Multiple Sclerosis

Treatment of relapsing-remitting multiple sclerosis with interferon beta-1a produces a decline in brain volume over the first 3 months and follows a course consistent with pseudoatrophy that is likely caused by “hydrodynamic changes related to resolution of inflammation, edema, and cellular infiltration rather than the loss of actual brain tissue,” according to Michael G. Dwyer, Ph.D., of the State University of New York at Buffalo, and his coauthors.

The investigators’ open-label trial, which involved 23 relapsing-remitting multiple sclerosis (RRMS) patients given interferon (IFN) beta-1a 44 mcg (Rebif) subcutaneously three times a week, and 15 healthy controls, is the first to study the effect of subcutaneous IFN beta-1a on early changes in brain volume and its relationship to changes in inflammatory markers (BMC Neurol. 2015 Nov 11;15:232. doi:10.1186/s12883-015-0488-9).

©solitude72/iStockphoto

Dr. Dwyer and his colleagues did not find a loss in white matter as reported by previous studies investigating pseudoatrophy in the beginning of treatment for RRMS, but instead found that the atrophy was largely driven by gray matter loss. They observed significant mean brain volume loss of –0.95% and gray matter loss of –1.52% in the first 3 months in RRMS patients, compared with controls, which was significantly correlated with decreased pro-inflammatory IL-17 F–expressing CD4-positive or CD8-positive T cells. Change in white matter volume experienced by IFN beta-1a–treated patients, compared with controls, did not differ at 3 months (–0.41%), from 3 to 6 months (0.30%), or from baseline to 6 months (–0.21%). The decrease in mean brain volume, however, slowed to just –0.08% from month 3 to 6, and was –0.91% from baseline to 6 months. Gray matter loss was not significant in RRMS patients from 3 to 6 months (–0.46%), but was significant from baseline to 6 months (–1.66%).

The lack of significant changes in white matter volume may have been affected, the investigators said, by a lack of statistical power to detect its change and the susceptibility of cortical gray matter measurement to “partial volume errors owing to its thin and convoluted nature.”

The findings are “supportive of an early anti-inflammatory therapeutic effect for IFN beta-1a,” the investigators wrote, and also send a message to use caution in applying MRI to measure disease progression via brain atrophy by having patients with RRMS with active disease who are starting on disease-modifying drug therapy obtain a baseline for MRI measures of brain volume “only after several months of therapy, once the pseudoatrophy effect has run its course, rather than at the beginning of therapy.”

EMD Serono and Pfizer sponsored the study. Nine of the 13 authors had financial disclosures with companies that market MS drugs, including EMD Serono and Pfizer.

jevans@frontlinemedcom.com

Treatment of relapsing-remitting multiple sclerosis with interferon beta-1a produces a decline in brain volume over the first 3 months and follows a course consistent with pseudoatrophy that is likely caused by “hydrodynamic changes related to resolution of inflammation, edema, and cellular infiltration rather than the loss of actual brain tissue,” according to Michael G. Dwyer, Ph.D., of the State University of New York at Buffalo, and his coauthors.

The investigators’ open-label trial, which involved 23 relapsing-remitting multiple sclerosis (RRMS) patients given interferon (IFN) beta-1a 44 mcg (Rebif) subcutaneously three times a week, and 15 healthy controls, is the first to study the effect of subcutaneous IFN beta-1a on early changes in brain volume and its relationship to changes in inflammatory markers (BMC Neurol. 2015 Nov 11;15:232. doi:10.1186/s12883-015-0488-9).

©solitude72/iStockphoto

Dr. Dwyer and his colleagues did not find a loss in white matter as reported by previous studies investigating pseudoatrophy in the beginning of treatment for RRMS, but instead found that the atrophy was largely driven by gray matter loss. They observed significant mean brain volume loss of –0.95% and gray matter loss of –1.52% in the first 3 months in RRMS patients, compared with controls, which was significantly correlated with decreased pro-inflammatory IL-17 F–expressing CD4-positive or CD8-positive T cells. Change in white matter volume experienced by IFN beta-1a–treated patients, compared with controls, did not differ at 3 months (–0.41%), from 3 to 6 months (0.30%), or from baseline to 6 months (–0.21%). The decrease in mean brain volume, however, slowed to just –0.08% from month 3 to 6, and was –0.91% from baseline to 6 months. Gray matter loss was not significant in RRMS patients from 3 to 6 months (–0.46%), but was significant from baseline to 6 months (–1.66%).

The lack of significant changes in white matter volume may have been affected, the investigators said, by a lack of statistical power to detect its change and the susceptibility of cortical gray matter measurement to “partial volume errors owing to its thin and convoluted nature.”

