Multiple Sclerosis Hub

NATIONAL HARBOR, MD—Patients with highly active relapsing-remitting multiple sclerosis (RRMS) have durable improvement for more than five years with alemtuzumab use, according to data presented at the 2016 CMSC Annual Meeting. In a phase III trial, 45% of patients treated with alemtuzumab also sustained a six-month reduction in disability.

Barry A. Singer, MD

In the CARE-MS II study, alemtuzumab was associated with more significant improvement in clinical and MRI outcomes over two years, compared with subcutaneous interferon beta-1a, in patients with active RRMS who had had a poor response to prior therapy at baseline. An extension study was initiated to evaluate the five-year efficacy of alemtuzumab treatment in a subset of patients with RRMS and highly active disease at baseline. Barry A. Singer, MD, Assistant Professor of Clinical Neurology at Washington University in St. Louis, and his colleagues defined highly active disease as two or more relapses in the year before randomization and gadolinium-enhanced lesions at baseline. In the study, 24% of patients receiving alemtuzumab met the criteria for highly active disease.

During the trial, patients randomized to alemtuzumab (12 mg/day) were given two courses of treatment for five consecutive days at baseline and treatment for three consecutive days in the 12th month. In the extension study, patients were only allowed to receive alemtuzumab retreatment if they had a relapse or MRI activity on disease-modifying treatment.

In more than five years, at least 80% of patients receiving alemtuzumab who had had an inadequate response to prior therapy were free of relapses in each individual year. Sixty-two percent of patients had no alemtuzumab retreatment or other disease-modifying therapies. Results also showed that 97% of patients did not receive another disease-modifying therapy.

In this cohort, no evidence of disease activity was reported in 71%, 63%, and 67% of patients during years three, four, and five, as well as in 53% of patients during years zero to five. Arrhythmias remained low in each individual year of the extension study. Expanded Disability Status Scale (EDSS) scores also showed improvement with alemtuzumab use through years zero to five. In addition, sustained reduction in disability was achieved by 53% of patients during years zero to five.

“Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for patients with highly active RRMS,” said Dr. Singer and his colleagues.

This study was supported by Genzyme and Bayer HealthCare Pharmaceuticals.

—Erica Robinson

NATIONAL HARBOR, MD—Patients with highly active relapsing-remitting multiple sclerosis (RRMS) have durable improvement for more than five years with alemtuzumab use, according to data presented at the 2016 CMSC Annual Meeting. In a phase III trial, 45% of patients treated with alemtuzumab also sustained a six-month reduction in disability.

Barry A. Singer, MD

In the CARE-MS II study, alemtuzumab was associated with more significant improvement in clinical and MRI outcomes over two years, compared with subcutaneous interferon beta-1a, in patients with active RRMS who had had a poor response to prior therapy at baseline. An extension study was initiated to evaluate the five-year efficacy of alemtuzumab treatment in a subset of patients with RRMS and highly active disease at baseline. Barry A. Singer, MD, Assistant Professor of Clinical Neurology at Washington University in St. Louis, and his colleagues defined highly active disease as two or more relapses in the year before randomization and gadolinium-enhanced lesions at baseline. In the study, 24% of patients receiving alemtuzumab met the criteria for highly active disease.

During the trial, patients randomized to alemtuzumab (12 mg/day) were given two courses of treatment for five consecutive days at baseline and treatment for three consecutive days in the 12th month. In the extension study, patients were only allowed to receive alemtuzumab retreatment if they had a relapse or MRI activity on disease-modifying treatment.

In more than five years, at least 80% of patients receiving alemtuzumab who had had an inadequate response to prior therapy were free of relapses in each individual year. Sixty-two percent of patients had no alemtuzumab retreatment or other disease-modifying therapies. Results also showed that 97% of patients did not receive another disease-modifying therapy.

In this cohort, no evidence of disease activity was reported in 71%, 63%, and 67% of patients during years three, four, and five, as well as in 53% of patients during years zero to five. Arrhythmias remained low in each individual year of the extension study. Expanded Disability Status Scale (EDSS) scores also showed improvement with alemtuzumab use through years zero to five. In addition, sustained reduction in disability was achieved by 53% of patients during years zero to five.

“Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for patients with highly active RRMS,” said Dr. Singer and his colleagues.

This study was supported by Genzyme and Bayer HealthCare Pharmaceuticals.

—Erica Robinson

NATIONAL HARBOR, MD—Patients with highly active relapsing-remitting multiple sclerosis (RRMS) have durable improvement for more than five years with alemtuzumab use, according to data presented at the 2016 CMSC Annual Meeting. In a phase III trial, 45% of patients treated with alemtuzumab also sustained a six-month reduction in disability.

Barry A. Singer, MD

In the CARE-MS II study, alemtuzumab was associated with more significant improvement in clinical and MRI outcomes over two years, compared with subcutaneous interferon beta-1a, in patients with active RRMS who had had a poor response to prior therapy at baseline. An extension study was initiated to evaluate the five-year efficacy of alemtuzumab treatment in a subset of patients with RRMS and highly active disease at baseline. Barry A. Singer, MD, Assistant Professor of Clinical Neurology at Washington University in St. Louis, and his colleagues defined highly active disease as two or more relapses in the year before randomization and gadolinium-enhanced lesions at baseline. In the study, 24% of patients receiving alemtuzumab met the criteria for highly active disease.

During the trial, patients randomized to alemtuzumab (12 mg/day) were given two courses of treatment for five consecutive days at baseline and treatment for three consecutive days in the 12th month. In the extension study, patients were only allowed to receive alemtuzumab retreatment if they had a relapse or MRI activity on disease-modifying treatment.

In more than five years, at least 80% of patients receiving alemtuzumab who had had an inadequate response to prior therapy were free of relapses in each individual year. Sixty-two percent of patients had no alemtuzumab retreatment or other disease-modifying therapies. Results also showed that 97% of patients did not receive another disease-modifying therapy.

In this cohort, no evidence of disease activity was reported in 71%, 63%, and 67% of patients during years three, four, and five, as well as in 53% of patients during years zero to five. Arrhythmias remained low in each individual year of the extension study. Expanded Disability Status Scale (EDSS) scores also showed improvement with alemtuzumab use through years zero to five. In addition, sustained reduction in disability was achieved by 53% of patients during years zero to five.

“Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for patients with highly active RRMS,” said Dr. Singer and his colleagues.

This study was supported by Genzyme and Bayer HealthCare Pharmaceuticals.

—Erica Robinson

NATIONAL HARBOR, MD—Long-term follow-up from the BENEFIT trial, in which patients with clinically isolated syndrome (CIS) were treated with interferon beta-1b, confirmed the relationship between MRI metrics and clinical outcomes after 11 years of treatment, according to data presented at the 2016 CMSC Annual Meeting. Results also indicated that patients with more active disease tended to have smaller cervical spinal cord volumes and that cognition (as measured by mental processing speed) was related to number of lesions.

Patients with CIS who had early treatment with interferon beta-1b in the BENEFIT trial maintained an overall favorable disease course, with some clinical differences that favored treatment start at CIS, including lower annualized relapse rate (ARR), higher Paced Auditory Serial Addition Task (PASAT) score, and longer time to clinically definite multiple sclerosis (MS). “The 11-year follow-up of this trial provides an opportunity to assess the relationship between long-term clinical outcomes and structural assessments by MRI and optical coherence tomography (OCT),” said Edward J. Fox, MD, PhD, a neurologist at Central Texas Neurology Consultants in Round Rock, Texas, and colleagues.

Edward J. Fox, MD, PhD

The objective of the present study was to assess correlations between clinical, MRI, and OCT outcomes over 11 years. In the original BENEFIT trial, patients with CIS who had two or more silent brain lesions were randomized to 250 µg of interferon beta-1b (ie, early treatment) or placebo (ie, delayed treatment) subcutaneously every other day. Patients remained on placebo until conversion to clinically definite MS or for two years, whichever came first. Eleven years after initial randomization, all patients were approached to undergo cross-sectional follow-up that included clinical, MRI, and OCT assessment.

Clinical parameters included ARR, Expanded Disability Status Score (EDSS), Kurtzke Functional Status Scale (KFSS), MS Functional Composite (MSFC), PASAT score, and Symbol-Digit Modality Test (SDMT). Correlation was also assessed between mental processing speed (the sum of the z scores for PASAT and SDMT adjusted for education status, age, and sex) and selected MRI parameters.

Of the 468 patients originally randomized, 278 (71.3%) participated in the BENEFIT 11 follow-up study. This population included 167 patients in the original early-treatment group (57.2% of the original cohort) and 111 patients from the original delayed-treatment group (63.1% of the original cohort).

Year 11 MRI and OCT assessments were conducted in 191 patients (68.7%) and 86 patients (30.9%, two patients missing data), respectively. Little difference between the early- and delayed-treatments groups, with respect to MRI and OCT findings, was noted, with the exception of a difference in median number of T1-hypointense lesions. The early-treatment group had 4.0 lesions, and the delayed-treatment group had 2.0 lesions.

Regarding MRI, significant positive correlations in the overall BENEFIT 11 population were observed between ARR and volume of T1 lesions (r = 0.212), ARR and volume of T2 lesions (r = 0.216), EDSS score and T1 hypointensity volume (r = 0.281), and EDSS and T2 volume (r = 0.244). Significant negative correlations in the overall BENEFIT 11 population were observed between ARR and mean upper cervical cord area (MUCCA) (r = –0.208), EDSS and MUCCA (r = –0.194), and MSFC and T1 lesion volume (r = –0.183) and T2 lesion volume (r = –0.213). Mental processing speed correlated negatively with number of T1 lesions (r = –0.176).

Regarding OCT, significant positive correlations in the BENEFIT 11 population were observed between PASAT and minimum global retinal nerve fiber layer thickness (r = 0.271). Significant negative correlations were observed between ARR and global retinal nerve fiber layer thickness (r = –0.233) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.239), T1 lesion volume and minimum global retinal nerve fiber layer thickness (r = 0.255) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.340), and T2 lesion volume and global retinal nerve fiber layer thickness (r = 0.307) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.392). No significant correlations were found between OCT parameters and EDSS, KFSS, MSFC, SDMT, normalized brain volume, mean cortical thickness, normalized thalamic volume, or visual acuity.

“Results from BENEFIT 11 confirmed the relationship between MRI measures of disease and long-term outcomes,” said Dr. Fox and colleagues. “Significant correlations of lesion volume with EDSS, ARR, and MSFC, as well as with minimum global retinal nerve fiber layer thickness and papillomacular bundle-retinal nerve fiber layer thickness were found, while MUCCA significantly correlated with EDSS and ARR.” These findings, the researchers said, highlight the importance of monitoring MRI activity for assessing disease status.

This study was supported by Bayer HealthCare Pharmaceuticals.

—Glenn S. Williams

NATIONAL HARBOR, MD—Long-term follow-up from the BENEFIT trial, in which patients with clinically isolated syndrome (CIS) were treated with interferon beta-1b, confirmed the relationship between MRI metrics and clinical outcomes after 11 years of treatment, according to data presented at the 2016 CMSC Annual Meeting. Results also indicated that patients with more active disease tended to have smaller cervical spinal cord volumes and that cognition (as measured by mental processing speed) was related to number of lesions.

Patients with CIS who had early treatment with interferon beta-1b in the BENEFIT trial maintained an overall favorable disease course, with some clinical differences that favored treatment start at CIS, including lower annualized relapse rate (ARR), higher Paced Auditory Serial Addition Task (PASAT) score, and longer time to clinically definite multiple sclerosis (MS). “The 11-year follow-up of this trial provides an opportunity to assess the relationship between long-term clinical outcomes and structural assessments by MRI and optical coherence tomography (OCT),” said Edward J. Fox, MD, PhD, a neurologist at Central Texas Neurology Consultants in Round Rock, Texas, and colleagues.

Edward J. Fox, MD, PhD

The objective of the present study was to assess correlations between clinical, MRI, and OCT outcomes over 11 years. In the original BENEFIT trial, patients with CIS who had two or more silent brain lesions were randomized to 250 µg of interferon beta-1b (ie, early treatment) or placebo (ie, delayed treatment) subcutaneously every other day. Patients remained on placebo until conversion to clinically definite MS or for two years, whichever came first. Eleven years after initial randomization, all patients were approached to undergo cross-sectional follow-up that included clinical, MRI, and OCT assessment.

Clinical parameters included ARR, Expanded Disability Status Score (EDSS), Kurtzke Functional Status Scale (KFSS), MS Functional Composite (MSFC), PASAT score, and Symbol-Digit Modality Test (SDMT). Correlation was also assessed between mental processing speed (the sum of the z scores for PASAT and SDMT adjusted for education status, age, and sex) and selected MRI parameters.

Of the 468 patients originally randomized, 278 (71.3%) participated in the BENEFIT 11 follow-up study. This population included 167 patients in the original early-treatment group (57.2% of the original cohort) and 111 patients from the original delayed-treatment group (63.1% of the original cohort).

