ICYMI Multiple Sclerosis

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

DALLAS—Neurologists who treat patients with multiple sclerosis (MS) sometimes must consider whether it is safe to administer vaccines to these individuals. The current literature indicates that live and killed vaccines are safe for patients with MS, according to a review presented at the 2014 Cooperative Meeting of CMSC and ACTRIMS.

In addition, current disease-modifying therapies (DMTs) generally do not appear to affect the efficacy of vaccines. Fingolimod is the one DMT that raises concerns, however. Before starting fingolimod in a patient with MS, neurologists routinely assess the patient for an immune response to varicella zoster virus (VZV). If the results are negative, most neurologists will vaccinate the patient before treating him or her with fingolimod, said Patricia K. Coyle, MD, Director of the MS Comprehensive Care Center at Stony Brook Neurosciences Institute in New York.

Vaccines, Infections, and Relapses
Several studies suggest an association between benign viral infections and an increased MS relapse rate. One theory is that the infection increases the relapse rate by activating the immune system. As many as one-third of relapses are associated with a prior infection, said Dr. Coyle. “Therefore, vaccines should be beneficial in MS if they prevent infection, so long as they’re relatively safe,” she added. But vaccinations should not be administered during or shortly after relapses.

A 2001 study published in the New England Journal of Medicine followed 643 patients with MS for a four-year period. The patients’ rate of relapses was 2.3% during periods when they received a vaccination, compared with a range of 2.8% to 4% during periods when patients were not being vaccinated. The authors concluded that vaccines are not associated with an increased risk of relapses.

After reviewing studies of vaccines in patients with MS, the MS Council for Clinical Practice Guidelines concluded in 2002 that the evidence supported strategies to minimize infections that can trigger relapses. The panel also concluded that the vaccines for influenza, hepatitis B, varicella, tetanus, and Bacillus Calmette–Guérin were safe for patients with MS. The council endorsed killed vaccines and recommended that neurologists wait for four to six weeks after the onset of a relapse before vaccinating a patient with MS. Physicians should be consulted, however, before administering a live vaccine to a patient receiving an immunosuppressive agent, the panel added.

Specific Vaccines and MS
Researchers also have examined the safety of specific vaccines in patients with MS. The seasonal influenza vaccine may be the best-studied vaccine in this population. The consensus is that the killed virus vaccine is safe, even for patients on a DMT, but that the live vaccine should be avoided.

Three vaccines have raised concerns for patients with MS. Several reports associated the hepatitis B vaccine with demyelinating episodes, but, after reviewing the evidence, the Institute of Medicine concluded that it was safe for patients with MS. Similarly, the literature contains reports of immune-mediated complications of the human papillomavirus (HPV) vaccine in patients with MS, but the vaccine is now accepted as safe in this population.

One case report has discouraged physicians from giving yellow fever vaccine to patients with MS. This vaccine was associated with increased clinical attacks and increased MRI lesion activity, although the report contained a small number of patients. The vaccine is contraindicated in patients who take immunosuppression or immunomodulatory therapies.

A large case–control study presented at the 66th Annual Meeting of the American Academy of Neurology included 780 patients with MS and 3,885 controls. The researchers found no association between an increased risk of demyelinating disease and the hepatitis B vaccine, the HPV vaccine, or any other vaccine. Younger individuals appeared to have an increased risk of CNS expression of disease during the first 30 days after vaccination, but the association was not linked to any specific vaccine. “The ultimate conclusion of this database study was that there was no need to change our current vaccine policy in MS,” said Dr. Coyle.

DMTs and Vaccinations
Researchers also have studied whether DMTs affect a patient’s response to vaccinations. Interferon betas are associated with normal humoral and cellular immune responses to the influenza vaccine. Investigators know of no negative effects of glatiramer acetate that relate to vaccines. Natalizumab is associated with normal humoral responses to the influenza, tetanus, and keyhole limpet hemocyanin vaccines. Researchers found an association between teriflunomide and normal immune responses to the influenza and rabies vaccines. No data about dimethyl fumarate’s effect on vaccine response exist, but the National MS Society does not recommend administering live vaccines to patients with MS who take this drug, said Dr. Coyle.

A pilot study indicated that alemtuzumab is associated with normal responses to the meningococcus, pneumococcus, and diphtheria–pertussis–tetanus vaccines in most individuals. The vaccine did not work, however, if patients were vaccinated within several months of their treatment cycle. “The recommendation for alemtuzumab is that you either vaccinate before you give the therapy, or you wait at least six months after the treatment cycle,” said Dr. Coyle. If a neurologist vaccinates the patient six months after the treatment cycle, he or she should measure the patient’s antibody levels about a month later to confirm that the vaccine is working, she added.

Of all DMTs, fingolimod appears to have the most influence on a patient’s response to vaccination. The drug decreases the humoral response to the influenza, tetanus, and pneumococcal vaccines. Before initiating fingolimod, a neurologist should screen the patient for VZV antibodies. If the results are negative or show a low titer of VZV antibodies, neurologists may vaccinate the patient before starting fingolimod. Initiation of therapy should be delayed a month after completion of the vaccination, said Dr. Coyle. Patients taking fingolimod should not receive a live vaccine, and post treatment vaccination should be delayed until two months after the drug is stopped, she added

—Erik Greb

DALLAS—Neurologists who treat patients with multiple sclerosis (MS) sometimes must consider whether it is safe to administer vaccines to these individuals. The current literature indicates that live and killed vaccines are safe for patients with MS, according to a review presented at the 2014 Cooperative Meeting of CMSC and ACTRIMS.

In addition, current disease-modifying therapies (DMTs) generally do not appear to affect the efficacy of vaccines. Fingolimod is the one DMT that raises concerns, however. Before starting fingolimod in a patient with MS, neurologists routinely assess the patient for an immune response to varicella zoster virus (VZV). If the results are negative, most neurologists will vaccinate the patient before treating him or her with fingolimod, said Patricia K. Coyle, MD, Director of the MS Comprehensive Care Center at Stony Brook Neurosciences Institute in New York.

Vaccines, Infections, and Relapses
Several studies suggest an association between benign viral infections and an increased MS relapse rate. One theory is that the infection increases the relapse rate by activating the immune system. As many as one-third of relapses are associated with a prior infection, said Dr. Coyle. “Therefore, vaccines should be beneficial in MS if they prevent infection, so long as they’re relatively safe,” she added. But vaccinations should not be administered during or shortly after relapses.

