinal cord MRI is additionally recommended if the brain MRI is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MRI with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline prior to starting or modifying therapy. A routine brain MRI should be considered every six months to two years for all patients with relapsing MS. The standardized brain MRI protocol includes 3D T1-weighted, 3D T2-FLAIR (fluid-attenuated inversion recovery), 3D T2-weighted, post single-dose gadolinium-enhanced T1-weighted, and a diffusion-weighted sequence.

According to the 2015 Revised CMSC MRI Protocol, a simplified progressive multifocal leukoencephalopathy (PML) surveillance protocol includes FLAIR and diffusion-weighted imaging sequences only.

The spinal cord MRI protocol includes sagittal T1-weighted and proton density, short-time inversion recovery (STIR) or phase-sensitive inversion recovery (PSIR), axial T2- or T2*-weighted through suspicious lesions, and, in some cases, post-contrast gadolinium-enhanced T1-weighted imaging.

The task force’s revised guideline specifies that the clinical question being addressed should be provided in the requisition for the MRI. The radiology report should be descriptive with results referenced to previous studies. MRI studies should be permanently retained and available.

The 2015 revision incorporates new information and practice recommendations, and modification as modern imaging techniques (eg, 3D) have become more robust and available.

Key changes to the MRI protocol since the last revision in 2006 include an emphasis on 3D sequences for brain MRI, a PML-specific monitoring protocol, and an optional orbit MRI protocol for severe optic neuritis.

Key changes to the clinical guidelines since the 2006 revision include more specific guidance on timing of brain MRI for patients on disease-modifying therapy, timing of brain MRI for PML surveillance, updated evidence on the value of MRI changes in determining treatment effectiveness, and inclusion of radiologically isolated syndrome.

INDIANAPOLIS—For patients with multiple sclerosis (MS), making treatment decisions is a complex undertaking. The decisions involve clinical factors such as symptom severity, level of disability, and disease duration. Physician recommendations play a major role, but insurance coverage and financial situation also may be factors. Important changes to insurance coverage in the last few years may have required some patients to change their disease-modifying therapies (DMTs) for financial rather than clinical reasons.

To examine this issue, Stacey S. Cofield, PhD, a biostatistician at the University of Alabama at Birmingham, and her colleagues utilized patient-reported data from the NARCOMS registry to describe the insurance status of patient participants and how insurance and financial situation affect their DMT choices. Their findings were reported at the 2015 CMSC Annual Meeting.

The NARCOMS Fall 2014 Update survey included the following questions about health insurance and DMT choices related to insurance: current health insurance (Yes/No), health insurance for the prior six months (Yes/No), comparison of current health insurance to 12 months prior (better, worse, unchanged), and how insurance/financial situation has influenced treatment of MS. Dr. Cofield and colleagues reported on only registry participants who completed the survey online. Data entry for paper forms collected during the Fall 2014 Update is ongoing.

Of the 5,106 participants who completed the survey online, 4,507 (96.9%) completed the health insurance questions, 78.8% were female (mean age 56.7), and 62.1% had relapsing-remitting MS. Nearly all (99.5%) participants had health insurance. Likewise, nearly all (98.6%) had insurance for the prior six months, with 68.6% reporting insurance coverage had not changed in the prior year, while 23.0% reported worse coverage compared to 12 months ago. Coverage did not differ by gender or MS type, but more females reported their insurance coverage to be worse compared to 12 months ago (23.9% vs 19.7%). More respondents with progressive MS reported no change in coverage compared to those with relapsing-remitting MS (73.3% vs 66.8%). When asked about influence of insurance or financial situation on DMT choice, 30.0% reported not taking DMT by choice or physician recommendation, 15.9% took their DMT of choice with full coverage, 46.6% with a co-pay, 19.1% with free/discounted drug program, 3.6% were able to switch DMTs with insurance approval, 1.3% would like to switch but could not due to lack of insurance approval/coverage, while 2.4% had to stop/change/skip DMTs due to higher co-pays, and 1.6% did not take DMTs because they did not have insurance or insurance denied the DMT.

Dr. Cofield reported that most participants in the NARCOMS MS patient registry did not perceive major impacts from their insurance or financial situation with regard to DMT choice. Many patients, however, rely on assistance for DMT coverage or are not able to take a DMT as directed or at all due to their current insurance or financial situation.

INDIANAPOLIS—For patients with multiple sclerosis (MS), making treatment decisions is a complex undertaking. The decisions involve clinical factors such as symptom severity, level of disability, and disease duration. Physician recommendations play a major role, but insurance coverage and financial situation also may be factors. Important changes to insurance coverage in the last few years may have required some patients to change their disease-modifying therapies (DMTs) for financial rather than clinical reasons.

To examine this issue, Stacey S. Cofield, PhD, a biostatistician at the University of Alabama at Birmingham, and her colleagues utilized patient-reported data from the NARCOMS registry to describe the insurance status of patient participants and how insurance and financial situation affect their DMT choices. Their findings were reported at the 2015 CMSC Annual Meeting.

The NARCOMS Fall 2014 Update survey included the following questions about health insurance and DMT choices related to insurance: current health insurance (Yes/No), health insurance for the prior six months (Yes/No), comparison of current health insurance to 12 months prior (better, worse, unchanged), and how insurance/financial situation has influenced treatment of MS. Dr. Cofield and colleagues reported on only registry participants who completed the survey online. Data entry for paper forms collected during the Fall 2014 Update is ongoing.

Of the 5,106 participants who completed the survey online, 4,507 (96.9%) completed the health insurance questions, 78.8% were female (mean age 56.7), and 62.1% had relapsing-remitting MS. Nearly all (99.5%) participants had health insurance. Likewise, nearly all (98.6%) had insurance for the prior six months, with 68.6% reporting insurance coverage had not changed in the prior year, while 23.0% reported worse coverage compared to 12 months ago. Coverage did not differ by gender or MS type, but more females reported their insurance coverage to be worse compared to 12 months ago (23.9% vs 19.7%). More respondents with progressive MS reported no change in coverage compared to those with relapsing-remitting MS (73.3% vs 66.8%). When asked about influence of insurance or financial situation on DMT choice, 30.0% reported not taking DMT by choice or physician recommendation, 15.9% took their DMT of choice with full coverage, 46.6% with a co-pay, 19.1% with free/discounted drug program, 3.6% were able to switch DMTs with insurance approval, 1.3% would like to switch but could not due to lack of insurance approval/coverage, while 2.4% had to stop/change/skip DMTs due to higher co-pays, and 1.6% did not take DMTs because they did not have insurance or insurance denied the DMT.

Dr. Cofield reported that most participants in the NARCOMS MS patient registry did not perceive major impacts from their insurance or financial situation with regard to DMT choice. Many patients, however, rely on assistance for DMT coverage or are not able to take a DMT as directed or at all due to their current insurance or financial situation.

