Neurology

BERLIN – Higher vitamin D levels at multiple sclerosis onset were predictive of higher cognitive function 11 years on, and heavy smokers took a “clinically significant” cognitive hit, according to a recent study.

“Higher vitamin D in the first years after [clinically isolated syndrome] was associated with better cognitive function and lower neuronal injury at year 11,” said Marianna Cortese, MD, presenting her findings during a late-breaking abstracts session at the annual congress of the European Society for Education and Treatment in Multiple Sclerosis.

“Vitamin D supplementation during the early years with the disease might be neuroprotective,” she said.

According to Dr. Cortese, 40%-70% of patients with MS will experience cognitive decline across their disease course; there is no currently known specific treatment for cognitive decline.

Smoking, low levels of vitamin D [as 25(OH)D], and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS, and have been associated with more active MS and progressive disease, but whether these factors predict cognitive status had not been known, said Dr. Cortese of the Harvard T.H. Chan School of Public Health.

Accordingly, she said, investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The study is an observational study that followed 278 participants with clinically isolated syndrome (CIS) in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled trial of interferon beta-1b for early treatment of clinically isolated syndrome. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first 2 years after CIS to predict progression outcomes at year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline, and at study months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used for EBV seropositivity.

In terms of outcome measurements, the cognitive performance measure used in the study was the Paced Auditory Serial Addition Test, a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study years 1, 2, 5, and 11. At study year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the study design adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease seen on baseline magnetic resonance imaging, body mass index, and whether the patient was treated with steroids during the initial CIS.

“Higher quintiles of mean vitamin D levels during the first 2 years were associated with lower odds of scoring worse on the PASAT at year 11,” said Dr. Cortese (P-trend = .028). The significant trend across the quintiles “suggests a dose-response relationship,” she said.* For vitamin D levels over the first 5 years, the P-trend was .049. Dr. Cortese explained that “scoring worse” meant scoring below the median.

Looking at the effect of early vitamin D levels another way, incremental increases of 50 nmol/L of mean 25(OH)D in study months 6-24 predicted 65% lower odds of having a PASAT score below the median at year 11 (P = .027). “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Turning to the effect of smoking on cognitive function at year 11, Dr. Cortese explained that cotinine levels obtained during the first 2 years were all used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker (N = 125). If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the small number of patients (N = 9) who were very heavy smokers, with cotinine levels over 191 ng/mL.

“Smokers – compared to nonsmokers – had a significantly lower standardized PASAT score at year 11,” said Dr. Cortese (P trend = .042 in age- and sex-adjusted analysis; P-trend = .056 in full multivariable analysis). “Actually, smokers had an up to 0.6-standard deviation-lower PASAT score at year 11 when we looked at heavy smokers. ...This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.”

Dr. Cortese pointed out that early smoking, again, showed a dose-response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients.”

Epstein-Barr antibodies were not associated with cognitive function at year 11, according to the analysis (P-trend = .93).

“The findings of neuroaxonal injury at year 11 using serum neurofilament light-chain measures corroborated the main findings on cognitive function at year 11,” said Dr. Cortese.

For a 50-nmol higher vitamin D level within the first 5 years, neurofilament light chain levels at year 11 were 20% lower, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first 5 years had neurofilament light chain levels 20% higher than other participants: “So they did worse. They had more neuroaxonal loss,” said Dr. Cortese. No association was seen between neurofilament light chain levels at year 11 and early EBV status, she said.

Though just cognitive function data from BENEFIT-11 were reported by Dr. Cortese, she said that radiologic and other clinical data are also being studied and will be reported in the future.

Dr. Cortese reported that she had no conflicts of interest. Several coauthors reported financial relationships with multiple pharmaceutical companies. The study was supported by the National Institutes of Health and the National Multiple Sclerosis Society, with clinical support from Bayer HealthCare.

[email protected]

SOURCE: Cortese M et al. ECTRIMS 2018, Late breaking abstracts session.

*Correction, 10/25/18: An earlier version of this article mischaracterized the relationship between vitamin D scores during the first 2 years and PASAT scores at year 11. 

BERLIN – Higher vitamin D levels at multiple sclerosis onset were predictive of higher cognitive function 11 years on, and heavy smokers took a “clinically significant” cognitive hit, according to a recent study.

“Higher vitamin D in the first years after [clinically isolated syndrome] was associated with better cognitive function and lower neuronal injury at year 11,” said Marianna Cortese, MD, presenting her findings during a late-breaking abstracts session at the annual congress of the European Society for Education and Treatment in Multiple Sclerosis.

“Vitamin D supplementation during the early years with the disease might be neuroprotective,” she said.

According to Dr. Cortese, 40%-70% of patients with MS will experience cognitive decline across their disease course; there is no currently known specific treatment for cognitive decline.

Smoking, low levels of vitamin D [as 25(OH)D], and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS, and have been associated with more active MS and progressive disease, but whether these factors predict cognitive status had not been known, said Dr. Cortese of the Harvard T.H. Chan School of Public Health.

Accordingly, she said, investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The study is an observational study that followed 278 participants with clinically isolated syndrome (CIS) in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled trial of interferon beta-1b for early treatment of clinically isolated syndrome. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first 2 years after CIS to predict progression outcomes at year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline, and at study months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used for EBV seropositivity.

In terms of outcome measurements, the cognitive performance measure used in the study was the Paced Auditory Serial Addition Test, a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study years 1, 2, 5, and 11. At study year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the study design adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease seen on baseline magnetic resonance imaging, body mass index, and whether the patient was treated with steroids during the initial CIS.

“Higher quintiles of mean vitamin D levels during the first 2 years were associated with lower odds of scoring worse on the PASAT at year 11,” said Dr. Cortese (P-trend = .028). The significant trend across the quintiles “suggests a dose-response relationship,” she said.* For vitamin D levels over the first 5 years, the P-trend was .049. Dr. Cortese explained that “scoring worse” meant scoring below the median.

Looking at the effect of early vitamin D levels another way, incremental increases of 50 nmol/L of mean 25(OH)D in study months 6-24 predicted 65% lower odds of having a PASAT score below the median at year 11 (P = .027). “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Turning to the effect of smoking on cognitive function at year 11, Dr. Cortese explained that cotinine levels obtained during the first 2 years were all used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker (N = 125). If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the small number of patients (N = 9) who were very heavy smokers, with cotinine levels over 191 ng/mL.

“Smokers – compared to nonsmokers – had a significantly lower standardized PASAT score at year 11,” said Dr. Cortese (P trend = .042 in age- and sex-adjusted analysis; P-trend = .056 in full multivariable analysis). “Actually, smokers had an up to 0.6-standard deviation-lower PASAT score at year 11 when we looked at heavy smokers. ...This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.”

Dr. Cortese pointed out that early smoking, again, showed a dose-response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients.”

Epstein-Barr antibodies were not associated with cognitive function at year 11, according to the analysis (P-trend = .93).

“The findings of neuroaxonal injury at year 11 using serum neurofilament light-chain measures corroborated the main findings on cognitive function at year 11,” said Dr. Cortese.