A 2001 study published in the New England Journal of Medicine followed 643 patients with MS for a four-year period. The patients’ rate of relapses was 2.3% during periods when they received a vaccination, compared with a range of 2.8% to 4% during periods when patients were not being vaccinated. The authors concluded that vaccines are not associated with an increased risk of relapses.

After reviewing studies of vaccines in patients with MS, the MS Council for Clinical Practice Guidelines concluded in 2002 that the evidence supported strategies to minimize infections that can trigger relapses. The panel also concluded that the vaccines for influenza, hepatitis B, varicella, tetanus, and Bacillus Calmette–Guérin were safe for patients with MS. The council endorsed killed vaccines and recommended that neurologists wait for four to six weeks after the onset of a relapse before vaccinating a patient with MS. Physicians should be consulted, however, before administering a live vaccine to a patient receiving an immunosuppressive agent, the panel added.

Specific Vaccines and MS
Researchers also have examined the safety of specific vaccines in patients with MS. The seasonal influenza vaccine may be the best-studied vaccine in this population. The consensus is that the killed virus vaccine is safe, even for patients on a DMT, but that the live vaccine should be avoided.

Three vaccines have raised concerns for patients with MS. Several reports associated the hepatitis B vaccine with demyelinating episodes, but, after reviewing the evidence, the Institute of Medicine concluded that it was safe for patients with MS. Similarly, the literature contains reports of immune-mediated complications of the human papillomavirus (HPV) vaccine in patients with MS, but the vaccine is now accepted as safe in this population.

One case report has discouraged physicians from giving yellow fever vaccine to patients with MS. This vaccine was associated with increased clinical attacks and increased MRI lesion activity, although the report contained a small number of patients. The vaccine is contraindicated in patients who take immunosuppression or immunomodulatory therapies.

A large case–control study presented at the 66th Annual Meeting of the American Academy of Neurology included 780 patients with MS and 3,885 controls. The researchers found no association between an increased risk of demyelinating disease and the hepatitis B vaccine, the HPV vaccine, or any other vaccine. Younger individuals appeared to have an increased risk of CNS expression of disease during the first 30 days after vaccination, but the association was not linked to any specific vaccine. “The ultimate conclusion of this database study was that there was no need to change our current vaccine policy in MS,” said Dr. Coyle.

DMTs and Vaccinations
Researchers also have studied whether DMTs affect a patient’s response to vaccinations. Interferon betas are associated with normal humoral and cellular immune responses to the influenza vaccine. Investigators know of no negative effects of glatiramer acetate that relate to vaccines. Natalizumab is associated with normal humoral responses to the influenza, tetanus, and keyhole limpet hemocyanin vaccines. Researchers found an association between teriflunomide and normal immune responses to the influenza and rabies vaccines. No data about dimethyl fumarate’s effect on vaccine response exist, but the National MS Society does not recommend administering live vaccines to patients with MS who take this drug, said Dr. Coyle.

A pilot study indicated that alemtuzumab is associated with normal responses to the meningococcus, pneumococcus, and diphtheria–pertussis–tetanus vaccines in most individuals. The vaccine did not work, however, if patients were vaccinated within several months of their treatment cycle. “The recommendation for alemtuzumab is that you either vaccinate before you give the therapy, or you wait at least six months after the treatment cycle,” said Dr. Coyle. If a neurologist vaccinates the patient six months after the treatment cycle, he or she should measure the patient’s antibody levels about a month later to confirm that the vaccine is working, she added.

Of all DMTs, fingolimod appears to have the most influence on a patient’s response to vaccination. The drug decreases the humoral response to the influenza, tetanus, and pneumococcal vaccines. Before initiating fingolimod, a neurologist should screen the patient for VZV antibodies. If the results are negative or show a low titer of VZV antibodies, neurologists may vaccinate the patient before starting fingolimod. Initiation of therapy should be delayed a month after completion of the vaccination, said Dr. Coyle. Patients taking fingolimod should not receive a live vaccine, and post treatment vaccination should be delayed until two months after the drug is stopped, she added

—Erik Greb

DALLAS—Neurologists who treat patients with multiple sclerosis (MS) sometimes must consider whether it is safe to administer vaccines to these individuals. The current literature indicates that live and killed vaccines are safe for patients with MS, according to a review presented at the 2014 Cooperative Meeting of CMSC and ACTRIMS.

In addition, current disease-modifying therapies (DMTs) generally do not appear to affect the efficacy of vaccines. Fingolimod is the one DMT that raises concerns, however. Before starting fingolimod in a patient with MS, neurologists routinely assess the patient for an immune response to varicella zoster virus (VZV). If the results are negative, most neurologists will vaccinate the patient before treating him or her with fingolimod, said Patricia K. Coyle, MD, Director of the MS Comprehensive Care Center at Stony Brook Neurosciences Institute in New York.

Vaccines, Infections, and Relapses
Several studies suggest an association between benign viral infections and an increased MS relapse rate. One theory is that the infection increases the relapse rate by activating the immune system. As many as one-third of relapses are associated with a prior infection, said Dr. Coyle. “Therefore, vaccines should be beneficial in MS if they prevent infection, so long as they’re relatively safe,” she added. But vaccinations should not be administered during or shortly after relapses.

A 2001 study published in the New England Journal of Medicine followed 643 patients with MS for a four-year period. The patients’ rate of relapses was 2.3% during periods when they received a vaccination, compared with a range of 2.8% to 4% during periods when patients were not being vaccinated. The authors concluded that vaccines are not associated with an increased risk of relapses.

After reviewing studies of vaccines in patients with MS, the MS Council for Clinical Practice Guidelines concluded in 2002 that the evidence supported strategies to minimize infections that can trigger relapses. The panel also concluded that the vaccines for influenza, hepatitis B, varicella, tetanus, and Bacillus Calmette–Guérin were safe for patients with MS. The council endorsed killed vaccines and recommended that neurologists wait for four to six weeks after the onset of a relapse before vaccinating a patient with MS. Physicians should be consulted, however, before administering a live vaccine to a patient receiving an immunosuppressive agent, the panel added.