The findings are “supportive of an early anti-inflammatory therapeutic effect for IFN beta-1a,” the investigators wrote, and also send a message to use caution in applying MRI to measure disease progression via brain atrophy by having patients with RRMS with active disease who are starting on disease-modifying drug therapy obtain a baseline for MRI measures of brain volume “only after several months of therapy, once the pseudoatrophy effect has run its course, rather than at the beginning of therapy.”

EMD Serono and Pfizer sponsored the study. Nine of the 13 authors had financial disclosures with companies that market MS drugs, including EMD Serono and Pfizer.

jevans@frontlinemedcom.com

Treatment of relapsing-remitting multiple sclerosis with interferon beta-1a produces a decline in brain volume over the first 3 months and follows a course consistent with pseudoatrophy that is likely caused by “hydrodynamic changes related to resolution of inflammation, edema, and cellular infiltration rather than the loss of actual brain tissue,” according to Michael G. Dwyer, Ph.D., of the State University of New York at Buffalo, and his coauthors.

The investigators’ open-label trial, which involved 23 relapsing-remitting multiple sclerosis (RRMS) patients given interferon (IFN) beta-1a 44 mcg (Rebif) subcutaneously three times a week, and 15 healthy controls, is the first to study the effect of subcutaneous IFN beta-1a on early changes in brain volume and its relationship to changes in inflammatory markers (BMC Neurol. 2015 Nov 11;15:232. doi:10.1186/s12883-015-0488-9).

©solitude72/iStockphoto

Dr. Dwyer and his colleagues did not find a loss in white matter as reported by previous studies investigating pseudoatrophy in the beginning of treatment for RRMS, but instead found that the atrophy was largely driven by gray matter loss. They observed significant mean brain volume loss of –0.95% and gray matter loss of –1.52% in the first 3 months in RRMS patients, compared with controls, which was significantly correlated with decreased pro-inflammatory IL-17 F–expressing CD4-positive or CD8-positive T cells. Change in white matter volume experienced by IFN beta-1a–treated patients, compared with controls, did not differ at 3 months (–0.41%), from 3 to 6 months (0.30%), or from baseline to 6 months (–0.21%). The decrease in mean brain volume, however, slowed to just –0.08% from month 3 to 6, and was –0.91% from baseline to 6 months. Gray matter loss was not significant in RRMS patients from 3 to 6 months (–0.46%), but was significant from baseline to 6 months (–1.66%).

The lack of significant changes in white matter volume may have been affected, the investigators said, by a lack of statistical power to detect its change and the susceptibility of cortical gray matter measurement to “partial volume errors owing to its thin and convoluted nature.”

The findings are “supportive of an early anti-inflammatory therapeutic effect for IFN beta-1a,” the investigators wrote, and also send a message to use caution in applying MRI to measure disease progression via brain atrophy by having patients with RRMS with active disease who are starting on disease-modifying drug therapy obtain a baseline for MRI measures of brain volume “only after several months of therapy, once the pseudoatrophy effect has run its course, rather than at the beginning of therapy.”

EMD Serono and Pfizer sponsored the study. Nine of the 13 authors had financial disclosures with companies that market MS drugs, including EMD Serono and Pfizer.

jevans@frontlinemedcom.com

There may be a benefit to exclusive breastfeeding for women with multiple sclerosis (MS). Women with MS who breastfed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth, compared with women who did not breastfeed exclusively, according to an article published online ahead of print August 31 in JAMA Neurology.

Previous investigations found that about 20% to 30% of women with MS experience a relapse within three to four months post partum. Currently, there are no therapies or interventions to prevent a relapse, and data on the effect of breastfeeding on postpartum MS relapse are conflicting.

Kerstin Hellwig, MD, a neurologist at St. Josef-Hospital at Ruhr-University Bochum in Germany, and colleagues collected data from 201 pregnant women with relapsing-remitting MS. Each woman was monitored for any relapse for as long as one year after birth. Of these participants, 120 (59.7%) chose to breastfeed exclusively for at least two months, while 42 (20.9%) opted for a combined breastfeeding–supplemental regimen, and 39 (19.4%) did not intend to breastfeed at all. Most of the women (88.6%) in the study cohort had used disease-modifying therapies (DMTs) before pregnancy.

Of the women who breastfed exclusively, 29 (24.2%) experienced a relapse within six months post partum, compared with 31 (38.3%) of those who did not breastfeed exclusively. The effect of exclusive breastfeeding “seems to be plausible,” Dr. Hellwig and coauthors said, since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menses.

Dr. Hellwig and colleagues also reported that, compared with women who breastfed exclusively, those who resumed DMTs early had a higher risk of postpartum relapse.