For a 50-nmol higher vitamin D level within the first 5 years, neurofilament light chain levels at year 11 were 20% lower, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first 5 years had neurofilament light chain levels 20% higher than other participants: “So they did worse. They had more neuroaxonal loss,” said Dr. Cortese. No association was seen between neurofilament light chain levels at year 11 and early EBV status, she said.

Though just cognitive function data from BENEFIT-11 were reported by Dr. Cortese, she said that radiologic and other clinical data are also being studied and will be reported in the future.

Dr. Cortese reported that she had no conflicts of interest. Several coauthors reported financial relationships with multiple pharmaceutical companies. The study was supported by the National Institutes of Health and the National Multiple Sclerosis Society, with clinical support from Bayer HealthCare.

[email protected]

SOURCE: Cortese M et al. ECTRIMS 2018, Late breaking abstracts session.

*Correction, 10/25/18: An earlier version of this article mischaracterized the relationship between vitamin D scores during the first 2 years and PASAT scores at year 11. 

BERLIN – Higher vitamin D levels at multiple sclerosis onset were predictive of higher cognitive function 11 years on, and heavy smokers took a “clinically significant” cognitive hit, according to a recent study.

“Higher vitamin D in the first years after [clinically isolated syndrome] was associated with better cognitive function and lower neuronal injury at year 11,” said Marianna Cortese, MD, presenting her findings during a late-breaking abstracts session at the annual congress of the European Society for Education and Treatment in Multiple Sclerosis.

“Vitamin D supplementation during the early years with the disease might be neuroprotective,” she said.

According to Dr. Cortese, 40%-70% of patients with MS will experience cognitive decline across their disease course; there is no currently known specific treatment for cognitive decline.

Smoking, low levels of vitamin D [as 25(OH)D], and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS, and have been associated with more active MS and progressive disease, but whether these factors predict cognitive status had not been known, said Dr. Cortese of the Harvard T.H. Chan School of Public Health.

Accordingly, she said, investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The study is an observational study that followed 278 participants with clinically isolated syndrome (CIS) in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled trial of interferon beta-1b for early treatment of clinically isolated syndrome. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first 2 years after CIS to predict progression outcomes at year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline, and at study months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used for EBV seropositivity.

In terms of outcome measurements, the cognitive performance measure used in the study was the Paced Auditory Serial Addition Test, a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study years 1, 2, 5, and 11. At study year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the study design adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease seen on baseline magnetic resonance imaging, body mass index, and whether the patient was treated with steroids during the initial CIS.

“Higher quintiles of mean vitamin D levels during the first 2 years were associated with lower odds of scoring worse on the PASAT at year 11,” said Dr. Cortese (P-trend = .028). The significant trend across the quintiles “suggests a dose-response relationship,” she said.* For vitamin D levels over the first 5 years, the P-trend was .049. Dr. Cortese explained that “scoring worse” meant scoring below the median.

Looking at the effect of early vitamin D levels another way, incremental increases of 50 nmol/L of mean 25(OH)D in study months 6-24 predicted 65% lower odds of having a PASAT score below the median at year 11 (P = .027). “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Turning to the effect of smoking on cognitive function at year 11, Dr. Cortese explained that cotinine levels obtained during the first 2 years were all used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker (N = 125). If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the small number of patients (N = 9) who were very heavy smokers, with cotinine levels over 191 ng/mL.

“Smokers – compared to nonsmokers – had a significantly lower standardized PASAT score at year 11,” said Dr. Cortese (P trend = .042 in age- and sex-adjusted analysis; P-trend = .056 in full multivariable analysis). “Actually, smokers had an up to 0.6-standard deviation-lower PASAT score at year 11 when we looked at heavy smokers. ...This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.”

Dr. Cortese pointed out that early smoking, again, showed a dose-response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients.”

Epstein-Barr antibodies were not associated with cognitive function at year 11, according to the analysis (P-trend = .93).

“The findings of neuroaxonal injury at year 11 using serum neurofilament light-chain measures corroborated the main findings on cognitive function at year 11,” said Dr. Cortese.

For a 50-nmol higher vitamin D level within the first 5 years, neurofilament light chain levels at year 11 were 20% lower, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first 5 years had neurofilament light chain levels 20% higher than other participants: “So they did worse. They had more neuroaxonal loss,” said Dr. Cortese. No association was seen between neurofilament light chain levels at year 11 and early EBV status, she said.

Though just cognitive function data from BENEFIT-11 were reported by Dr. Cortese, she said that radiologic and other clinical data are also being studied and will be reported in the future.

Dr. Cortese reported that she had no conflicts of interest. Several coauthors reported financial relationships with multiple pharmaceutical companies. The study was supported by the National Institutes of Health and the National Multiple Sclerosis Society, with clinical support from Bayer HealthCare.

[email protected]

SOURCE: Cortese M et al. ECTRIMS 2018, Late breaking abstracts session.

*Correction, 10/25/18: An earlier version of this article mischaracterized the relationship between vitamin D scores during the first 2 years and PASAT scores at year 11. 

BERLIN – Spinal cord volume deficits in patients with multiple sclerosis may contribute to clinical disability that appears out of proportion to lesion load on brain imaging, according to new research.

Kari Oakes/MDedge News

In a pool of 362 patients with mild to moderate MS-related disability but identical white matter lesion load identified by MRI, those with higher disability had significantly lower spinal cord volumes when compared against those with disability scores in the mild range (P less than .001).

Though brain MRI is a key tool used to track disease severity and progression in MS, some patients have relatively high disability but a low burden of white matter intracerebral lesions on MRI. Little is known about spinal cord volume in MS patients with pronounced dissociation between intracerebral lesion load and disability, Michaela Andelova, MD, said in an interview during a poster session at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Dr. Andelova, of Charles University, Prague, said that she and her colleagues hypothesized that spinal cord volume would differ between patients who had varying levels of disability, despite identical white matter lesion load.

To test this, she and her colleagues looked at records of 1,245 patients with relapsing-remitting MS. They divided them into three groups by severity of clinical disability, and also by extent of cerebral T2 hyperintense lesion load. The investigators identified a group of patients (n = 53) whose total volume of T2-weighted hyperintense lesions was less than 3 mL, but whose Expanded Disability Status Scale (EDSS) scores were at least 3.5; this was the low lesion load/high disability (LLHD) group.

Dr. Andelova and her colleagues then identified another group of patients (n = 71) who had a volume of T2-weighted hyperintensities that was greater than 9 mL, but whose EDSS score was less than 1.5. This was the high lesion load/low disability (HLLD) group.

The remaining patients (n = 1,121), who did not have these paradoxical associations, were analyzed separately.

For all patients, mean upper cervical cord area (MUCCA) was also measured. Using images acquired by a 3 T MRI scanner, MUCCA was calculated as the mean sum of spinal cord area in 21 slices centered at the C3/4 intervertebral disk, using an in-house, semiautomated method.

“Despite higher disability, LLHD patients demonstrated significantly higher normalized total brain volume, higher normalized volumes of thalamus and callosum, and smaller lateral ventricles than [the] HLLD group,” wrote Dr. Andelova and her collaborators.