Specific Vaccines and MS
Researchers also have examined the safety of specific vaccines in patients with MS. The seasonal influenza vaccine may be the best-studied vaccine in this population. The consensus is that the killed virus vaccine is safe, even for patients on a DMT, but that the live vaccine should be avoided.

Three vaccines have raised concerns for patients with MS. Several reports associated the hepatitis B vaccine with demyelinating episodes, but, after reviewing the evidence, the Institute of Medicine concluded that it was safe for patients with MS. Similarly, the literature contains reports of immune-mediated complications of the human papillomavirus (HPV) vaccine in patients with MS, but the vaccine is now accepted as safe in this population.

One case report has discouraged physicians from giving yellow fever vaccine to patients with MS. This vaccine was associated with increased clinical attacks and increased MRI lesion activity, although the report contained a small number of patients. The vaccine is contraindicated in patients who take immunosuppression or immunomodulatory therapies.

A large case–control study presented at the 66th Annual Meeting of the American Academy of Neurology included 780 patients with MS and 3,885 controls. The researchers found no association between an increased risk of demyelinating disease and the hepatitis B vaccine, the HPV vaccine, or any other vaccine. Younger individuals appeared to have an increased risk of CNS expression of disease during the first 30 days after vaccination, but the association was not linked to any specific vaccine. “The ultimate conclusion of this database study was that there was no need to change our current vaccine policy in MS,” said Dr. Coyle.

DMTs and Vaccinations
Researchers also have studied whether DMTs affect a patient’s response to vaccinations. Interferon betas are associated with normal humoral and cellular immune responses to the influenza vaccine. Investigators know of no negative effects of glatiramer acetate that relate to vaccines. Natalizumab is associated with normal humoral responses to the influenza, tetanus, and keyhole limpet hemocyanin vaccines. Researchers found an association between teriflunomide and normal immune responses to the influenza and rabies vaccines. No data about dimethyl fumarate’s effect on vaccine response exist, but the National MS Society does not recommend administering live vaccines to patients with MS who take this drug, said Dr. Coyle.

A pilot study indicated that alemtuzumab is associated with normal responses to the meningococcus, pneumococcus, and diphtheria–pertussis–tetanus vaccines in most individuals. The vaccine did not work, however, if patients were vaccinated within several months of their treatment cycle. “The recommendation for alemtuzumab is that you either vaccinate before you give the therapy, or you wait at least six months after the treatment cycle,” said Dr. Coyle. If a neurologist vaccinates the patient six months after the treatment cycle, he or she should measure the patient’s antibody levels about a month later to confirm that the vaccine is working, she added.

Of all DMTs, fingolimod appears to have the most influence on a patient’s response to vaccination. The drug decreases the humoral response to the influenza, tetanus, and pneumococcal vaccines. Before initiating fingolimod, a neurologist should screen the patient for VZV antibodies. If the results are negative or show a low titer of VZV antibodies, neurologists may vaccinate the patient before starting fingolimod. Initiation of therapy should be delayed a month after completion of the vaccination, said Dr. Coyle. Patients taking fingolimod should not receive a live vaccine, and post treatment vaccination should be delayed until two months after the drug is stopped, she added

—Erik Greb

PHILADELPHIA—Alfacalcidol, a synthetic analog of vitamin D, significantly reduces fatigue related to multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The drug also may result in significant improvements in psychologic and social quality of life. No serious adverse events are associated with alfacalcidol, which appears to have a rate of adverse events similar to that of placebo.

In a six-month study, alfacalcidol reduced the number of acute relapses in patients with MS. This result suggests that fatigue, like relapses, is a symptom of disease activity, said Anat Achiron, MD, PhD, Director of the MS Center at the Sheba Medical Center in Tel Hashomer, Israel. “By decreasing fatigue and relapses, you can achieve the same goal,” she added.

Comparing Alfacalcido With Placebo
The trial was designed as a two-stage process to enrich the study population with patients with MS whose fatigue is significant. Dr. Achiron and colleagues administered the Fatigue Severity Scale to 600 patients with relapsing-remitting MS to analyze the effect of alfacalcidol on MS-related fatigue. A total of 500 patients responded to the questionnaire, and 259 patients who gave a score of 3 or higher to the ninth item (ie, “Fatigue interferes with my work, family, or social life”) were included in the second stage of enrollment.

A total of 158 patients between ages 18 and 55 who had an Expanded Disability Status Scale (EDSS) score of 5 or lower and a Fatigue Impact Scale (FIS) score of 40 or higher were eligible. Of these patients, 80 were randomized to receive 1 µg/day of alfacalcidol, and 78 were randomized to placebo. All patients completed the FIS and RAYS quality of life questionnaire at baseline. Patients were treated for six months, at which point they completed the FIS and RAYS questionnaires again. The researchers conducted follow-up visits with the patients two months after the cessation of treatment.

The primary end point was improvement in FIS score, which was defined as a 30% decrease. The secondary end points were change in the RAYS quality of life scale, change in EDSS score, and the number of acute relapses.

Reduced Fatigue and Relapses
The investigators found no significant differences at baseline between the study groups with respect to age, gender distribution, age of disease onset, EDSS score, and duration of fatigue. The level of fatigue was high at baseline; mean FIS score was 80 in the treatment group and 78 among controls, “suggesting that the patients had significant fatigue that affected their lives,” said Dr. Achiron. At six months, the relative FIS score decreased for all study participants. Only patients who received alfacalcidol, however, had a decrease in FIS score of at least 30%. FIS score was reduced by a mean of 41.6% among alfacalcidol-treated patients. The reduction was most noticeable on the cognitive subscale of FIS, compared with the physical and social subscales, said Dr. Achiron.

RAYS quality of life score improved at six months for patients treated with alfacalcidol. Physical quality of life did not change, but psychologic and social quality of life improved significantly in patients who received alfacalcidol. EDSS score did not change for any participants.

In addition, the number of relapses was significantly lower among participants receiving alfacalcidol, and the percentage of relapse-free patients was higher in the treatment group than in the control group. The difference between groups in the number of relapses was already evident at four months. The association between alfacalcidol and a reduction in relapses is consistent with literature suggesting that vitamin D enhances the apoptosis of autoreactive T cells, said Dr. Achiron.

“Alfacalcidol is a safe and effective treatment strategy for treating fatigue in MS,” she concluded.