“Relapse in the first six months post partum may be diminished by exclusive breastfeeding, but once regular feedings are introduced, disease activity is likely to return,” Dr. Hellwig and colleagues said. “Taken together, our findings suggest that exclusive breastfeeding acts like a modestly effective treatment with a natural end date.” The researchers concluded that “Women with MS should be supported if they choose to breastfeed exclusively, since it clearly does not increase the risk of postpartum relapse.”

—Ashley Payton

There may be a benefit to exclusive breastfeeding for women with multiple sclerosis (MS). Women with MS who breastfed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth, compared with women who did not breastfeed exclusively, according to an article published online ahead of print August 31 in JAMA Neurology.

Previous investigations found that about 20% to 30% of women with MS experience a relapse within three to four months post partum. Currently, there are no therapies or interventions to prevent a relapse, and data on the effect of breastfeeding on postpartum MS relapse are conflicting.

Kerstin Hellwig, MD, a neurologist at St. Josef-Hospital at Ruhr-University Bochum in Germany, and colleagues collected data from 201 pregnant women with relapsing-remitting MS. Each woman was monitored for any relapse for as long as one year after birth. Of these participants, 120 (59.7%) chose to breastfeed exclusively for at least two months, while 42 (20.9%) opted for a combined breastfeeding–supplemental regimen, and 39 (19.4%) did not intend to breastfeed at all. Most of the women (88.6%) in the study cohort had used disease-modifying therapies (DMTs) before pregnancy.

Of the women who breastfed exclusively, 29 (24.2%) experienced a relapse within six months post partum, compared with 31 (38.3%) of those who did not breastfeed exclusively. The effect of exclusive breastfeeding “seems to be plausible,” Dr. Hellwig and coauthors said, since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menses.

Dr. Hellwig and colleagues also reported that, compared with women who breastfed exclusively, those who resumed DMTs early had a higher risk of postpartum relapse.

“Relapse in the first six months post partum may be diminished by exclusive breastfeeding, but once regular feedings are introduced, disease activity is likely to return,” Dr. Hellwig and colleagues said. “Taken together, our findings suggest that exclusive breastfeeding acts like a modestly effective treatment with a natural end date.” The researchers concluded that “Women with MS should be supported if they choose to breastfeed exclusively, since it clearly does not increase the risk of postpartum relapse.”

—Ashley Payton

There may be a benefit to exclusive breastfeeding for women with multiple sclerosis (MS). Women with MS who breastfed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth, compared with women who did not breastfeed exclusively, according to an article published online ahead of print August 31 in JAMA Neurology.

Previous investigations found that about 20% to 30% of women with MS experience a relapse within three to four months post partum. Currently, there are no therapies or interventions to prevent a relapse, and data on the effect of breastfeeding on postpartum MS relapse are conflicting.

Kerstin Hellwig, MD, a neurologist at St. Josef-Hospital at Ruhr-University Bochum in Germany, and colleagues collected data from 201 pregnant women with relapsing-remitting MS. Each woman was monitored for any relapse for as long as one year after birth. Of these participants, 120 (59.7%) chose to breastfeed exclusively for at least two months, while 42 (20.9%) opted for a combined breastfeeding–supplemental regimen, and 39 (19.4%) did not intend to breastfeed at all. Most of the women (88.6%) in the study cohort had used disease-modifying therapies (DMTs) before pregnancy.

Of the women who breastfed exclusively, 29 (24.2%) experienced a relapse within six months post partum, compared with 31 (38.3%) of those who did not breastfeed exclusively. The effect of exclusive breastfeeding “seems to be plausible,” Dr. Hellwig and coauthors said, since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menses.

Dr. Hellwig and colleagues also reported that, compared with women who breastfed exclusively, those who resumed DMTs early had a higher risk of postpartum relapse.

“Relapse in the first six months post partum may be diminished by exclusive breastfeeding, but once regular feedings are introduced, disease activity is likely to return,” Dr. Hellwig and colleagues said. “Taken together, our findings suggest that exclusive breastfeeding acts like a modestly effective treatment with a natural end date.” The researchers concluded that “Women with MS should be supported if they choose to breastfeed exclusively, since it clearly does not increase the risk of postpartum relapse.”

—Ashley Payton

CHICAGO—Transcranial direct-current stimulation (tDCS) reduces fatigue and improves aspects of verbal memory in patients with multiple sclerosis (MS), according to data from a pilot study presented at the 140th Annual Meeting of the American Neurological Association. The stimulation may not consistently improve working memory, however, contrary to the researchers’ expectations.

Cognitive dysfunction, including working memory deficits, and fatigue are common and debilitating symptoms of MS, said Tracy D. Vannorsdall, PhD, Assistant Professor of Neurology and Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine in Baltimore. Prior studies have shown that tDCS enhances working memory in healthy adults. To see if tDCS might improve working memory in patients with MS, Dr. Vannorsdall and her research colleagues conducted a sham-controlled, single-blind crossover study.