However, the LLHD patients had MUCCA values that were significantly lower than the other groups: The nonparadoxical group’s mean MUCCA was 84.02 mm², while the HLLD group had a mean MUCCA of 85.75 mm². This difference was not statistically significant. By contrast, the LLHD group’s mean MUCCA was significantly smaller, at 80.40 mm² (P = .023 versus nonparadoxical patients, and P = .007 versus HLLD patients).

Looking at the data another way, Dr. Andelova and her colleagues compared 362 evenly divided patients with moderate disability (EDSS 3.5-6.5) with matched patients who had mild MS-related disability (EDSS less than 3) and identical cerebral lesion loads. They found that MUCCA was significantly smaller in the moderate disability group (78.86 versus 84.44 mm²; P less than .001).

In addition to having identical lesions loads, the mild and moderate disability groups didn’t differ significantly in normalized total brain volume or regional brain volumes. The group with moderate disability did have slightly less white matter volume (P = .039), Dr. Andelova pointed out.

All differences found between groups retained statistical significance even after adjustment for such potential confounders as age, sex, and duration of disease, Dr. Andelova said.

“Reduced spinal cord volume may explain part of the clinical-radiological paradox in patients who have high disability despite low intracranial lesion load,” Dr. Andelova and her collaborators wrote. “In line with this finding, relatively preserved spinal cord volume may be associated with functional reserve and less physical disability in patients with low disability despite high cerebral lesion load.”

Further work looking more precisely at cerebral lesion distribution and quantitative MRI investigation of lesion distribution is in the works for Dr. Andelova and her collaborators. They are hoping to see some association between various distribution patterns and accelerated spinal atrophy.

The research was supported by the Czech government. Dr. Andelova and several of her collaborators reported financial relationships with pharmaceutical companies.

[email protected]

SOURCE: Andelova M et al. Mult Scler. 2018;24(Suppl 2):211, Abstract P477.

BERLIN – Spinal cord volume deficits in patients with multiple sclerosis may contribute to clinical disability that appears out of proportion to lesion load on brain imaging, according to new research.

Kari Oakes/MDedge News

In a pool of 362 patients with mild to moderate MS-related disability but identical white matter lesion load identified by MRI, those with higher disability had significantly lower spinal cord volumes when compared against those with disability scores in the mild range (P less than .001).

Though brain MRI is a key tool used to track disease severity and progression in MS, some patients have relatively high disability but a low burden of white matter intracerebral lesions on MRI. Little is known about spinal cord volume in MS patients with pronounced dissociation between intracerebral lesion load and disability, Michaela Andelova, MD, said in an interview during a poster session at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Dr. Andelova, of Charles University, Prague, said that she and her colleagues hypothesized that spinal cord volume would differ between patients who had varying levels of disability, despite identical white matter lesion load.

To test this, she and her colleagues looked at records of 1,245 patients with relapsing-remitting MS. They divided them into three groups by severity of clinical disability, and also by extent of cerebral T2 hyperintense lesion load. The investigators identified a group of patients (n = 53) whose total volume of T2-weighted hyperintense lesions was less than 3 mL, but whose Expanded Disability Status Scale (EDSS) scores were at least 3.5; this was the low lesion load/high disability (LLHD) group.

Dr. Andelova and her colleagues then identified another group of patients (n = 71) who had a volume of T2-weighted hyperintensities that was greater than 9 mL, but whose EDSS score was less than 1.5. This was the high lesion load/low disability (HLLD) group.

The remaining patients (n = 1,121), who did not have these paradoxical associations, were analyzed separately.

For all patients, mean upper cervical cord area (MUCCA) was also measured. Using images acquired by a 3 T MRI scanner, MUCCA was calculated as the mean sum of spinal cord area in 21 slices centered at the C3/4 intervertebral disk, using an in-house, semiautomated method.

“Despite higher disability, LLHD patients demonstrated significantly higher normalized total brain volume, higher normalized volumes of thalamus and callosum, and smaller lateral ventricles than [the] HLLD group,” wrote Dr. Andelova and her collaborators.

However, the LLHD patients had MUCCA values that were significantly lower than the other groups: The nonparadoxical group’s mean MUCCA was 84.02 mm², while the HLLD group had a mean MUCCA of 85.75 mm². This difference was not statistically significant. By contrast, the LLHD group’s mean MUCCA was significantly smaller, at 80.40 mm² (P = .023 versus nonparadoxical patients, and P = .007 versus HLLD patients).

Looking at the data another way, Dr. Andelova and her colleagues compared 362 evenly divided patients with moderate disability (EDSS 3.5-6.5) with matched patients who had mild MS-related disability (EDSS less than 3) and identical cerebral lesion loads. They found that MUCCA was significantly smaller in the moderate disability group (78.86 versus 84.44 mm²; P less than .001).

In addition to having identical lesions loads, the mild and moderate disability groups didn’t differ significantly in normalized total brain volume or regional brain volumes. The group with moderate disability did have slightly less white matter volume (P = .039), Dr. Andelova pointed out.

All differences found between groups retained statistical significance even after adjustment for such potential confounders as age, sex, and duration of disease, Dr. Andelova said.

“Reduced spinal cord volume may explain part of the clinical-radiological paradox in patients who have high disability despite low intracranial lesion load,” Dr. Andelova and her collaborators wrote. “In line with this finding, relatively preserved spinal cord volume may be associated with functional reserve and less physical disability in patients with low disability despite high cerebral lesion load.”

Further work looking more precisely at cerebral lesion distribution and quantitative MRI investigation of lesion distribution is in the works for Dr. Andelova and her collaborators. They are hoping to see some association between various distribution patterns and accelerated spinal atrophy.

The research was supported by the Czech government. Dr. Andelova and several of her collaborators reported financial relationships with pharmaceutical companies.

[email protected]

SOURCE: Andelova M et al. Mult Scler. 2018;24(Suppl 2):211, Abstract P477.

BERLIN – Spinal cord volume deficits in patients with multiple sclerosis may contribute to clinical disability that appears out of proportion to lesion load on brain imaging, according to new research.

Kari Oakes/MDedge News

In a pool of 362 patients with mild to moderate MS-related disability but identical white matter lesion load identified by MRI, those with higher disability had significantly lower spinal cord volumes when compared against those with disability scores in the mild range (P less than .001).

Though brain MRI is a key tool used to track disease severity and progression in MS, some patients have relatively high disability but a low burden of white matter intracerebral lesions on MRI. Little is known about spinal cord volume in MS patients with pronounced dissociation between intracerebral lesion load and disability, Michaela Andelova, MD, said in an interview during a poster session at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Dr. Andelova, of Charles University, Prague, said that she and her colleagues hypothesized that spinal cord volume would differ between patients who had varying levels of disability, despite identical white matter lesion load.

To test this, she and her colleagues looked at records of 1,245 patients with relapsing-remitting MS. They divided them into three groups by severity of clinical disability, and also by extent of cerebral T2 hyperintense lesion load. The investigators identified a group of patients (n = 53) whose total volume of T2-weighted hyperintense lesions was less than 3 mL, but whose Expanded Disability Status Scale (EDSS) scores were at least 3.5; this was the low lesion load/high disability (LLHD) group.