Year 11 MRI and OCT assessments were conducted in 191 patients (68.7%) and 86 patients (30.9%, two patients missing data), respectively. Little difference between the early- and delayed-treatments groups, with respect to MRI and OCT findings, was noted, with the exception of a difference in median number of T1-hypointense lesions. The early-treatment group had 4.0 lesions, and the delayed-treatment group had 2.0 lesions.

Regarding MRI, significant positive correlations in the overall BENEFIT 11 population were observed between ARR and volume of T1 lesions (r = 0.212), ARR and volume of T2 lesions (r = 0.216), EDSS score and T1 hypointensity volume (r = 0.281), and EDSS and T2 volume (r = 0.244). Significant negative correlations in the overall BENEFIT 11 population were observed between ARR and mean upper cervical cord area (MUCCA) (r = –0.208), EDSS and MUCCA (r = –0.194), and MSFC and T1 lesion volume (r = –0.183) and T2 lesion volume (r = –0.213). Mental processing speed correlated negatively with number of T1 lesions (r = –0.176).

Regarding OCT, significant positive correlations in the BENEFIT 11 population were observed between PASAT and minimum global retinal nerve fiber layer thickness (r = 0.271). Significant negative correlations were observed between ARR and global retinal nerve fiber layer thickness (r = –0.233) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.239), T1 lesion volume and minimum global retinal nerve fiber layer thickness (r = 0.255) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.340), and T2 lesion volume and global retinal nerve fiber layer thickness (r = 0.307) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.392). No significant correlations were found between OCT parameters and EDSS, KFSS, MSFC, SDMT, normalized brain volume, mean cortical thickness, normalized thalamic volume, or visual acuity.

“Results from BENEFIT 11 confirmed the relationship between MRI measures of disease and long-term outcomes,” said Dr. Fox and colleagues. “Significant correlations of lesion volume with EDSS, ARR, and MSFC, as well as with minimum global retinal nerve fiber layer thickness and papillomacular bundle-retinal nerve fiber layer thickness were found, while MUCCA significantly correlated with EDSS and ARR.” These findings, the researchers said, highlight the importance of monitoring MRI activity for assessing disease status.

This study was supported by Bayer HealthCare Pharmaceuticals.

—Glenn S. Williams

NATIONAL HARBOR, MD—Long-term follow-up from the BENEFIT trial, in which patients with clinically isolated syndrome (CIS) were treated with interferon beta-1b, confirmed the relationship between MRI metrics and clinical outcomes after 11 years of treatment, according to data presented at the 2016 CMSC Annual Meeting. Results also indicated that patients with more active disease tended to have smaller cervical spinal cord volumes and that cognition (as measured by mental processing speed) was related to number of lesions.

Patients with CIS who had early treatment with interferon beta-1b in the BENEFIT trial maintained an overall favorable disease course, with some clinical differences that favored treatment start at CIS, including lower annualized relapse rate (ARR), higher Paced Auditory Serial Addition Task (PASAT) score, and longer time to clinically definite multiple sclerosis (MS). “The 11-year follow-up of this trial provides an opportunity to assess the relationship between long-term clinical outcomes and structural assessments by MRI and optical coherence tomography (OCT),” said Edward J. Fox, MD, PhD, a neurologist at Central Texas Neurology Consultants in Round Rock, Texas, and colleagues.

Edward J. Fox, MD, PhD

The objective of the present study was to assess correlations between clinical, MRI, and OCT outcomes over 11 years. In the original BENEFIT trial, patients with CIS who had two or more silent brain lesions were randomized to 250 µg of interferon beta-1b (ie, early treatment) or placebo (ie, delayed treatment) subcutaneously every other day. Patients remained on placebo until conversion to clinically definite MS or for two years, whichever came first. Eleven years after initial randomization, all patients were approached to undergo cross-sectional follow-up that included clinical, MRI, and OCT assessment.

Clinical parameters included ARR, Expanded Disability Status Score (EDSS), Kurtzke Functional Status Scale (KFSS), MS Functional Composite (MSFC), PASAT score, and Symbol-Digit Modality Test (SDMT). Correlation was also assessed between mental processing speed (the sum of the z scores for PASAT and SDMT adjusted for education status, age, and sex) and selected MRI parameters.

Of the 468 patients originally randomized, 278 (71.3%) participated in the BENEFIT 11 follow-up study. This population included 167 patients in the original early-treatment group (57.2% of the original cohort) and 111 patients from the original delayed-treatment group (63.1% of the original cohort).

Year 11 MRI and OCT assessments were conducted in 191 patients (68.7%) and 86 patients (30.9%, two patients missing data), respectively. Little difference between the early- and delayed-treatments groups, with respect to MRI and OCT findings, was noted, with the exception of a difference in median number of T1-hypointense lesions. The early-treatment group had 4.0 lesions, and the delayed-treatment group had 2.0 lesions.

Regarding MRI, significant positive correlations in the overall BENEFIT 11 population were observed between ARR and volume of T1 lesions (r = 0.212), ARR and volume of T2 lesions (r = 0.216), EDSS score and T1 hypointensity volume (r = 0.281), and EDSS and T2 volume (r = 0.244). Significant negative correlations in the overall BENEFIT 11 population were observed between ARR and mean upper cervical cord area (MUCCA) (r = –0.208), EDSS and MUCCA (r = –0.194), and MSFC and T1 lesion volume (r = –0.183) and T2 lesion volume (r = –0.213). Mental processing speed correlated negatively with number of T1 lesions (r = –0.176).

Regarding OCT, significant positive correlations in the BENEFIT 11 population were observed between PASAT and minimum global retinal nerve fiber layer thickness (r = 0.271). Significant negative correlations were observed between ARR and global retinal nerve fiber layer thickness (r = –0.233) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.239), T1 lesion volume and minimum global retinal nerve fiber layer thickness (r = 0.255) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.340), and T2 lesion volume and global retinal nerve fiber layer thickness (r = 0.307) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.392). No significant correlations were found between OCT parameters and EDSS, KFSS, MSFC, SDMT, normalized brain volume, mean cortical thickness, normalized thalamic volume, or visual acuity.

“Results from BENEFIT 11 confirmed the relationship between MRI measures of disease and long-term outcomes,” said Dr. Fox and colleagues. “Significant correlations of lesion volume with EDSS, ARR, and MSFC, as well as with minimum global retinal nerve fiber layer thickness and papillomacular bundle-retinal nerve fiber layer thickness were found, while MUCCA significantly correlated with EDSS and ARR.” These findings, the researchers said, highlight the importance of monitoring MRI activity for assessing disease status.

This study was supported by Bayer HealthCare Pharmaceuticals.

—Glenn S. Williams

NATIONAL HARBOR, MD—Patients and prescribers agree that efficacy is the highest priority in decision making for first-line multiple sclerosis (MS) treatment, according to the results of an online survey reported at the 2016 CMSC Annual Meeting. Preferences were similar across segments of patient age categories, sex, education, insurance, and disease severity. Furthermore, prescribers place higher importance on the risk of serious side effects than do patients for first-line disease-modifying treatments (DMTs).

Edward J. Fox, MD, PhD

“Even though this study suggests that patients and neurologists prefer high-efficacy agents, real-world practice and market share of DMTs do not reflect this preference,” said Edward J. Fox, MD, PhD, a neurologist at Central Texas Neurology Consultants in Round Rock, Texas, and his coauthors. “Knowledge of preferred attributes for first-line treatment from the patient and neurologist perspectives can help to better inform communication regarding treatment decision making.”

To evaluate preferences for features of first-line DMTs among patients with relapsing-remitting MS and neurologists, Dr. Fox and his coinvestigators used PatientsLikeMe, an online, patient-powered social networking community, to recruit patients. Neurologists were recruited from the WebMD network. Maximum Difference Scaling (MDS), a type of best–worst scaling, was used to design online choice experiments in which respondents were shown a series of items and asked to indicate what they consider the most and least important factor when selecting a DMT. The factors included efficacy parameters (ie, slowing of disability progression, prevention of new MRI lesions, and reduction of relapse frequency), risk of serious side effects, tolerability, route of administration (ie, oral, injectable, infusion), cost, and neurologist recommendation.

A total of 193 patients and 225 neurologists responded. Preferences among patients and neurologists were similar. Items related to efficacy were of high importance among both groups. For both patients and neurologists, the items related to efficacy were preferred similarly, in decreasing order of importance: slowing disability progression, decreasing relapse frequency, and preventing new MRI lesions.

For first-line treatment selection, neurologists considered risk of serious side effects of higher importance than preventing new MRI lesions, but of lower importance than slowing disability progression or reducing relapse severity. Patients ranked the risk of serious side effects as of average importance, compared with the three efficacy items.

Patients and neurologists viewed tolerable side effects as an important factor after efficacy and safety in first-line and switch DMT preference. In both groups, parenteral drug administration was least preferred, in comparison with all other factors.

This study was supported by Novartis Pharmaceuticals.

—Glenn S. Williams

NATIONAL HARBOR, MD—Patients and prescribers agree that efficacy is the highest priority in decision making for first-line multiple sclerosis (MS) treatment, according to the results of an online survey reported at the 2016 CMSC Annual Meeting. Preferences were similar across segments of patient age categories, sex, education, insurance, and disease severity. Furthermore, prescribers place higher importance on the risk of serious side effects than do patients for first-line disease-modifying treatments (DMTs).

Edward J. Fox, MD, PhD

“Even though this study suggests that patients and neurologists prefer high-efficacy agents, real-world practice and market share of DMTs do not reflect this preference,” said Edward J. Fox, MD, PhD, a neurologist at Central Texas Neurology Consultants in Round Rock, Texas, and his coauthors. “Knowledge of preferred attributes for first-line treatment from the patient and neurologist perspectives can help to better inform communication regarding treatment decision making.”

To evaluate preferences for features of first-line DMTs among patients with relapsing-remitting MS and neurologists, Dr. Fox and his coinvestigators used PatientsLikeMe, an online, patient-powered social networking community, to recruit patients. Neurologists were recruited from the WebMD network. Maximum Difference Scaling (MDS), a type of best–worst scaling, was used to design online choice experiments in which respondents were shown a series of items and asked to indicate what they consider the most and least important factor when selecting a DMT. The factors included efficacy parameters (ie, slowing of disability progression, prevention of new MRI lesions, and reduction of relapse frequency), risk of serious side effects, tolerability, route of administration (ie, oral, injectable, infusion), cost, and neurologist recommendation.

A total of 193 patients and 225 neurologists responded. Preferences among patients and neurologists were similar. Items related to efficacy were of high importance among both groups. For both patients and neurologists, the items related to efficacy were preferred similarly, in decreasing order of importance: slowing disability progression, decreasing relapse frequency, and preventing new MRI lesions.

For first-line treatment selection, neurologists considered risk of serious side effects of higher importance than preventing new MRI lesions, but of lower importance than slowing disability progression or reducing relapse severity. Patients ranked the risk of serious side effects as of average importance, compared with the three efficacy items.

Patients and neurologists viewed tolerable side effects as an important factor after efficacy and safety in first-line and switch DMT preference. In both groups, parenteral drug administration was least preferred, in comparison with all other factors.

This study was supported by Novartis Pharmaceuticals.

—Glenn S. Williams

NATIONAL HARBOR, MD—Patients and prescribers agree that efficacy is the highest priority in decision making for first-line multiple sclerosis (MS) treatment, according to the results of an online survey reported at the 2016 CMSC Annual Meeting. Preferences were similar across segments of patient age categories, sex, education, insurance, and disease severity. Furthermore, prescribers place higher importance on the risk of serious side effects than do patients for first-line disease-modifying treatments (DMTs).

Edward J. Fox, MD, PhD

“Even though this study suggests that patients and neurologists prefer high-efficacy agents, real-world practice and market share of DMTs do not reflect this preference,” said Edward J. Fox, MD, PhD, a neurologist at Central Texas Neurology Consultants in Round Rock, Texas, and his coauthors. “Knowledge of preferred attributes for first-line treatment from the patient and neurologist perspectives can help to better inform communication regarding treatment decision making.”

To evaluate preferences for features of first-line DMTs among patients with relapsing-remitting MS and neurologists, Dr. Fox and his coinvestigators used PatientsLikeMe, an online, patient-powered social networking community, to recruit patients. Neurologists were recruited from the WebMD network. Maximum Difference Scaling (MDS), a type of best–worst scaling, was used to design online choice experiments in which respondents were shown a series of items and asked to indicate what they consider the most and least important factor when selecting a DMT. The factors included efficacy parameters (ie, slowing of disability progression, prevention of new MRI lesions, and reduction of relapse frequency), risk of serious side effects, tolerability, route of administration (ie, oral, injectable, infusion), cost, and neurologist recommendation.

A total of 193 patients and 225 neurologists responded. Preferences among patients and neurologists were similar. Items related to efficacy were of high importance among both groups. For both patients and neurologists, the items related to efficacy were preferred similarly, in decreasing order of importance: slowing disability progression, decreasing relapse frequency, and preventing new MRI lesions.