—Erik Greb

PHILADELPHIA—Alfacalcidol, a synthetic analog of vitamin D, significantly reduces fatigue related to multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The drug also may result in significant improvements in psychologic and social quality of life. No serious adverse events are associated with alfacalcidol, which appears to have a rate of adverse events similar to that of placebo.

In a six-month study, alfacalcidol reduced the number of acute relapses in patients with MS. This result suggests that fatigue, like relapses, is a symptom of disease activity, said Anat Achiron, MD, PhD, Director of the MS Center at the Sheba Medical Center in Tel Hashomer, Israel. “By decreasing fatigue and relapses, you can achieve the same goal,” she added.

Comparing Alfacalcido With Placebo
The trial was designed as a two-stage process to enrich the study population with patients with MS whose fatigue is significant. Dr. Achiron and colleagues administered the Fatigue Severity Scale to 600 patients with relapsing-remitting MS to analyze the effect of alfacalcidol on MS-related fatigue. A total of 500 patients responded to the questionnaire, and 259 patients who gave a score of 3 or higher to the ninth item (ie, “Fatigue interferes with my work, family, or social life”) were included in the second stage of enrollment.

A total of 158 patients between ages 18 and 55 who had an Expanded Disability Status Scale (EDSS) score of 5 or lower and a Fatigue Impact Scale (FIS) score of 40 or higher were eligible. Of these patients, 80 were randomized to receive 1 µg/day of alfacalcidol, and 78 were randomized to placebo. All patients completed the FIS and RAYS quality of life questionnaire at baseline. Patients were treated for six months, at which point they completed the FIS and RAYS questionnaires again. The researchers conducted follow-up visits with the patients two months after the cessation of treatment.

The primary end point was improvement in FIS score, which was defined as a 30% decrease. The secondary end points were change in the RAYS quality of life scale, change in EDSS score, and the number of acute relapses.

Reduced Fatigue and Relapses
The investigators found no significant differences at baseline between the study groups with respect to age, gender distribution, age of disease onset, EDSS score, and duration of fatigue. The level of fatigue was high at baseline; mean FIS score was 80 in the treatment group and 78 among controls, “suggesting that the patients had significant fatigue that affected their lives,” said Dr. Achiron. At six months, the relative FIS score decreased for all study participants. Only patients who received alfacalcidol, however, had a decrease in FIS score of at least 30%. FIS score was reduced by a mean of 41.6% among alfacalcidol-treated patients. The reduction was most noticeable on the cognitive subscale of FIS, compared with the physical and social subscales, said Dr. Achiron.

RAYS quality of life score improved at six months for patients treated with alfacalcidol. Physical quality of life did not change, but psychologic and social quality of life improved significantly in patients who received alfacalcidol. EDSS score did not change for any participants.

In addition, the number of relapses was significantly lower among participants receiving alfacalcidol, and the percentage of relapse-free patients was higher in the treatment group than in the control group. The difference between groups in the number of relapses was already evident at four months. The association between alfacalcidol and a reduction in relapses is consistent with literature suggesting that vitamin D enhances the apoptosis of autoreactive T cells, said Dr. Achiron.

“Alfacalcidol is a safe and effective treatment strategy for treating fatigue in MS,” she concluded.

—Erik Greb

PHILADELPHIA—Alfacalcidol, a synthetic analog of vitamin D, significantly reduces fatigue related to multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The drug also may result in significant improvements in psychologic and social quality of life. No serious adverse events are associated with alfacalcidol, which appears to have a rate of adverse events similar to that of placebo.

In a six-month study, alfacalcidol reduced the number of acute relapses in patients with MS. This result suggests that fatigue, like relapses, is a symptom of disease activity, said Anat Achiron, MD, PhD, Director of the MS Center at the Sheba Medical Center in Tel Hashomer, Israel. “By decreasing fatigue and relapses, you can achieve the same goal,” she added.

Comparing Alfacalcido With Placebo
The trial was designed as a two-stage process to enrich the study population with patients with MS whose fatigue is significant. Dr. Achiron and colleagues administered the Fatigue Severity Scale to 600 patients with relapsing-remitting MS to analyze the effect of alfacalcidol on MS-related fatigue. A total of 500 patients responded to the questionnaire, and 259 patients who gave a score of 3 or higher to the ninth item (ie, “Fatigue interferes with my work, family, or social life”) were included in the second stage of enrollment.

A total of 158 patients between ages 18 and 55 who had an Expanded Disability Status Scale (EDSS) score of 5 or lower and a Fatigue Impact Scale (FIS) score of 40 or higher were eligible. Of these patients, 80 were randomized to receive 1 µg/day of alfacalcidol, and 78 were randomized to placebo. All patients completed the FIS and RAYS quality of life questionnaire at baseline. Patients were treated for six months, at which point they completed the FIS and RAYS questionnaires again. The researchers conducted follow-up visits with the patients two months after the cessation of treatment.

The primary end point was improvement in FIS score, which was defined as a 30% decrease. The secondary end points were change in the RAYS quality of life scale, change in EDSS score, and the number of acute relapses.

Reduced Fatigue and Relapses
The investigators found no significant differences at baseline between the study groups with respect to age, gender distribution, age of disease onset, EDSS score, and duration of fatigue. The level of fatigue was high at baseline; mean FIS score was 80 in the treatment group and 78 among controls, “suggesting that the patients had significant fatigue that affected their lives,” said Dr. Achiron. At six months, the relative FIS score decreased for all study participants. Only patients who received alfacalcidol, however, had a decrease in FIS score of at least 30%. FIS score was reduced by a mean of 41.6% among alfacalcidol-treated patients. The reduction was most noticeable on the cognitive subscale of FIS, compared with the physical and social subscales, said Dr. Achiron.

RAYS quality of life score improved at six months for patients treated with alfacalcidol. Physical quality of life did not change, but psychologic and social quality of life improved significantly in patients who received alfacalcidol. EDSS score did not change for any participants.

In addition, the number of relapses was significantly lower among participants receiving alfacalcidol, and the percentage of relapse-free patients was higher in the treatment group than in the control group. The difference between groups in the number of relapses was already evident at four months. The association between alfacalcidol and a reduction in relapses is consistent with literature suggesting that vitamin D enhances the apoptosis of autoreactive T cells, said Dr. Achiron.

“Alfacalcidol is a safe and effective treatment strategy for treating fatigue in MS,” she concluded.