Dr. Andelova and her colleagues then identified another group of patients (n = 71) who had a volume of T2-weighted hyperintensities that was greater than 9 mL, but whose EDSS score was less than 1.5. This was the high lesion load/low disability (HLLD) group.

The remaining patients (n = 1,121), who did not have these paradoxical associations, were analyzed separately.

For all patients, mean upper cervical cord area (MUCCA) was also measured. Using images acquired by a 3 T MRI scanner, MUCCA was calculated as the mean sum of spinal cord area in 21 slices centered at the C3/4 intervertebral disk, using an in-house, semiautomated method.

“Despite higher disability, LLHD patients demonstrated significantly higher normalized total brain volume, higher normalized volumes of thalamus and callosum, and smaller lateral ventricles than [the] HLLD group,” wrote Dr. Andelova and her collaborators.

However, the LLHD patients had MUCCA values that were significantly lower than the other groups: The nonparadoxical group’s mean MUCCA was 84.02 mm², while the HLLD group had a mean MUCCA of 85.75 mm². This difference was not statistically significant. By contrast, the LLHD group’s mean MUCCA was significantly smaller, at 80.40 mm² (P = .023 versus nonparadoxical patients, and P = .007 versus HLLD patients).

Looking at the data another way, Dr. Andelova and her colleagues compared 362 evenly divided patients with moderate disability (EDSS 3.5-6.5) with matched patients who had mild MS-related disability (EDSS less than 3) and identical cerebral lesion loads. They found that MUCCA was significantly smaller in the moderate disability group (78.86 versus 84.44 mm²; P less than .001).

In addition to having identical lesions loads, the mild and moderate disability groups didn’t differ significantly in normalized total brain volume or regional brain volumes. The group with moderate disability did have slightly less white matter volume (P = .039), Dr. Andelova pointed out.

All differences found between groups retained statistical significance even after adjustment for such potential confounders as age, sex, and duration of disease, Dr. Andelova said.

“Reduced spinal cord volume may explain part of the clinical-radiological paradox in patients who have high disability despite low intracranial lesion load,” Dr. Andelova and her collaborators wrote. “In line with this finding, relatively preserved spinal cord volume may be associated with functional reserve and less physical disability in patients with low disability despite high cerebral lesion load.”

Further work looking more precisely at cerebral lesion distribution and quantitative MRI investigation of lesion distribution is in the works for Dr. Andelova and her collaborators. They are hoping to see some association between various distribution patterns and accelerated spinal atrophy.

The research was supported by the Czech government. Dr. Andelova and several of her collaborators reported financial relationships with pharmaceutical companies.

[email protected]

SOURCE: Andelova M et al. Mult Scler. 2018;24(Suppl 2):211, Abstract P477.

BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Michele G. Sullivan/MDedge News

But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.

Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.

Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.

That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.

A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).

Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.

Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.

Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).

Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.

By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.

Dr. Rossor and his coauthors had no financial disclosures.

[email protected]

SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.

BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Michele G. Sullivan/MDedge News

But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.

Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.

Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.

That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.

A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).

Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.

Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.

Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).

Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.

By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.

Dr. Rossor and his coauthors had no financial disclosures.

[email protected]

SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.

BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Michele G. Sullivan/MDedge News

But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.

Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.

Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.

That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.

A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).

Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.

Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.

Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).

Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.

By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.

Dr. Rossor and his coauthors had no financial disclosures.

[email protected]

SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.

BERLIN – The optimal time to start disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) is within 6 months of disease onset, according to real-world data from the Big Multiple Sclerosis Data Network.

Sara Freeman/MDedge News

Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).

Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).

“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.

For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.

“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.

The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.

The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.

The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.

SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.

BERLIN – The optimal time to start disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) is within 6 months of disease onset, according to real-world data from the Big Multiple Sclerosis Data Network.

Sara Freeman/MDedge News

Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).

Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).

“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.

For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.

“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.

The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.

The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.

The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.

SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.

BERLIN – The optimal time to start disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) is within 6 months of disease onset, according to real-world data from the Big Multiple Sclerosis Data Network.

Sara Freeman/MDedge News

Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).

Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).

“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.

For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.

“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.

The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.

The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.

The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.

SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.

BERLIN – Depression and bipolar disorder are major risk factors for worsening disability in people with multiple sclerosis, according to the results of a large Swedish registry-based study.

Sara Freeman/MDedge News

The presence of depression increased the risk of having a sustained Expanded Disability Status Scale (EDSS) score of 3.0 by 54% and 4.0 by 87%, and it doubled the risk of an EDSS of 6.0.

Selective serotonin reuptake inhibitor treatment also upped the risk of greater disability, with patients exposed to SSRIs having a 40% increased risk of a sustained EDSS of 3.0, a 97% chance of having a sustained EDSS of 4.0, and 2.2-fold increased risk of a sustained EDSS of 6.0.

“We know that mood disorders are highly prevalent in people with multiple sclerosis,” Stefanie Binzer, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. She gave her presentation at the meeting on Oct. 10, which was World Mental Health Day.

The presence of mood disorders is associated with reduced quality of life, said Dr. Binzer of the department of clinical neuroscience at the Karolinska Institute in Stockholm. Furthermore, depression is the major risk factor for suicidality in patients with MS. However, before this study the effect of having a comorbid mood disorder on MS patients’ disability levels had not been established.

The investigators analyzed data from 5,875 patients in the Swedish MS registry between 2001 and 2014. By matching these patients to records in the Swedish National Patient Registry and the Swedish National Prescribed Drug Registry, they found that 8.5% (n = 502) had an International Classification of Diseases, 10th revision (ICD-10), code for depression. Of these, 261 had received a diagnosis of depression before their diagnosis of MS.

Of 3,817 patients with MS onset between 2005 and 2014, 27.4% (n = 1,048) had collected at least one prescription for an SSRI.

“What we found was that MS patients with either an ICD code for depression or having been exposed to SSRIs had a significantly increased risk of reaching EDSS 3.0,” Dr. Binzer reported. The age at which patients reached these milestones were younger in both groups when compared with MS patients without depression, she observed.

“The difference between the groups [MS with and MS without depression] seemed to increased with EDSS,” Dr. Binzer said.

Although not statistically significant, there was a trend for patients with depression to be more likely to convert to secondary progressive MS, with a hazard ratio of 1.38 (95% confidence interval, 0.91-2.1).

“For a sensitivity analysis, we found that those who had depression prior to their first MS symptom, the median age when they reached EDSS 3.0 and 4.0 was reduced by 3 and 7 years, respectively,” Dr. Binzer said, adding that, unfortunately, there wasn’t enough power to look at the other endpoints.

In regard to bipolar disorder, 1.5% (n = 200) of 13,125 MS patients diagnosed between 1973 and 2014 were identified with this mood disorder. Its presence significantly increased the risk of MS patients reaching an EDSS score of 4.0 by 58% (95% CI, 1.1-2.28), but not EDSS 3.0 (HR = 1.34; 95% CI, 0.94-1.92) or 6.0 (HR = 1.16; 95% CI, 0.79-1.69). The latter could be due to smaller sample size, Dr. Binzer suggested.