INDIANAPOLIS—For patients with multiple sclerosis (MS), making treatment decisions is a complex undertaking. The decisions involve clinical factors such as symptom severity, level of disability, and disease duration. Physician recommendations play a major role, but insurance coverage and financial situation also may be factors. Important changes to insurance coverage in the last few years may have required some patients to change their disease-modifying therapies (DMTs) for financial rather than clinical reasons.

To examine this issue, Stacey S. Cofield, PhD, a biostatistician at the University of Alabama at Birmingham, and her colleagues utilized patient-reported data from the NARCOMS registry to describe the insurance status of patient participants and how insurance and financial situation affect their DMT choices. Their findings were reported at the 2015 CMSC Annual Meeting.

The NARCOMS Fall 2014 Update survey included the following questions about health insurance and DMT choices related to insurance: current health insurance (Yes/No), health insurance for the prior six months (Yes/No), comparison of current health insurance to 12 months prior (better, worse, unchanged), and how insurance/financial situation has influenced treatment of MS. Dr. Cofield and colleagues reported on only registry participants who completed the survey online. Data entry for paper forms collected during the Fall 2014 Update is ongoing.

Of the 5,106 participants who completed the survey online, 4,507 (96.9%) completed the health insurance questions, 78.8% were female (mean age 56.7), and 62.1% had relapsing-remitting MS. Nearly all (99.5%) participants had health insurance. Likewise, nearly all (98.6%) had insurance for the prior six months, with 68.6% reporting insurance coverage had not changed in the prior year, while 23.0% reported worse coverage compared to 12 months ago. Coverage did not differ by gender or MS type, but more females reported their insurance coverage to be worse compared to 12 months ago (23.9% vs 19.7%). More respondents with progressive MS reported no change in coverage compared to those with relapsing-remitting MS (73.3% vs 66.8%). When asked about influence of insurance or financial situation on DMT choice, 30.0% reported not taking DMT by choice or physician recommendation, 15.9% took their DMT of choice with full coverage, 46.6% with a co-pay, 19.1% with free/discounted drug program, 3.6% were able to switch DMTs with insurance approval, 1.3% would like to switch but could not due to lack of insurance approval/coverage, while 2.4% had to stop/change/skip DMTs due to higher co-pays, and 1.6% did not take DMTs because they did not have insurance or insurance denied the DMT.

Dr. Cofield reported that most participants in the NARCOMS MS patient registry did not perceive major impacts from their insurance or financial situation with regard to DMT choice. Many patients, however, rely on assistance for DMT coverage or are not able to take a DMT as directed or at all due to their current insurance or financial situation.

INDIANAPOLIS—Cognitive behavioral therapy (CBT) can be an effective treatment for psychiatric and interpersonal problems in patients with multiple sclerosis (MS), according to research presented at the 2015 CMSC Annual Meeting. Data indicate that CBT can reduce anxiety and depression and improve marital satisfaction and marital communication.

CBT is a form of psychotherapy that identifies patterns of thought and behavior that change with depression or other mood disorders, said Frederick W. Foley, PhD, Professor of Psychology at Yeshiva University in Bronx, New York. The treatment helps people change these patterns of thinking and behavior to lessen the symptoms of the mood disorder or achieve remission.

Dr. Foley and colleagues examined 40 patients with MS in a study published in Journal of Consulting and Clinical Psychology. The investigators randomized the participants to current available care or stress inoculation training (SIT), which included CBT and progressive deep-muscle relaxation training adapted for patients with MS. At the end of the trial, Dr. Foley and colleagues found that participants randomized to SIT had significantly less depression, anxiety, and distress, compared with participants who received current available care. In addition, individuals randomized to SIT used more problem-focused coping strategies than those randomized to current available care.

In a pilot study published in Multiple Sclerosis in 2001, Dr. Foley and colleagues tested the efficacy of a counseling intervention that included CBT in nine couples with MS and sexual dysfunction. The intervention included 12 counseling sessions, communication with the MS medical treatment team, education, and tailoring of symptomatic treatments so that they would interfere less with sexual function. Repeated measures analysis of variance indicated that the couples had significant improvements in affective and problem-solving communication, marital satisfaction, and sexual satisfaction during the treatment, compared with a phase of the study during which they were on a waiting list. Patients with MS and their spouses reported similar levels of improvement.

CBT also may improve marital communication for patients with MS and cognitive disorders. In a study published in Journal of Neurologic Rehabilitation, Dr. Foley and colleagues developed templates to enable patients and their spouses to communicate. The investigators taught participants listening skills, how to empathize with their spouses using templates, and how to make positive (ie, noncritical) requests. In addition, the researchers instructed participants in how to provide feedback when their spouse’s behavior is not acceptable, as well as how to make positive requests for changes in behavior. This intervention has not been studied in a randomized controlled trial, however.

—Erik Greb

INDIANAPOLIS—Cognitive behavioral therapy (CBT) can be an effective treatment for psychiatric and interpersonal problems in patients with multiple sclerosis (MS), according to research presented at the 2015 CMSC Annual Meeting. Data indicate that CBT can reduce anxiety and depression and improve marital satisfaction and marital communication.

CBT is a form of psychotherapy that identifies patterns of thought and behavior that change with depression or other mood disorders, said Frederick W. Foley, PhD, Professor of Psychology at Yeshiva University in Bronx, New York. The treatment helps people change these patterns of thinking and behavior to lessen the symptoms of the mood disorder or achieve remission.

Dr. Foley and colleagues examined 40 patients with MS in a study published in Journal of Consulting and Clinical Psychology. The investigators randomized the participants to current available care or stress inoculation training (SIT), which included CBT and progressive deep-muscle relaxation training adapted for patients with MS. At the end of the trial, Dr. Foley and colleagues found that participants randomized to SIT had significantly less depression, anxiety, and distress, compared with participants who received current available care. In addition, individuals randomized to SIT used more problem-focused coping strategies than those randomized to current available care.

In a pilot study published in Multiple Sclerosis in 2001, Dr. Foley and colleagues tested the efficacy of a counseling intervention that included CBT in nine couples with MS and sexual dysfunction. The intervention included 12 counseling sessions, communication with the MS medical treatment team, education, and tailoring of symptomatic treatments so that they would interfere less with sexual function. Repeated measures analysis of variance indicated that the couples had significant improvements in affective and problem-solving communication, marital satisfaction, and sexual satisfaction during the treatment, compared with a phase of the study during which they were on a waiting list. Patients with MS and their spouses reported similar levels of improvement.