—Erik Greb

There is a growing social and medical impetus to legalize cannabis not only for recreational use, but also for the treatment of neurologic disorders such as multiple sclerosis (MS). Although some studies have shown that cannabis may relieve spasticity, pain, and other symptoms in patients with MS, a new study by Pavisian et al sounds a cautionary note. The authors suggest that cannabis further compromises a brain already impaired from tissue damage in MS. One reason that the authors found functional MRI changes, but not structural MRI changes, might be that physiologic changes occurred before structural changes, which would not be unexpected. In addition, smoking may be a factor in MS worsening. Could smoking cigarettes rather than cannabis be the reason for the cognitive change among study participants? In the end, these findings suggest that cannabis may be a double-edged sword in MS, and possibly in other brain disorders. Further testing, including a prospective study of patients randomized to smoking cannabis or placebo, would be an important step toward confirming Pavisian’s results.

—Stuart D. Cook, MD
Professor of Neurology, Department of Neurosciences,
Rutgers, the State University of New Jersey,
New Jersey Medical School,
Newark, NJ

There is a growing social and medical impetus to legalize cannabis not only for recreational use, but also for the treatment of neurologic disorders such as multiple sclerosis (MS). Although some studies have shown that cannabis may relieve spasticity, pain, and other symptoms in patients with MS, a new study by Pavisian et al sounds a cautionary note. The authors suggest that cannabis further compromises a brain already impaired from tissue damage in MS. One reason that the authors found functional MRI changes, but not structural MRI changes, might be that physiologic changes occurred before structural changes, which would not be unexpected. In addition, smoking may be a factor in MS worsening. Could smoking cigarettes rather than cannabis be the reason for the cognitive change among study participants? In the end, these findings suggest that cannabis may be a double-edged sword in MS, and possibly in other brain disorders. Further testing, including a prospective study of patients randomized to smoking cannabis or placebo, would be an important step toward confirming Pavisian’s results.

—Stuart D. Cook, MD
Professor of Neurology, Department of Neurosciences,
Rutgers, the State University of New Jersey,
New Jersey Medical School,
Newark, NJ

There is a growing social and medical impetus to legalize cannabis not only for recreational use, but also for the treatment of neurologic disorders such as multiple sclerosis (MS). Although some studies have shown that cannabis may relieve spasticity, pain, and other symptoms in patients with MS, a new study by Pavisian et al sounds a cautionary note. The authors suggest that cannabis further compromises a brain already impaired from tissue damage in MS. One reason that the authors found functional MRI changes, but not structural MRI changes, might be that physiologic changes occurred before structural changes, which would not be unexpected. In addition, smoking may be a factor in MS worsening. Could smoking cigarettes rather than cannabis be the reason for the cognitive change among study participants? In the end, these findings suggest that cannabis may be a double-edged sword in MS, and possibly in other brain disorders. Further testing, including a prospective study of patients randomized to smoking cannabis or placebo, would be an important step toward confirming Pavisian’s results.

—Stuart D. Cook, MD
Professor of Neurology, Department of Neurosciences,
Rutgers, the State University of New Jersey,
New Jersey Medical School,
Newark, NJ

PHILADELPHIA—Ofatumumab reduces new T1 gadolinium-enhancing lesions by more than 90%, compared with placebo, among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The monoclonal antibody appears to deplete B cells in a dose-dependent manner.

Investigators found no difference between drug and placebo in the rate of adverse events, and the majority of the adverse events were mild to moderate. The most common adverse events were injection-related reactions.

Ofatumumab is a fully human anti-CD20 monoclonal antibody that binds even at low levels of CD20. The drug “induces B cell lysis quite efficiently, primarily through antibody-dependent cellular cytotoxicity,” said Amit Bar-Or, MD, Professor of Neurology and Neurosurgery at McGill University in Montreal. Ofatumumab is indicated for the treatment of chronic lymphocytic leukemia.

Comparing Doses of Ofatumumab
Dr. Bar-Or and colleagues conducted a placebo-controlled trial to determine the MRI efficacy, tolerability, and safety of subcutaneous injections of ofatumumab in patients with relapsing-remitting MS. The study’s primary end point was the cumulative number of new T1 gadolinium-enhancing brain lesions at 12 weeks.

The researchers randomized 231 individuals with relapsing-remitting MS to either placebo, 3 mg of ofatumumab every three months, 30 mg of ofatumumab every three months, 60 mg of ofatumumab every three months, or 60 mg of ofatumumab every month. The study began with a 24-week double-blind treatment phase, followed by a 20-week individualized follow-up phase. Dr. Bar-Or reported on the primary outcome as assessed at week 12.

Eligible patients were between ages 18 and 55 and had an Expanded Disability Status Scale score between 0 and 5.5. Baseline patient characteristics were well balanced among the study groups with respect to sex, race, age, and disease duration. At baseline, patients’ number of relapses within the past 24 months ranged from 1.7 to 1.9. More than 90% of participants completed the 24-week treatment phase of the study.

Ofatumumab Reduced New Lesions by More Than 90%
The dosing regimens were associated with a dose-dependent decrease in circulating B cells, and mathematical modeling indicated that a 50% decrease in B cells would be expected with a dose of less than 3 mg of ofatumumab. Individuals who received 3 mg of drug every three months had a 70% reduction in new gadolinium-enhancing lesions, relative to controls. New gadolinium-enhancing lesions in the brain were reduced by more than 90%, relative to controls, in patients who received the three dose regimens of 30 mg of ofatumumab or more.

Over the 24-week treatment phase, six adverse events led to withdrawal from the study (all of these occurring in the treatment arms). The investigators found no differences in the rate of infectious adverse events between the study groups, including placebo treated. Infectious adverse events included nasopharyngitis, urinary tract infection, and respiratory tract infection, but these outcomes were infrequent “and no different from what we have seen in prior anti-CD20–depleting regimens,” said Dr. Bar-Or.

Injection-Related Reactions Were the Most Common Adverse Events
Five individuals had serious adverse events during the first 12 weeks. Another serious adverse event occurred between weeks 12 and 24. The serious adverse events included injection-related reactions, cholelithiasis, cytokine release syndrome, and hypokalemia. Four of these events occurred in patients receiving 60 mg of ofatumumab every month.