A Sham Stimulation Control

The investigators recruited five patients with secondary progressive MS from the Johns Hopkins MS Center. All participants were right-handed native English speakers, and three of the participants were women. Participants were between the ages of 42 and 57, with an average age of 50. They had a mean estimated IQ of 119 and a mean 18.4 years of schooling.

Participants completed cognitive testing before and after receiving 2 mA of anodal or sham stimulation to the left dorsolateral prefrontal cortex for 30 minutes once per day for five consecutive days. Investigators administered the current using a NeuroConn Stimulator Plus. For the sham stimulation, researchers increased the anodal current to 2 mA and decreased it to 0 mA over 30 seconds. After a four-week washout period, participants repeated the study procedures under the stimulation condition to which they had not been assigned originally.

Evaluating Cognition

Participants completed the Minimal Assessment of Cognitive Functioning in MS, a seven-subtest battery that assesses verbal learning and memory, visuospatial learning and memory, working memory, processing speed, verbal fluency, executive functioning, and perceptual accuracy. Participants also completed self-report measures of mood and fatigue and responded to a mental and physical side effects questionnaire. The researchers performed two-tailed paired-samples t-tests to compare changes in scores across anodal and sham conditions.

No adverse events occurred. Depression scale ratings did not significantly change during tDCS, compared with sham stimulation.

Fatigue Severity Scale

Participants’ scores on the Fatigue Severity Scale increased by 7 points over the course of five days of sham stimulation, compared with a decrease of 4.6 points over the course of anodal stimulation.

In addition, researchers observed a trend toward improved verbal immediate recall under the anodal condition, compared with sham stimulation. Anodal stimulation also was associated with better performance across most cognitive tests, but the differences were not significant. The study was underpowered to detect whether reduced fatigue contributed to the improvements in cognition. “These preliminary findings suggest that tDCS may ameliorate fatigue and cognitive dysfunction in secondary progressive MS,” concluded the researchers. Future studies will investigate the mechanism of these effects.

—Jake Remaly

CHICAGO—Transcranial direct-current stimulation (tDCS) reduces fatigue and improves aspects of verbal memory in patients with multiple sclerosis (MS), according to data from a pilot study presented at the 140th Annual Meeting of the American Neurological Association. The stimulation may not consistently improve working memory, however, contrary to the researchers’ expectations.

Cognitive dysfunction, including working memory deficits, and fatigue are common and debilitating symptoms of MS, said Tracy D. Vannorsdall, PhD, Assistant Professor of Neurology and Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine in Baltimore. Prior studies have shown that tDCS enhances working memory in healthy adults. To see if tDCS might improve working memory in patients with MS, Dr. Vannorsdall and her research colleagues conducted a sham-controlled, single-blind crossover study.

A Sham Stimulation Control

The investigators recruited five patients with secondary progressive MS from the Johns Hopkins MS Center. All participants were right-handed native English speakers, and three of the participants were women. Participants were between the ages of 42 and 57, with an average age of 50. They had a mean estimated IQ of 119 and a mean 18.4 years of schooling.

Participants completed cognitive testing before and after receiving 2 mA of anodal or sham stimulation to the left dorsolateral prefrontal cortex for 30 minutes once per day for five consecutive days. Investigators administered the current using a NeuroConn Stimulator Plus. For the sham stimulation, researchers increased the anodal current to 2 mA and decreased it to 0 mA over 30 seconds. After a four-week washout period, participants repeated the study procedures under the stimulation condition to which they had not been assigned originally.

Evaluating Cognition

Participants completed the Minimal Assessment of Cognitive Functioning in MS, a seven-subtest battery that assesses verbal learning and memory, visuospatial learning and memory, working memory, processing speed, verbal fluency, executive functioning, and perceptual accuracy. Participants also completed self-report measures of mood and fatigue and responded to a mental and physical side effects questionnaire. The researchers performed two-tailed paired-samples t-tests to compare changes in scores across anodal and sham conditions.

No adverse events occurred. Depression scale ratings did not significantly change during tDCS, compared with sham stimulation.

Fatigue Severity Scale

Participants’ scores on the Fatigue Severity Scale increased by 7 points over the course of five days of sham stimulation, compared with a decrease of 4.6 points over the course of anodal stimulation.

In addition, researchers observed a trend toward improved verbal immediate recall under the anodal condition, compared with sham stimulation. Anodal stimulation also was associated with better performance across most cognitive tests, but the differences were not significant. The study was underpowered to detect whether reduced fatigue contributed to the improvements in cognition. “These preliminary findings suggest that tDCS may ameliorate fatigue and cognitive dysfunction in secondary progressive MS,” concluded the researchers. Future studies will investigate the mechanism of these effects.