For first-line treatment selection, neurologists considered risk of serious side effects of higher importance than preventing new MRI lesions, but of lower importance than slowing disability progression or reducing relapse severity. Patients ranked the risk of serious side effects as of average importance, compared with the three efficacy items.

Patients and neurologists viewed tolerable side effects as an important factor after efficacy and safety in first-line and switch DMT preference. In both groups, parenteral drug administration was least preferred, in comparison with all other factors.

This study was supported by Novartis Pharmaceuticals.

—Glenn S. Williams

VANCOUVER—The misdiagnosis of multiple sclerosis (MS) is a problem with significant consequences for patients, as well as the health care system, according to Andrew J. Solomon, MD, Assistant Professor in the Department of Neurological Sciences at the University of Vermont in Burlington. “Overreliance on MRI abnormalities in the setting of atypical syndromes and unverified prior symptoms may be a major cause of misdiagnosis,” Dr. Solomon said at the 68th Annual Meeting of the American Academy of Neurology.

Dr. Solomon and colleagues conducted a simple survey in 2012. They asked 122 MS specialists if they recalled seeing a patient who was incorrectly diagnosed with MS over the last year. Nearly all (95%) had evaluated such patients. As a follow-up, Dr. Solomon and colleagues designed the present study, which evaluated the characteristics of a large population of patients who had been misdiagnosed with MS. “We wanted to determine what the diagnoses were that were being mistaken for MS and what the risks were that were associated with these misdiagnoses.” Their pilot study also probed the causes of misdiagnosis, particularly relating to the current McDonald MS diagnostic criteria.

Twenty-three MS specialists from the University of Vermont, Oregon Health and Science University, Washington University, and the Mayo Clinic participated in this study. The investigators defined two categories: definite and probable misdiagnosis. Patients were identified by participating neurologists during clinical evaluations either prospectively during the 13 months of the study or shortly prior to study initiation. Patients were classified as having definite misdiagnosis when an alternative diagnosis was definitively made based on clinical, laboratory, and neuroimaging evaluation and probable misdiagnosis when an alternative diagnosis was suspected and diagnostic criteria for MS were not met.

Migraine Was Mistaken for MS

The researchers identified 110 patients who were misdiagnosed with MS; 85% were women, and the mean age was 49. About one-quarter (24%) were initially misdiagnosed by a neurologist with fellowship training or a practice focus in MS, and 32% were initially misdiagnosed by a neurologist without such training. For 42%, it was difficult to determine the level of training of the initial neurologist. Nearly half (46%) were classified as definite misdiagnosis, and 54% fell into the probable misdiagnosis category. Neurologists informed 107 (97%) of the patients that their MS diagnosis was incorrect. Almost 30% had been misdiagnosed with MS for three to nine years; 33% had been misdiagnosed for 10 years or longer.

Of the syndromes and diagnoses that were commonly mistaken for MS, the top five represented two-thirds (66%) of all the misdiagnoses that were identified. Migraine, alone or in combination with other disorders, accounted for 22%. Fibromyalgia, along with another alternative cause of MRI abnormalities, accounted for 15%. A category labeled nonspecific or nonlocalized neurologic symptoms—symptoms that were not typical of demyelinating injury or CNS injury—with an abnormal MRI accounted for 12%. Conversion or psychogenic disorder accounted for 11%, and neuromyelitis optica (NMO) spectrum disorder accounted for 6%.

Disease-modifying therapy (DMT) had been initiated in 70% of these patients. About one-third (36%) had received more than one DMT for MS, and a number had received two, three, or four therapies. Thirteen percent had been exposed to natalizumab, a number had received oral therapies for MS, and a few patients had received mitoxantrone. Nearly one-quarter (24%) at some time were on a DMT with a known risk of PML. Almost 30% had been exposed to DMT for three to nine years. Almost 30% had been on DMT for 10 years or longer.

Cerebrospinal fluid (CSF) was available for 52 patients from the time of initial diagnosis, prior to study entry. In 54%, the CSF was normal, including oligoclonal bands and normal IgG. In eight patients, the study neurologists thought that there was an erroneous interpretation of CSF, meaning, for instance, oligoclonal bands were positive in CSF as well as serum.

The study neurologists concluded that 30% of the patients experienced some morbidity as a direct result of an MS misdiagnosis. Morbidities included inadequate treatment of their correct diagnosis, exposure to DMT, and other consequences. In 72% of all patients, study neurologists identified clear evidence of an earlier missed opportunity to make the correct diagnosis.

Imaging and Misdiagnosis

In 65% of cases, study neurologists concluded that inappropriate application of MS diagnostic criteria to a neurologic symptom atypical for a demyelinating attack contributed to misdiagnosis. Inappropriate application of diagnostic criteria to a historical episode of neurologic symptoms without any corroborating objective evidence of a lesion was noted in almost half the cases.

In more than 30% of cases, an erroneous determination of juxtacortical or periventricular lesion location was thought to have contributed to misdiagnosis. In 60%, the study neurologists cited misdiagnosis related to overreliance on MRI abnormalities, meaning dissemination in time, to confirm a diagnosis of MS in a patient with nonspecific neurologic symptoms.

“We all know the differential diagnosis of MS is broad, and a number of rare disorders can mimic MS,” Dr. Solomon said. “But here it was migraine, fibromyalgia, and a number of other disorders that are quite common that mimicked MS and were mistaken for MS.” Most of these diagnoses, with the exception of NMO, lack a specific biomarker. “What this means is that the correct diagnosis in many of these cases relies on our clinical skills and critical thinking, not just MRI. The problem is not confined to nonspecialists. MS specialists can also make mistakes.”

Study neurologists reported that in almost two-thirds of cases, atypical symptoms for a demyelinating attack contributed to misdiagnosis. “Perhaps this reflects a misunderstanding of what constitutes a typical demyelinating attack and when we should rely on our diagnostic criteria alone,” Dr. Solomon said. In half, historical episodes of neurologic dysfunction, without corroborating objective findings, contributed to misdiagnosis. “This means that patients came in and they had reported historical episodes—episodes of numbness or tingling or blurry vision—where there were no objective exam findings, evoked potentials, imaging findings, to corroborate those symptoms, yet perhaps these episodes were used to meet dissemination in time.”

MRI abnormalities incorrectly attributed to MS in patients without typical demyelinating symptoms contributed to more than half of the misdiagnoses. “It is important to highlight that our MRI criteria, as part of our MS diagnostic criteria, were not developed to differentiate MS from other disorders. The MRI criteria for MS were meant to identify patients at high risk for MS after typical clinical presentations for demyelination,” Dr. Solomon said.

The Importance of Diagnostic Criteria

“Making a diagnosis of MS is challenging. It is important to acknowledge that,” Dr. Solomon said. Common diagnoses and syndromes are often mistaken for MS. But there is significant risk and morbidity associated with misdiagnosis. “The best way to prevent misdiagnosis may be strict adherence and proper use of our MS diagnostic criteria. In patients with atypical clinical presentations or in patients with nonspecific MRI abnormalities, we may need to do more. We may need to monitor longer, do more imaging, make sure we get CSF. That may prevent misdiagnosis in a number of cases.”

Dr. Solomon also stressed the need for continued vigilance for misdiagnosis in patients with an existing MS diagnosis. “We should be thinking, ‘Is this really MS?’ each time we see a new patient, rather than simply accepting that diagnosis.” And lastly, Dr. Solomon recommended that future MS diagnostic criteria should balance the benefit of prompt diagnosis and initiation of DMT versus the potential risks of misdiagnosis.

—Glenn S. Williams

VANCOUVER—The misdiagnosis of multiple sclerosis (MS) is a problem with significant consequences for patients, as well as the health care system, according to Andrew J. Solomon, MD, Assistant Professor in the Department of Neurological Sciences at the University of Vermont in Burlington. “Overreliance on MRI abnormalities in the setting of atypical syndromes and unverified prior symptoms may be a major cause of misdiagnosis,” Dr. Solomon said at the 68th Annual Meeting of the American Academy of Neurology.

Dr. Solomon and colleagues conducted a simple survey in 2012. They asked 122 MS specialists if they recalled seeing a patient who was incorrectly diagnosed with MS over the last year. Nearly all (95%) had evaluated such patients. As a follow-up, Dr. Solomon and colleagues designed the present study, which evaluated the characteristics of a large population of patients who had been misdiagnosed with MS. “We wanted to determine what the diagnoses were that were being mistaken for MS and what the risks were that were associated with these misdiagnoses.” Their pilot study also probed the causes of misdiagnosis, particularly relating to the current McDonald MS diagnostic criteria.

Twenty-three MS specialists from the University of Vermont, Oregon Health and Science University, Washington University, and the Mayo Clinic participated in this study. The investigators defined two categories: definite and probable misdiagnosis. Patients were identified by participating neurologists during clinical evaluations either prospectively during the 13 months of the study or shortly prior to study initiation. Patients were classified as having definite misdiagnosis when an alternative diagnosis was definitively made based on clinical, laboratory, and neuroimaging evaluation and probable misdiagnosis when an alternative diagnosis was suspected and diagnostic criteria for MS were not met.

Migraine Was Mistaken for MS

The researchers identified 110 patients who were misdiagnosed with MS; 85% were women, and the mean age was 49. About one-quarter (24%) were initially misdiagnosed by a neurologist with fellowship training or a practice focus in MS, and 32% were initially misdiagnosed by a neurologist without such training. For 42%, it was difficult to determine the level of training of the initial neurologist. Nearly half (46%) were classified as definite misdiagnosis, and 54% fell into the probable misdiagnosis category. Neurologists informed 107 (97%) of the patients that their MS diagnosis was incorrect. Almost 30% had been misdiagnosed with MS for three to nine years; 33% had been misdiagnosed for 10 years or longer.

Of the syndromes and diagnoses that were commonly mistaken for MS, the top five represented two-thirds (66%) of all the misdiagnoses that were identified. Migraine, alone or in combination with other disorders, accounted for 22%. Fibromyalgia, along with another alternative cause of MRI abnormalities, accounted for 15%. A category labeled nonspecific or nonlocalized neurologic symptoms—symptoms that were not typical of demyelinating injury or CNS injury—with an abnormal MRI accounted for 12%. Conversion or psychogenic disorder accounted for 11%, and neuromyelitis optica (NMO) spectrum disorder accounted for 6%.

Disease-modifying therapy (DMT) had been initiated in 70% of these patients. About one-third (36%) had received more than one DMT for MS, and a number had received two, three, or four therapies. Thirteen percent had been exposed to natalizumab, a number had received oral therapies for MS, and a few patients had received mitoxantrone. Nearly one-quarter (24%) at some time were on a DMT with a known risk of PML. Almost 30% had been exposed to DMT for three to nine years. Almost 30% had been on DMT for 10 years or longer.

Cerebrospinal fluid (CSF) was available for 52 patients from the time of initial diagnosis, prior to study entry. In 54%, the CSF was normal, including oligoclonal bands and normal IgG. In eight patients, the study neurologists thought that there was an erroneous interpretation of CSF, meaning, for instance, oligoclonal bands were positive in CSF as well as serum.

The study neurologists concluded that 30% of the patients experienced some morbidity as a direct result of an MS misdiagnosis. Morbidities included inadequate treatment of their correct diagnosis, exposure to DMT, and other consequences. In 72% of all patients, study neurologists identified clear evidence of an earlier missed opportunity to make the correct diagnosis.

Imaging and Misdiagnosis

In 65% of cases, study neurologists concluded that inappropriate application of MS diagnostic criteria to a neurologic symptom atypical for a demyelinating attack contributed to misdiagnosis. Inappropriate application of diagnostic criteria to a historical episode of neurologic symptoms without any corroborating objective evidence of a lesion was noted in almost half the cases.

In more than 30% of cases, an erroneous determination of juxtacortical or periventricular lesion location was thought to have contributed to misdiagnosis. In 60%, the study neurologists cited misdiagnosis related to overreliance on MRI abnormalities, meaning dissemination in time, to confirm a diagnosis of MS in a patient with nonspecific neurologic symptoms.

“We all know the differential diagnosis of MS is broad, and a number of rare disorders can mimic MS,” Dr. Solomon said. “But here it was migraine, fibromyalgia, and a number of other disorders that are quite common that mimicked MS and were mistaken for MS.” Most of these diagnoses, with the exception of NMO, lack a specific biomarker. “What this means is that the correct diagnosis in many of these cases relies on our clinical skills and critical thinking, not just MRI. The problem is not confined to nonspecialists. MS specialists can also make mistakes.”

Study neurologists reported that in almost two-thirds of cases, atypical symptoms for a demyelinating attack contributed to misdiagnosis. “Perhaps this reflects a misunderstanding of what constitutes a typical demyelinating attack and when we should rely on our diagnostic criteria alone,” Dr. Solomon said. In half, historical episodes of neurologic dysfunction, without corroborating objective findings, contributed to misdiagnosis. “This means that patients came in and they had reported historical episodes—episodes of numbness or tingling or blurry vision—where there were no objective exam findings, evoked potentials, imaging findings, to corroborate those symptoms, yet perhaps these episodes were used to meet dissemination in time.”