CBT also may improve marital communication for patients with MS and cognitive disorders. In a study published in Journal of Neurologic Rehabilitation, Dr. Foley and colleagues developed templates to enable patients and their spouses to communicate. The investigators taught participants listening skills, how to empathize with their spouses using templates, and how to make positive (ie, noncritical) requests. In addition, the researchers instructed participants in how to provide feedback when their spouse’s behavior is not acceptable, as well as how to make positive requests for changes in behavior. This intervention has not been studied in a randomized controlled trial, however.

—Erik Greb

INDIANAPOLIS—Cognitive behavioral therapy (CBT) can be an effective treatment for psychiatric and interpersonal problems in patients with multiple sclerosis (MS), according to research presented at the 2015 CMSC Annual Meeting. Data indicate that CBT can reduce anxiety and depression and improve marital satisfaction and marital communication.

CBT is a form of psychotherapy that identifies patterns of thought and behavior that change with depression or other mood disorders, said Frederick W. Foley, PhD, Professor of Psychology at Yeshiva University in Bronx, New York. The treatment helps people change these patterns of thinking and behavior to lessen the symptoms of the mood disorder or achieve remission.

Dr. Foley and colleagues examined 40 patients with MS in a study published in Journal of Consulting and Clinical Psychology. The investigators randomized the participants to current available care or stress inoculation training (SIT), which included CBT and progressive deep-muscle relaxation training adapted for patients with MS. At the end of the trial, Dr. Foley and colleagues found that participants randomized to SIT had significantly less depression, anxiety, and distress, compared with participants who received current available care. In addition, individuals randomized to SIT used more problem-focused coping strategies than those randomized to current available care.

In a pilot study published in Multiple Sclerosis in 2001, Dr. Foley and colleagues tested the efficacy of a counseling intervention that included CBT in nine couples with MS and sexual dysfunction. The intervention included 12 counseling sessions, communication with the MS medical treatment team, education, and tailoring of symptomatic treatments so that they would interfere less with sexual function. Repeated measures analysis of variance indicated that the couples had significant improvements in affective and problem-solving communication, marital satisfaction, and sexual satisfaction during the treatment, compared with a phase of the study during which they were on a waiting list. Patients with MS and their spouses reported similar levels of improvement.

CBT also may improve marital communication for patients with MS and cognitive disorders. In a study published in Journal of Neurologic Rehabilitation, Dr. Foley and colleagues developed templates to enable patients and their spouses to communicate. The investigators taught participants listening skills, how to empathize with their spouses using templates, and how to make positive (ie, noncritical) requests. In addition, the researchers instructed participants in how to provide feedback when their spouse’s behavior is not acceptable, as well as how to make positive requests for changes in behavior. This intervention has not been studied in a randomized controlled trial, however.

—Erik Greb

INDIANAPOLIS—NeuroTrax computerized cognitive testing (NT-CCT) provides an easy, independent, objective screening tool highly predictive of employment status in patients with multiple sclerosis (MS), according to research presented at the 2015 CMSC Annual Meeting. Lead author Mark Gudesblatt, MD, and colleagues said that objective assessment of cognitive function, such as NT-CCT provides, is an important adjunct to Expanded Disability Status Scale (EDSS) in routine MS care. Dr. Gudesblatt is a neurologist at South Shore Neurologic Associates in Patchogue, New York.

Cognitive impairment is common in patients with MS. Routine cognitive screening in MS care, however, is not common. Employment status may be affected by cognitive impairment, but this may not be apparent on routine EDSS assessment. “MS affects cognitive domains differently in people with MS,” said Dr. Gudesblatt. “Easily available and utilized objective cognitive screens are needed to evaluate cognition in MS independent of EDSS or MRI.”

The Symbol Digit Modalities Test (SDMT) is not commonly used in routine MS care. As a single-score cognitive measure, the SDMT does not provide information about individual cognitive domains or the presence or degree of impairment in multiple domains. Computerized cognitive screening tools, in comparison, provide scores for individual cognitive domains.

To explore the predictability and effect size between the SDMT and the NT-CCT domains in patients with MS who self-reported their employment status, Dr. Gudesblatt and colleagues conducted a retrospective review of patients with MS referred for screening cognitive testing in the course of routine clinical care. Patients were evaluated with the oral version of the SDMT and the NT-CCT on the same day.

The study included 113 MS patients, mean age 48.9, and 85% were female. The standardized SDMT score significantly correlated with NT-CCT Global Cognitive Score (GCS) and executive function. The SDMT and NT-CCT GCS both predicted employment status. The effect size of the NT-CCT GCS was 0.83, and for SDMT it was 0.70. For the NT-CCT Executive Function index the effect size was 0.87. In the NeuroTrax Catch Game, with scores standardized for age and education, overall score predicted employment. Unemployed patients with MS had NT-CCT cognitive domain index scores less than one standard deviation below average for cognitively health age and education norms.

“Unemployed patients with MS demonstrated reduced cognitive function relative to employed patients,” Dr. Gudesblatt and colleagues reported. SDMT and NT-CCT screening both significantly differentiate patients with MS who are employed and those who are not. However, NT-CCT predictability of employment provided a greater effect size for this differentiation.

INDIANAPOLIS—NeuroTrax computerized cognitive testing (NT-CCT) provides an easy, independent, objective screening tool highly predictive of employment status in patients with multiple sclerosis (MS), according to research presented at the 2015 CMSC Annual Meeting. Lead author Mark Gudesblatt, MD, and colleagues said that objective assessment of cognitive function, such as NT-CCT provides, is an important adjunct to Expanded Disability Status Scale (EDSS) in routine MS care. Dr. Gudesblatt is a neurologist at South Shore Neurologic Associates in Patchogue, New York.

Cognitive impairment is common in patients with MS. Routine cognitive screening in MS care, however, is not common. Employment status may be affected by cognitive impairment, but this may not be apparent on routine EDSS assessment. “MS affects cognitive domains differently in people with MS,” said Dr. Gudesblatt. “Easily available and utilized objective cognitive screens are needed to evaluate cognition in MS independent of EDSS or MRI.”

The Symbol Digit Modalities Test (SDMT) is not commonly used in routine MS care. As a single-score cognitive measure, the SDMT does not provide information about individual cognitive domains or the presence or degree of impairment in multiple domains. Computerized cognitive screening tools, in comparison, provide scores for individual cognitive domains.

To explore the predictability and effect size between the SDMT and the NT-CCT domains in patients with MS who self-reported their employment status, Dr. Gudesblatt and colleagues conducted a retrospective review of patients with MS referred for screening cognitive testing in the course of routine clinical care. Patients were evaluated with the oral version of the SDMT and the NT-CCT on the same day.