“There was no evidence of clinically meaningful changes in laboratory parameters or vital signs,” said Dr. Bar-Or. “There was no evidence of clinically meaningful immunogenicity, including development of human antihuman antibodies, which occurred in only four individuals at low levels and did not appear to impact treatment effect. There were no cases of opportunistic infections, including progressive multifocal lleukoencephalopathy.”

—Erik Greb

PHILADELPHIA—Ofatumumab reduces new T1 gadolinium-enhancing lesions by more than 90%, compared with placebo, among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The monoclonal antibody appears to deplete B cells in a dose-dependent manner.

Investigators found no difference between drug and placebo in the rate of adverse events, and the majority of the adverse events were mild to moderate. The most common adverse events were injection-related reactions.

Ofatumumab is a fully human anti-CD20 monoclonal antibody that binds even at low levels of CD20. The drug “induces B cell lysis quite efficiently, primarily through antibody-dependent cellular cytotoxicity,” said Amit Bar-Or, MD, Professor of Neurology and Neurosurgery at McGill University in Montreal. Ofatumumab is indicated for the treatment of chronic lymphocytic leukemia.

Comparing Doses of Ofatumumab
Dr. Bar-Or and colleagues conducted a placebo-controlled trial to determine the MRI efficacy, tolerability, and safety of subcutaneous injections of ofatumumab in patients with relapsing-remitting MS. The study’s primary end point was the cumulative number of new T1 gadolinium-enhancing brain lesions at 12 weeks.

The researchers randomized 231 individuals with relapsing-remitting MS to either placebo, 3 mg of ofatumumab every three months, 30 mg of ofatumumab every three months, 60 mg of ofatumumab every three months, or 60 mg of ofatumumab every month. The study began with a 24-week double-blind treatment phase, followed by a 20-week individualized follow-up phase. Dr. Bar-Or reported on the primary outcome as assessed at week 12.

Eligible patients were between ages 18 and 55 and had an Expanded Disability Status Scale score between 0 and 5.5. Baseline patient characteristics were well balanced among the study groups with respect to sex, race, age, and disease duration. At baseline, patients’ number of relapses within the past 24 months ranged from 1.7 to 1.9. More than 90% of participants completed the 24-week treatment phase of the study.

Ofatumumab Reduced New Lesions by More Than 90%
The dosing regimens were associated with a dose-dependent decrease in circulating B cells, and mathematical modeling indicated that a 50% decrease in B cells would be expected with a dose of less than 3 mg of ofatumumab. Individuals who received 3 mg of drug every three months had a 70% reduction in new gadolinium-enhancing lesions, relative to controls. New gadolinium-enhancing lesions in the brain were reduced by more than 90%, relative to controls, in patients who received the three dose regimens of 30 mg of ofatumumab or more.

Over the 24-week treatment phase, six adverse events led to withdrawal from the study (all of these occurring in the treatment arms). The investigators found no differences in the rate of infectious adverse events between the study groups, including placebo treated. Infectious adverse events included nasopharyngitis, urinary tract infection, and respiratory tract infection, but these outcomes were infrequent “and no different from what we have seen in prior anti-CD20–depleting regimens,” said Dr. Bar-Or.

Injection-Related Reactions Were the Most Common Adverse Events
Five individuals had serious adverse events during the first 12 weeks. Another serious adverse event occurred between weeks 12 and 24. The serious adverse events included injection-related reactions, cholelithiasis, cytokine release syndrome, and hypokalemia. Four of these events occurred in patients receiving 60 mg of ofatumumab every month.

“There was no evidence of clinically meaningful changes in laboratory parameters or vital signs,” said Dr. Bar-Or. “There was no evidence of clinically meaningful immunogenicity, including development of human antihuman antibodies, which occurred in only four individuals at low levels and did not appear to impact treatment effect. There were no cases of opportunistic infections, including progressive multifocal lleukoencephalopathy.”

—Erik Greb

PHILADELPHIA—Ofatumumab reduces new T1 gadolinium-enhancing lesions by more than 90%, compared with placebo, among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The monoclonal antibody appears to deplete B cells in a dose-dependent manner.

Investigators found no difference between drug and placebo in the rate of adverse events, and the majority of the adverse events were mild to moderate. The most common adverse events were injection-related reactions.

Ofatumumab is a fully human anti-CD20 monoclonal antibody that binds even at low levels of CD20. The drug “induces B cell lysis quite efficiently, primarily through antibody-dependent cellular cytotoxicity,” said Amit Bar-Or, MD, Professor of Neurology and Neurosurgery at McGill University in Montreal. Ofatumumab is indicated for the treatment of chronic lymphocytic leukemia.

Comparing Doses of Ofatumumab
Dr. Bar-Or and colleagues conducted a placebo-controlled trial to determine the MRI efficacy, tolerability, and safety of subcutaneous injections of ofatumumab in patients with relapsing-remitting MS. The study’s primary end point was the cumulative number of new T1 gadolinium-enhancing brain lesions at 12 weeks.

The researchers randomized 231 individuals with relapsing-remitting MS to either placebo, 3 mg of ofatumumab every three months, 30 mg of ofatumumab every three months, 60 mg of ofatumumab every three months, or 60 mg of ofatumumab every month. The study began with a 24-week double-blind treatment phase, followed by a 20-week individualized follow-up phase. Dr. Bar-Or reported on the primary outcome as assessed at week 12.

Eligible patients were between ages 18 and 55 and had an Expanded Disability Status Scale score between 0 and 5.5. Baseline patient characteristics were well balanced among the study groups with respect to sex, race, age, and disease duration. At baseline, patients’ number of relapses within the past 24 months ranged from 1.7 to 1.9. More than 90% of participants completed the 24-week treatment phase of the study.

Ofatumumab Reduced New Lesions by More Than 90%
The dosing regimens were associated with a dose-dependent decrease in circulating B cells, and mathematical modeling indicated that a 50% decrease in B cells would be expected with a dose of less than 3 mg of ofatumumab. Individuals who received 3 mg of drug every three months had a 70% reduction in new gadolinium-enhancing lesions, relative to controls. New gadolinium-enhancing lesions in the brain were reduced by more than 90%, relative to controls, in patients who received the three dose regimens of 30 mg of ofatumumab or more.