MRI abnormalities incorrectly attributed to MS in patients without typical demyelinating symptoms contributed to more than half of the misdiagnoses. “It is important to highlight that our MRI criteria, as part of our MS diagnostic criteria, were not developed to differentiate MS from other disorders. The MRI criteria for MS were meant to identify patients at high risk for MS after typical clinical presentations for demyelination,” Dr. Solomon said.

The Importance of Diagnostic Criteria

“Making a diagnosis of MS is challenging. It is important to acknowledge that,” Dr. Solomon said. Common diagnoses and syndromes are often mistaken for MS. But there is significant risk and morbidity associated with misdiagnosis. “The best way to prevent misdiagnosis may be strict adherence and proper use of our MS diagnostic criteria. In patients with atypical clinical presentations or in patients with nonspecific MRI abnormalities, we may need to do more. We may need to monitor longer, do more imaging, make sure we get CSF. That may prevent misdiagnosis in a number of cases.”

Dr. Solomon also stressed the need for continued vigilance for misdiagnosis in patients with an existing MS diagnosis. “We should be thinking, ‘Is this really MS?’ each time we see a new patient, rather than simply accepting that diagnosis.” And lastly, Dr. Solomon recommended that future MS diagnostic criteria should balance the benefit of prompt diagnosis and initiation of DMT versus the potential risks of misdiagnosis.

—Glenn S. Williams

VANCOUVER—The misdiagnosis of multiple sclerosis (MS) is a problem with significant consequences for patients, as well as the health care system, according to Andrew J. Solomon, MD, Assistant Professor in the Department of Neurological Sciences at the University of Vermont in Burlington. “Overreliance on MRI abnormalities in the setting of atypical syndromes and unverified prior symptoms may be a major cause of misdiagnosis,” Dr. Solomon said at the 68th Annual Meeting of the American Academy of Neurology.

Dr. Solomon and colleagues conducted a simple survey in 2012. They asked 122 MS specialists if they recalled seeing a patient who was incorrectly diagnosed with MS over the last year. Nearly all (95%) had evaluated such patients. As a follow-up, Dr. Solomon and colleagues designed the present study, which evaluated the characteristics of a large population of patients who had been misdiagnosed with MS. “We wanted to determine what the diagnoses were that were being mistaken for MS and what the risks were that were associated with these misdiagnoses.” Their pilot study also probed the causes of misdiagnosis, particularly relating to the current McDonald MS diagnostic criteria.

Twenty-three MS specialists from the University of Vermont, Oregon Health and Science University, Washington University, and the Mayo Clinic participated in this study. The investigators defined two categories: definite and probable misdiagnosis. Patients were identified by participating neurologists during clinical evaluations either prospectively during the 13 months of the study or shortly prior to study initiation. Patients were classified as having definite misdiagnosis when an alternative diagnosis was definitively made based on clinical, laboratory, and neuroimaging evaluation and probable misdiagnosis when an alternative diagnosis was suspected and diagnostic criteria for MS were not met.

Migraine Was Mistaken for MS

The researchers identified 110 patients who were misdiagnosed with MS; 85% were women, and the mean age was 49. About one-quarter (24%) were initially misdiagnosed by a neurologist with fellowship training or a practice focus in MS, and 32% were initially misdiagnosed by a neurologist without such training. For 42%, it was difficult to determine the level of training of the initial neurologist. Nearly half (46%) were classified as definite misdiagnosis, and 54% fell into the probable misdiagnosis category. Neurologists informed 107 (97%) of the patients that their MS diagnosis was incorrect. Almost 30% had been misdiagnosed with MS for three to nine years; 33% had been misdiagnosed for 10 years or longer.

Of the syndromes and diagnoses that were commonly mistaken for MS, the top five represented two-thirds (66%) of all the misdiagnoses that were identified. Migraine, alone or in combination with other disorders, accounted for 22%. Fibromyalgia, along with another alternative cause of MRI abnormalities, accounted for 15%. A category labeled nonspecific or nonlocalized neurologic symptoms—symptoms that were not typical of demyelinating injury or CNS injury—with an abnormal MRI accounted for 12%. Conversion or psychogenic disorder accounted for 11%, and neuromyelitis optica (NMO) spectrum disorder accounted for 6%.

Disease-modifying therapy (DMT) had been initiated in 70% of these patients. About one-third (36%) had received more than one DMT for MS, and a number had received two, three, or four therapies. Thirteen percent had been exposed to natalizumab, a number had received oral therapies for MS, and a few patients had received mitoxantrone. Nearly one-quarter (24%) at some time were on a DMT with a known risk of PML. Almost 30% had been exposed to DMT for three to nine years. Almost 30% had been on DMT for 10 years or longer.

Cerebrospinal fluid (CSF) was available for 52 patients from the time of initial diagnosis, prior to study entry. In 54%, the CSF was normal, including oligoclonal bands and normal IgG. In eight patients, the study neurologists thought that there was an erroneous interpretation of CSF, meaning, for instance, oligoclonal bands were positive in CSF as well as serum.

The study neurologists concluded that 30% of the patients experienced some morbidity as a direct result of an MS misdiagnosis. Morbidities included inadequate treatment of their correct diagnosis, exposure to DMT, and other consequences. In 72% of all patients, study neurologists identified clear evidence of an earlier missed opportunity to make the correct diagnosis.

Imaging and Misdiagnosis

In 65% of cases, study neurologists concluded that inappropriate application of MS diagnostic criteria to a neurologic symptom atypical for a demyelinating attack contributed to misdiagnosis. Inappropriate application of diagnostic criteria to a historical episode of neurologic symptoms without any corroborating objective evidence of a lesion was noted in almost half the cases.

In more than 30% of cases, an erroneous determination of juxtacortical or periventricular lesion location was thought to have contributed to misdiagnosis. In 60%, the study neurologists cited misdiagnosis related to overreliance on MRI abnormalities, meaning dissemination in time, to confirm a diagnosis of MS in a patient with nonspecific neurologic symptoms.

“We all know the differential diagnosis of MS is broad, and a number of rare disorders can mimic MS,” Dr. Solomon said. “But here it was migraine, fibromyalgia, and a number of other disorders that are quite common that mimicked MS and were mistaken for MS.” Most of these diagnoses, with the exception of NMO, lack a specific biomarker. “What this means is that the correct diagnosis in many of these cases relies on our clinical skills and critical thinking, not just MRI. The problem is not confined to nonspecialists. MS specialists can also make mistakes.”

Study neurologists reported that in almost two-thirds of cases, atypical symptoms for a demyelinating attack contributed to misdiagnosis. “Perhaps this reflects a misunderstanding of what constitutes a typical demyelinating attack and when we should rely on our diagnostic criteria alone,” Dr. Solomon said. In half, historical episodes of neurologic dysfunction, without corroborating objective findings, contributed to misdiagnosis. “This means that patients came in and they had reported historical episodes—episodes of numbness or tingling or blurry vision—where there were no objective exam findings, evoked potentials, imaging findings, to corroborate those symptoms, yet perhaps these episodes were used to meet dissemination in time.”

MRI abnormalities incorrectly attributed to MS in patients without typical demyelinating symptoms contributed to more than half of the misdiagnoses. “It is important to highlight that our MRI criteria, as part of our MS diagnostic criteria, were not developed to differentiate MS from other disorders. The MRI criteria for MS were meant to identify patients at high risk for MS after typical clinical presentations for demyelination,” Dr. Solomon said.

The Importance of Diagnostic Criteria

“Making a diagnosis of MS is challenging. It is important to acknowledge that,” Dr. Solomon said. Common diagnoses and syndromes are often mistaken for MS. But there is significant risk and morbidity associated with misdiagnosis. “The best way to prevent misdiagnosis may be strict adherence and proper use of our MS diagnostic criteria. In patients with atypical clinical presentations or in patients with nonspecific MRI abnormalities, we may need to do more. We may need to monitor longer, do more imaging, make sure we get CSF. That may prevent misdiagnosis in a number of cases.”

Dr. Solomon also stressed the need for continued vigilance for misdiagnosis in patients with an existing MS diagnosis. “We should be thinking, ‘Is this really MS?’ each time we see a new patient, rather than simply accepting that diagnosis.” And lastly, Dr. Solomon recommended that future MS diagnostic criteria should balance the benefit of prompt diagnosis and initiation of DMT versus the potential risks of misdiagnosis.

—Glenn S. Williams

Daclizumab (Zinbryta) has been approved as a patient-injected, once-monthly treatment for adults with relapsing forms of multiple sclerosis (MS), according to the Food and Drug Administration.

Daclizumab has serious safety risks, including severe and potentially life-threatening liver injury and immune disorders, and should generally be used only when patients have an inadequate response to two or more MS drugs, the FDA said in a press release. The drug has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.

Liver function tests should be performed before starting daclizumab, and liver function should be monitored monthly before each dose, and for up to 6 months after the last dose. Immune disorders associated with use of daclizumab include noninfectious colitis, skin reactions, and lymphadenopathy. Other highlighted warnings include anaphylaxis and angioedema, increased risk of infections, and symptoms of depression and suicidal ideation.

Daclizumab was associated with a reduction in clinical relapses in a comparator trial of 1,841 participants who received either daclizumab or interferon beta-1a (Avonex) and were studied for 144 weeks. Fewer relapses also were seen with daclizumab than with placebo in a second 52-week study of 412 participants.

The most common adverse reactions reported by patients receiving daclizumab in the comparator trial included nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, eczema, and enlargement of lymph nodes. The most common adverse reactions reported in the placebo trial were depression, rash, and increased levels of alanine aminotransferase.

Daclizumab will be marketed as Zinbryta by Biogen.

Read the FDA’s full statement on the FDA website.

acruz@frontlinemedcom.com

Daclizumab (Zinbryta) has been approved as a patient-injected, once-monthly treatment for adults with relapsing forms of multiple sclerosis (MS), according to the Food and Drug Administration.

Daclizumab has serious safety risks, including severe and potentially life-threatening liver injury and immune disorders, and should generally be used only when patients have an inadequate response to two or more MS drugs, the FDA said in a press release. The drug has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.

Liver function tests should be performed before starting daclizumab, and liver function should be monitored monthly before each dose, and for up to 6 months after the last dose. Immune disorders associated with use of daclizumab include noninfectious colitis, skin reactions, and lymphadenopathy. Other highlighted warnings include anaphylaxis and angioedema, increased risk of infections, and symptoms of depression and suicidal ideation.

Daclizumab was associated with a reduction in clinical relapses in a comparator trial of 1,841 participants who received either daclizumab or interferon beta-1a (Avonex) and were studied for 144 weeks. Fewer relapses also were seen with daclizumab than with placebo in a second 52-week study of 412 participants.

The most common adverse reactions reported by patients receiving daclizumab in the comparator trial included nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, eczema, and enlargement of lymph nodes. The most common adverse reactions reported in the placebo trial were depression, rash, and increased levels of alanine aminotransferase.

Daclizumab will be marketed as Zinbryta by Biogen.

Read the FDA’s full statement on the FDA website.

acruz@frontlinemedcom.com

Daclizumab (Zinbryta) has been approved as a patient-injected, once-monthly treatment for adults with relapsing forms of multiple sclerosis (MS), according to the Food and Drug Administration.

Daclizumab has serious safety risks, including severe and potentially life-threatening liver injury and immune disorders, and should generally be used only when patients have an inadequate response to two or more MS drugs, the FDA said in a press release. The drug has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.

Liver function tests should be performed before starting daclizumab, and liver function should be monitored monthly before each dose, and for up to 6 months after the last dose. Immune disorders associated with use of daclizumab include noninfectious colitis, skin reactions, and lymphadenopathy. Other highlighted warnings include anaphylaxis and angioedema, increased risk of infections, and symptoms of depression and suicidal ideation.

Daclizumab was associated with a reduction in clinical relapses in a comparator trial of 1,841 participants who received either daclizumab or interferon beta-1a (Avonex) and were studied for 144 weeks. Fewer relapses also were seen with daclizumab than with placebo in a second 52-week study of 412 participants.

The most common adverse reactions reported by patients receiving daclizumab in the comparator trial included nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, eczema, and enlargement of lymph nodes. The most common adverse reactions reported in the placebo trial were depression, rash, and increased levels of alanine aminotransferase.

Daclizumab will be marketed as Zinbryta by Biogen.

Read the FDA’s full statement on the FDA website.

acruz@frontlinemedcom.com

VANCOUVER—“This exploratory analysis supports the original findings in ORACLE-MS: treatment with two short courses of cladribine tablets significantly delayed conversion to clinically definite multiple sclerosis (MS) in patients with clinically isolated syndrome,” said lead author Mark S. Freedman, HBSc, MSc, MD, at the 68th Annual Meeting of the American Academy of Neurology. In addition, Dr. Freedman and colleagues found that, compared with placebo, cladribine tablets (3.5 mg/kg) significantly reduce the risk of next attack or disability worsening in patients with early relapsing MS, as defined by the McDonald 2010 criteria.