—Jake Remaly

CHICAGO—Transcranial direct-current stimulation (tDCS) reduces fatigue and improves aspects of verbal memory in patients with multiple sclerosis (MS), according to data from a pilot study presented at the 140th Annual Meeting of the American Neurological Association. The stimulation may not consistently improve working memory, however, contrary to the researchers’ expectations.

Cognitive dysfunction, including working memory deficits, and fatigue are common and debilitating symptoms of MS, said Tracy D. Vannorsdall, PhD, Assistant Professor of Neurology and Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine in Baltimore. Prior studies have shown that tDCS enhances working memory in healthy adults. To see if tDCS might improve working memory in patients with MS, Dr. Vannorsdall and her research colleagues conducted a sham-controlled, single-blind crossover study.

A Sham Stimulation Control

The investigators recruited five patients with secondary progressive MS from the Johns Hopkins MS Center. All participants were right-handed native English speakers, and three of the participants were women. Participants were between the ages of 42 and 57, with an average age of 50. They had a mean estimated IQ of 119 and a mean 18.4 years of schooling.

Participants completed cognitive testing before and after receiving 2 mA of anodal or sham stimulation to the left dorsolateral prefrontal cortex for 30 minutes once per day for five consecutive days. Investigators administered the current using a NeuroConn Stimulator Plus. For the sham stimulation, researchers increased the anodal current to 2 mA and decreased it to 0 mA over 30 seconds. After a four-week washout period, participants repeated the study procedures under the stimulation condition to which they had not been assigned originally.

Evaluating Cognition

Participants completed the Minimal Assessment of Cognitive Functioning in MS, a seven-subtest battery that assesses verbal learning and memory, visuospatial learning and memory, working memory, processing speed, verbal fluency, executive functioning, and perceptual accuracy. Participants also completed self-report measures of mood and fatigue and responded to a mental and physical side effects questionnaire. The researchers performed two-tailed paired-samples t-tests to compare changes in scores across anodal and sham conditions.

No adverse events occurred. Depression scale ratings did not significantly change during tDCS, compared with sham stimulation.

Fatigue Severity Scale

Participants’ scores on the Fatigue Severity Scale increased by 7 points over the course of five days of sham stimulation, compared with a decrease of 4.6 points over the course of anodal stimulation.

In addition, researchers observed a trend toward improved verbal immediate recall under the anodal condition, compared with sham stimulation. Anodal stimulation also was associated with better performance across most cognitive tests, but the differences were not significant. The study was underpowered to detect whether reduced fatigue contributed to the improvements in cognition. “These preliminary findings suggest that tDCS may ameliorate fatigue and cognitive dysfunction in secondary progressive MS,” concluded the researchers. Future studies will investigate the mechanism of these effects.

—Jake Remaly

Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online ahead of print October 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for inflammatory bowel disease and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between inflammatory bowel disease and demyelinating disease.

Researchers examined the issue by analyzing data from nationwide Danish health registries for patients with inflammatory bowel disease and medication exposure. They identified 4,504 patients treated during a 14-year period who had inflammatory bowel disease and took anti-TNF agents, and 16,429 patients with inflammatory bowel disease matched for sex, age, and disease duration who did not take the medications, according to Nynne Nyboe Andersen, MD, a doctoral student in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and her associates.

Eleven patients in the group exposed to medication had central demyelinating events. Two patients had multiple sclerosis, five patients had optic neuritis, and four patients had other central demyelinating disease. Medication-exposed patients had 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events. Five patients had multiple sclerosis, six patients had optic neuritis, one patient had transverse myelitis, and five patients had other central demyelinating disease. The unexposed group had 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, according to the investigators. These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers. “If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” said Dr. Nyboe Andersen.

—Mary Ann Moon

Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online ahead of print October 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for inflammatory bowel disease and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between inflammatory bowel disease and demyelinating disease.

Researchers examined the issue by analyzing data from nationwide Danish health registries for patients with inflammatory bowel disease and medication exposure. They identified 4,504 patients treated during a 14-year period who had inflammatory bowel disease and took anti-TNF agents, and 16,429 patients with inflammatory bowel disease matched for sex, age, and disease duration who did not take the medications, according to Nynne Nyboe Andersen, MD, a doctoral student in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and her associates.

Eleven patients in the group exposed to medication had central demyelinating events. Two patients had multiple sclerosis, five patients had optic neuritis, and four patients had other central demyelinating disease. Medication-exposed patients had 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events. Five patients had multiple sclerosis, six patients had optic neuritis, one patient had transverse myelitis, and five patients had other central demyelinating disease. The unexposed group had 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, according to the investigators. These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers. “If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” said Dr. Nyboe Andersen.