Over the 24-week treatment phase, six adverse events led to withdrawal from the study (all of these occurring in the treatment arms). The investigators found no differences in the rate of infectious adverse events between the study groups, including placebo treated. Infectious adverse events included nasopharyngitis, urinary tract infection, and respiratory tract infection, but these outcomes were infrequent “and no different from what we have seen in prior anti-CD20–depleting regimens,” said Dr. Bar-Or.

Injection-Related Reactions Were the Most Common Adverse Events
Five individuals had serious adverse events during the first 12 weeks. Another serious adverse event occurred between weeks 12 and 24. The serious adverse events included injection-related reactions, cholelithiasis, cytokine release syndrome, and hypokalemia. Four of these events occurred in patients receiving 60 mg of ofatumumab every month.

“There was no evidence of clinically meaningful changes in laboratory parameters or vital signs,” said Dr. Bar-Or. “There was no evidence of clinically meaningful immunogenicity, including development of human antihuman antibodies, which occurred in only four individuals at low levels and did not appear to impact treatment effect. There were no cases of opportunistic infections, including progressive multifocal lleukoencephalopathy.”

—Erik Greb

DALLAS—A multiple sclerosis (MS) performance test administered by a patient using an iPad-based app is superior to an MS performance test administered by a technician, according to research presented at the 2014 Cooperative Meeting of CMSC and ACTRIMS. The study could prompt changes in the way that data are collected and interpreted for the purposes of clinical trials and disease management, according to Richard Rudick, MD, Vice President of Development Sciences at Biogen Idec in Cambridge, Massachusetts.

The research suggests that unfiltered, accurate patient data could be transferred in real time to the cloud, where it would be available for immediate viewing and for future study. This method of data storage would give clinicians new ways to “collect, display, aggregate, and analyze neurologic performance,” said Dr. Rudick.

iPad Test Distinguished Patients From Controls
Dr. Rudick and his colleagues developed the app-based MS performance test (MSPT) to simulate the technician-based test in all respects. The app-based test comprises a walking speed test, a manual dexterity test, a low-contrast visual acuity test, and a processing speed test. These items approximate the traditional, technician-administered timed 25-foot walk test, the nine-hole peg test, the Sloan low-contrast visual acuity test, and the Symbol Digit Modalities Test.

The cross-sectional validation study matched 49 healthy controls with 51 patients according to age, sex, and education. Roughly three-quarters of the study arm had relapsing MS, and a quarter had the progressive form of the disease.

Participants were tested at a single site with each modality. Tests occurred once in the morning and once in the afternoon. The test and retest results were consistent and correlative, according to Dr. Rudick. “They were highly reliable, whether the technician did it, or the iPad,” he said. Because data for all aspects of each test were comparable, Dr. Rudick concluded that the tests were measuring the same things.

The most important question was how well the app-based test distinguished patients with MS from controls, compared with the technician-based test, according to Dr. Rudick. “In virtually every case, except for the visual [test], the iPad actually does a little bit better than the technician in distinguishing the MS patients from the healthy controls,” he said.

In addition, scores on both tests were highly similar. For the timed 25-foot walk test administered by the technician, the mean score in the MS group was 7, and the mean score for the walking speed test in the MS group was 7.26. In the healthy controls group, the mean score for the technician-given test was 4.24. That group’s mean score for the self-given walking speed test was 4.27.

Technicians Are Still Necessary
Patient-reported outcomes were also consistent with both forms of the tests. In general, however, patient-reported cognitive impairment does not correlate with the results of neurocognitive testing. “What does seem to correlate with patients reporting cognitive impairment is if they are depressed. Then the depression score matches the patient-reported cognitive impairment better than the actual cognitive test score does,” said Dr. Rudick.

Many physician assistants, registered nurses, and physicians may be ready to embrace this app-based technology, but it may not be appropriate for some patients, such as those who walk with difficulty. “You still need a technician to instruct and encourage patients,” said Neil Jouvenat, a physician assistant at the University of Nebraska Medical Center in Omaha. “If the iPad were to instruct a patient to ‘get up now, strap this to your back, and walk 25 feet,’ they won’t because they don’t really think they can. There is a fine line between someone who can walk a certain distance and someone who can’t.” The technician can help in those situations, he added.

The Technology May Aid Clinical Trials
The app holds promise for individuals who would have been excluded from clinical trials in the past, such as patients who live in rural areas. In addition, the collection of normative data from healthy adults will mean that clinical interpretations of MSPT scores will have broader utility in MS patients and groups, and the technology can be adapted to yield additional data such as specific measurements for balance and speed.

Technology such as this has the power to “revolutionize” disease management, particularly if information is collected in a central database that is accessible to any clinician or researcher, said Patricia Coyle, MD, Professor of Psychiatry and Neurology and Director of the MS Comprehensive Care Center at Stony Brook University in New York. “There are only so many MS patients, and we don’t have a good idea of their disease activity. They’re not tracked. No one’s trying to pull that data together,” she said. But having these data “potentially would mean revolutionizing” the field.

—Whitney McKnight

DALLAS—A multiple sclerosis (MS) performance test administered by a patient using an iPad-based app is superior to an MS performance test administered by a technician, according to research presented at the 2014 Cooperative Meeting of CMSC and ACTRIMS. The study could prompt changes in the way that data are collected and interpreted for the purposes of clinical trials and disease management, according to Richard Rudick, MD, Vice President of Development Sciences at Biogen Idec in Cambridge, Massachusetts.

The research suggests that unfiltered, accurate patient data could be transferred in real time to the cloud, where it would be available for immediate viewing and for future study. This method of data storage would give clinicians new ways to “collect, display, aggregate, and analyze neurologic performance,” said Dr. Rudick.

iPad Test Distinguished Patients From Controls
Dr. Rudick and his colleagues developed the app-based MS performance test (MSPT) to simulate the technician-based test in all respects. The app-based test comprises a walking speed test, a manual dexterity test, a low-contrast visual acuity test, and a processing speed test. These items approximate the traditional, technician-administered timed 25-foot walk test, the nine-hole peg test, the Sloan low-contrast visual acuity test, and the Symbol Digit Modalities Test.

The cross-sectional validation study matched 49 healthy controls with 51 patients according to age, sex, and education. Roughly three-quarters of the study arm had relapsing MS, and a quarter had the progressive form of the disease.