Mark S. Freedman, HBSc, MSc, MD

In 2014, the ORACLE-MS study in patients with a first clinical demyelinating event who were at high risk of converting to MS showed that cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of clinically definite MS, compared with placebo. The ORACLE-MS study recruited patients with early-stage disease by excluding patients who were already considered to have MS according to the McDonald 2005 diagnostic criteria. The revision of the McDonald criteria in 2010 allowed a diagnosis of MS in patients with a single event and evidence of dissemination in time and space from a single MRI scan.

For the present study, Dr. Freedman, who is Professor of Neurology at the University of Ottawa, and colleagues conducted an exploratory analysis of whether cladribine tablets reduced the risk of a second attack or confirmed disability progression in patients who would now be described as having early relapsing MS, according to the McDonald 2010 criteria.

In the ORACLE-MS study cohort, patients were between ages 18 and 55 with a first demyelinating event within 75 days before screening, two or more clinically silent lesions of 3 mm or more on T2-weighted brain MRI scan, and an Expanded Disability Status Scale (EDSS) score of 5 or less. Patients were randomized in equal groups to placebo, cladribine 3.5 mg/kg, or cladribine 5.25 mg/kg. For the present study, baseline MRI scans (excluding the spinal cord) were retrospectively reviewed for MS diagnosis according to the McDonald 2010 criteria.

The exploratory end point in this analysis was time to next attack or EDSS progression in patients who met McDonald 2010 criteria at baseline and in those patients who did not fulfill the revised criteria (ie, those with clinically isolated syndrome).

After applying the McDonald 2010 MS diagnostic criteria, Dr. Freedman and colleagues considered 223 (36.2%) of the 616 participants in ORACLE-MS to have had MS at baseline.

Among these patients, cladribine tablets 3.5 mg/kg significantly reduced the risk of next attack or disability worsening by 74% versus placebo.

In patients who did not meet the McDonald 2010 criteria at baseline, cladribine tablets 3.5 mg/kg also significantly reduced the risk of next attack or disability worsening by 63% versus placebo. Cladribine tablets 5.25 mg/kg also significantly reduced the risk of next attack or disability worsening by 75% versus placebo. This study was sponsored by EMD Serono.

—Glenn S. Williams

VANCOUVER—“This exploratory analysis supports the original findings in ORACLE-MS: treatment with two short courses of cladribine tablets significantly delayed conversion to clinically definite multiple sclerosis (MS) in patients with clinically isolated syndrome,” said lead author Mark S. Freedman, HBSc, MSc, MD, at the 68th Annual Meeting of the American Academy of Neurology. In addition, Dr. Freedman and colleagues found that, compared with placebo, cladribine tablets (3.5 mg/kg) significantly reduce the risk of next attack or disability worsening in patients with early relapsing MS, as defined by the McDonald 2010 criteria.

Mark S. Freedman, HBSc, MSc, MD

In 2014, the ORACLE-MS study in patients with a first clinical demyelinating event who were at high risk of converting to MS showed that cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of clinically definite MS, compared with placebo. The ORACLE-MS study recruited patients with early-stage disease by excluding patients who were already considered to have MS according to the McDonald 2005 diagnostic criteria. The revision of the McDonald criteria in 2010 allowed a diagnosis of MS in patients with a single event and evidence of dissemination in time and space from a single MRI scan.

For the present study, Dr. Freedman, who is Professor of Neurology at the University of Ottawa, and colleagues conducted an exploratory analysis of whether cladribine tablets reduced the risk of a second attack or confirmed disability progression in patients who would now be described as having early relapsing MS, according to the McDonald 2010 criteria.

In the ORACLE-MS study cohort, patients were between ages 18 and 55 with a first demyelinating event within 75 days before screening, two or more clinically silent lesions of 3 mm or more on T2-weighted brain MRI scan, and an Expanded Disability Status Scale (EDSS) score of 5 or less. Patients were randomized in equal groups to placebo, cladribine 3.5 mg/kg, or cladribine 5.25 mg/kg. For the present study, baseline MRI scans (excluding the spinal cord) were retrospectively reviewed for MS diagnosis according to the McDonald 2010 criteria.

The exploratory end point in this analysis was time to next attack or EDSS progression in patients who met McDonald 2010 criteria at baseline and in those patients who did not fulfill the revised criteria (ie, those with clinically isolated syndrome).

After applying the McDonald 2010 MS diagnostic criteria, Dr. Freedman and colleagues considered 223 (36.2%) of the 616 participants in ORACLE-MS to have had MS at baseline.

Among these patients, cladribine tablets 3.5 mg/kg significantly reduced the risk of next attack or disability worsening by 74% versus placebo.

In patients who did not meet the McDonald 2010 criteria at baseline, cladribine tablets 3.5 mg/kg also significantly reduced the risk of next attack or disability worsening by 63% versus placebo. Cladribine tablets 5.25 mg/kg also significantly reduced the risk of next attack or disability worsening by 75% versus placebo. This study was sponsored by EMD Serono.

—Glenn S. Williams

VANCOUVER—“This exploratory analysis supports the original findings in ORACLE-MS: treatment with two short courses of cladribine tablets significantly delayed conversion to clinically definite multiple sclerosis (MS) in patients with clinically isolated syndrome,” said lead author Mark S. Freedman, HBSc, MSc, MD, at the 68th Annual Meeting of the American Academy of Neurology. In addition, Dr. Freedman and colleagues found that, compared with placebo, cladribine tablets (3.5 mg/kg) significantly reduce the risk of next attack or disability worsening in patients with early relapsing MS, as defined by the McDonald 2010 criteria.

Mark S. Freedman, HBSc, MSc, MD

In 2014, the ORACLE-MS study in patients with a first clinical demyelinating event who were at high risk of converting to MS showed that cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of clinically definite MS, compared with placebo. The ORACLE-MS study recruited patients with early-stage disease by excluding patients who were already considered to have MS according to the McDonald 2005 diagnostic criteria. The revision of the McDonald criteria in 2010 allowed a diagnosis of MS in patients with a single event and evidence of dissemination in time and space from a single MRI scan.

For the present study, Dr. Freedman, who is Professor of Neurology at the University of Ottawa, and colleagues conducted an exploratory analysis of whether cladribine tablets reduced the risk of a second attack or confirmed disability progression in patients who would now be described as having early relapsing MS, according to the McDonald 2010 criteria.

In the ORACLE-MS study cohort, patients were between ages 18 and 55 with a first demyelinating event within 75 days before screening, two or more clinically silent lesions of 3 mm or more on T2-weighted brain MRI scan, and an Expanded Disability Status Scale (EDSS) score of 5 or less. Patients were randomized in equal groups to placebo, cladribine 3.5 mg/kg, or cladribine 5.25 mg/kg. For the present study, baseline MRI scans (excluding the spinal cord) were retrospectively reviewed for MS diagnosis according to the McDonald 2010 criteria.

The exploratory end point in this analysis was time to next attack or EDSS progression in patients who met McDonald 2010 criteria at baseline and in those patients who did not fulfill the revised criteria (ie, those with clinically isolated syndrome).

After applying the McDonald 2010 MS diagnostic criteria, Dr. Freedman and colleagues considered 223 (36.2%) of the 616 participants in ORACLE-MS to have had MS at baseline.

Among these patients, cladribine tablets 3.5 mg/kg significantly reduced the risk of next attack or disability worsening by 74% versus placebo.

In patients who did not meet the McDonald 2010 criteria at baseline, cladribine tablets 3.5 mg/kg also significantly reduced the risk of next attack or disability worsening by 63% versus placebo. Cladribine tablets 5.25 mg/kg also significantly reduced the risk of next attack or disability worsening by 75% versus placebo. This study was sponsored by EMD Serono.

—Glenn S. Williams

VANCOUVER—Among patients with secondary progressive multiple sclerosis (MS), natalizumab does not delay progression of ambulatory disability, according to phase III trial results presented at the 68th Annual Meeting of the American Academy of Neurology. The drug may slow progression of upper-extremity disability, however, researchers said.

Natalizumab, a recombinant humanized monoclonal antibody against alpha-4 beta-1 integrin, reduces inflammation by inhibiting the transmigration of leukocytes into the brain. It is FDA-approved to treat relapsing-remitting MS, and data have suggested that the drug also may benefit patients with progressive forms of MS.

To investigate whether natalizumab slows disability progression unrelated to relapses in patients with secondary progressive MS, Deborah Steiner, MD, Medical Director at Biogen, and colleagues conducted ASCEND, a multicenter, double-blind, placebo-controlled, randomized trial.

The primary end point was the proportion of participants with confirmed disability progression on the EDSS, Nine-Hole Peg Test, or Timed 25-Foot Walk at six months and at the end of the trial. On the EDSS, progression was defined as an increase of at least 1.0 from a baseline EDSS score of 5.5 or less, or an increase of at least 0.5 from a baseline EDSS score of 6 or more. On the Timed 25-Foot Walk, progression was defined as an increase of 20% or more from baseline. On the Nine-Hole Peg Test, progression was defined as an increase of 20% or more on either hand.

ASCEND did not meet its primary end point. The proportion of progressors was higher in the placebo-treated group (48%) than in the natalizumab-treated group (44%), but the difference was not statistically significant.

Natalizumab treatment was, how­ever, associated with a statistically significant reduction of upper-extremity disability progression, as measured by the Nine-Hole Peg Test. Fifteen percent of participants who received natalizumab had confirmed disability progression on the Nine-Hole Peg Test, compared with 23% of participants who received placebo (odds ratio, 0.56). Dr. Steiner noted that ABILHAND, a patient-reported upper-extremity outcome, clearly differentiated Nine-Hole Peg Test progressors from nonprogressors. This finding “confirms the meaningfulness” of the treatment’s effect on upper extremity disability, the researchers said.

On the Nine-Hole Peg Test, estimated probabilities of confirmed progression over two years showed increased separation over time between the natalizumab and placebo arms. “In contrast, no significant separation over time was observed between natalizumab- and placebo-treated patients on the Timed 25-Foot Walk (38.3% vs 39.2%) or EDSS (17.4% vs 16.7%) components of the primary end point,” the researchers said.

“There’s a striking contrast between the lack of effect on ambulatory function … and the effect on upper-extremity function,” Dr. Steiner said.

Natalizumab was generally well tolerated, with adverse events consistent with its known safety profile.

The study was supported by Biogen in Cambridge, Massachusetts.

—Jake Remaly

VANCOUVER—Among patients with secondary progressive multiple sclerosis (MS), natalizumab does not delay progression of ambulatory disability, according to phase III trial results presented at the 68th Annual Meeting of the American Academy of Neurology. The drug may slow progression of upper-extremity disability, however, researchers said.

Natalizumab, a recombinant humanized monoclonal antibody against alpha-4 beta-1 integrin, reduces inflammation by inhibiting the transmigration of leukocytes into the brain. It is FDA-approved to treat relapsing-remitting MS, and data have suggested that the drug also may benefit patients with progressive forms of MS.

To investigate whether natalizumab slows disability progression unrelated to relapses in patients with secondary progressive MS, Deborah Steiner, MD, Medical Director at Biogen, and colleagues conducted ASCEND, a multicenter, double-blind, placebo-controlled, randomized trial.

The primary end point was the proportion of participants with confirmed disability progression on the EDSS, Nine-Hole Peg Test, or Timed 25-Foot Walk at six months and at the end of the trial. On the EDSS, progression was defined as an increase of at least 1.0 from a baseline EDSS score of 5.5 or less, or an increase of at least 0.5 from a baseline EDSS score of 6 or more. On the Timed 25-Foot Walk, progression was defined as an increase of 20% or more from baseline. On the Nine-Hole Peg Test, progression was defined as an increase of 20% or more on either hand.

ASCEND did not meet its primary end point. The proportion of progressors was higher in the placebo-treated group (48%) than in the natalizumab-treated group (44%), but the difference was not statistically significant.

Natalizumab treatment was, how­ever, associated with a statistically significant reduction of upper-extremity disability progression, as measured by the Nine-Hole Peg Test. Fifteen percent of participants who received natalizumab had confirmed disability progression on the Nine-Hole Peg Test, compared with 23% of participants who received placebo (odds ratio, 0.56). Dr. Steiner noted that ABILHAND, a patient-reported upper-extremity outcome, clearly differentiated Nine-Hole Peg Test progressors from nonprogressors. This finding “confirms the meaningfulness” of the treatment’s effect on upper extremity disability, the researchers said.

On the Nine-Hole Peg Test, estimated probabilities of confirmed progression over two years showed increased separation over time between the natalizumab and placebo arms. “In contrast, no significant separation over time was observed between natalizumab- and placebo-treated patients on the Timed 25-Foot Walk (38.3% vs 39.2%) or EDSS (17.4% vs 16.7%) components of the primary end point,” the researchers said.

“There’s a striking contrast between the lack of effect on ambulatory function … and the effect on upper-extremity function,” Dr. Steiner said.