The investigators’ analysis of the results stratified by sex, conducted because men tend to fare worse than women with MS and progress faster, showed that for both depression and bipolar disorder, men were at significantly higher risk of reaching sustained disability milestones. Indeed, compared with women, men with depression had a 61% increased risk and those with bipolar disorder a 31% increased risk of reaching an EDSS score of 6.0. They also had 51% and 32% increased risks of conversion to secondary progressive MS.

“We don’t know the mechanisms that underlie these associations,” Dr. Binzer noted. “Irrespective of the underlying mechanisms, [the study] clearly shows that it’s imperative that we recognize, early, mood disorders in MS patients, and manage them effectively in order to provide better care and hopefully reduce MS disability worsening.”

The research was funded by the Swedish Research Council and the Swedish Brain Foundation. Dr. Binzer has received speaker fees and travel grants from Biogen.

SOURCE: Binzer S et al. Mult Scler. 2018;24(Suppl 2):41. Abstract 99.

BERLIN – Depression and bipolar disorder are major risk factors for worsening disability in people with multiple sclerosis, according to the results of a large Swedish registry-based study.

Sara Freeman/MDedge News

The presence of depression increased the risk of having a sustained Expanded Disability Status Scale (EDSS) score of 3.0 by 54% and 4.0 by 87%, and it doubled the risk of an EDSS of 6.0.

Selective serotonin reuptake inhibitor treatment also upped the risk of greater disability, with patients exposed to SSRIs having a 40% increased risk of a sustained EDSS of 3.0, a 97% chance of having a sustained EDSS of 4.0, and 2.2-fold increased risk of a sustained EDSS of 6.0.

“We know that mood disorders are highly prevalent in people with multiple sclerosis,” Stefanie Binzer, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. She gave her presentation at the meeting on Oct. 10, which was World Mental Health Day.

The presence of mood disorders is associated with reduced quality of life, said Dr. Binzer of the department of clinical neuroscience at the Karolinska Institute in Stockholm. Furthermore, depression is the major risk factor for suicidality in patients with MS. However, before this study the effect of having a comorbid mood disorder on MS patients’ disability levels had not been established.

The investigators analyzed data from 5,875 patients in the Swedish MS registry between 2001 and 2014. By matching these patients to records in the Swedish National Patient Registry and the Swedish National Prescribed Drug Registry, they found that 8.5% (n = 502) had an International Classification of Diseases, 10th revision (ICD-10), code for depression. Of these, 261 had received a diagnosis of depression before their diagnosis of MS.

Of 3,817 patients with MS onset between 2005 and 2014, 27.4% (n = 1,048) had collected at least one prescription for an SSRI.

“What we found was that MS patients with either an ICD code for depression or having been exposed to SSRIs had a significantly increased risk of reaching EDSS 3.0,” Dr. Binzer reported. The age at which patients reached these milestones were younger in both groups when compared with MS patients without depression, she observed.

“The difference between the groups [MS with and MS without depression] seemed to increased with EDSS,” Dr. Binzer said.

Although not statistically significant, there was a trend for patients with depression to be more likely to convert to secondary progressive MS, with a hazard ratio of 1.38 (95% confidence interval, 0.91-2.1).

“For a sensitivity analysis, we found that those who had depression prior to their first MS symptom, the median age when they reached EDSS 3.0 and 4.0 was reduced by 3 and 7 years, respectively,” Dr. Binzer said, adding that, unfortunately, there wasn’t enough power to look at the other endpoints.

In regard to bipolar disorder, 1.5% (n = 200) of 13,125 MS patients diagnosed between 1973 and 2014 were identified with this mood disorder. Its presence significantly increased the risk of MS patients reaching an EDSS score of 4.0 by 58% (95% CI, 1.1-2.28), but not EDSS 3.0 (HR = 1.34; 95% CI, 0.94-1.92) or 6.0 (HR = 1.16; 95% CI, 0.79-1.69). The latter could be due to smaller sample size, Dr. Binzer suggested.

The investigators’ analysis of the results stratified by sex, conducted because men tend to fare worse than women with MS and progress faster, showed that for both depression and bipolar disorder, men were at significantly higher risk of reaching sustained disability milestones. Indeed, compared with women, men with depression had a 61% increased risk and those with bipolar disorder a 31% increased risk of reaching an EDSS score of 6.0. They also had 51% and 32% increased risks of conversion to secondary progressive MS.

“We don’t know the mechanisms that underlie these associations,” Dr. Binzer noted. “Irrespective of the underlying mechanisms, [the study] clearly shows that it’s imperative that we recognize, early, mood disorders in MS patients, and manage them effectively in order to provide better care and hopefully reduce MS disability worsening.”

The research was funded by the Swedish Research Council and the Swedish Brain Foundation. Dr. Binzer has received speaker fees and travel grants from Biogen.

SOURCE: Binzer S et al. Mult Scler. 2018;24(Suppl 2):41. Abstract 99.

BERLIN – Depression and bipolar disorder are major risk factors for worsening disability in people with multiple sclerosis, according to the results of a large Swedish registry-based study.

Sara Freeman/MDedge News

The presence of depression increased the risk of having a sustained Expanded Disability Status Scale (EDSS) score of 3.0 by 54% and 4.0 by 87%, and it doubled the risk of an EDSS of 6.0.

Selective serotonin reuptake inhibitor treatment also upped the risk of greater disability, with patients exposed to SSRIs having a 40% increased risk of a sustained EDSS of 3.0, a 97% chance of having a sustained EDSS of 4.0, and 2.2-fold increased risk of a sustained EDSS of 6.0.

“We know that mood disorders are highly prevalent in people with multiple sclerosis,” Stefanie Binzer, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. She gave her presentation at the meeting on Oct. 10, which was World Mental Health Day.

The presence of mood disorders is associated with reduced quality of life, said Dr. Binzer of the department of clinical neuroscience at the Karolinska Institute in Stockholm. Furthermore, depression is the major risk factor for suicidality in patients with MS. However, before this study the effect of having a comorbid mood disorder on MS patients’ disability levels had not been established.

The investigators analyzed data from 5,875 patients in the Swedish MS registry between 2001 and 2014. By matching these patients to records in the Swedish National Patient Registry and the Swedish National Prescribed Drug Registry, they found that 8.5% (n = 502) had an International Classification of Diseases, 10th revision (ICD-10), code for depression. Of these, 261 had received a diagnosis of depression before their diagnosis of MS.

Of 3,817 patients with MS onset between 2005 and 2014, 27.4% (n = 1,048) had collected at least one prescription for an SSRI.

“What we found was that MS patients with either an ICD code for depression or having been exposed to SSRIs had a significantly increased risk of reaching EDSS 3.0,” Dr. Binzer reported. The age at which patients reached these milestones were younger in both groups when compared with MS patients without depression, she observed.

“The difference between the groups [MS with and MS without depression] seemed to increased with EDSS,” Dr. Binzer said.

Although not statistically significant, there was a trend for patients with depression to be more likely to convert to secondary progressive MS, with a hazard ratio of 1.38 (95% confidence interval, 0.91-2.1).

“For a sensitivity analysis, we found that those who had depression prior to their first MS symptom, the median age when they reached EDSS 3.0 and 4.0 was reduced by 3 and 7 years, respectively,” Dr. Binzer said, adding that, unfortunately, there wasn’t enough power to look at the other endpoints.