—Mary Ann Moon

Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online ahead of print October 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for inflammatory bowel disease and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between inflammatory bowel disease and demyelinating disease.

Researchers examined the issue by analyzing data from nationwide Danish health registries for patients with inflammatory bowel disease and medication exposure. They identified 4,504 patients treated during a 14-year period who had inflammatory bowel disease and took anti-TNF agents, and 16,429 patients with inflammatory bowel disease matched for sex, age, and disease duration who did not take the medications, according to Nynne Nyboe Andersen, MD, a doctoral student in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and her associates.

Eleven patients in the group exposed to medication had central demyelinating events. Two patients had multiple sclerosis, five patients had optic neuritis, and four patients had other central demyelinating disease. Medication-exposed patients had 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events. Five patients had multiple sclerosis, six patients had optic neuritis, one patient had transverse myelitis, and five patients had other central demyelinating disease. The unexposed group had 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, according to the investigators. These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers. “If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” said Dr. Nyboe Andersen.

—Mary Ann Moon

As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability, according to a study of 794 patients with relapsing-remitting multiple sclerosis aged 18 to 55 years. Researchers found:

• Estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo, confirming study sensitivity.

• For gadolinium-enhancing, the estimated ratio of generic drug to brand drug was within the predefined equivalence margin.

• The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups.

Citation: Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2154.

As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability, according to a study of 794 patients with relapsing-remitting multiple sclerosis aged 18 to 55 years. Researchers found:

• Estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo, confirming study sensitivity.

• For gadolinium-enhancing, the estimated ratio of generic drug to brand drug was within the predefined equivalence margin.

• The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups.

Citation: Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2154.

As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability, according to a study of 794 patients with relapsing-remitting multiple sclerosis aged 18 to 55 years. Researchers found:

• Estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo, confirming study sensitivity.

• For gadolinium-enhancing, the estimated ratio of generic drug to brand drug was within the predefined equivalence margin.

• The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups.

Citation: Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2154.

Among patients with multiple sclerosis (MS) treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI, according to a study of 1,482 patients with relapsing-remitting MS treated with interferon beta-1b. Researchers found:

• Average 25(OH)D levels were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI.

• A 50.0-nmol/L increase in serum 25(OH)D levels was associated with a 31% lower rate of new lesions.

• The lowest rate of new lesions was seen in patients with 25(OH)D levels greater than 100.0 nmol/L.

• No significant associations were seen between 25(OH)D levels and change in brain volume, relapse rates, or Expanded Disability Status Scale score.

• Results were consistent following adjustments for DRB1*15 or vitamin D-binding protein status.

Citation: Fitzgerald KC, Menger KL, Kӧchert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2742.

Among patients with multiple sclerosis (MS) treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI, according to a study of 1,482 patients with relapsing-remitting MS treated with interferon beta-1b. Researchers found:

• Average 25(OH)D levels were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI.

• A 50.0-nmol/L increase in serum 25(OH)D levels was associated with a 31% lower rate of new lesions.

• The lowest rate of new lesions was seen in patients with 25(OH)D levels greater than 100.0 nmol/L.

• No significant associations were seen between 25(OH)D levels and change in brain volume, relapse rates, or Expanded Disability Status Scale score.

• Results were consistent following adjustments for DRB1*15 or vitamin D-binding protein status.

Citation: Fitzgerald KC, Menger KL, Kӧchert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2742.

Among patients with multiple sclerosis (MS) treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI, according to a study of 1,482 patients with relapsing-remitting MS treated with interferon beta-1b. Researchers found:

• Average 25(OH)D levels were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI.

• A 50.0-nmol/L increase in serum 25(OH)D levels was associated with a 31% lower rate of new lesions.

• The lowest rate of new lesions was seen in patients with 25(OH)D levels greater than 100.0 nmol/L.

• No significant associations were seen between 25(OH)D levels and change in brain volume, relapse rates, or Expanded Disability Status Scale score.

• Results were consistent following adjustments for DRB1*15 or vitamin D-binding protein status.

Citation: Fitzgerald KC, Menger KL, Kӧchert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. [Published online ahead of print October 12, 2015]. JAMA Neurol. doi: 10.1001/jamaneurol.2015.2742.

Ocrelizumab reduced both relapses and disability progression to a significantly greater extent than did interferon beta-1a in patients with relapsing-remitting multiple sclerosis in two large phase III trials.

The selective B-cell–targeting monoclonal antibody cut the annualized relapse rate by almost half when compared against interferon beta-1a and significantly reduced the risk of confirmed disability progression at both 12 and 24 weeks, Dr. Stephen Hauser reported at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis in Barcelona.

designer491/Thinkstock

Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20-positive B cells, succeeded on secondary outcomes as well, reducing T1 gadolinium-enhancing lesions by more than 90%, and the emergence or enhancement of T2 hyperintense lesions by 80%, said Dr. Hauser, chair of neurology at the University of California, San Francisco.