Natalizumab was generally well tolerated, with adverse events consistent with its known safety profile.

The study was supported by Biogen in Cambridge, Massachusetts.

—Jake Remaly

VANCOUVER—Among patients with secondary progressive multiple sclerosis (MS), natalizumab does not delay progression of ambulatory disability, according to phase III trial results presented at the 68th Annual Meeting of the American Academy of Neurology. The drug may slow progression of upper-extremity disability, however, researchers said.

Natalizumab, a recombinant humanized monoclonal antibody against alpha-4 beta-1 integrin, reduces inflammation by inhibiting the transmigration of leukocytes into the brain. It is FDA-approved to treat relapsing-remitting MS, and data have suggested that the drug also may benefit patients with progressive forms of MS.

To investigate whether natalizumab slows disability progression unrelated to relapses in patients with secondary progressive MS, Deborah Steiner, MD, Medical Director at Biogen, and colleagues conducted ASCEND, a multicenter, double-blind, placebo-controlled, randomized trial.

The primary end point was the proportion of participants with confirmed disability progression on the EDSS, Nine-Hole Peg Test, or Timed 25-Foot Walk at six months and at the end of the trial. On the EDSS, progression was defined as an increase of at least 1.0 from a baseline EDSS score of 5.5 or less, or an increase of at least 0.5 from a baseline EDSS score of 6 or more. On the Timed 25-Foot Walk, progression was defined as an increase of 20% or more from baseline. On the Nine-Hole Peg Test, progression was defined as an increase of 20% or more on either hand.

ASCEND did not meet its primary end point. The proportion of progressors was higher in the placebo-treated group (48%) than in the natalizumab-treated group (44%), but the difference was not statistically significant.

Natalizumab treatment was, how­ever, associated with a statistically significant reduction of upper-extremity disability progression, as measured by the Nine-Hole Peg Test. Fifteen percent of participants who received natalizumab had confirmed disability progression on the Nine-Hole Peg Test, compared with 23% of participants who received placebo (odds ratio, 0.56). Dr. Steiner noted that ABILHAND, a patient-reported upper-extremity outcome, clearly differentiated Nine-Hole Peg Test progressors from nonprogressors. This finding “confirms the meaningfulness” of the treatment’s effect on upper extremity disability, the researchers said.

On the Nine-Hole Peg Test, estimated probabilities of confirmed progression over two years showed increased separation over time between the natalizumab and placebo arms. “In contrast, no significant separation over time was observed between natalizumab- and placebo-treated patients on the Timed 25-Foot Walk (38.3% vs 39.2%) or EDSS (17.4% vs 16.7%) components of the primary end point,” the researchers said.

“There’s a striking contrast between the lack of effect on ambulatory function … and the effect on upper-extremity function,” Dr. Steiner said.

Natalizumab was generally well tolerated, with adverse events consistent with its known safety profile.

The study was supported by Biogen in Cambridge, Massachusetts.

—Jake Remaly

VANCOUVER – The risk of dimethyl fumarate lymphopenia – and perhaps progressive multifocal leukoencephalopathy – is greatest in patients 60 years or older and those with baseline absolute lymphocyte counts below 2 x 109/L, according to a review of 206 patients with relapsing-remitting or progressive multiple sclerosis from the University of Rochester (N.Y.).

A total of 87 patients (42%), all of whom were on dimethyl fumarate (DMF; Tecfidera) for at least 3 months, developed lymphopenia with an absolute lymphocyte count (ALC) below 0.91 x 10⁹/L. That’s not a surprise; lymphopenia is a well-known side effect of the drug, and the rates in Rochester were similar to what was reported in clinical trials. The greatest concern with DMF lymphopenia is subsequent progressive multifocal leukoencephalopathy (PML); a handful of cases have been reported in lymphopenic patients, none in the University of Rochester review.

What was surprising was that in the 34 patients aged 60 years or older, 24 (71%) developed lymphopenia, versus 62 (36%) of the 172 under 60 years old (P = .0005). Meanwhile, of 93 patients with baseline ALCs below 2 x 10⁹/L, 49 (53%) became lymphopenic, versus 34 of 104 patients (33%) who started DMF with higher lymphocyte counts (P = .0006). A total of nine patients in the study did not have a baseline ALC available.

M. Alexander Otto/Frontline Medical News

“If I had a patient who was 70 years old with a low baseline lymphocyte count, [these findings] would weigh into my decisions about choosing” this medication. “Age and baseline ALC may guide future selection of patients for DMF therapy,” neurologist and investigator Dr. Jessica Robb said at the annual meeting of the American Academy of Neurology.

Also, because higher grade lymphopenia didn’t resolve in most cases until the drug was stopped, “if I had a patient who developed more severe grade 3 or 4 lymphopenia, I would probably have a lower threshold for” discontinuation. “I would probably think about changing medication more quickly rather than leaving them on [DMF] and hoping that their lymphopenia resolves,” Dr. Robb said.

The Rochester findings are in line with a 2015 report from Washington University, St. Louis, that also indicated a higher risk of moderate to severe lymphopenia in older patients and those with lower baseline ALCs, as well as recent natalizumab (Tysabri) users. Grade 2 or worse lymphopenia “is unlikely to resolve while on the drug,” the St. Louis investigators concluded (Mult Scler J Exp Transl Clin. 2015 Jan-Dec;1:2055217315596994).

Taken together, the two studies are important because there’s otherwise not much else in the medical literature identifying DMF lymphopenia risk factors. Lymphopenia and PML are also concerns with other multiple sclerosis (MS) agents.

“The increased prevalence of lymphopenia in older patients and in patients with a lower baseline ALC suggests a failure of lymphopoiesis triggered by DMF therapy. Indeed, lymphopoiesis declines with age due to thymic involution and decreased production of naive lymphocytes. ... Whether these consequences of normal aging could be amplified by DMF is an avenue for future study,” the St. Louis team said.

“The significance of increased risk for lymphopenia in patients recently exposed to natalizumab is not immediately obvious. ... Natalizumab is known to expand circulating leukocytes, including progenitor cells. If in turn, DMF causes lymphocyte apoptosis or arrest of differentiation, then patients sequentially exposed to natalizumab and DMF might have a larger number of circulating lymphocytes vulnerable to DMF effects than other patients,” they said.

Food and Drug Administration labeling for DMF recommends lymphocyte counts at baseline, 6 months, and every 6-12 months thereafter. However, European regulators recently recommended lymphocyte counts at baseline and every 3 months to catch problems early, as well as baseline MRIs as references for possible PML.

Standard, 240-mg twice-daily dosing was used at the University of Rochester, and the mean age in the study was 49 years. The majority of patients were women, and the mean duration of MS was 11 years. Almost three-quarters of the patients were new to immunosuppression, and none of the patients developed serious infections.

The University of Rochester team noted a higher rate of grade 1 lymphopenia than reported in clinical trials (18% vs. 10%). Twelve patients (6%) discontinued DMF because of lymphopenia.

Dr. Robb and the other investigators had no relevant disclosures.

aotto@frontlinemedcom.com

VANCOUVER – The risk of dimethyl fumarate lymphopenia – and perhaps progressive multifocal leukoencephalopathy – is greatest in patients 60 years or older and those with baseline absolute lymphocyte counts below 2 x 109/L, according to a review of 206 patients with relapsing-remitting or progressive multiple sclerosis from the University of Rochester (N.Y.).

A total of 87 patients (42%), all of whom were on dimethyl fumarate (DMF; Tecfidera) for at least 3 months, developed lymphopenia with an absolute lymphocyte count (ALC) below 0.91 x 10⁹/L. That’s not a surprise; lymphopenia is a well-known side effect of the drug, and the rates in Rochester were similar to what was reported in clinical trials. The greatest concern with DMF lymphopenia is subsequent progressive multifocal leukoencephalopathy (PML); a handful of cases have been reported in lymphopenic patients, none in the University of Rochester review.

What was surprising was that in the 34 patients aged 60 years or older, 24 (71%) developed lymphopenia, versus 62 (36%) of the 172 under 60 years old (P = .0005). Meanwhile, of 93 patients with baseline ALCs below 2 x 10⁹/L, 49 (53%) became lymphopenic, versus 34 of 104 patients (33%) who started DMF with higher lymphocyte counts (P = .0006). A total of nine patients in the study did not have a baseline ALC available.

M. Alexander Otto/Frontline Medical News

“If I had a patient who was 70 years old with a low baseline lymphocyte count, [these findings] would weigh into my decisions about choosing” this medication. “Age and baseline ALC may guide future selection of patients for DMF therapy,” neurologist and investigator Dr. Jessica Robb said at the annual meeting of the American Academy of Neurology.

Also, because higher grade lymphopenia didn’t resolve in most cases until the drug was stopped, “if I had a patient who developed more severe grade 3 or 4 lymphopenia, I would probably have a lower threshold for” discontinuation. “I would probably think about changing medication more quickly rather than leaving them on [DMF] and hoping that their lymphopenia resolves,” Dr. Robb said.

The Rochester findings are in line with a 2015 report from Washington University, St. Louis, that also indicated a higher risk of moderate to severe lymphopenia in older patients and those with lower baseline ALCs, as well as recent natalizumab (Tysabri) users. Grade 2 or worse lymphopenia “is unlikely to resolve while on the drug,” the St. Louis investigators concluded (Mult Scler J Exp Transl Clin. 2015 Jan-Dec;1:2055217315596994).

Taken together, the two studies are important because there’s otherwise not much else in the medical literature identifying DMF lymphopenia risk factors. Lymphopenia and PML are also concerns with other multiple sclerosis (MS) agents.

“The increased prevalence of lymphopenia in older patients and in patients with a lower baseline ALC suggests a failure of lymphopoiesis triggered by DMF therapy. Indeed, lymphopoiesis declines with age due to thymic involution and decreased production of naive lymphocytes. ... Whether these consequences of normal aging could be amplified by DMF is an avenue for future study,” the St. Louis team said.

“The significance of increased risk for lymphopenia in patients recently exposed to natalizumab is not immediately obvious. ... Natalizumab is known to expand circulating leukocytes, including progenitor cells. If in turn, DMF causes lymphocyte apoptosis or arrest of differentiation, then patients sequentially exposed to natalizumab and DMF might have a larger number of circulating lymphocytes vulnerable to DMF effects than other patients,” they said.

Food and Drug Administration labeling for DMF recommends lymphocyte counts at baseline, 6 months, and every 6-12 months thereafter. However, European regulators recently recommended lymphocyte counts at baseline and every 3 months to catch problems early, as well as baseline MRIs as references for possible PML.

Standard, 240-mg twice-daily dosing was used at the University of Rochester, and the mean age in the study was 49 years. The majority of patients were women, and the mean duration of MS was 11 years. Almost three-quarters of the patients were new to immunosuppression, and none of the patients developed serious infections.

The University of Rochester team noted a higher rate of grade 1 lymphopenia than reported in clinical trials (18% vs. 10%). Twelve patients (6%) discontinued DMF because of lymphopenia.

Dr. Robb and the other investigators had no relevant disclosures.

aotto@frontlinemedcom.com

VANCOUVER – The risk of dimethyl fumarate lymphopenia – and perhaps progressive multifocal leukoencephalopathy – is greatest in patients 60 years or older and those with baseline absolute lymphocyte counts below 2 x 109/L, according to a review of 206 patients with relapsing-remitting or progressive multiple sclerosis from the University of Rochester (N.Y.).

A total of 87 patients (42%), all of whom were on dimethyl fumarate (DMF; Tecfidera) for at least 3 months, developed lymphopenia with an absolute lymphocyte count (ALC) below 0.91 x 10⁹/L. That’s not a surprise; lymphopenia is a well-known side effect of the drug, and the rates in Rochester were similar to what was reported in clinical trials. The greatest concern with DMF lymphopenia is subsequent progressive multifocal leukoencephalopathy (PML); a handful of cases have been reported in lymphopenic patients, none in the University of Rochester review.

What was surprising was that in the 34 patients aged 60 years or older, 24 (71%) developed lymphopenia, versus 62 (36%) of the 172 under 60 years old (P = .0005). Meanwhile, of 93 patients with baseline ALCs below 2 x 10⁹/L, 49 (53%) became lymphopenic, versus 34 of 104 patients (33%) who started DMF with higher lymphocyte counts (P = .0006). A total of nine patients in the study did not have a baseline ALC available.

M. Alexander Otto/Frontline Medical News

“If I had a patient who was 70 years old with a low baseline lymphocyte count, [these findings] would weigh into my decisions about choosing” this medication. “Age and baseline ALC may guide future selection of patients for DMF therapy,” neurologist and investigator Dr. Jessica Robb said at the annual meeting of the American Academy of Neurology.

Also, because higher grade lymphopenia didn’t resolve in most cases until the drug was stopped, “if I had a patient who developed more severe grade 3 or 4 lymphopenia, I would probably have a lower threshold for” discontinuation. “I would probably think about changing medication more quickly rather than leaving them on [DMF] and hoping that their lymphopenia resolves,” Dr. Robb said.