In regard to bipolar disorder, 1.5% (n = 200) of 13,125 MS patients diagnosed between 1973 and 2014 were identified with this mood disorder. Its presence significantly increased the risk of MS patients reaching an EDSS score of 4.0 by 58% (95% CI, 1.1-2.28), but not EDSS 3.0 (HR = 1.34; 95% CI, 0.94-1.92) or 6.0 (HR = 1.16; 95% CI, 0.79-1.69). The latter could be due to smaller sample size, Dr. Binzer suggested.

The investigators’ analysis of the results stratified by sex, conducted because men tend to fare worse than women with MS and progress faster, showed that for both depression and bipolar disorder, men were at significantly higher risk of reaching sustained disability milestones. Indeed, compared with women, men with depression had a 61% increased risk and those with bipolar disorder a 31% increased risk of reaching an EDSS score of 6.0. They also had 51% and 32% increased risks of conversion to secondary progressive MS.

“We don’t know the mechanisms that underlie these associations,” Dr. Binzer noted. “Irrespective of the underlying mechanisms, [the study] clearly shows that it’s imperative that we recognize, early, mood disorders in MS patients, and manage them effectively in order to provide better care and hopefully reduce MS disability worsening.”

The research was funded by the Swedish Research Council and the Swedish Brain Foundation. Dr. Binzer has received speaker fees and travel grants from Biogen.

SOURCE: Binzer S et al. Mult Scler. 2018;24(Suppl 2):41. Abstract 99.

BERLIN – The 2017 McDonald criteria boosted the rate of definitive multiple sclerosis (MS) diagnosis in children by 40%, compared with the 2010 criteria.

Michele G. Sullivan/MDedge News

The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”

The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).

Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.

The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.

All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.

At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).

Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.

The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.

That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.

“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.

She disclosed financial relationships with several pharmaceutical companies.

[email protected]

SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64

BERLIN – The 2017 McDonald criteria boosted the rate of definitive multiple sclerosis (MS) diagnosis in children by 40%, compared with the 2010 criteria.

Michele G. Sullivan/MDedge News

The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”

The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).

Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.

The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.

All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.

At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).

Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.

The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.

That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.

“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.

She disclosed financial relationships with several pharmaceutical companies.

[email protected]

SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64

BERLIN – The 2017 McDonald criteria boosted the rate of definitive multiple sclerosis (MS) diagnosis in children by 40%, compared with the 2010 criteria.

Michele G. Sullivan/MDedge News

The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”

The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).

Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.

The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.

All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.

At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).

Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.

The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.

That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.

“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.

She disclosed financial relationships with several pharmaceutical companies.

[email protected]

SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64

BERLIN – The risk of cancer – and breast cancer in particular – was not elevated above background levels in a large cohort of multiple sclerosis patients taking disease-modifying therapies.

Those findings from the large Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.

After statistical adjustment and use of rituximab (Rituxan) as the standard, the hazard ratio (HR) for any malignancy with fingolimod (Gilenya) was 1.74 (95% confidence interval, 0.92-3.28). For natalizumab (Tysabri), the malignancy HR was 1.06 (95% CI, 0.53-2.10), said Peter Alping, a PhD student in the department of clinical neuroscience at the Karolinska Institute, Stockholm.

Only limited data exist for real-world multiple sclerosis (MS) cohorts who have been exposed to novel disease-modifying therapies, said Mr. Alping, presenting the findings at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens differ, as do patient characteristics, he noted. However, surveillance for risk of malignancy is important in these therapies, he said, “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers.”

The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping, with raw data showing four breast cancers in the ocrelizumab population. However, this would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers seen in the placebo group (N Engl J Med. 2017;376:209-20).

“To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.

To answer the question, he and his colleagues from the Karolinska Institute sought to compare the risk of cancer in MS patients who were treated with rituximab, fingolimod, and natalizumab.

To do this, they conducted a nationwide cohort study using the Swedish MS registry, looking at treatment episodes between 2011 and 2016. In Sweden, the MS registry is also linked to the overall patient registry, as well as registries for cancer and prescription drug use. In addition, patient data are linked to national census data.

Mr. Alping and his colleagues looked at data for the first instance of use for an MS patient of rituximab, natalizumab, and/or fingolimod between the years 2011 and 2016. Then, they matched patient records from the general population by age, sex, and geographic location, enrolling the matched controls at the same time point as the MS match entered the study.

Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.

The statistical analysis, Mr. Alping said, used an ever-treated approach and didn’t attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, for any previous history of cancer, and for MS disease characteristics.

At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. A little less than one-third of the patients (26.3%-31.6%) were male, and the mean age was 35-43 years. Most patients (66%-86%) had undergone one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20-2.88. Few patients (0.9%-1.7%) had any history of previous cancer.

Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.

Looking just at breast cancer, rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.

However, using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted hazard ratio for any malignancy under the various treatment conditions. Using this analysis, the HR for any cancer with fingolimod was 1.74 (95% CI, 0.92-3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53-2.10).

Among just women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06-12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.

Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.

“For malignant cancer of any type, we found no increased risk for rituximab, compared to fingolimod and natalizumab,” Mr. Alping said, pointing to the wide confidence intervals in all the adjusted data. The incidence of breast cancer in women who have taken rituximab, he said, is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab.

“The overall cancer risk and risk of breast cancer might not be major concerns short term when treating MS patients with rituximab relative to other disease-modifying therapies,” he said.

The study was partially funded by the Patient-Centered Outcomes Research Institute. Mr. Alping reported no conflicts of interest. One study author reported relationships with several pharmaceutical companies.

[email protected]

SOURCE: Alping P et al. Mult Scler. 2018;24(Suppl 2):36. Abstract 89.

BERLIN – The risk of cancer – and breast cancer in particular – was not elevated above background levels in a large cohort of multiple sclerosis patients taking disease-modifying therapies.

Those findings from the large Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.

After statistical adjustment and use of rituximab (Rituxan) as the standard, the hazard ratio (HR) for any malignancy with fingolimod (Gilenya) was 1.74 (95% confidence interval, 0.92-3.28). For natalizumab (Tysabri), the malignancy HR was 1.06 (95% CI, 0.53-2.10), said Peter Alping, a PhD student in the department of clinical neuroscience at the Karolinska Institute, Stockholm.

Only limited data exist for real-world multiple sclerosis (MS) cohorts who have been exposed to novel disease-modifying therapies, said Mr. Alping, presenting the findings at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens differ, as do patient characteristics, he noted. However, surveillance for risk of malignancy is important in these therapies, he said, “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers.”

The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping, with raw data showing four breast cancers in the ocrelizumab population. However, this would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers seen in the placebo group (N Engl J Med. 2017;376:209-20).

“To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.

To answer the question, he and his colleagues from the Karolinska Institute sought to compare the risk of cancer in MS patients who were treated with rituximab, fingolimod, and natalizumab.

To do this, they conducted a nationwide cohort study using the Swedish MS registry, looking at treatment episodes between 2011 and 2016. In Sweden, the MS registry is also linked to the overall patient registry, as well as registries for cancer and prescription drug use. In addition, patient data are linked to national census data.