The study included 113 MS patients, mean age 48.9, and 85% were female. The standardized SDMT score significantly correlated with NT-CCT Global Cognitive Score (GCS) and executive function. The SDMT and NT-CCT GCS both predicted employment status. The effect size of the NT-CCT GCS was 0.83, and for SDMT it was 0.70. For the NT-CCT Executive Function index the effect size was 0.87. In the NeuroTrax Catch Game, with scores standardized for age and education, overall score predicted employment. Unemployed patients with MS had NT-CCT cognitive domain index scores less than one standard deviation below average for cognitively health age and education norms.

“Unemployed patients with MS demonstrated reduced cognitive function relative to employed patients,” Dr. Gudesblatt and colleagues reported. SDMT and NT-CCT screening both significantly differentiate patients with MS who are employed and those who are not. However, NT-CCT predictability of employment provided a greater effect size for this differentiation.

INDIANAPOLIS—NeuroTrax computerized cognitive testing (NT-CCT) provides an easy, independent, objective screening tool highly predictive of employment status in patients with multiple sclerosis (MS), according to research presented at the 2015 CMSC Annual Meeting. Lead author Mark Gudesblatt, MD, and colleagues said that objective assessment of cognitive function, such as NT-CCT provides, is an important adjunct to Expanded Disability Status Scale (EDSS) in routine MS care. Dr. Gudesblatt is a neurologist at South Shore Neurologic Associates in Patchogue, New York.

Cognitive impairment is common in patients with MS. Routine cognitive screening in MS care, however, is not common. Employment status may be affected by cognitive impairment, but this may not be apparent on routine EDSS assessment. “MS affects cognitive domains differently in people with MS,” said Dr. Gudesblatt. “Easily available and utilized objective cognitive screens are needed to evaluate cognition in MS independent of EDSS or MRI.”

The Symbol Digit Modalities Test (SDMT) is not commonly used in routine MS care. As a single-score cognitive measure, the SDMT does not provide information about individual cognitive domains or the presence or degree of impairment in multiple domains. Computerized cognitive screening tools, in comparison, provide scores for individual cognitive domains.

To explore the predictability and effect size between the SDMT and the NT-CCT domains in patients with MS who self-reported their employment status, Dr. Gudesblatt and colleagues conducted a retrospective review of patients with MS referred for screening cognitive testing in the course of routine clinical care. Patients were evaluated with the oral version of the SDMT and the NT-CCT on the same day.

The study included 113 MS patients, mean age 48.9, and 85% were female. The standardized SDMT score significantly correlated with NT-CCT Global Cognitive Score (GCS) and executive function. The SDMT and NT-CCT GCS both predicted employment status. The effect size of the NT-CCT GCS was 0.83, and for SDMT it was 0.70. For the NT-CCT Executive Function index the effect size was 0.87. In the NeuroTrax Catch Game, with scores standardized for age and education, overall score predicted employment. Unemployed patients with MS had NT-CCT cognitive domain index scores less than one standard deviation below average for cognitively health age and education norms.

“Unemployed patients with MS demonstrated reduced cognitive function relative to employed patients,” Dr. Gudesblatt and colleagues reported. SDMT and NT-CCT screening both significantly differentiate patients with MS who are employed and those who are not. However, NT-CCT predictability of employment provided a greater effect size for this differentiation.

The concept that biotin, a water-soluble vitamin, could have a beneficial effect on the course of multiple sclerosis (MS) is biologically plausible. Biotin activates acetyl-CoA carboxylase, a potential rate-limiting enzyme in myelin synthesis, and has multiple other biochemical effects.

In a small consecutive pilot study in 2015 that was neither placebo-controlled, blinded, nor randomized, Sedel et al found a suggestion of high-dose biotin’s clinical efficacy in patients with progressive MS.

The follow-up study by Tourbah et al expanded and confirmed the clinical efficacy of high-dose biotin (in the form of MD1003) in progressive forms of MS. In contrast to the prior trial, this trial was a double-blind, placebo-controlled, randomized study of 154 patients treated with 300 mg of biotin or placebo daily for 48 weeks. The results indicated that 13.6% of 103 biotin-treated patients had improvement of disability, using change in Expanded Disability Status Scale score or Timed 25-Foot Walk from baseline, as compared with 51 placebo-treated patients. No serious side effects were reported.

Few, if any, studies have shown sustained clinical improvement in patients with progressive forms of MS to date. As is often the case, however, some patients with ostensibly progressive MS may have evidence of clinical relapses, as seen in the biotin trials, or subclinical MRI relapses, as seen by new T2 or enhancing lesions in other studies, that may respond transiently to corticosteroids or disease-modifying therapies.

The mechanism of action of biotin in progressive MS, if validated in other studies, is not well defined. Possibilities include remyelination, axonal regeneration, inhibition of free oxygen radicals, and other effects. Biotin’s efficacy probably is not due to immunosuppression, however.

The results of Dr. Tourbah’s study are consistent with previous animal and human data that indicate biotin’s excellent safety profile. For this reason, and in light of the lack of treatment efficacy in progressive MS, additional robust Phase III studies of biotin should be carried out in an attempt to corroborate and expand these findings. This effort should include a larger number of patients with a longer study duration and additional clinical, neuropsychologic, and MRI studies.

—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz
Professor of Neurology and Neurosciences
Rutgers, The State University of New Jersey
Newark, NJ

The concept that biotin, a water-soluble vitamin, could have a beneficial effect on the course of multiple sclerosis (MS) is biologically plausible. Biotin activates acetyl-CoA carboxylase, a potential rate-limiting enzyme in myelin synthesis, and has multiple other biochemical effects.

In a small consecutive pilot study in 2015 that was neither placebo-controlled, blinded, nor randomized, Sedel et al found a suggestion of high-dose biotin’s clinical efficacy in patients with progressive MS.

The follow-up study by Tourbah et al expanded and confirmed the clinical efficacy of high-dose biotin (in the form of MD1003) in progressive forms of MS. In contrast to the prior trial, this trial was a double-blind, placebo-controlled, randomized study of 154 patients treated with 300 mg of biotin or placebo daily for 48 weeks. The results indicated that 13.6% of 103 biotin-treated patients had improvement of disability, using change in Expanded Disability Status Scale score or Timed 25-Foot Walk from baseline, as compared with 51 placebo-treated patients. No serious side effects were reported.

Few, if any, studies have shown sustained clinical improvement in patients with progressive forms of MS to date. As is often the case, however, some patients with ostensibly progressive MS may have evidence of clinical relapses, as seen in the biotin trials, or subclinical MRI relapses, as seen by new T2 or enhancing lesions in other studies, that may respond transiently to corticosteroids or disease-modifying therapies.

The mechanism of action of biotin in progressive MS, if validated in other studies, is not well defined. Possibilities include remyelination, axonal regeneration, inhibition of free oxygen radicals, and other effects. Biotin’s efficacy probably is not due to immunosuppression, however.