The data are from two identically designed phase III trials conducted by Genentech. OPERA 1 and OPERA 2 enrolled 1,656 patients with relapsing-remitting multiple sclerosis (RRMS). They were randomized to either 600-mg ocrelizumab IV infusions every 24 weeks plus placebo subcutaneous injections three times weekly or to 44-mcg subcutaneous injections of interferon beta-1a (Rebif) thrice weekly plus placebo IV infusions every 24 weeks. Both studies were conducted for 96 weeks.

The patients were a typical RRMS cohort: young (mean 37 years) and mostly women (66%). The mean baseline score on the Extended Disability Status Scale was 2.77 and the mean time since diagnosis about 4 years. Patients had about 1.5 relapses in the first and second year before entering the studies; about one-third (595) were naive to treatment.

Compared with interferon beta-1a, ocrelizumab reduced the annualized relapse rate by 46% in OPERA 1 and 47% in OPERA 2. It also posted 43% and 37% risk reductions in confirmed disability progression sustained for both 12 and 24 weeks.

On imaging measures, ocrelizumab bested interferon beta-1a as well. It conferred a 94% and 95% reduction in the total number of T1 gadolinium-enhancing lesions and a 77% and 83% reduction in the total number of new and/or enlarging hyperintense T2 lesions. An exploratory analysis suggested that the drug reduced the rate of whole brain volume, compared with interferon beta-1a.

A pooled safety analysis comprised 83% of the entire study population. Adverse events were similar in both treatment groups overall. Infusion reactions were significantly more common with ocrelizumab than with interferon beta-1a (34% vs. 9.7%). There were similar rates of serious adverse events, including serious infections (6.9% and 8.7%), and there were no cases of progressive multifocal leukoencephalopathy.

Long-term safety investigations are still ongoing, Genentech’s Dr. Peter Chin said in an interview. Ocrelizumab was originally developed by Roche and Biogen for rheumatoid arthritis. But in 2010, the companies halted development of the drug when an interim safety analysis found a significantly increased incidence of serious infections.

While Genentech will keep monitoring for those problems, they may be less likely to develop in MS patients than in patients with RA, said Dr. Chin, principal medical director for Genentech-Roche Global Neuroscience Development.

“Patients with RRMS are typically younger and, overall, healthier, than those with RA, without many of the comorbidities that predispose them to opportunistic infections,” he said. “They also tend to be taking concurrent immunosuppressive drugs, which increases their risk in a way we wouldn’t see in most MS patients.”

Dr. Hauser noted that he has received financial support from F. Hoffmann-La Roche, Symbiotix, and Bionure.

msullivan@frontlinemedcom.com

Ocrelizumab reduced both relapses and disability progression to a significantly greater extent than did interferon beta-1a in patients with relapsing-remitting multiple sclerosis in two large phase III trials.

The selective B-cell–targeting monoclonal antibody cut the annualized relapse rate by almost half when compared against interferon beta-1a and significantly reduced the risk of confirmed disability progression at both 12 and 24 weeks, Dr. Stephen Hauser reported at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis in Barcelona.

designer491/Thinkstock

Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20-positive B cells, succeeded on secondary outcomes as well, reducing T1 gadolinium-enhancing lesions by more than 90%, and the emergence or enhancement of T2 hyperintense lesions by 80%, said Dr. Hauser, chair of neurology at the University of California, San Francisco.

The data are from two identically designed phase III trials conducted by Genentech. OPERA 1 and OPERA 2 enrolled 1,656 patients with relapsing-remitting multiple sclerosis (RRMS). They were randomized to either 600-mg ocrelizumab IV infusions every 24 weeks plus placebo subcutaneous injections three times weekly or to 44-mcg subcutaneous injections of interferon beta-1a (Rebif) thrice weekly plus placebo IV infusions every 24 weeks. Both studies were conducted for 96 weeks.

The patients were a typical RRMS cohort: young (mean 37 years) and mostly women (66%). The mean baseline score on the Extended Disability Status Scale was 2.77 and the mean time since diagnosis about 4 years. Patients had about 1.5 relapses in the first and second year before entering the studies; about one-third (595) were naive to treatment.

Compared with interferon beta-1a, ocrelizumab reduced the annualized relapse rate by 46% in OPERA 1 and 47% in OPERA 2. It also posted 43% and 37% risk reductions in confirmed disability progression sustained for both 12 and 24 weeks.

On imaging measures, ocrelizumab bested interferon beta-1a as well. It conferred a 94% and 95% reduction in the total number of T1 gadolinium-enhancing lesions and a 77% and 83% reduction in the total number of new and/or enlarging hyperintense T2 lesions. An exploratory analysis suggested that the drug reduced the rate of whole brain volume, compared with interferon beta-1a.