The Rochester findings are in line with a 2015 report from Washington University, St. Louis, that also indicated a higher risk of moderate to severe lymphopenia in older patients and those with lower baseline ALCs, as well as recent natalizumab (Tysabri) users. Grade 2 or worse lymphopenia “is unlikely to resolve while on the drug,” the St. Louis investigators concluded (Mult Scler J Exp Transl Clin. 2015 Jan-Dec;1:2055217315596994).

Taken together, the two studies are important because there’s otherwise not much else in the medical literature identifying DMF lymphopenia risk factors. Lymphopenia and PML are also concerns with other multiple sclerosis (MS) agents.

“The increased prevalence of lymphopenia in older patients and in patients with a lower baseline ALC suggests a failure of lymphopoiesis triggered by DMF therapy. Indeed, lymphopoiesis declines with age due to thymic involution and decreased production of naive lymphocytes. ... Whether these consequences of normal aging could be amplified by DMF is an avenue for future study,” the St. Louis team said.

“The significance of increased risk for lymphopenia in patients recently exposed to natalizumab is not immediately obvious. ... Natalizumab is known to expand circulating leukocytes, including progenitor cells. If in turn, DMF causes lymphocyte apoptosis or arrest of differentiation, then patients sequentially exposed to natalizumab and DMF might have a larger number of circulating lymphocytes vulnerable to DMF effects than other patients,” they said.

Food and Drug Administration labeling for DMF recommends lymphocyte counts at baseline, 6 months, and every 6-12 months thereafter. However, European regulators recently recommended lymphocyte counts at baseline and every 3 months to catch problems early, as well as baseline MRIs as references for possible PML.

Standard, 240-mg twice-daily dosing was used at the University of Rochester, and the mean age in the study was 49 years. The majority of patients were women, and the mean duration of MS was 11 years. Almost three-quarters of the patients were new to immunosuppression, and none of the patients developed serious infections.

The University of Rochester team noted a higher rate of grade 1 lymphopenia than reported in clinical trials (18% vs. 10%). Twelve patients (6%) discontinued DMF because of lymphopenia.

Dr. Robb and the other investigators had no relevant disclosures.

aotto@frontlinemedcom.com

VANCOUVER – Ocrelizumab, a B-cell depleting humanized monoclonal antibody being developed by Hoffman–La Roche, consistently outperformed interferon beta-1a (Rebif) for relapsing multiple sclerosis in two phase III trials reported at the annual meeting of the American Academy of Neurology.

The identical trials, dubbed OPERA I and OPERA II, each had about 800 patients. Subjects were randomized one-to-one to intravenous ocrelizumab 600 mg every 24 weeks or to subcutaneous interferon beta-1a 44 micrograms three times weekly over 96 weeks. Patients had early disease; a significant portion were naive to multiple sclerosis (MS) treatments.

At 96 weeks, 47.9% and 47.5% of ocrelizumab patients versus 29.2% and 25.1% of interferon patients had no evidence of disease activity (NEDA) in the two studies. NEDA is a composite score defined as no relapses, no confirmed disability progression, and no new or enlarging T2 or gadolinium-enhancing T1 lesions.

Across both studies, relapses occurred in about 20% of ocrelizumab patients versus about 35% of interferon patients. About 10% of ocrelizumab, but about 15% of interferon patients, had clinical disease progression. Similarly, about 10% of ocrelizumab patients developed new gadolinium-enhancing lesions, compared with about 35% in the interferon groups. New or enlarging T2 lesions were found in about 40% in the ocrelizumab groups but in more than 60% in the interferon arms.

After week 24, 96% percent of ocrelizumab patients, compared with 60%-70% on interferon, were free of new or enlarging T2 lesions.

In short, ocrelizumab “resulted in greater achievement of NEDA versus [interferon] over 96 weeks, with elimination of new/enlarging T2 lesions in nearly all patients after week 24,” the researchers concluded.

“These are very impressive numbers,” especially because ocrelizumab was compared with a standard treatment. “There was a wonderful constancy of results” across the trials; “a very highly effective treatment is emerging for multiple sclerosis,” said investigator and presenter Dr. Anthony Traboulsee, a neurologist at the University of British Columbia, Vancouver, who also noted that in many cases, patients opted to stay on ocrelizumab at the end of the trials.

Dr. Traboulsee did not present safety data. A previous report of 24-week results found that infusion reactions were significantly more common with ocrelizumab than with interferon beta-1a (34% vs. 9.7%). Otherwise, there were similar rates of serious adverse events, including serious infections, and there were no cases of progressive multifocal leukoencephalopathy (PML). The PML and infection findings are especially important; Roche shelved earlier attempts to develop the biologic for lupus and rheumatoid arthritis due to serious and opportunistic infections, some of which were fatal.

Roche plans to submit its approval package to the Food and Drug Administration in the first half of 2016; the tentative brand name is Ocrevus. FDA granted the biologic breakthrough, fast-track status for primary progressive MS based on the strength of an earlier phase III trial. At present, there are no MS agents indicated for primary progressive disease.

Patients in OPERA were 37 years old, on average, and two-thirds were women. The mean baseline score on the Extended Disability Status Scale was 2.77, and the mean time since diagnosis was about 4 years. Patients had about 1.5 relapses in the first and second year before entering the studies.

The positive results – and the increasing buzz about ocrelizumab in the MS community – raise the question of how it will fit into the MS armamentarium if it’s approved, which seems likely. A review in Therapeutic Advances in Neurological Disorders tackled the issue in January, before the OPERA results were made public (2016 Jan; 9[1]:44-52).

It’s unclear if ocrelizumab will become the go-to option when patients progress on first-line agents such as interferon and glatiramer acetate. Phase II data suggest ocrelizumab’s “effect on clinical disease activity [seems] to be of the same magnitude compared with that of fingolimod and natalizumab,” and will likely be an alternative to natalizumab and alemtuzumab. “Ocrelizumab seems to have a more favourable risk–benefit profile compared with natalizumab in JC [John Cunningham] virus antibody–positive patients, whereas natalizumab in JC virus antibody–negative patients appears safer. Hence, ocrelizumab could be an attractive option among second-line therapies in patients who are JC virus antibody positive, whereas natalizumab or alternatively oral fingolimod would be the first choice among second-line therapies in JC virus antibody–negative patients,” said authors Dr. Per Soelberg Sorensen and Dr. Morten Blinkenberg, both MS neurologists at the University of Copenhagen.

“It needs to be emphasized that long-term data on the safety of ocrelizumab in the treatment of MS is warranted, and therefore post-marketing safety programs will be needed.” The risk of PML with long-term use is unknown. “Another unsolved question is whether ocrelizumab therapy should be applied at fixed intervals, e.g. every 6 months [as in OPERA], or if re-treatment should be guided by the recovery of CD19-positive B cells,” they said.

In any case, infusion reactions with ocrelizumab should be less than with rituximab (Rituxan), another B-cell depleter used off-label for MS, because ocrelizumab is a more humanized antibody.

OPERA 1 and 2 were funded by Hoffmann–La Roche. Dr. Traboulsee is a paid speaker, consultant, and researcher for the company. Other investigators also reported various ties to Roche; several are employees. The review authors had no disclosures.

aotto@frontlinemedcom.com

VANCOUVER – Ocrelizumab, a B-cell depleting humanized monoclonal antibody being developed by Hoffman–La Roche, consistently outperformed interferon beta-1a (Rebif) for relapsing multiple sclerosis in two phase III trials reported at the annual meeting of the American Academy of Neurology.

The identical trials, dubbed OPERA I and OPERA II, each had about 800 patients. Subjects were randomized one-to-one to intravenous ocrelizumab 600 mg every 24 weeks or to subcutaneous interferon beta-1a 44 micrograms three times weekly over 96 weeks. Patients had early disease; a significant portion were naive to multiple sclerosis (MS) treatments.

At 96 weeks, 47.9% and 47.5% of ocrelizumab patients versus 29.2% and 25.1% of interferon patients had no evidence of disease activity (NEDA) in the two studies. NEDA is a composite score defined as no relapses, no confirmed disability progression, and no new or enlarging T2 or gadolinium-enhancing T1 lesions.

Across both studies, relapses occurred in about 20% of ocrelizumab patients versus about 35% of interferon patients. About 10% of ocrelizumab, but about 15% of interferon patients, had clinical disease progression. Similarly, about 10% of ocrelizumab patients developed new gadolinium-enhancing lesions, compared with about 35% in the interferon groups. New or enlarging T2 lesions were found in about 40% in the ocrelizumab groups but in more than 60% in the interferon arms.

After week 24, 96% percent of ocrelizumab patients, compared with 60%-70% on interferon, were free of new or enlarging T2 lesions.

In short, ocrelizumab “resulted in greater achievement of NEDA versus [interferon] over 96 weeks, with elimination of new/enlarging T2 lesions in nearly all patients after week 24,” the researchers concluded.

“These are very impressive numbers,” especially because ocrelizumab was compared with a standard treatment. “There was a wonderful constancy of results” across the trials; “a very highly effective treatment is emerging for multiple sclerosis,” said investigator and presenter Dr. Anthony Traboulsee, a neurologist at the University of British Columbia, Vancouver, who also noted that in many cases, patients opted to stay on ocrelizumab at the end of the trials.

Dr. Traboulsee did not present safety data. A previous report of 24-week results found that infusion reactions were significantly more common with ocrelizumab than with interferon beta-1a (34% vs. 9.7%). Otherwise, there were similar rates of serious adverse events, including serious infections, and there were no cases of progressive multifocal leukoencephalopathy (PML). The PML and infection findings are especially important; Roche shelved earlier attempts to develop the biologic for lupus and rheumatoid arthritis due to serious and opportunistic infections, some of which were fatal.

Roche plans to submit its approval package to the Food and Drug Administration in the first half of 2016; the tentative brand name is Ocrevus. FDA granted the biologic breakthrough, fast-track status for primary progressive MS based on the strength of an earlier phase III trial. At present, there are no MS agents indicated for primary progressive disease.

Patients in OPERA were 37 years old, on average, and two-thirds were women. The mean baseline score on the Extended Disability Status Scale was 2.77, and the mean time since diagnosis was about 4 years. Patients had about 1.5 relapses in the first and second year before entering the studies.

The positive results – and the increasing buzz about ocrelizumab in the MS community – raise the question of how it will fit into the MS armamentarium if it’s approved, which seems likely. A review in Therapeutic Advances in Neurological Disorders tackled the issue in January, before the OPERA results were made public (2016 Jan; 9[1]:44-52).

It’s unclear if ocrelizumab will become the go-to option when patients progress on first-line agents such as interferon and glatiramer acetate. Phase II data suggest ocrelizumab’s “effect on clinical disease activity [seems] to be of the same magnitude compared with that of fingolimod and natalizumab,” and will likely be an alternative to natalizumab and alemtuzumab. “Ocrelizumab seems to have a more favourable risk–benefit profile compared with natalizumab in JC [John Cunningham] virus antibody–positive patients, whereas natalizumab in JC virus antibody–negative patients appears safer. Hence, ocrelizumab could be an attractive option among second-line therapies in patients who are JC virus antibody positive, whereas natalizumab or alternatively oral fingolimod would be the first choice among second-line therapies in JC virus antibody–negative patients,” said authors Dr. Per Soelberg Sorensen and Dr. Morten Blinkenberg, both MS neurologists at the University of Copenhagen.

“It needs to be emphasized that long-term data on the safety of ocrelizumab in the treatment of MS is warranted, and therefore post-marketing safety programs will be needed.” The risk of PML with long-term use is unknown. “Another unsolved question is whether ocrelizumab therapy should be applied at fixed intervals, e.g. every 6 months [as in OPERA], or if re-treatment should be guided by the recovery of CD19-positive B cells,” they said.

In any case, infusion reactions with ocrelizumab should be less than with rituximab (Rituxan), another B-cell depleter used off-label for MS, because ocrelizumab is a more humanized antibody.

OPERA 1 and 2 were funded by Hoffmann–La Roche. Dr. Traboulsee is a paid speaker, consultant, and researcher for the company. Other investigators also reported various ties to Roche; several are employees. The review authors had no disclosures.

aotto@frontlinemedcom.com

VANCOUVER – Ocrelizumab, a B-cell depleting humanized monoclonal antibody being developed by Hoffman–La Roche, consistently outperformed interferon beta-1a (Rebif) for relapsing multiple sclerosis in two phase III trials reported at the annual meeting of the American Academy of Neurology.

The identical trials, dubbed OPERA I and OPERA II, each had about 800 patients. Subjects were randomized one-to-one to intravenous ocrelizumab 600 mg every 24 weeks or to subcutaneous interferon beta-1a 44 micrograms three times weekly over 96 weeks. Patients had early disease; a significant portion were naive to multiple sclerosis (MS) treatments.

At 96 weeks, 47.9% and 47.5% of ocrelizumab patients versus 29.2% and 25.1% of interferon patients had no evidence of disease activity (NEDA) in the two studies. NEDA is a composite score defined as no relapses, no confirmed disability progression, and no new or enlarging T2 or gadolinium-enhancing T1 lesions.