The results of Dr. Tourbah’s study are consistent with previous animal and human data that indicate biotin’s excellent safety profile. For this reason, and in light of the lack of treatment efficacy in progressive MS, additional robust Phase III studies of biotin should be carried out in an attempt to corroborate and expand these findings. This effort should include a larger number of patients with a longer study duration and additional clinical, neuropsychologic, and MRI studies.

—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz
Professor of Neurology and Neurosciences
Rutgers, The State University of New Jersey
Newark, NJ

The concept that biotin, a water-soluble vitamin, could have a beneficial effect on the course of multiple sclerosis (MS) is biologically plausible. Biotin activates acetyl-CoA carboxylase, a potential rate-limiting enzyme in myelin synthesis, and has multiple other biochemical effects.

In a small consecutive pilot study in 2015 that was neither placebo-controlled, blinded, nor randomized, Sedel et al found a suggestion of high-dose biotin’s clinical efficacy in patients with progressive MS.

The follow-up study by Tourbah et al expanded and confirmed the clinical efficacy of high-dose biotin (in the form of MD1003) in progressive forms of MS. In contrast to the prior trial, this trial was a double-blind, placebo-controlled, randomized study of 154 patients treated with 300 mg of biotin or placebo daily for 48 weeks. The results indicated that 13.6% of 103 biotin-treated patients had improvement of disability, using change in Expanded Disability Status Scale score or Timed 25-Foot Walk from baseline, as compared with 51 placebo-treated patients. No serious side effects were reported.

Few, if any, studies have shown sustained clinical improvement in patients with progressive forms of MS to date. As is often the case, however, some patients with ostensibly progressive MS may have evidence of clinical relapses, as seen in the biotin trials, or subclinical MRI relapses, as seen by new T2 or enhancing lesions in other studies, that may respond transiently to corticosteroids or disease-modifying therapies.

The mechanism of action of biotin in progressive MS, if validated in other studies, is not well defined. Possibilities include remyelination, axonal regeneration, inhibition of free oxygen radicals, and other effects. Biotin’s efficacy probably is not due to immunosuppression, however.

The results of Dr. Tourbah’s study are consistent with previous animal and human data that indicate biotin’s excellent safety profile. For this reason, and in light of the lack of treatment efficacy in progressive MS, additional robust Phase III studies of biotin should be carried out in an attempt to corroborate and expand these findings. This effort should include a larger number of patients with a longer study duration and additional clinical, neuropsychologic, and MRI studies.

—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz
Professor of Neurology and Neurosciences
Rutgers, The State University of New Jersey
Newark, NJ

WASHINGTON, DC—Biotin may result in clinical improvement among patients with progressive multiple sclerosis (MS) and decrease the risk of progression, according to a study described at the 67th Annual Meeting of the American Academy of Neurology. The drug appears not to be associated with any significant adverse events.

Many MS therapies have reduced relapses effectively but have failed to produce significant and sustained reductions in disability. In an open-label study published in 2015, patients with progressive MS who received high doses of biotin had 22% clinical improvement, mainly in the Expanded Disability Status Scale (EDSS). Ayman Tourbah, MD, PhD, Professor of Neurology at Centre Hospitalier Universitaire in Reims, France, and colleagues subsequently conducted a Phase III trial of MD1003, a highly concentrated pharmaceutical grade of biotin, at 16 MS reference centers.

Comparing MD1003 and Placebo
Eligible participants were between ages 18 and 75, had primary or secondary progressive MS, had an EDSS score between 4.5 and 7, and had disease progression within the previous two years, as measured by EDSS. Patients were excluded from the study if they had initiated a new disease-modifying therapy during the three months before enrollment or if they had received symptomatic treatment with fampridine within one month of enrollment.

The researchers screened 166 patients and included 154 of them in a two-to-one randomization. In all, 103 patients received daily 300-mg doses of MD1003, and 51 patients received placebo. Slightly more patients in the active arm had primary progressive MS, compared with the placebo group. Also, slightly more patients were taking fampridine in the placebo group, compared with the active group. The researchers noted no other differences between the treatment arms.

The study’s primary end point was the proportion of patients with improvement at month nine that was confirmed at month 12 using EDSS or the Timed 25-Foot Walk (T25FW), compared with baseline measures. EDSS improvement was defined as a decrease of at least one point for patients with a baseline EDSS between 4.5 and 5.5, and as a decrease of at least 0.5 points for patients with a baseline EDSS between 6 and 7. T25FW was considered improved if it decreased by at least 20%, compared with baseline.

Treated Patients Had Sustained Improvement
At the end of the study, 13 patients in the active arm had met the primary end point, compared with none of the patients in the placebo arm. The difference between groups was statistically significant. Twice as many patients met the primary end point with the EDSS, compared with the T25FW. The investigators found no major differences between the group of patients treated with MD1003 and the group of patients who met the primary end point.

A secondary analysis indicated that mean EDSS improved at the initial phase of the trial for participants in the treatment arm, and their improvement was sustained throughout the study. The placebo group had an initial improvement in mean EDSS, but EDSS worsened at all subsequent time points. After 12 months, the difference between the two groups in the mean change in EDSS was statistically significant.

In addition, 13.6% of patients in the placebo group had EDSS progression that was confirmed at two subsequent visits. In contrast, 4.2% of patients receiving MD1003 had progression at month nine that was confirmed at month 12. The difference between groups was not statistically significant, however. Nevertheless, the data indicate a 67% decrease in the risk of progression for patients receiving MD1003, compared with controls, said Dr. Tourbah. Similar trends were observed for the T25FW.

The researchers found no difference in adverse events between the treatment groups. Twice as many patients in the placebo group had relapses, compared with the active arm. High doses of biotin may interfere with immunoassays that use biotinylated antibodies or substrates, however, thus requiring patients and physicians to be informed adequately.

Biotin is a water-soluble coenzyme that is thought to promote myelination and enhance energy supply. “High doses of biotin may feed the Krebs cycle to increase adenosine triphosphate synthesis and energy production, thus possibly reversing virtual hypoxia and protecting neurons from degeneration,” said Dr. Tourbah.

—Erik Greb

WASHINGTON, DC—Biotin may result in clinical improvement among patients with progressive multiple sclerosis (MS) and decrease the risk of progression, according to a study described at the 67th Annual Meeting of the American Academy of Neurology. The drug appears not to be associated with any significant adverse events.

Many MS therapies have reduced relapses effectively but have failed to produce significant and sustained reductions in disability. In an open-label study published in 2015, patients with progressive MS who received high doses of biotin had 22% clinical improvement, mainly in the Expanded Disability Status Scale (EDSS). Ayman Tourbah, MD, PhD, Professor of Neurology at Centre Hospitalier Universitaire in Reims, France, and colleagues subsequently conducted a Phase III trial of MD1003, a highly concentrated pharmaceutical grade of biotin, at 16 MS reference centers.