A pooled safety analysis comprised 83% of the entire study population. Adverse events were similar in both treatment groups overall. Infusion reactions were significantly more common with ocrelizumab than with interferon beta-1a (34% vs. 9.7%). There were similar rates of serious adverse events, including serious infections (6.9% and 8.7%), and there were no cases of progressive multifocal leukoencephalopathy.

Long-term safety investigations are still ongoing, Genentech’s Dr. Peter Chin said in an interview. Ocrelizumab was originally developed by Roche and Biogen for rheumatoid arthritis. But in 2010, the companies halted development of the drug when an interim safety analysis found a significantly increased incidence of serious infections.

While Genentech will keep monitoring for those problems, they may be less likely to develop in MS patients than in patients with RA, said Dr. Chin, principal medical director for Genentech-Roche Global Neuroscience Development.

“Patients with RRMS are typically younger and, overall, healthier, than those with RA, without many of the comorbidities that predispose them to opportunistic infections,” he said. “They also tend to be taking concurrent immunosuppressive drugs, which increases their risk in a way we wouldn’t see in most MS patients.”

Dr. Hauser noted that he has received financial support from F. Hoffmann-La Roche, Symbiotix, and Bionure.

msullivan@frontlinemedcom.com

Ocrelizumab reduced both relapses and disability progression to a significantly greater extent than did interferon beta-1a in patients with relapsing-remitting multiple sclerosis in two large phase III trials.

The selective B-cell–targeting monoclonal antibody cut the annualized relapse rate by almost half when compared against interferon beta-1a and significantly reduced the risk of confirmed disability progression at both 12 and 24 weeks, Dr. Stephen Hauser reported at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis in Barcelona.

designer491/Thinkstock

Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20-positive B cells, succeeded on secondary outcomes as well, reducing T1 gadolinium-enhancing lesions by more than 90%, and the emergence or enhancement of T2 hyperintense lesions by 80%, said Dr. Hauser, chair of neurology at the University of California, San Francisco.

The data are from two identically designed phase III trials conducted by Genentech. OPERA 1 and OPERA 2 enrolled 1,656 patients with relapsing-remitting multiple sclerosis (RRMS). They were randomized to either 600-mg ocrelizumab IV infusions every 24 weeks plus placebo subcutaneous injections three times weekly or to 44-mcg subcutaneous injections of interferon beta-1a (Rebif) thrice weekly plus placebo IV infusions every 24 weeks. Both studies were conducted for 96 weeks.

The patients were a typical RRMS cohort: young (mean 37 years) and mostly women (66%). The mean baseline score on the Extended Disability Status Scale was 2.77 and the mean time since diagnosis about 4 years. Patients had about 1.5 relapses in the first and second year before entering the studies; about one-third (595) were naive to treatment.

Compared with interferon beta-1a, ocrelizumab reduced the annualized relapse rate by 46% in OPERA 1 and 47% in OPERA 2. It also posted 43% and 37% risk reductions in confirmed disability progression sustained for both 12 and 24 weeks.

On imaging measures, ocrelizumab bested interferon beta-1a as well. It conferred a 94% and 95% reduction in the total number of T1 gadolinium-enhancing lesions and a 77% and 83% reduction in the total number of new and/or enlarging hyperintense T2 lesions. An exploratory analysis suggested that the drug reduced the rate of whole brain volume, compared with interferon beta-1a.

A pooled safety analysis comprised 83% of the entire study population. Adverse events were similar in both treatment groups overall. Infusion reactions were significantly more common with ocrelizumab than with interferon beta-1a (34% vs. 9.7%). There were similar rates of serious adverse events, including serious infections (6.9% and 8.7%), and there were no cases of progressive multifocal leukoencephalopathy.

Long-term safety investigations are still ongoing, Genentech’s Dr. Peter Chin said in an interview. Ocrelizumab was originally developed by Roche and Biogen for rheumatoid arthritis. But in 2010, the companies halted development of the drug when an interim safety analysis found a significantly increased incidence of serious infections.

While Genentech will keep monitoring for those problems, they may be less likely to develop in MS patients than in patients with RA, said Dr. Chin, principal medical director for Genentech-Roche Global Neuroscience Development.

“Patients with RRMS are typically younger and, overall, healthier, than those with RA, without many of the comorbidities that predispose them to opportunistic infections,” he said. “They also tend to be taking concurrent immunosuppressive drugs, which increases their risk in a way we wouldn’t see in most MS patients.”

Dr. Hauser noted that he has received financial support from F. Hoffmann-La Roche, Symbiotix, and Bionure.

msullivan@frontlinemedcom.com