Mr. Alping and his colleagues looked at data for the first instance of use for an MS patient of rituximab, natalizumab, and/or fingolimod between the years 2011 and 2016. Then, they matched patient records from the general population by age, sex, and geographic location, enrolling the matched controls at the same time point as the MS match entered the study.

Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.

The statistical analysis, Mr. Alping said, used an ever-treated approach and didn’t attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, for any previous history of cancer, and for MS disease characteristics.

At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. A little less than one-third of the patients (26.3%-31.6%) were male, and the mean age was 35-43 years. Most patients (66%-86%) had undergone one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20-2.88. Few patients (0.9%-1.7%) had any history of previous cancer.

Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.

Looking just at breast cancer, rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.

However, using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted hazard ratio for any malignancy under the various treatment conditions. Using this analysis, the HR for any cancer with fingolimod was 1.74 (95% CI, 0.92-3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53-2.10).

Among just women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06-12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.

Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.

“For malignant cancer of any type, we found no increased risk for rituximab, compared to fingolimod and natalizumab,” Mr. Alping said, pointing to the wide confidence intervals in all the adjusted data. The incidence of breast cancer in women who have taken rituximab, he said, is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab.

“The overall cancer risk and risk of breast cancer might not be major concerns short term when treating MS patients with rituximab relative to other disease-modifying therapies,” he said.

The study was partially funded by the Patient-Centered Outcomes Research Institute. Mr. Alping reported no conflicts of interest. One study author reported relationships with several pharmaceutical companies.

[email protected]

SOURCE: Alping P et al. Mult Scler. 2018;24(Suppl 2):36. Abstract 89.

BERLIN – The risk of cancer – and breast cancer in particular – was not elevated above background levels in a large cohort of multiple sclerosis patients taking disease-modifying therapies.

Those findings from the large Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.

After statistical adjustment and use of rituximab (Rituxan) as the standard, the hazard ratio (HR) for any malignancy with fingolimod (Gilenya) was 1.74 (95% confidence interval, 0.92-3.28). For natalizumab (Tysabri), the malignancy HR was 1.06 (95% CI, 0.53-2.10), said Peter Alping, a PhD student in the department of clinical neuroscience at the Karolinska Institute, Stockholm.

Only limited data exist for real-world multiple sclerosis (MS) cohorts who have been exposed to novel disease-modifying therapies, said Mr. Alping, presenting the findings at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens differ, as do patient characteristics, he noted. However, surveillance for risk of malignancy is important in these therapies, he said, “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers.”

The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping, with raw data showing four breast cancers in the ocrelizumab population. However, this would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers seen in the placebo group (N Engl J Med. 2017;376:209-20).

“To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.

To answer the question, he and his colleagues from the Karolinska Institute sought to compare the risk of cancer in MS patients who were treated with rituximab, fingolimod, and natalizumab.

To do this, they conducted a nationwide cohort study using the Swedish MS registry, looking at treatment episodes between 2011 and 2016. In Sweden, the MS registry is also linked to the overall patient registry, as well as registries for cancer and prescription drug use. In addition, patient data are linked to national census data.

Mr. Alping and his colleagues looked at data for the first instance of use for an MS patient of rituximab, natalizumab, and/or fingolimod between the years 2011 and 2016. Then, they matched patient records from the general population by age, sex, and geographic location, enrolling the matched controls at the same time point as the MS match entered the study.

Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.

The statistical analysis, Mr. Alping said, used an ever-treated approach and didn’t attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, for any previous history of cancer, and for MS disease characteristics.

At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. A little less than one-third of the patients (26.3%-31.6%) were male, and the mean age was 35-43 years. Most patients (66%-86%) had undergone one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20-2.88. Few patients (0.9%-1.7%) had any history of previous cancer.

Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.

Looking just at breast cancer, rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.

However, using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted hazard ratio for any malignancy under the various treatment conditions. Using this analysis, the HR for any cancer with fingolimod was 1.74 (95% CI, 0.92-3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53-2.10).

Among just women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06-12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.

Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.

“For malignant cancer of any type, we found no increased risk for rituximab, compared to fingolimod and natalizumab,” Mr. Alping said, pointing to the wide confidence intervals in all the adjusted data. The incidence of breast cancer in women who have taken rituximab, he said, is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab.

“The overall cancer risk and risk of breast cancer might not be major concerns short term when treating MS patients with rituximab relative to other disease-modifying therapies,” he said.

The study was partially funded by the Patient-Centered Outcomes Research Institute. Mr. Alping reported no conflicts of interest. One study author reported relationships with several pharmaceutical companies.

[email protected]

SOURCE: Alping P et al. Mult Scler. 2018;24(Suppl 2):36. Abstract 89.

Short-term prescription NSAIDs appeared safe in high-risk patients with musculoskeletal disease and chronic kidney disease (CKD), hypertension, or heart failure, in a retrospective, observational study.

The findings of the study challenge the Choosing Wisely campaign of the American Society of Nephrology, which recommends against NSAIDs for high-risk patients, according to lead author Zachary Bouck, MPH, of the department of medicine at Sunnybrook Health Sciences Centre in Toronto, and his coauthors.

“While these recommendations offer basic analgesics and nonpharmacological treatments as preferable alternatives, it is both possible and disconcerting that some physicians might instead prescribe opioids, which typically pose elevated risk of adverse events and dependence vs. NSAIDs,” the investigators wrote. The report is in JAMA Internal Medicine.

They sought to estimate the frequency and characteristics of NSAID prescriptions while also looking for associations with acute renal and cardiovascular complications. The retrospective, observational study involved 814,049 adults with musculoskeletal disease and 7,365 primary care physicians in Ontario, Canada. All patients were aged 65 years and older, and had been diagnosed with hypertension, chronic kidney disease, or heart failure in the past year. Instances in which a patient was prescribed an NSAID within 7 days of presentation were included.

To assess for associations between prescription NSAIDs and negative outcomes, the investigators searched for renal or cardiovascular complications within 37 days of presentation. Over-the-counter NSAID usage was not evaluated.

There were 224,825 visits. An NSAID was prescribed after 9.3% of these visits.

Renal and cardiovascular outcomes were similar between high-risk patients who received a prescription NSAID and those who did not (absolute risk reduction, .0003; P = .74).

“The similarity in risk between users and nonusers, each group primarily consisting of patients with hypertension, suggests that the short-term association of NSAIDs in high-risk patients with musculoskeletal pain may not be as dangerous as initially thought,” the authors concluded.

The investigators found that prescribing rates varied widely, ranging from 6.7% to 14.4% of different health regions, and from 0.9% to 60.3% among 688 primary care practices, with “substantial variation in use” among primary care physicians.

The authors acknowledged limitations, including the use of administrative data, but noted that their study, showing substantial variations in NSAID prescribing, “along with the identification of patient and physician characteristics associated with NSAID use, presents an opportunity for quality improvement, with some potential targets for any resulting interventions,” they wrote.

The Institute for Clinical Evaluative Sciences funded the study. The authors reported compensation from the Canadian Institute of Health Research, the department of family and community medicine at the University of Toronto, the Heart and Stroke Foundation of Canada, and Women’s College Hospital.

SOURCE: Bouck et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4273.

Short-term prescription NSAIDs appeared safe in high-risk patients with musculoskeletal disease and chronic kidney disease (CKD), hypertension, or heart failure, in a retrospective, observational study.

The findings of the study challenge the Choosing Wisely campaign of the American Society of Nephrology, which recommends against NSAIDs for high-risk patients, according to lead author Zachary Bouck, MPH, of the department of medicine at Sunnybrook Health Sciences Centre in Toronto, and his coauthors.

“While these recommendations offer basic analgesics and nonpharmacological treatments as preferable alternatives, it is both possible and disconcerting that some physicians might instead prescribe opioids, which typically pose elevated risk of adverse events and dependence vs. NSAIDs,” the investigators wrote. The report is in JAMA Internal Medicine.

They sought to estimate the frequency and characteristics of NSAID prescriptions while also looking for associations with acute renal and cardiovascular complications. The retrospective, observational study involved 814,049 adults with musculoskeletal disease and 7,365 primary care physicians in Ontario, Canada. All patients were aged 65 years and older, and had been diagnosed with hypertension, chronic kidney disease, or heart failure in the past year. Instances in which a patient was prescribed an NSAID within 7 days of presentation were included.

To assess for associations between prescription NSAIDs and negative outcomes, the investigators searched for renal or cardiovascular complications within 37 days of presentation. Over-the-counter NSAID usage was not evaluated.

There were 224,825 visits. An NSAID was prescribed after 9.3% of these visits.

Renal and cardiovascular outcomes were similar between high-risk patients who received a prescription NSAID and those who did not (absolute risk reduction, .0003; P = .74).

“The similarity in risk between users and nonusers, each group primarily consisting of patients with hypertension, suggests that the short-term association of NSAIDs in high-risk patients with musculoskeletal pain may not be as dangerous as initially thought,” the authors concluded.

The investigators found that prescribing rates varied widely, ranging from 6.7% to 14.4% of different health regions, and from 0.9% to 60.3% among 688 primary care practices, with “substantial variation in use” among primary care physicians.

The authors acknowledged limitations, including the use of administrative data, but noted that their study, showing substantial variations in NSAID prescribing, “along with the identification of patient and physician characteristics associated with NSAID use, presents an opportunity for quality improvement, with some potential targets for any resulting interventions,” they wrote.

The Institute for Clinical Evaluative Sciences funded the study. The authors reported compensation from the Canadian Institute of Health Research, the department of family and community medicine at the University of Toronto, the Heart and Stroke Foundation of Canada, and Women’s College Hospital.

SOURCE: Bouck et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4273.

Short-term prescription NSAIDs appeared safe in high-risk patients with musculoskeletal disease and chronic kidney disease (CKD), hypertension, or heart failure, in a retrospective, observational study.

The findings of the study challenge the Choosing Wisely campaign of the American Society of Nephrology, which recommends against NSAIDs for high-risk patients, according to lead author Zachary Bouck, MPH, of the department of medicine at Sunnybrook Health Sciences Centre in Toronto, and his coauthors.

“While these recommendations offer basic analgesics and nonpharmacological treatments as preferable alternatives, it is both possible and disconcerting that some physicians might instead prescribe opioids, which typically pose elevated risk of adverse events and dependence vs. NSAIDs,” the investigators wrote. The report is in JAMA Internal Medicine.

They sought to estimate the frequency and characteristics of NSAID prescriptions while also looking for associations with acute renal and cardiovascular complications. The retrospective, observational study involved 814,049 adults with musculoskeletal disease and 7,365 primary care physicians in Ontario, Canada. All patients were aged 65 years and older, and had been diagnosed with hypertension, chronic kidney disease, or heart failure in the past year. Instances in which a patient was prescribed an NSAID within 7 days of presentation were included.

To assess for associations between prescription NSAIDs and negative outcomes, the investigators searched for renal or cardiovascular complications within 37 days of presentation. Over-the-counter NSAID usage was not evaluated.

There were 224,825 visits. An NSAID was prescribed after 9.3% of these visits.

Renal and cardiovascular outcomes were similar between high-risk patients who received a prescription NSAID and those who did not (absolute risk reduction, .0003; P = .74).

“The similarity in risk between users and nonusers, each group primarily consisting of patients with hypertension, suggests that the short-term association of NSAIDs in high-risk patients with musculoskeletal pain may not be as dangerous as initially thought,” the authors concluded.

The investigators found that prescribing rates varied widely, ranging from 6.7% to 14.4% of different health regions, and from 0.9% to 60.3% among 688 primary care practices, with “substantial variation in use” among primary care physicians.

The authors acknowledged limitations, including the use of administrative data, but noted that their study, showing substantial variations in NSAID prescribing, “along with the identification of patient and physician characteristics associated with NSAID use, presents an opportunity for quality improvement, with some potential targets for any resulting interventions,” they wrote.

The Institute for Clinical Evaluative Sciences funded the study. The authors reported compensation from the Canadian Institute of Health Research, the department of family and community medicine at the University of Toronto, the Heart and Stroke Foundation of Canada, and Women’s College Hospital.

SOURCE: Bouck et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4273.

Background: Previous studies have shown that perioperative gabapentin has no effect on remote pain cessation but have not linked it with effects on remote opioid cessation. Also, most trials were limited to immediate postoperative use during hospital admission; limited data were available with extensive postoperative longitudinal follow-up.

One caveat to the outcomes is that use of a gabapentin regimen may have increased after discharge date, which could have biased the outcome.

Bottom line: Perioperative gabapentin may promote opioid cessation and prevent the development of chronic opioid use after surgery.

Citation: Hah J et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort. JAMA Surg. 2018;153(4):303-11.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Previous studies have shown that perioperative gabapentin has no effect on remote pain cessation but have not linked it with effects on remote opioid cessation. Also, most trials were limited to immediate postoperative use during hospital admission; limited data were available with extensive postoperative longitudinal follow-up.

One caveat to the outcomes is that use of a gabapentin regimen may have increased after discharge date, which could have biased the outcome.

Bottom line: Perioperative gabapentin may promote opioid cessation and prevent the development of chronic opioid use after surgery.

Citation: Hah J et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort. JAMA Surg. 2018;153(4):303-11.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Previous studies have shown that perioperative gabapentin has no effect on remote pain cessation but have not linked it with effects on remote opioid cessation. Also, most trials were limited to immediate postoperative use during hospital admission; limited data were available with extensive postoperative longitudinal follow-up.

One caveat to the outcomes is that use of a gabapentin regimen may have increased after discharge date, which could have biased the outcome.

Bottom line: Perioperative gabapentin may promote opioid cessation and prevent the development of chronic opioid use after surgery.

Citation: Hah J et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort. JAMA Surg. 2018;153(4):303-11.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

SAN FRANCISCO – Children exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

Dr. Crowell explained the problem, and what her work means for practice in an interview at the meeting.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

SAN FRANCISCO – Children exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

Dr. Crowell explained the problem, and what her work means for practice in an interview at the meeting.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

SAN FRANCISCO – Children exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

Dr. Crowell explained the problem, and what her work means for practice in an interview at the meeting.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.