Comparing MD1003 and Placebo
Eligible participants were between ages 18 and 75, had primary or secondary progressive MS, had an EDSS score between 4.5 and 7, and had disease progression within the previous two years, as measured by EDSS. Patients were excluded from the study if they had initiated a new disease-modifying therapy during the three months before enrollment or if they had received symptomatic treatment with fampridine within one month of enrollment.

The researchers screened 166 patients and included 154 of them in a two-to-one randomization. In all, 103 patients received daily 300-mg doses of MD1003, and 51 patients received placebo. Slightly more patients in the active arm had primary progressive MS, compared with the placebo group. Also, slightly more patients were taking fampridine in the placebo group, compared with the active group. The researchers noted no other differences between the treatment arms.

The study’s primary end point was the proportion of patients with improvement at month nine that was confirmed at month 12 using EDSS or the Timed 25-Foot Walk (T25FW), compared with baseline measures. EDSS improvement was defined as a decrease of at least one point for patients with a baseline EDSS between 4.5 and 5.5, and as a decrease of at least 0.5 points for patients with a baseline EDSS between 6 and 7. T25FW was considered improved if it decreased by at least 20%, compared with baseline.

Treated Patients Had Sustained Improvement
At the end of the study, 13 patients in the active arm had met the primary end point, compared with none of the patients in the placebo arm. The difference between groups was statistically significant. Twice as many patients met the primary end point with the EDSS, compared with the T25FW. The investigators found no major differences between the group of patients treated with MD1003 and the group of patients who met the primary end point.

A secondary analysis indicated that mean EDSS improved at the initial phase of the trial for participants in the treatment arm, and their improvement was sustained throughout the study. The placebo group had an initial improvement in mean EDSS, but EDSS worsened at all subsequent time points. After 12 months, the difference between the two groups in the mean change in EDSS was statistically significant.

In addition, 13.6% of patients in the placebo group had EDSS progression that was confirmed at two subsequent visits. In contrast, 4.2% of patients receiving MD1003 had progression at month nine that was confirmed at month 12. The difference between groups was not statistically significant, however. Nevertheless, the data indicate a 67% decrease in the risk of progression for patients receiving MD1003, compared with controls, said Dr. Tourbah. Similar trends were observed for the T25FW.

The researchers found no difference in adverse events between the treatment groups. Twice as many patients in the placebo group had relapses, compared with the active arm. High doses of biotin may interfere with immunoassays that use biotinylated antibodies or substrates, however, thus requiring patients and physicians to be informed adequately.

Biotin is a water-soluble coenzyme that is thought to promote myelination and enhance energy supply. “High doses of biotin may feed the Krebs cycle to increase adenosine triphosphate synthesis and energy production, thus possibly reversing virtual hypoxia and protecting neurons from degeneration,” said Dr. Tourbah.

—Erik Greb

WASHINGTON, DC—Biotin may result in clinical improvement among patients with progressive multiple sclerosis (MS) and decrease the risk of progression, according to a study described at the 67th Annual Meeting of the American Academy of Neurology. The drug appears not to be associated with any significant adverse events.

Many MS therapies have reduced relapses effectively but have failed to produce significant and sustained reductions in disability. In an open-label study published in 2015, patients with progressive MS who received high doses of biotin had 22% clinical improvement, mainly in the Expanded Disability Status Scale (EDSS). Ayman Tourbah, MD, PhD, Professor of Neurology at Centre Hospitalier Universitaire in Reims, France, and colleagues subsequently conducted a Phase III trial of MD1003, a highly concentrated pharmaceutical grade of biotin, at 16 MS reference centers.

Comparing MD1003 and Placebo
Eligible participants were between ages 18 and 75, had primary or secondary progressive MS, had an EDSS score between 4.5 and 7, and had disease progression within the previous two years, as measured by EDSS. Patients were excluded from the study if they had initiated a new disease-modifying therapy during the three months before enrollment or if they had received symptomatic treatment with fampridine within one month of enrollment.

The researchers screened 166 patients and included 154 of them in a two-to-one randomization. In all, 103 patients received daily 300-mg doses of MD1003, and 51 patients received placebo. Slightly more patients in the active arm had primary progressive MS, compared with the placebo group. Also, slightly more patients were taking fampridine in the placebo group, compared with the active group. The researchers noted no other differences between the treatment arms.

The study’s primary end point was the proportion of patients with improvement at month nine that was confirmed at month 12 using EDSS or the Timed 25-Foot Walk (T25FW), compared with baseline measures. EDSS improvement was defined as a decrease of at least one point for patients with a baseline EDSS between 4.5 and 5.5, and as a decrease of at least 0.5 points for patients with a baseline EDSS between 6 and 7. T25FW was considered improved if it decreased by at least 20%, compared with baseline.

Treated Patients Had Sustained Improvement
At the end of the study, 13 patients in the active arm had met the primary end point, compared with none of the patients in the placebo arm. The difference between groups was statistically significant. Twice as many patients met the primary end point with the EDSS, compared with the T25FW. The investigators found no major differences between the group of patients treated with MD1003 and the group of patients who met the primary end point.

A secondary analysis indicated that mean EDSS improved at the initial phase of the trial for participants in the treatment arm, and their improvement was sustained throughout the study. The placebo group had an initial improvement in mean EDSS, but EDSS worsened at all subsequent time points. After 12 months, the difference between the two groups in the mean change in EDSS was statistically significant.

In addition, 13.6% of patients in the placebo group had EDSS progression that was confirmed at two subsequent visits. In contrast, 4.2% of patients receiving MD1003 had progression at month nine that was confirmed at month 12. The difference between groups was not statistically significant, however. Nevertheless, the data indicate a 67% decrease in the risk of progression for patients receiving MD1003, compared with controls, said Dr. Tourbah. Similar trends were observed for the T25FW.

The researchers found no difference in adverse events between the treatment groups. Twice as many patients in the placebo group had relapses, compared with the active arm. High doses of biotin may interfere with immunoassays that use biotinylated antibodies or substrates, however, thus requiring patients and physicians to be informed adequately.

Biotin is a water-soluble coenzyme that is thought to promote myelination and enhance energy supply. “High doses of biotin may feed the Krebs cycle to increase adenosine triphosphate synthesis and energy production, thus possibly reversing virtual hypoxia and protecting neurons from degeneration,” said Dr. Tourbah.

—Erik Greb

WASHINGTON, DC—Treatment with daclizumab high-yield process (DAC HYP), a first-in-class immunomodulator administered subcutaneously once per month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis (MS) than was interferon (IFN) β-1a therapy, according to results from the international DECIDE study presented at the 67th Annual Meeting of the American Academy of Neurology.