Participants were tested at a single site with each modality. Tests occurred once in the morning and once in the afternoon. The test and retest results were consistent and correlative, according to Dr. Rudick. “They were highly reliable, whether the technician did it, or the iPad,” he said. Because data for all aspects of each test were comparable, Dr. Rudick concluded that the tests were measuring the same things.

The most important question was how well the app-based test distinguished patients with MS from controls, compared with the technician-based test, according to Dr. Rudick. “In virtually every case, except for the visual [test], the iPad actually does a little bit better than the technician in distinguishing the MS patients from the healthy controls,” he said.

In addition, scores on both tests were highly similar. For the timed 25-foot walk test administered by the technician, the mean score in the MS group was 7, and the mean score for the walking speed test in the MS group was 7.26. In the healthy controls group, the mean score for the technician-given test was 4.24. That group’s mean score for the self-given walking speed test was 4.27.

Technicians Are Still Necessary
Patient-reported outcomes were also consistent with both forms of the tests. In general, however, patient-reported cognitive impairment does not correlate with the results of neurocognitive testing. “What does seem to correlate with patients reporting cognitive impairment is if they are depressed. Then the depression score matches the patient-reported cognitive impairment better than the actual cognitive test score does,” said Dr. Rudick.

Many physician assistants, registered nurses, and physicians may be ready to embrace this app-based technology, but it may not be appropriate for some patients, such as those who walk with difficulty. “You still need a technician to instruct and encourage patients,” said Neil Jouvenat, a physician assistant at the University of Nebraska Medical Center in Omaha. “If the iPad were to instruct a patient to ‘get up now, strap this to your back, and walk 25 feet,’ they won’t because they don’t really think they can. There is a fine line between someone who can walk a certain distance and someone who can’t.” The technician can help in those situations, he added.

The Technology May Aid Clinical Trials
The app holds promise for individuals who would have been excluded from clinical trials in the past, such as patients who live in rural areas. In addition, the collection of normative data from healthy adults will mean that clinical interpretations of MSPT scores will have broader utility in MS patients and groups, and the technology can be adapted to yield additional data such as specific measurements for balance and speed.

Technology such as this has the power to “revolutionize” disease management, particularly if information is collected in a central database that is accessible to any clinician or researcher, said Patricia Coyle, MD, Professor of Psychiatry and Neurology and Director of the MS Comprehensive Care Center at Stony Brook University in New York. “There are only so many MS patients, and we don’t have a good idea of their disease activity. They’re not tracked. No one’s trying to pull that data together,” she said. But having these data “potentially would mean revolutionizing” the field.

—Whitney McKnight

DALLAS—A multiple sclerosis (MS) performance test administered by a patient using an iPad-based app is superior to an MS performance test administered by a technician, according to research presented at the 2014 Cooperative Meeting of CMSC and ACTRIMS. The study could prompt changes in the way that data are collected and interpreted for the purposes of clinical trials and disease management, according to Richard Rudick, MD, Vice President of Development Sciences at Biogen Idec in Cambridge, Massachusetts.

The research suggests that unfiltered, accurate patient data could be transferred in real time to the cloud, where it would be available for immediate viewing and for future study. This method of data storage would give clinicians new ways to “collect, display, aggregate, and analyze neurologic performance,” said Dr. Rudick.

iPad Test Distinguished Patients From Controls
Dr. Rudick and his colleagues developed the app-based MS performance test (MSPT) to simulate the technician-based test in all respects. The app-based test comprises a walking speed test, a manual dexterity test, a low-contrast visual acuity test, and a processing speed test. These items approximate the traditional, technician-administered timed 25-foot walk test, the nine-hole peg test, the Sloan low-contrast visual acuity test, and the Symbol Digit Modalities Test.

The cross-sectional validation study matched 49 healthy controls with 51 patients according to age, sex, and education. Roughly three-quarters of the study arm had relapsing MS, and a quarter had the progressive form of the disease.

Participants were tested at a single site with each modality. Tests occurred once in the morning and once in the afternoon. The test and retest results were consistent and correlative, according to Dr. Rudick. “They were highly reliable, whether the technician did it, or the iPad,” he said. Because data for all aspects of each test were comparable, Dr. Rudick concluded that the tests were measuring the same things.

The most important question was how well the app-based test distinguished patients with MS from controls, compared with the technician-based test, according to Dr. Rudick. “In virtually every case, except for the visual [test], the iPad actually does a little bit better than the technician in distinguishing the MS patients from the healthy controls,” he said.

In addition, scores on both tests were highly similar. For the timed 25-foot walk test administered by the technician, the mean score in the MS group was 7, and the mean score for the walking speed test in the MS group was 7.26. In the healthy controls group, the mean score for the technician-given test was 4.24. That group’s mean score for the self-given walking speed test was 4.27.

Technicians Are Still Necessary
Patient-reported outcomes were also consistent with both forms of the tests. In general, however, patient-reported cognitive impairment does not correlate with the results of neurocognitive testing. “What does seem to correlate with patients reporting cognitive impairment is if they are depressed. Then the depression score matches the patient-reported cognitive impairment better than the actual cognitive test score does,” said Dr. Rudick.

Many physician assistants, registered nurses, and physicians may be ready to embrace this app-based technology, but it may not be appropriate for some patients, such as those who walk with difficulty. “You still need a technician to instruct and encourage patients,” said Neil Jouvenat, a physician assistant at the University of Nebraska Medical Center in Omaha. “If the iPad were to instruct a patient to ‘get up now, strap this to your back, and walk 25 feet,’ they won’t because they don’t really think they can. There is a fine line between someone who can walk a certain distance and someone who can’t.” The technician can help in those situations, he added.

The Technology May Aid Clinical Trials
The app holds promise for individuals who would have been excluded from clinical trials in the past, such as patients who live in rural areas. In addition, the collection of normative data from healthy adults will mean that clinical interpretations of MSPT scores will have broader utility in MS patients and groups, and the technology can be adapted to yield additional data such as specific measurements for balance and speed.

Technology such as this has the power to “revolutionize” disease management, particularly if information is collected in a central database that is accessible to any clinician or researcher, said Patricia Coyle, MD, Professor of Psychiatry and Neurology and Director of the MS Comprehensive Care Center at Stony Brook University in New York. “There are only so many MS patients, and we don’t have a good idea of their disease activity. They’re not tracked. No one’s trying to pull that data together,” she said. But having these data “potentially would mean revolutionizing” the field.

—Whitney McKnight