Across both studies, relapses occurred in about 20% of ocrelizumab patients versus about 35% of interferon patients. About 10% of ocrelizumab, but about 15% of interferon patients, had clinical disease progression. Similarly, about 10% of ocrelizumab patients developed new gadolinium-enhancing lesions, compared with about 35% in the interferon groups. New or enlarging T2 lesions were found in about 40% in the ocrelizumab groups but in more than 60% in the interferon arms.

After week 24, 96% percent of ocrelizumab patients, compared with 60%-70% on interferon, were free of new or enlarging T2 lesions.

In short, ocrelizumab “resulted in greater achievement of NEDA versus [interferon] over 96 weeks, with elimination of new/enlarging T2 lesions in nearly all patients after week 24,” the researchers concluded.

“These are very impressive numbers,” especially because ocrelizumab was compared with a standard treatment. “There was a wonderful constancy of results” across the trials; “a very highly effective treatment is emerging for multiple sclerosis,” said investigator and presenter Dr. Anthony Traboulsee, a neurologist at the University of British Columbia, Vancouver, who also noted that in many cases, patients opted to stay on ocrelizumab at the end of the trials.

Dr. Traboulsee did not present safety data. A previous report of 24-week results found that infusion reactions were significantly more common with ocrelizumab than with interferon beta-1a (34% vs. 9.7%). Otherwise, there were similar rates of serious adverse events, including serious infections, and there were no cases of progressive multifocal leukoencephalopathy (PML). The PML and infection findings are especially important; Roche shelved earlier attempts to develop the biologic for lupus and rheumatoid arthritis due to serious and opportunistic infections, some of which were fatal.

Roche plans to submit its approval package to the Food and Drug Administration in the first half of 2016; the tentative brand name is Ocrevus. FDA granted the biologic breakthrough, fast-track status for primary progressive MS based on the strength of an earlier phase III trial. At present, there are no MS agents indicated for primary progressive disease.

Patients in OPERA were 37 years old, on average, and two-thirds were women. The mean baseline score on the Extended Disability Status Scale was 2.77, and the mean time since diagnosis was about 4 years. Patients had about 1.5 relapses in the first and second year before entering the studies.

The positive results – and the increasing buzz about ocrelizumab in the MS community – raise the question of how it will fit into the MS armamentarium if it’s approved, which seems likely. A review in Therapeutic Advances in Neurological Disorders tackled the issue in January, before the OPERA results were made public (2016 Jan; 9[1]:44-52).

It’s unclear if ocrelizumab will become the go-to option when patients progress on first-line agents such as interferon and glatiramer acetate. Phase II data suggest ocrelizumab’s “effect on clinical disease activity [seems] to be of the same magnitude compared with that of fingolimod and natalizumab,” and will likely be an alternative to natalizumab and alemtuzumab. “Ocrelizumab seems to have a more favourable risk–benefit profile compared with natalizumab in JC [John Cunningham] virus antibody–positive patients, whereas natalizumab in JC virus antibody–negative patients appears safer. Hence, ocrelizumab could be an attractive option among second-line therapies in patients who are JC virus antibody positive, whereas natalizumab or alternatively oral fingolimod would be the first choice among second-line therapies in JC virus antibody–negative patients,” said authors Dr. Per Soelberg Sorensen and Dr. Morten Blinkenberg, both MS neurologists at the University of Copenhagen.

“It needs to be emphasized that long-term data on the safety of ocrelizumab in the treatment of MS is warranted, and therefore post-marketing safety programs will be needed.” The risk of PML with long-term use is unknown. “Another unsolved question is whether ocrelizumab therapy should be applied at fixed intervals, e.g. every 6 months [as in OPERA], or if re-treatment should be guided by the recovery of CD19-positive B cells,” they said.

In any case, infusion reactions with ocrelizumab should be less than with rituximab (Rituxan), another B-cell depleter used off-label for MS, because ocrelizumab is a more humanized antibody.

OPERA 1 and 2 were funded by Hoffmann–La Roche. Dr. Traboulsee is a paid speaker, consultant, and researcher for the company. Other investigators also reported various ties to Roche; several are employees. The review authors had no disclosures.

aotto@frontlinemedcom.com

ATLANTA – Nearly half of 2,100 multiple sclerosis (MS) patients enrolled at baseline in the Sonya Slifka Longitudinal Multiple Sclerosis Study reported experiencing emotional distress, and 9% of those patients reported difficulties with accessing mental health services.

Younger patients, those with more recently diagnosed illness, and those with more frequent MS relapses were more likely to experience emotional distress, Dr. Laura Safar of Brigham and Women’s Hospital, Boston, said at the annual meeting of the American Psychiatric Association.

HUNG KUO CHUN/Thinkstock

The Sonya Slifka study was an 8-year population-based cohort study that, at last report, included more than 4,000 MS patients from across the United States, with varying disease duration. Dr. Safar reported on baseline mental health data from the study.

Patients with MS may experience symptoms involving any part of the central nervous system, including psychiatric symptoms such as depression, anxiety, and cognitive disorders, she said, noting that these are highly prevalent, but often go unrecognized and untreated by primary care doctors and neurologists.

Prior studies have suggested that depression occurs in 25%-80% of patients, depending on the study setting. The rates are higher in those with MS than in the general population or in those with other neurologic and chronic medical conditions, she said.

In the Sonya Slifka study, 77% of patients were women with an average age of 50 years and disease duration ranging from 1 week to 64 years. Most were white. The disease distribution was representative of that seen in the general MS population, with most (57%) having relapsing-remitting disease, 25% having secondary progressive disease, and the remaining patients having primary progressive disease or progressing-relapsing disease (Mult Scler. 2006 Feb;12[1]:24-38).

Reported disability levels varied from none/very mild to severe and requiring a wheelchair or scooter or being bedridden.

Of the 48% of patients reporting emotional distress, most reported having mild to moderate distress, but 40% reported severe distress.

Nearly half (46%) of patients reported accomplishing less than normal because of emotional difficulties, and 31% said they worked less carefully than usual.

Emotional distress was more common in patients who were younger, divorced or never married, unemployed, and in those with lower education and income levels. Emotional distress was associated with shorter duration of illness, with having multiple relapses in the prior year (highest rates were among those with five or more relapses), and with moderate disability level.

Emotional distress was also associated with poorer perceived general health, and those with higher levels of emotional distress tended to experience all or many of the symptoms on the baseline questionnaire.

Further, those with emotional distress tended to lack health insurance and to have problems accessing health care and necessary prescription medications. About one-fourth of the patients had seen a mental health professional in the prior year and nearly 8% wanted to; 2% said they had been referred to a mental health professional, and 93% of these patients had emotional distress, including 6% with severe distress.

Reasons given by these patients for not seeing a mental health professional were cost, difficulty getting an appointment, and too long of a wait.

The findings suggest that in clinical settings it is important to screen MS patients for emotional distress and depression and to treat or refer accordingly, Dr. Safar said.

“As we know from other medical illnesses, this will improve adherence to MS treatment and will improve the prognosis,” she added.

Dr. Safar reported having no disclosures.

sworcester@frontlinemedcom.com

ATLANTA – Nearly half of 2,100 multiple sclerosis (MS) patients enrolled at baseline in the Sonya Slifka Longitudinal Multiple Sclerosis Study reported experiencing emotional distress, and 9% of those patients reported difficulties with accessing mental health services.

Younger patients, those with more recently diagnosed illness, and those with more frequent MS relapses were more likely to experience emotional distress, Dr. Laura Safar of Brigham and Women’s Hospital, Boston, said at the annual meeting of the American Psychiatric Association.

HUNG KUO CHUN/Thinkstock

The Sonya Slifka study was an 8-year population-based cohort study that, at last report, included more than 4,000 MS patients from across the United States, with varying disease duration. Dr. Safar reported on baseline mental health data from the study.

Patients with MS may experience symptoms involving any part of the central nervous system, including psychiatric symptoms such as depression, anxiety, and cognitive disorders, she said, noting that these are highly prevalent, but often go unrecognized and untreated by primary care doctors and neurologists.

Prior studies have suggested that depression occurs in 25%-80% of patients, depending on the study setting. The rates are higher in those with MS than in the general population or in those with other neurologic and chronic medical conditions, she said.

In the Sonya Slifka study, 77% of patients were women with an average age of 50 years and disease duration ranging from 1 week to 64 years. Most were white. The disease distribution was representative of that seen in the general MS population, with most (57%) having relapsing-remitting disease, 25% having secondary progressive disease, and the remaining patients having primary progressive disease or progressing-relapsing disease (Mult Scler. 2006 Feb;12[1]:24-38).

Reported disability levels varied from none/very mild to severe and requiring a wheelchair or scooter or being bedridden.

Of the 48% of patients reporting emotional distress, most reported having mild to moderate distress, but 40% reported severe distress.

Nearly half (46%) of patients reported accomplishing less than normal because of emotional difficulties, and 31% said they worked less carefully than usual.

Emotional distress was more common in patients who were younger, divorced or never married, unemployed, and in those with lower education and income levels. Emotional distress was associated with shorter duration of illness, with having multiple relapses in the prior year (highest rates were among those with five or more relapses), and with moderate disability level.

Emotional distress was also associated with poorer perceived general health, and those with higher levels of emotional distress tended to experience all or many of the symptoms on the baseline questionnaire.

Further, those with emotional distress tended to lack health insurance and to have problems accessing health care and necessary prescription medications. About one-fourth of the patients had seen a mental health professional in the prior year and nearly 8% wanted to; 2% said they had been referred to a mental health professional, and 93% of these patients had emotional distress, including 6% with severe distress.

Reasons given by these patients for not seeing a mental health professional were cost, difficulty getting an appointment, and too long of a wait.

The findings suggest that in clinical settings it is important to screen MS patients for emotional distress and depression and to treat or refer accordingly, Dr. Safar said.

“As we know from other medical illnesses, this will improve adherence to MS treatment and will improve the prognosis,” she added.

Dr. Safar reported having no disclosures.

sworcester@frontlinemedcom.com

ATLANTA – Nearly half of 2,100 multiple sclerosis (MS) patients enrolled at baseline in the Sonya Slifka Longitudinal Multiple Sclerosis Study reported experiencing emotional distress, and 9% of those patients reported difficulties with accessing mental health services.

Younger patients, those with more recently diagnosed illness, and those with more frequent MS relapses were more likely to experience emotional distress, Dr. Laura Safar of Brigham and Women’s Hospital, Boston, said at the annual meeting of the American Psychiatric Association.

HUNG KUO CHUN/Thinkstock

The Sonya Slifka study was an 8-year population-based cohort study that, at last report, included more than 4,000 MS patients from across the United States, with varying disease duration. Dr. Safar reported on baseline mental health data from the study.

Patients with MS may experience symptoms involving any part of the central nervous system, including psychiatric symptoms such as depression, anxiety, and cognitive disorders, she said, noting that these are highly prevalent, but often go unrecognized and untreated by primary care doctors and neurologists.

Prior studies have suggested that depression occurs in 25%-80% of patients, depending on the study setting. The rates are higher in those with MS than in the general population or in those with other neurologic and chronic medical conditions, she said.

In the Sonya Slifka study, 77% of patients were women with an average age of 50 years and disease duration ranging from 1 week to 64 years. Most were white. The disease distribution was representative of that seen in the general MS population, with most (57%) having relapsing-remitting disease, 25% having secondary progressive disease, and the remaining patients having primary progressive disease or progressing-relapsing disease (Mult Scler. 2006 Feb;12[1]:24-38).

Reported disability levels varied from none/very mild to severe and requiring a wheelchair or scooter or being bedridden.

Of the 48% of patients reporting emotional distress, most reported having mild to moderate distress, but 40% reported severe distress.

Nearly half (46%) of patients reported accomplishing less than normal because of emotional difficulties, and 31% said they worked less carefully than usual.

Emotional distress was more common in patients who were younger, divorced or never married, unemployed, and in those with lower education and income levels. Emotional distress was associated with shorter duration of illness, with having multiple relapses in the prior year (highest rates were among those with five or more relapses), and with moderate disability level.

Emotional distress was also associated with poorer perceived general health, and those with higher levels of emotional distress tended to experience all or many of the symptoms on the baseline questionnaire.

Further, those with emotional distress tended to lack health insurance and to have problems accessing health care and necessary prescription medications. About one-fourth of the patients had seen a mental health professional in the prior year and nearly 8% wanted to; 2% said they had been referred to a mental health professional, and 93% of these patients had emotional distress, including 6% with severe distress.

Reasons given by these patients for not seeing a mental health professional were cost, difficulty getting an appointment, and too long of a wait.

The findings suggest that in clinical settings it is important to screen MS patients for emotional distress and depression and to treat or refer accordingly, Dr. Safar said.

“As we know from other medical illnesses, this will improve adherence to MS treatment and will improve the prognosis,” she added.

Dr. Safar reported having no disclosures.

sworcester@frontlinemedcom.com