The efficacy of DAC HYP was consistently superior to that of once-weekly intramuscular IFN β-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over the study’s treatment period of 96 to 144 weeks, said Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel and of the DECIDE study’s advisory committee. DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” he said.

Treatment with DAC HYP was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which were “manageable with standard monitoring and medical interventions,” Dr. Kappos said.

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 receptor subunit CD25, which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

Reduction in Relapse Rate Was Highly Significant
The DECIDE phase III study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every four weeks and 922 patients to treatment with 30 mg of IFN β-1a administered intramuscularly once per week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of five years. Patients in both groups had had a similar mean number of relapses within the previous year (between 0.7 and 0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously. Their mean Expanded Disability Status Scale (EDSS) score was between 1.2 and 1.3. In both arms, approximately 30% of patients discontinued treatment. The percentage of patients that discontinued treatment because of adverse events was higher in the DAC HYP-treated group.

The annualized relapse rate—the study’s primary end point—was 0.393 among those on IFN β-1a, compared with 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant, Dr. Kappos said.

Secondary end points included the proportion of patients who remained relapse-free, which was higher among those on DAC HYP at various points during the study (eg, 73% vs 59% at week 96, and 67% vs 51% at week 144). The risk of relapse was reduced by 41%.

Other secondary end points were MRI-defined lesions at week 96. The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN β-1a. There were similar reductions in new T1 black holes, which were reduced by 52%, and in gadolinium-enhancing lesions, which were reduced by 65%. There was a significant positive effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At three months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN β-1a, although the effect was not statistically significant. At six months, the risk was reduced by 27%. The proportion of patients on DAC HYP with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5-point decrease on MSIS-29-PHYS) was reduced by 24%, compared with those on IFN β-1a. The reduction was not statistically significant.

Hepatic Abnormalities Were More Common in Daclizumab Patients
The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs 21%); when MS relapses were excluded, the rates were 15% and 10%. Treatment discontinuations due to an adverse event other than an MS relapse were 14% among those on DAC HYP, compared with 9% of those on IFN β-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs 57%), as was the rate of serious infectious adverse events (4% vs 2%). Cutaneous events were more common among those on DAC HYP (37% vs 19%), as were serious cutaneous adverse events (2% vs less than 1%).

Hepatic abnormalities were more common among those on DAC HYP, but were reversible, Dr. Kappos said. The rate of aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than five times the upper limit of normal (ULN) was 6% among those on DAC HYP, compared with 3% among those on IFN β-1a. The rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case in each group that met Hy’s law criteria, which are used to predict the potential of drugs to cause serious liver injury.

Biogen Idec and AbbVie Biotherapeutics funded the study.

—Elizabeth Mechcatie

WASHINGTON, DC—Treatment with daclizumab high-yield process (DAC HYP), a first-in-class immunomodulator administered subcutaneously once per month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis (MS) than was interferon (IFN) β-1a therapy, according to results from the international DECIDE study presented at the 67th Annual Meeting of the American Academy of Neurology.

The efficacy of DAC HYP was consistently superior to that of once-weekly intramuscular IFN β-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over the study’s treatment period of 96 to 144 weeks, said Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel and of the DECIDE study’s advisory committee. DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” he said.

Treatment with DAC HYP was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which were “manageable with standard monitoring and medical interventions,” Dr. Kappos said.

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 receptor subunit CD25, which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

Reduction in Relapse Rate Was Highly Significant
The DECIDE phase III study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every four weeks and 922 patients to treatment with 30 mg of IFN β-1a administered intramuscularly once per week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of five years. Patients in both groups had had a similar mean number of relapses within the previous year (between 0.7 and 0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously. Their mean Expanded Disability Status Scale (EDSS) score was between 1.2 and 1.3. In both arms, approximately 30% of patients discontinued treatment. The percentage of patients that discontinued treatment because of adverse events was higher in the DAC HYP-treated group.

The annualized relapse rate—the study’s primary end point—was 0.393 among those on IFN β-1a, compared with 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant, Dr. Kappos said.

Secondary end points included the proportion of patients who remained relapse-free, which was higher among those on DAC HYP at various points during the study (eg, 73% vs 59% at week 96, and 67% vs 51% at week 144). The risk of relapse was reduced by 41%.

Other secondary end points were MRI-defined lesions at week 96. The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN β-1a. There were similar reductions in new T1 black holes, which were reduced by 52%, and in gadolinium-enhancing lesions, which were reduced by 65%. There was a significant positive effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At three months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN β-1a, although the effect was not statistically significant. At six months, the risk was reduced by 27%. The proportion of patients on DAC HYP with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5-point decrease on MSIS-29-PHYS) was reduced by 24%, compared with those on IFN β-1a. The reduction was not statistically significant.

Hepatic Abnormalities Were More Common in Daclizumab Patients
The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs 21%); when MS relapses were excluded, the rates were 15% and 10%. Treatment discontinuations due to an adverse event other than an MS relapse were 14% among those on DAC HYP, compared with 9% of those on IFN β-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs 57%), as was the rate of serious infectious adverse events (4% vs 2%). Cutaneous events were more common among those on DAC HYP (37% vs 19%), as were serious cutaneous adverse events (2% vs less than 1%).

Hepatic abnormalities were more common among those on DAC HYP, but were reversible, Dr. Kappos said. The rate of aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than five times the upper limit of normal (ULN) was 6% among those on DAC HYP, compared with 3% among those on IFN β-1a. The rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case in each group that met Hy’s law criteria, which are used to predict the potential of drugs to cause serious liver injury.

Biogen Idec and AbbVie Biotherapeutics funded the study.

—Elizabeth Mechcatie

WASHINGTON, DC—Treatment with daclizumab high-yield process (DAC HYP), a first-in-class immunomodulator administered subcutaneously once per month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis (MS) than was interferon (IFN) β-1a therapy, according to results from the international DECIDE study presented at the 67th Annual Meeting of the American Academy of Neurology.

The efficacy of DAC HYP was consistently superior to that of once-weekly intramuscular IFN β-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over the study’s treatment period of 96 to 144 weeks, said Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel and of the DECIDE study’s advisory committee. DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” he said.

Treatment with DAC HYP was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which were “manageable with standard monitoring and medical interventions,” Dr. Kappos said.

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 receptor subunit CD25, which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

Reduction in Relapse Rate Was Highly Significant
The DECIDE phase III study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every four weeks and 922 patients to treatment with 30 mg of IFN β-1a administered intramuscularly once per week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of five years. Patients in both groups had had a similar mean number of relapses within the previous year (between 0.7 and 0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously. Their mean Expanded Disability Status Scale (EDSS) score was between 1.2 and 1.3. In both arms, approximately 30% of patients discontinued treatment. The percentage of patients that discontinued treatment because of adverse events was higher in the DAC HYP-treated group.

The annualized relapse rate—the study’s primary end point—was 0.393 among those on IFN β-1a, compared with 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant, Dr. Kappos said.

Secondary end points included the proportion of patients who remained relapse-free, which was higher among those on DAC HYP at various points during the study (eg, 73% vs 59% at week 96, and 67% vs 51% at week 144). The risk of relapse was reduced by 41%.

Other secondary end points were MRI-defined lesions at week 96. The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN β-1a. There were similar reductions in new T1 black holes, which were reduced by 52%, and in gadolinium-enhancing lesions, which were reduced by 65%. There was a significant positive effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At three months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN β-1a, although the effect was not statistically significant. At six months, the risk was reduced by 27%. The proportion of patients on DAC HYP with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5-point decrease on MSIS-29-PHYS) was reduced by 24%, compared with those on IFN β-1a. The reduction was not statistically significant.

Hepatic Abnormalities Were More Common in Daclizumab Patients
The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs 21%); when MS relapses were excluded, the rates were 15% and 10%. Treatment discontinuations due to an adverse event other than an MS relapse were 14% among those on DAC HYP, compared with 9% of those on IFN β-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs 57%), as was the rate of serious infectious adverse events (4% vs 2%). Cutaneous events were more common among those on DAC HYP (37% vs 19%), as were serious cutaneous adverse events (2% vs less than 1%).

Hepatic abnormalities were more common among those on DAC HYP, but were reversible, Dr. Kappos said. The rate of aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than five times the upper limit of normal (ULN) was 6% among those on DAC HYP, compared with 3% among those on IFN β-1a. The rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case in each group that met Hy’s law criteria, which are used to predict the potential of drugs to cause serious liver injury.

Biogen Idec and AbbVie Biotherapeutics funded the study.

—Elizabeth Mechcatie

After a fall, more than a quarter of MS patients report delayed initial recovery of laying on the floor or ground for more than 10 minutes, and a smaller fraction reported a long lie of 1 hour or more, according to a secondary analysis of 700 patients ages 55 and older from the North America Committee on Multiple Sclerosis registry.

Researchers used participants’ self-reported information about their most recent fall to determine rates of delayed initial recovery and a long lie and found:

• Of the 322 patients with fall information, 27.6% reported delayed initial recovery and 4.7% reported a long lie. 

• Factors associated with delayed initial recovery include longer disease duration (odds ratio [OR], 1.03), fall leading to fracture (OR, 2.73), needing help to get up (OR, 3.94), depression (OR, 1.96), and leg weakness (OR, 2.14).

Citation: Bisson EJ, Peterson EW, Finlayson M. Delayed initial recovery and long lie following a fall among middle-aged and older adults with multiple sclerosis. Arch Phys Med Rehabil. 2015. pii: S0003-9993(15)00378-0. doi:10.1016/j.apmr.2015.04.012.

Commentary: MS is a chronic disease that impacts patients in many different ways. Concerns are typically focused on relapse rates and MRI changes. Disease burden may include limitation of ambulation, impaired balance or vision, and cognitive problems. All of these problems might result in increased risk of falling. Economic impact related to MS also includes factors related to falling. Increased risk of falls—and the subsequent fear of falling—might limit independence and reduce quality of life. The costs related to injury from falling, restricted daily activities from this fear of falling, and attendant anxiety are not only likely significant costs but chronic costs as well. This article points out that fall risk evaluation and fall prevention are unmet needs in the continuum of MS care. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

After a fall, more than a quarter of MS patients report delayed initial recovery of laying on the floor or ground for more than 10 minutes, and a smaller fraction reported a long lie of 1 hour or more, according to a secondary analysis of 700 patients ages 55 and older from the North America Committee on Multiple Sclerosis registry.

Researchers used participants’ self-reported information about their most recent fall to determine rates of delayed initial recovery and a long lie and found:

• Of the 322 patients with fall information, 27.6% reported delayed initial recovery and 4.7% reported a long lie. 

• Factors associated with delayed initial recovery include longer disease duration (odds ratio [OR], 1.03), fall leading to fracture (OR, 2.73), needing help to get up (OR, 3.94), depression (OR, 1.96), and leg weakness (OR, 2.14).

Citation: Bisson EJ, Peterson EW, Finlayson M. Delayed initial recovery and long lie following a fall among middle-aged and older adults with multiple sclerosis. Arch Phys Med Rehabil. 2015. pii: S0003-9993(15)00378-0. doi:10.1016/j.apmr.2015.04.012.

Commentary: MS is a chronic disease that impacts patients in many different ways. Concerns are typically focused on relapse rates and MRI changes. Disease burden may include limitation of ambulation, impaired balance or vision, and cognitive problems. All of these problems might result in increased risk of falling. Economic impact related to MS also includes factors related to falling. Increased risk of falls—and the subsequent fear of falling—might limit independence and reduce quality of life. The costs related to injury from falling, restricted daily activities from this fear of falling, and attendant anxiety are not only likely significant costs but chronic costs as well. This article points out that fall risk evaluation and fall prevention are unmet needs in the continuum of MS care. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

After a fall, more than a quarter of MS patients report delayed initial recovery of laying on the floor or ground for more than 10 minutes, and a smaller fraction reported a long lie of 1 hour or more, according to a secondary analysis of 700 patients ages 55 and older from the North America Committee on Multiple Sclerosis registry.

Researchers used participants’ self-reported information about their most recent fall to determine rates of delayed initial recovery and a long lie and found:

• Of the 322 patients with fall information, 27.6% reported delayed initial recovery and 4.7% reported a long lie. 

• Factors associated with delayed initial recovery include longer disease duration (odds ratio [OR], 1.03), fall leading to fracture (OR, 2.73), needing help to get up (OR, 3.94), depression (OR, 1.96), and leg weakness (OR, 2.14).

Citation: Bisson EJ, Peterson EW, Finlayson M. Delayed initial recovery and long lie following a fall among middle-aged and older adults with multiple sclerosis. Arch Phys Med Rehabil. 2015. pii: S0003-9993(15)00378-0. doi:10.1016/j.apmr.2015.04.012.

Commentary: MS is a chronic disease that impacts patients in many different ways. Concerns are typically focused on relapse rates and MRI changes. Disease burden may include limitation of ambulation, impaired balance or vision, and cognitive problems. All of these problems might result in increased risk of falling. Economic impact related to MS also includes factors related to falling. Increased risk of falls—and the subsequent fear of falling—might limit independence and reduce quality of life. The costs related to injury from falling, restricted daily activities from this fear of falling, and attendant anxiety are not only likely significant costs but chronic costs as well. This article points out that fall risk evaluation and fall prevention are unmet needs in the continuum of MS care. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY