Multiple Sclerosis

SEATTLE – In patients with multiple sclerosis (MS), black holes are associated with worse cognitive function, including processing speed and visuospatial memory, according to an investigation presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Black holes are not associated with physical function, however. Evaluating black holes as part of routine clinical practice could be a quick method for screening people with MS for referral to a comprehensive cognitive assessment, said the authors.

Black holes (also known as T1-hypointense lesions) can be used as a marker of axonal loss and neuronal tissue destruction in patients with MS. Loss of axons and destruction of neuronal tissue contribute to cognitive and physical disability, but the literature contains few data about whether black holes correlate with cognitive and physical outcomes in MS.

Serkan Özakbas, MD, professor of neurology at Dokuz Eylül University in Izmir, Turkey, and colleagues examined 226 patients with MS to investigate this potential correlation. The population’s median Expanded Disability Status Scale score was 1.5. The researchers categorized participants into two groups according whether they had at least one black hole or not. They assessed patients’ cognitive function by administering the Brief International Cognitive Assessment for MS (BICAMS), which comprises the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test II (CVLT-II), and the Brief Visuospatial Memory Test–Revised (BVMTR). They evaluated participants’ physical function using the Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), 6-Minute Walk Test (6MWT), Timed Up and Go (TUG), and 12-Item MS Walking Scale (MSWS-12).

In all, 116 (43.6%) participants had at least one black hole, and 150 (56.4%) had no black hole. Dr. Özakbas and colleagues found no significant difference between patients with and without black holes on the T25FW, 9HPT, 6MWT, TUG, MSWS-12, and CVLT-II. Patients without a black hole, however, had significantly higher SDMT (49.0 vs 42.9) and BVMTR (26.3 vs 23.3) scores, compared with those with at least one black hole.

“This study suggests that presence of black holes is related to cognitive function, but not to physical function,” the researchers concluded.

The investigators had no disclosures and conducted their study without financial support.
 

[email protected]

SOURCE: Özakbas S et al. CMSC 2019, Abstract IMG02.

SEATTLE – In patients with multiple sclerosis (MS), black holes are associated with worse cognitive function, including processing speed and visuospatial memory, according to an investigation presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Black holes are not associated with physical function, however. Evaluating black holes as part of routine clinical practice could be a quick method for screening people with MS for referral to a comprehensive cognitive assessment, said the authors.

Black holes (also known as T1-hypointense lesions) can be used as a marker of axonal loss and neuronal tissue destruction in patients with MS. Loss of axons and destruction of neuronal tissue contribute to cognitive and physical disability, but the literature contains few data about whether black holes correlate with cognitive and physical outcomes in MS.

Serkan Özakbas, MD, professor of neurology at Dokuz Eylül University in Izmir, Turkey, and colleagues examined 226 patients with MS to investigate this potential correlation. The population’s median Expanded Disability Status Scale score was 1.5. The researchers categorized participants into two groups according whether they had at least one black hole or not. They assessed patients’ cognitive function by administering the Brief International Cognitive Assessment for MS (BICAMS), which comprises the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test II (CVLT-II), and the Brief Visuospatial Memory Test–Revised (BVMTR). They evaluated participants’ physical function using the Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), 6-Minute Walk Test (6MWT), Timed Up and Go (TUG), and 12-Item MS Walking Scale (MSWS-12).

In all, 116 (43.6%) participants had at least one black hole, and 150 (56.4%) had no black hole. Dr. Özakbas and colleagues found no significant difference between patients with and without black holes on the T25FW, 9HPT, 6MWT, TUG, MSWS-12, and CVLT-II. Patients without a black hole, however, had significantly higher SDMT (49.0 vs 42.9) and BVMTR (26.3 vs 23.3) scores, compared with those with at least one black hole.

“This study suggests that presence of black holes is related to cognitive function, but not to physical function,” the researchers concluded.

The investigators had no disclosures and conducted their study without financial support.
 

[email protected]

SOURCE: Özakbas S et al. CMSC 2019, Abstract IMG02.

SEATTLE – In patients with multiple sclerosis (MS), black holes are associated with worse cognitive function, including processing speed and visuospatial memory, according to an investigation presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Black holes are not associated with physical function, however. Evaluating black holes as part of routine clinical practice could be a quick method for screening people with MS for referral to a comprehensive cognitive assessment, said the authors.

Black holes (also known as T1-hypointense lesions) can be used as a marker of axonal loss and neuronal tissue destruction in patients with MS. Loss of axons and destruction of neuronal tissue contribute to cognitive and physical disability, but the literature contains few data about whether black holes correlate with cognitive and physical outcomes in MS.

Serkan Özakbas, MD, professor of neurology at Dokuz Eylül University in Izmir, Turkey, and colleagues examined 226 patients with MS to investigate this potential correlation. The population’s median Expanded Disability Status Scale score was 1.5. The researchers categorized participants into two groups according whether they had at least one black hole or not. They assessed patients’ cognitive function by administering the Brief International Cognitive Assessment for MS (BICAMS), which comprises the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test II (CVLT-II), and the Brief Visuospatial Memory Test–Revised (BVMTR). They evaluated participants’ physical function using the Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), 6-Minute Walk Test (6MWT), Timed Up and Go (TUG), and 12-Item MS Walking Scale (MSWS-12).

In all, 116 (43.6%) participants had at least one black hole, and 150 (56.4%) had no black hole. Dr. Özakbas and colleagues found no significant difference between patients with and without black holes on the T25FW, 9HPT, 6MWT, TUG, MSWS-12, and CVLT-II. Patients without a black hole, however, had significantly higher SDMT (49.0 vs 42.9) and BVMTR (26.3 vs 23.3) scores, compared with those with at least one black hole.

“This study suggests that presence of black holes is related to cognitive function, but not to physical function,” the researchers concluded.

The investigators had no disclosures and conducted their study without financial support.
 

[email protected]

SOURCE: Özakbas S et al. CMSC 2019, Abstract IMG02.

SEATTLE – Among patients with multiple sclerosis (MS), functional gastrointestinal (GI) disorders are prevalent and associated with health-related quality of life, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Managing patients’ psychiatric comorbidities could effectively reduce the burden of functional GI disorders, the researchers said.

Knowledge about the prevalence of functional GI disorders in the population of patients with MS is limited. For the most part, previous studies in this population have focused on irritable bowel syndrome (IBS). A 2013 study by Levinthal et al. (Mult Scler Int. 2013. doi: 10.1155/2013/319201) investigated the prevalence of other functional GI disorders in MS, but the literature contains little information about the clinical and demographic characteristics associated with these disorders. In addition, the extent to which comorbid functional GI disorders influence health-related quality of life in MS is also unknown.

Ruth Ann Marrie, MD, PhD, professor of neurology at the University of Manitoba in Winnipeg, and colleagues sought to determine the prevalence of functional bowel disorders, the demographic and clinical characteristics associated with functional bowel disorders, and the effects of these disorders on health-related quality of life in a large, diverse population of persons with MS. In 2014, the investigators used the Rome III questionnaire to survey participants in the North American Research Committee on MS (NARCOMS) registry about functional bowel disorders. Participants also provided information about their sociodemographic characteristics, their disability status (using Patient-Determined Disease Steps), and any comorbid depression or anxiety, their health behaviors, and their health-related quality of life (using the RAND-12).

Dr. Marrie and colleagues used these data to determine the prevalence of IBS, functional bloating, functional constipation, functional diarrhea, and functional dyspepsia. They used multivariable logistic regression models to examine the factors associated with any functional GI disorder, and they used linear regression to analyze the association between functional GI disorders and health-related quality of life using linear regression.

Dr. Marrie and colleagues identified 6,312 eligible respondents. Approximately 77% of the population was female, and the sample’s mean age was 58.3 years. In all, 2,647 respondents (42%) had a functional GI disorder. The most common was IBS, which affected 28.2% of participants. The prevalence of all functional GI disorders increased with increasing disability. Depression and anxiety were associated with increased odds of IBS and functional dyspepsia. After adjustment for sociodemographic and clinical characteristics, functional GI disorders were associated with lower physical and mental health-related quality of life.

The research was not supported by outside funding. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.
 

[email protected]

SOURCE: Marrie RA et al. CMSC 2019, Abstract QOL13.

SEATTLE – Among patients with multiple sclerosis (MS), functional gastrointestinal (GI) disorders are prevalent and associated with health-related quality of life, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Managing patients’ psychiatric comorbidities could effectively reduce the burden of functional GI disorders, the researchers said.

Knowledge about the prevalence of functional GI disorders in the population of patients with MS is limited. For the most part, previous studies in this population have focused on irritable bowel syndrome (IBS). A 2013 study by Levinthal et al. (Mult Scler Int. 2013. doi: 10.1155/2013/319201) investigated the prevalence of other functional GI disorders in MS, but the literature contains little information about the clinical and demographic characteristics associated with these disorders. In addition, the extent to which comorbid functional GI disorders influence health-related quality of life in MS is also unknown.

Ruth Ann Marrie, MD, PhD, professor of neurology at the University of Manitoba in Winnipeg, and colleagues sought to determine the prevalence of functional bowel disorders, the demographic and clinical characteristics associated with functional bowel disorders, and the effects of these disorders on health-related quality of life in a large, diverse population of persons with MS. In 2014, the investigators used the Rome III questionnaire to survey participants in the North American Research Committee on MS (NARCOMS) registry about functional bowel disorders. Participants also provided information about their sociodemographic characteristics, their disability status (using Patient-Determined Disease Steps), and any comorbid depression or anxiety, their health behaviors, and their health-related quality of life (using the RAND-12).

Dr. Marrie and colleagues used these data to determine the prevalence of IBS, functional bloating, functional constipation, functional diarrhea, and functional dyspepsia. They used multivariable logistic regression models to examine the factors associated with any functional GI disorder, and they used linear regression to analyze the association between functional GI disorders and health-related quality of life using linear regression.

Dr. Marrie and colleagues identified 6,312 eligible respondents. Approximately 77% of the population was female, and the sample’s mean age was 58.3 years. In all, 2,647 respondents (42%) had a functional GI disorder. The most common was IBS, which affected 28.2% of participants. The prevalence of all functional GI disorders increased with increasing disability. Depression and anxiety were associated with increased odds of IBS and functional dyspepsia. After adjustment for sociodemographic and clinical characteristics, functional GI disorders were associated with lower physical and mental health-related quality of life.

The research was not supported by outside funding. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.
 

[email protected]

SOURCE: Marrie RA et al. CMSC 2019, Abstract QOL13.

SEATTLE – Among patients with multiple sclerosis (MS), functional gastrointestinal (GI) disorders are prevalent and associated with health-related quality of life, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Managing patients’ psychiatric comorbidities could effectively reduce the burden of functional GI disorders, the researchers said.

Knowledge about the prevalence of functional GI disorders in the population of patients with MS is limited. For the most part, previous studies in this population have focused on irritable bowel syndrome (IBS). A 2013 study by Levinthal et al. (Mult Scler Int. 2013. doi: 10.1155/2013/319201) investigated the prevalence of other functional GI disorders in MS, but the literature contains little information about the clinical and demographic characteristics associated with these disorders. In addition, the extent to which comorbid functional GI disorders influence health-related quality of life in MS is also unknown.

Ruth Ann Marrie, MD, PhD, professor of neurology at the University of Manitoba in Winnipeg, and colleagues sought to determine the prevalence of functional bowel disorders, the demographic and clinical characteristics associated with functional bowel disorders, and the effects of these disorders on health-related quality of life in a large, diverse population of persons with MS. In 2014, the investigators used the Rome III questionnaire to survey participants in the North American Research Committee on MS (NARCOMS) registry about functional bowel disorders. Participants also provided information about their sociodemographic characteristics, their disability status (using Patient-Determined Disease Steps), and any comorbid depression or anxiety, their health behaviors, and their health-related quality of life (using the RAND-12).

Dr. Marrie and colleagues used these data to determine the prevalence of IBS, functional bloating, functional constipation, functional diarrhea, and functional dyspepsia. They used multivariable logistic regression models to examine the factors associated with any functional GI disorder, and they used linear regression to analyze the association between functional GI disorders and health-related quality of life using linear regression.

Dr. Marrie and colleagues identified 6,312 eligible respondents. Approximately 77% of the population was female, and the sample’s mean age was 58.3 years. In all, 2,647 respondents (42%) had a functional GI disorder. The most common was IBS, which affected 28.2% of participants. The prevalence of all functional GI disorders increased with increasing disability. Depression and anxiety were associated with increased odds of IBS and functional dyspepsia. After adjustment for sociodemographic and clinical characteristics, functional GI disorders were associated with lower physical and mental health-related quality of life.

The research was not supported by outside funding. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.
 

[email protected]

SOURCE: Marrie RA et al. CMSC 2019, Abstract QOL13.

SEATTLE – Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years, according to an interim analysis of phase 4 study data.

A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”

The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.

Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.

In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.

“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
 

The FLUENT study

Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.

Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.

Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.

The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.

FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
 

Immune cell subsets

In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.

CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”

Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.

“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
 

A measure of CNS injury

In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.

Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.

The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.

Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
 

Adverse events

No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.

Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).

Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

[email protected]

SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.

SEATTLE – Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years, according to an interim analysis of phase 4 study data.

A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”

The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.

Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.

In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.

“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
 

The FLUENT study

Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.

Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.

Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.

The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.

FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
 

Immune cell subsets

In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.

CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”

Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.

“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
 

A measure of CNS injury

In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.

Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.

The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.

Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
 

Adverse events

No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.

Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).

Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

[email protected]

SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.

SEATTLE – Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years, according to an interim analysis of phase 4 study data.

A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”

The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.

Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.

In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.

“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
 

The FLUENT study

Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.

Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.

Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.

The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.

FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
 

Immune cell subsets

In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.

CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”

Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.

“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
 

A measure of CNS injury

In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.

Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.

The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.

Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
 

Adverse events

No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.

Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).

Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

[email protected]

SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.

SEATTLE – Treatment with 3.5 mg/kg of cladribine tablets effectively reduces relapse rate and the number of MRI lesions in patients with relapsing-remitting multiple sclerosis (MS), regardless of age. In addition, age does not affect the likelihood that a patient who receives cladribine will achieve no evidence of disease activity (NEDA), according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In the phase 3 CLARITY study, a cumulative dose of 3.5 mg/kg of cladribine over 2 years was associated with significantly reduced relapse rate and disability progression and improved MRI outcomes, compared with placebo. The drug’s efficacy persisted in patients who were switched to placebo in a 96-week extension study.
 

A post hoc analysis

A 2017 study by Weideman et al. suggested that disease-modifying treatment (DMT) is less effective in older patients. For this reason, Gavin Giovannoni, MBBCh, PhD, professor of neurology at Queen Mary University of London, and colleagues decided to investigate the effect of age on the efficacy of treatment with 3.5 mg/kg of cladribine. The investigators performed a post hoc analysis of the CLARITY and CLARITY extension studies of patients with relapsing-remitting MS. They categorized patients as older than 45 years or age 45 years or younger.

Patients enrolled in CLARITY were between ages 18 years and 65 years. They underwent MRI at pretrial assessment and at weeks 24, 48, and 96 or early termination. The investigators defined a qualifying relapse as one associated with changes in Kurtzke Functional Systems score and other specified clinical parameters. Qualifying relapses were confirmed by an independent evaluating physician who was blinded to treatment assignment.

In the CLARITY extension study, 98 participants who had received cladribine tablets 3.5 mg/kg in CLARITY were randomized to placebo for 2 additional years. Participants who continued on placebo in the CLARITY extension were evaluated according to age at entry into CLARITY.

Dr. Giovannoni and colleagues performed efficacy analyses for qualifying relapses; all relapses; and mean and cumulative numbers of new T1 gadolinium-enhancing lesions, active T2 lesions, and combined unique lesions. They defined NEDA as freedom from qualifying relapses, 6-month confirmed disability progression (as measured by the Expanded Disability Status Scale [EDSS] score), T1 gadolinium-enhancing lesions, and active T2 lesions. The investigators performed equivalent analyses for patients who received placebo in the CLARITY extension.
 

Age did not influence efficacy

Within each age group, participants in both treatment arms had similar baseline demographic and disease characteristics. In CLARITY, 221 patients were older than 45 years, and 649 were age 45 years or younger. In the CLARITY extension, 22 patients were older than 45 years, and 76 were age 45 years or younger. In CLARITY, but not the extension, the proportion of women was higher in the older group than in the younger group (77.7% vs. 66.1%). In CLARITY, patients aged 45 years or younger had a higher number of T1 gadolinium-enhancing lesions at baseline, compared with older patients.

At week 96 in CLARITY, the annual rate of qualifying relapses among patients older than 45 years was 0.14 for cladribine and 0.28 for placebo. Among patients aged 45 or younger, the annual rate of qualifying relapses was 0.15 for cladribine and 0.37 for placebo. For patients older than 45 years, the annual rate of all relapses was 0.28 for cladribine and 0.55 for placebo. For patients aged 45 years or younger, the annual rate of all relapses was 0.26 for cladribine and 0.65 for placebo. The treatment effect of cladribine, compared with placebo, on qualifying relapses and all relapses was similar for both age groups. In the CLARITY extension, the annualized relapse rate (ARR) was 0.17 in patients aged 45 years or younger and 0.05 in patients older than 45 years.

The mean number of new T1 gadolinium-enhancing lesions and cumulative new T1 gadolinium-enhancing lesions was reduced with cladribine, compared with placebo, in both age groups at week 96 in CLARITY. The mean number of active T2 lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.167 in patients older than 45 years and 0.667 in patients aged 45 years and younger. In addition, the mean number of combined unique lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.333 in patients older than 45 years and 0.667 in patients aged 45 years or younger.

The proportion of participants who achieved NEDA in CLARITY was 55.6% among patients older than 45 years who received cladribine, 39.6% among patients aged 45 years or younger who received cladribine, 28.2% among patients older than 45 years who received placebo, and 9.5% of patients aged 45 years or younger who received placebo. The odds ratio for achieving NEDA was significantly more favorable for the cladribine group, compared with the placebo group, in both age groups (3.19 for patients older than 45 years and 6.23 for patients aged 45 years or younger). In the CLARITY extension, the proportion of participants who achieved NEDA was 40.9% among patients older than 45 years and 28.2% among patients aged 45 years or younger.

“These data are consistent with previous analyses from CLARITY using a different age cutoff and with results from the overall study population,” said Dr. Giovannoni and colleagues.

Merck KGaA, which manufactures and markets cladribine, supported the study. Dr. Giovannoni and several of his coinvestigators have received speaker honoraria, consulting fees, or other funding from companies including Merck KGaA.

[email protected]

SEATTLE – Treatment with 3.5 mg/kg of cladribine tablets effectively reduces relapse rate and the number of MRI lesions in patients with relapsing-remitting multiple sclerosis (MS), regardless of age. In addition, age does not affect the likelihood that a patient who receives cladribine will achieve no evidence of disease activity (NEDA), according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In the phase 3 CLARITY study, a cumulative dose of 3.5 mg/kg of cladribine over 2 years was associated with significantly reduced relapse rate and disability progression and improved MRI outcomes, compared with placebo. The drug’s efficacy persisted in patients who were switched to placebo in a 96-week extension study.
 

A post hoc analysis

A 2017 study by Weideman et al. suggested that disease-modifying treatment (DMT) is less effective in older patients. For this reason, Gavin Giovannoni, MBBCh, PhD, professor of neurology at Queen Mary University of London, and colleagues decided to investigate the effect of age on the efficacy of treatment with 3.5 mg/kg of cladribine. The investigators performed a post hoc analysis of the CLARITY and CLARITY extension studies of patients with relapsing-remitting MS. They categorized patients as older than 45 years or age 45 years or younger.

Patients enrolled in CLARITY were between ages 18 years and 65 years. They underwent MRI at pretrial assessment and at weeks 24, 48, and 96 or early termination. The investigators defined a qualifying relapse as one associated with changes in Kurtzke Functional Systems score and other specified clinical parameters. Qualifying relapses were confirmed by an independent evaluating physician who was blinded to treatment assignment.

In the CLARITY extension study, 98 participants who had received cladribine tablets 3.5 mg/kg in CLARITY were randomized to placebo for 2 additional years. Participants who continued on placebo in the CLARITY extension were evaluated according to age at entry into CLARITY.

Dr. Giovannoni and colleagues performed efficacy analyses for qualifying relapses; all relapses; and mean and cumulative numbers of new T1 gadolinium-enhancing lesions, active T2 lesions, and combined unique lesions. They defined NEDA as freedom from qualifying relapses, 6-month confirmed disability progression (as measured by the Expanded Disability Status Scale [EDSS] score), T1 gadolinium-enhancing lesions, and active T2 lesions. The investigators performed equivalent analyses for patients who received placebo in the CLARITY extension.
 

Age did not influence efficacy

Within each age group, participants in both treatment arms had similar baseline demographic and disease characteristics. In CLARITY, 221 patients were older than 45 years, and 649 were age 45 years or younger. In the CLARITY extension, 22 patients were older than 45 years, and 76 were age 45 years or younger. In CLARITY, but not the extension, the proportion of women was higher in the older group than in the younger group (77.7% vs. 66.1%). In CLARITY, patients aged 45 years or younger had a higher number of T1 gadolinium-enhancing lesions at baseline, compared with older patients.

At week 96 in CLARITY, the annual rate of qualifying relapses among patients older than 45 years was 0.14 for cladribine and 0.28 for placebo. Among patients aged 45 or younger, the annual rate of qualifying relapses was 0.15 for cladribine and 0.37 for placebo. For patients older than 45 years, the annual rate of all relapses was 0.28 for cladribine and 0.55 for placebo. For patients aged 45 years or younger, the annual rate of all relapses was 0.26 for cladribine and 0.65 for placebo. The treatment effect of cladribine, compared with placebo, on qualifying relapses and all relapses was similar for both age groups. In the CLARITY extension, the annualized relapse rate (ARR) was 0.17 in patients aged 45 years or younger and 0.05 in patients older than 45 years.

The mean number of new T1 gadolinium-enhancing lesions and cumulative new T1 gadolinium-enhancing lesions was reduced with cladribine, compared with placebo, in both age groups at week 96 in CLARITY. The mean number of active T2 lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.167 in patients older than 45 years and 0.667 in patients aged 45 years and younger. In addition, the mean number of combined unique lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.333 in patients older than 45 years and 0.667 in patients aged 45 years or younger.

The proportion of participants who achieved NEDA in CLARITY was 55.6% among patients older than 45 years who received cladribine, 39.6% among patients aged 45 years or younger who received cladribine, 28.2% among patients older than 45 years who received placebo, and 9.5% of patients aged 45 years or younger who received placebo. The odds ratio for achieving NEDA was significantly more favorable for the cladribine group, compared with the placebo group, in both age groups (3.19 for patients older than 45 years and 6.23 for patients aged 45 years or younger). In the CLARITY extension, the proportion of participants who achieved NEDA was 40.9% among patients older than 45 years and 28.2% among patients aged 45 years or younger.

“These data are consistent with previous analyses from CLARITY using a different age cutoff and with results from the overall study population,” said Dr. Giovannoni and colleagues.

Merck KGaA, which manufactures and markets cladribine, supported the study. Dr. Giovannoni and several of his coinvestigators have received speaker honoraria, consulting fees, or other funding from companies including Merck KGaA.

[email protected]

SEATTLE – Treatment with 3.5 mg/kg of cladribine tablets effectively reduces relapse rate and the number of MRI lesions in patients with relapsing-remitting multiple sclerosis (MS), regardless of age. In addition, age does not affect the likelihood that a patient who receives cladribine will achieve no evidence of disease activity (NEDA), according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

In the phase 3 CLARITY study, a cumulative dose of 3.5 mg/kg of cladribine over 2 years was associated with significantly reduced relapse rate and disability progression and improved MRI outcomes, compared with placebo. The drug’s efficacy persisted in patients who were switched to placebo in a 96-week extension study.
 

A post hoc analysis

A 2017 study by Weideman et al. suggested that disease-modifying treatment (DMT) is less effective in older patients. For this reason, Gavin Giovannoni, MBBCh, PhD, professor of neurology at Queen Mary University of London, and colleagues decided to investigate the effect of age on the efficacy of treatment with 3.5 mg/kg of cladribine. The investigators performed a post hoc analysis of the CLARITY and CLARITY extension studies of patients with relapsing-remitting MS. They categorized patients as older than 45 years or age 45 years or younger.

Patients enrolled in CLARITY were between ages 18 years and 65 years. They underwent MRI at pretrial assessment and at weeks 24, 48, and 96 or early termination. The investigators defined a qualifying relapse as one associated with changes in Kurtzke Functional Systems score and other specified clinical parameters. Qualifying relapses were confirmed by an independent evaluating physician who was blinded to treatment assignment.

In the CLARITY extension study, 98 participants who had received cladribine tablets 3.5 mg/kg in CLARITY were randomized to placebo for 2 additional years. Participants who continued on placebo in the CLARITY extension were evaluated according to age at entry into CLARITY.

Dr. Giovannoni and colleagues performed efficacy analyses for qualifying relapses; all relapses; and mean and cumulative numbers of new T1 gadolinium-enhancing lesions, active T2 lesions, and combined unique lesions. They defined NEDA as freedom from qualifying relapses, 6-month confirmed disability progression (as measured by the Expanded Disability Status Scale [EDSS] score), T1 gadolinium-enhancing lesions, and active T2 lesions. The investigators performed equivalent analyses for patients who received placebo in the CLARITY extension.
 

Age did not influence efficacy

Within each age group, participants in both treatment arms had similar baseline demographic and disease characteristics. In CLARITY, 221 patients were older than 45 years, and 649 were age 45 years or younger. In the CLARITY extension, 22 patients were older than 45 years, and 76 were age 45 years or younger. In CLARITY, but not the extension, the proportion of women was higher in the older group than in the younger group (77.7% vs. 66.1%). In CLARITY, patients aged 45 years or younger had a higher number of T1 gadolinium-enhancing lesions at baseline, compared with older patients.

At week 96 in CLARITY, the annual rate of qualifying relapses among patients older than 45 years was 0.14 for cladribine and 0.28 for placebo. Among patients aged 45 or younger, the annual rate of qualifying relapses was 0.15 for cladribine and 0.37 for placebo. For patients older than 45 years, the annual rate of all relapses was 0.28 for cladribine and 0.55 for placebo. For patients aged 45 years or younger, the annual rate of all relapses was 0.26 for cladribine and 0.65 for placebo. The treatment effect of cladribine, compared with placebo, on qualifying relapses and all relapses was similar for both age groups. In the CLARITY extension, the annualized relapse rate (ARR) was 0.17 in patients aged 45 years or younger and 0.05 in patients older than 45 years.

The mean number of new T1 gadolinium-enhancing lesions and cumulative new T1 gadolinium-enhancing lesions was reduced with cladribine, compared with placebo, in both age groups at week 96 in CLARITY. The mean number of active T2 lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.167 in patients older than 45 years and 0.667 in patients aged 45 years and younger. In addition, the mean number of combined unique lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.333 in patients older than 45 years and 0.667 in patients aged 45 years or younger.

The proportion of participants who achieved NEDA in CLARITY was 55.6% among patients older than 45 years who received cladribine, 39.6% among patients aged 45 years or younger who received cladribine, 28.2% among patients older than 45 years who received placebo, and 9.5% of patients aged 45 years or younger who received placebo. The odds ratio for achieving NEDA was significantly more favorable for the cladribine group, compared with the placebo group, in both age groups (3.19 for patients older than 45 years and 6.23 for patients aged 45 years or younger). In the CLARITY extension, the proportion of participants who achieved NEDA was 40.9% among patients older than 45 years and 28.2% among patients aged 45 years or younger.

“These data are consistent with previous analyses from CLARITY using a different age cutoff and with results from the overall study population,” said Dr. Giovannoni and colleagues.

Merck KGaA, which manufactures and markets cladribine, supported the study. Dr. Giovannoni and several of his coinvestigators have received speaker honoraria, consulting fees, or other funding from companies including Merck KGaA.

[email protected]

Key clinical point: Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS.

Major finding: The rate of brain atrophy for untreated patients with primary progressive MS was about twice as fast as that for those with secondary progressive MS.

Study details: The randomized, placebo-controlled phase 2 SPRINT-MS trial of ibudilast included 134 patients with primary progressive MS and 121 with secondary progressive MS.

Disclosures: The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

Citation: Goodman A et al. AAN 2019, Abstract S12.007.

Key clinical point: Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS.

Major finding: The rate of brain atrophy for untreated patients with primary progressive MS was about twice as fast as that for those with secondary progressive MS.

Study details: The randomized, placebo-controlled phase 2 SPRINT-MS trial of ibudilast included 134 patients with primary progressive MS and 121 with secondary progressive MS.

Disclosures: The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

Citation: Goodman A et al. AAN 2019, Abstract S12.007.

Key clinical point: Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS.

Major finding: The rate of brain atrophy for untreated patients with primary progressive MS was about twice as fast as that for those with secondary progressive MS.

Study details: The randomized, placebo-controlled phase 2 SPRINT-MS trial of ibudilast included 134 patients with primary progressive MS and 121 with secondary progressive MS.

Disclosures: The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

Citation: Goodman A et al. AAN 2019, Abstract S12.007.

Key clinical point: Treatment with eculizumab substantially reduced risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica spectrum disorder.

Major finding: Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant (P less than .0001) effect in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse.

Study details: A phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT) including 143 adult patients.

Disclosures: The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

Citation: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

Key clinical point: Treatment with eculizumab substantially reduced risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica spectrum disorder.

Major finding: Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant (P less than .0001) effect in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse.

Study details: A phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT) including 143 adult patients.

Disclosures: The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

Citation: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

Key clinical point: Treatment with eculizumab substantially reduced risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica spectrum disorder.

Major finding: Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant (P less than .0001) effect in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse.

Study details: A phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT) including 143 adult patients.

Disclosures: The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

Citation: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

Key clinical point: Physicians face considerable uncertainty regarding how to treat pediatric patients with MS.

Major finding: About 65% of pediatric patients with multiple sclerosis do not receive disease-modifying therapy within 1 year of diagnosis.

Study details: Retrospective, observational study of claims data from 288 patients with pediatric MS.

Disclosures: Novartis funded the study, and Dr. Deshpande, who presented the findings, and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

Citation: Greenberg B et al. CMSC 2019, Abstract DXM02.

Key clinical point: Physicians face considerable uncertainty regarding how to treat pediatric patients with MS.

Major finding: About 65% of pediatric patients with multiple sclerosis do not receive disease-modifying therapy within 1 year of diagnosis.

Study details: Retrospective, observational study of claims data from 288 patients with pediatric MS.

Disclosures: Novartis funded the study, and Dr. Deshpande, who presented the findings, and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

Citation: Greenberg B et al. CMSC 2019, Abstract DXM02.

Key clinical point: Physicians face considerable uncertainty regarding how to treat pediatric patients with MS.

Major finding: About 65% of pediatric patients with multiple sclerosis do not receive disease-modifying therapy within 1 year of diagnosis.

Study details: Retrospective, observational study of claims data from 288 patients with pediatric MS.

Disclosures: Novartis funded the study, and Dr. Deshpande, who presented the findings, and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

Citation: Greenberg B et al. CMSC 2019, Abstract DXM02.

CSF levels of neurofilament light (NfL) are elevated in most neurologic conditions, according to an analysis published online ahead of print June 17 in JAMA Neurology. The biomarker has the potential to distinguish between frontotemporal dementia (FTD) and other dementia subtypes, as well as between Parkinson’s disease and atypical parkinsonian syndromes, said the investigators. It may be necessary to identify age- and sex-specific reference values for NfL, they added.

Neurologists have long understood CSF levels of NfL to be elevated in neurodegenerative conditions, but researchers previously had not compared these levels systematically among neurologic disorders. Similarly, the literature indicates a positive association between CSF NfL level and age in healthy controls, but this association has not been evaluated systematically in neurologic disorders. The resulting lack of clarity has impeded the use of NfL as a diagnostic biomarker.
 

A meta-analysis of CSF samples

Claire Bridel, MD, PhD, of the department of clinical chemistry at the VU University Medical Centre in Amsterdam and colleagues conducted a systematic review and meta-analysis to compare CSF levels of NfL among diagnoses, assess the associations of age and sex with NfL, and evaluate the potential of NfL as a diagnostic biomarker. The investigators searched PubMed for studies published between Jan. 1, 2006, and Jan. 1, 2016, that reported CSF levels of NfL in neurologic or psychiatric conditions or in healthy controls. They included only studies that used the same commercially available immunoassay that has been used in most studies since 2006. The literature indicates that this enzyme-linked immunosorbent assay is sensitive and robust. Dr. Bridel and colleagues contacted study authors and requested their individual-level data.

The investigators sorted the most common neurologic conditions into three groups of similar disorders. The first group included inflammatory conditions of the CNS, such as multiple sclerosis, clinically isolated syndrome (CIS), and optic neuritis. The second group included dementia syndromes (such as Alzheimer’s disease, FTD, vascular dementia, and dementia with Lewy bodies) and amyotrophic lateral sclerosis (ALS). The third category included parkinsonian syndromes such as Parkinson’s disease, Parkinson’s disease dementia, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The authors used generalized linear mixed-effects models to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels. They modeled cohort of origin as a random intercept.
 

NfL increased with age

Dr. Bridel and colleagues identified 153 relevant investigations, of which 44 met their inclusion criteria. The original investigators provided data sets for these studies, along with three previously unpublished data sets. The data sets included information from 10,059 participants (mean age, 59.7 years; 54.1% female). After excluding diagnostic categories with fewer than five observations per sex, Dr. Bridel and colleagues included data for 10,012 people in the analysis. In this population, the researchers identified 2,795 patients with inflammatory diseases of the CNS, 4,284 patients with dementia or predementia, 984 patients with parkinsonian disorders, and 1,332 healthy controls.

CSF level of NfL was elevated in most neurologic conditions, compared with healthy controls. The largest effect sizes were in cognitively impaired patients with HIV (21.36), patients with FTD/ALS (10.48), patients with ALS (7.58), and patients with Huntington’s disease (5.88).

In healthy controls, the level of NfL in CSF increased by 3.30% annually. The investigators also observed an association between age and CSF NfL level in people with subjective complaints, bipolar disorder, and most neurodegenerative conditions. They found no association, however, in patients with MS, HIV and cognitive impairment, and rapidly progressive neurodegenerative conditions (such as FTD, ALS, FTD/ALS, MSA, PSP, CBS, and Huntington’s disease). CSF level of NfL was 26.0% higher in men among healthy controls. This discrepancy also was observed in a minority of neurologic conditions, including MS, Alzheimer’s disease, vascular dementia, and Parkinson’s disease.

Mean CSF levels of NfL were similar between patients with inflammatory conditions of the CNS. Among dementias and related disorders, mean CNS level of NfL was significantly higher in FTD than in Alzheimer’s disease (2.08), vascular dementia (1.56), and dementia with Lewy bodies (2.50). Among parkinsonian syndromes, the mean CSF levels of NfL were higher in MSA, PSP, and CBS, compared with Parkinson’s disease.
 

Many factors influence NfL level in CSF

The association between CNS level of NfL with age among healthy controls “implies that age-specific reference values may be needed and that the diagnostic potential of CSF NfL may decrease with age,” said the researchers. The finding that CSF NfL level was higher in men in a minority of diagnoses has uncertain clinical significance, they added. Sex-specific reference values may be needed.

Dr. Bridel and colleagues found that age, sex, and cohort explained 46% of variation in CSF level of NfL, which suggests that many factors that determine this level have yet to be identified. Disease duration and disease severity could influence the CSF level of NfL, but the data sets that the investigators analyzed did not include this information.

Because CSF NfL level did not differ significantly between relapsing/remitting MS, secondary progressive MS, and primary progressive MS, this biomarker “may not differentiate acute inflammation-induced neuronal damage in the context of relapses from progressive neurodegeneration if the consequences of recent relapses or novel lesion formation are not considered,” said Dr. Bridel and colleagues. The findings do suggest, however, that CSF level of NfL can distinguish FTD from other dementias, as well as Parkinson’s disease from atypical parkinsonian syndromes. Furthermore, it is possible that the findings of this study can be translated to serum level of NfL, said the authors.

One of the study’s limitations was that diagnosis was based on clinical criteria, said Dr. Bridel and colleagues. In addition, the authors were unable to identify dementia of multifactorial origin, which might have reduced the differences in CSF NfL level distributions between dementia subtypes. Finally, the authors only analyzed studies that relied on a specific immunoassay for CSF NfL level.

The authors reported receiving funding from various pharmaceutical and biopharmaceutical companies, as well as from grants and research foundations. The funders did not influence the study design, data analysis, or interpretation, however.

[email protected]

SOURCE: Bridel C et al. JAMA Neurol. 2019 June 17. doi: 10.1001/jamaneurol.2019.1534.

CSF levels of neurofilament light (NfL) are elevated in most neurologic conditions, according to an analysis published online ahead of print June 17 in JAMA Neurology. The biomarker has the potential to distinguish between frontotemporal dementia (FTD) and other dementia subtypes, as well as between Parkinson’s disease and atypical parkinsonian syndromes, said the investigators. It may be necessary to identify age- and sex-specific reference values for NfL, they added.

Neurologists have long understood CSF levels of NfL to be elevated in neurodegenerative conditions, but researchers previously had not compared these levels systematically among neurologic disorders. Similarly, the literature indicates a positive association between CSF NfL level and age in healthy controls, but this association has not been evaluated systematically in neurologic disorders. The resulting lack of clarity has impeded the use of NfL as a diagnostic biomarker.
 

A meta-analysis of CSF samples

Claire Bridel, MD, PhD, of the department of clinical chemistry at the VU University Medical Centre in Amsterdam and colleagues conducted a systematic review and meta-analysis to compare CSF levels of NfL among diagnoses, assess the associations of age and sex with NfL, and evaluate the potential of NfL as a diagnostic biomarker. The investigators searched PubMed for studies published between Jan. 1, 2006, and Jan. 1, 2016, that reported CSF levels of NfL in neurologic or psychiatric conditions or in healthy controls. They included only studies that used the same commercially available immunoassay that has been used in most studies since 2006. The literature indicates that this enzyme-linked immunosorbent assay is sensitive and robust. Dr. Bridel and colleagues contacted study authors and requested their individual-level data.

The investigators sorted the most common neurologic conditions into three groups of similar disorders. The first group included inflammatory conditions of the CNS, such as multiple sclerosis, clinically isolated syndrome (CIS), and optic neuritis. The second group included dementia syndromes (such as Alzheimer’s disease, FTD, vascular dementia, and dementia with Lewy bodies) and amyotrophic lateral sclerosis (ALS). The third category included parkinsonian syndromes such as Parkinson’s disease, Parkinson’s disease dementia, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The authors used generalized linear mixed-effects models to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels. They modeled cohort of origin as a random intercept.
 

NfL increased with age

Dr. Bridel and colleagues identified 153 relevant investigations, of which 44 met their inclusion criteria. The original investigators provided data sets for these studies, along with three previously unpublished data sets. The data sets included information from 10,059 participants (mean age, 59.7 years; 54.1% female). After excluding diagnostic categories with fewer than five observations per sex, Dr. Bridel and colleagues included data for 10,012 people in the analysis. In this population, the researchers identified 2,795 patients with inflammatory diseases of the CNS, 4,284 patients with dementia or predementia, 984 patients with parkinsonian disorders, and 1,332 healthy controls.

CSF level of NfL was elevated in most neurologic conditions, compared with healthy controls. The largest effect sizes were in cognitively impaired patients with HIV (21.36), patients with FTD/ALS (10.48), patients with ALS (7.58), and patients with Huntington’s disease (5.88).

In healthy controls, the level of NfL in CSF increased by 3.30% annually. The investigators also observed an association between age and CSF NfL level in people with subjective complaints, bipolar disorder, and most neurodegenerative conditions. They found no association, however, in patients with MS, HIV and cognitive impairment, and rapidly progressive neurodegenerative conditions (such as FTD, ALS, FTD/ALS, MSA, PSP, CBS, and Huntington’s disease). CSF level of NfL was 26.0% higher in men among healthy controls. This discrepancy also was observed in a minority of neurologic conditions, including MS, Alzheimer’s disease, vascular dementia, and Parkinson’s disease.

Mean CSF levels of NfL were similar between patients with inflammatory conditions of the CNS. Among dementias and related disorders, mean CNS level of NfL was significantly higher in FTD than in Alzheimer’s disease (2.08), vascular dementia (1.56), and dementia with Lewy bodies (2.50). Among parkinsonian syndromes, the mean CSF levels of NfL were higher in MSA, PSP, and CBS, compared with Parkinson’s disease.
 

Many factors influence NfL level in CSF

The association between CNS level of NfL with age among healthy controls “implies that age-specific reference values may be needed and that the diagnostic potential of CSF NfL may decrease with age,” said the researchers. The finding that CSF NfL level was higher in men in a minority of diagnoses has uncertain clinical significance, they added. Sex-specific reference values may be needed.

Dr. Bridel and colleagues found that age, sex, and cohort explained 46% of variation in CSF level of NfL, which suggests that many factors that determine this level have yet to be identified. Disease duration and disease severity could influence the CSF level of NfL, but the data sets that the investigators analyzed did not include this information.

Because CSF NfL level did not differ significantly between relapsing/remitting MS, secondary progressive MS, and primary progressive MS, this biomarker “may not differentiate acute inflammation-induced neuronal damage in the context of relapses from progressive neurodegeneration if the consequences of recent relapses or novel lesion formation are not considered,” said Dr. Bridel and colleagues. The findings do suggest, however, that CSF level of NfL can distinguish FTD from other dementias, as well as Parkinson’s disease from atypical parkinsonian syndromes. Furthermore, it is possible that the findings of this study can be translated to serum level of NfL, said the authors.

One of the study’s limitations was that diagnosis was based on clinical criteria, said Dr. Bridel and colleagues. In addition, the authors were unable to identify dementia of multifactorial origin, which might have reduced the differences in CSF NfL level distributions between dementia subtypes. Finally, the authors only analyzed studies that relied on a specific immunoassay for CSF NfL level.

The authors reported receiving funding from various pharmaceutical and biopharmaceutical companies, as well as from grants and research foundations. The funders did not influence the study design, data analysis, or interpretation, however.

[email protected]

SOURCE: Bridel C et al. JAMA Neurol. 2019 June 17. doi: 10.1001/jamaneurol.2019.1534.

CSF levels of neurofilament light (NfL) are elevated in most neurologic conditions, according to an analysis published online ahead of print June 17 in JAMA Neurology. The biomarker has the potential to distinguish between frontotemporal dementia (FTD) and other dementia subtypes, as well as between Parkinson’s disease and atypical parkinsonian syndromes, said the investigators. It may be necessary to identify age- and sex-specific reference values for NfL, they added.

Neurologists have long understood CSF levels of NfL to be elevated in neurodegenerative conditions, but researchers previously had not compared these levels systematically among neurologic disorders. Similarly, the literature indicates a positive association between CSF NfL level and age in healthy controls, but this association has not been evaluated systematically in neurologic disorders. The resulting lack of clarity has impeded the use of NfL as a diagnostic biomarker.
 

A meta-analysis of CSF samples

Claire Bridel, MD, PhD, of the department of clinical chemistry at the VU University Medical Centre in Amsterdam and colleagues conducted a systematic review and meta-analysis to compare CSF levels of NfL among diagnoses, assess the associations of age and sex with NfL, and evaluate the potential of NfL as a diagnostic biomarker. The investigators searched PubMed for studies published between Jan. 1, 2006, and Jan. 1, 2016, that reported CSF levels of NfL in neurologic or psychiatric conditions or in healthy controls. They included only studies that used the same commercially available immunoassay that has been used in most studies since 2006. The literature indicates that this enzyme-linked immunosorbent assay is sensitive and robust. Dr. Bridel and colleagues contacted study authors and requested their individual-level data.

The investigators sorted the most common neurologic conditions into three groups of similar disorders. The first group included inflammatory conditions of the CNS, such as multiple sclerosis, clinically isolated syndrome (CIS), and optic neuritis. The second group included dementia syndromes (such as Alzheimer’s disease, FTD, vascular dementia, and dementia with Lewy bodies) and amyotrophic lateral sclerosis (ALS). The third category included parkinsonian syndromes such as Parkinson’s disease, Parkinson’s disease dementia, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The authors used generalized linear mixed-effects models to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels. They modeled cohort of origin as a random intercept.
 

NfL increased with age

Dr. Bridel and colleagues identified 153 relevant investigations, of which 44 met their inclusion criteria. The original investigators provided data sets for these studies, along with three previously unpublished data sets. The data sets included information from 10,059 participants (mean age, 59.7 years; 54.1% female). After excluding diagnostic categories with fewer than five observations per sex, Dr. Bridel and colleagues included data for 10,012 people in the analysis. In this population, the researchers identified 2,795 patients with inflammatory diseases of the CNS, 4,284 patients with dementia or predementia, 984 patients with parkinsonian disorders, and 1,332 healthy controls.

CSF level of NfL was elevated in most neurologic conditions, compared with healthy controls. The largest effect sizes were in cognitively impaired patients with HIV (21.36), patients with FTD/ALS (10.48), patients with ALS (7.58), and patients with Huntington’s disease (5.88).

In healthy controls, the level of NfL in CSF increased by 3.30% annually. The investigators also observed an association between age and CSF NfL level in people with subjective complaints, bipolar disorder, and most neurodegenerative conditions. They found no association, however, in patients with MS, HIV and cognitive impairment, and rapidly progressive neurodegenerative conditions (such as FTD, ALS, FTD/ALS, MSA, PSP, CBS, and Huntington’s disease). CSF level of NfL was 26.0% higher in men among healthy controls. This discrepancy also was observed in a minority of neurologic conditions, including MS, Alzheimer’s disease, vascular dementia, and Parkinson’s disease.

Mean CSF levels of NfL were similar between patients with inflammatory conditions of the CNS. Among dementias and related disorders, mean CNS level of NfL was significantly higher in FTD than in Alzheimer’s disease (2.08), vascular dementia (1.56), and dementia with Lewy bodies (2.50). Among parkinsonian syndromes, the mean CSF levels of NfL were higher in MSA, PSP, and CBS, compared with Parkinson’s disease.
 

Many factors influence NfL level in CSF

The association between CNS level of NfL with age among healthy controls “implies that age-specific reference values may be needed and that the diagnostic potential of CSF NfL may decrease with age,” said the researchers. The finding that CSF NfL level was higher in men in a minority of diagnoses has uncertain clinical significance, they added. Sex-specific reference values may be needed.

Dr. Bridel and colleagues found that age, sex, and cohort explained 46% of variation in CSF level of NfL, which suggests that many factors that determine this level have yet to be identified. Disease duration and disease severity could influence the CSF level of NfL, but the data sets that the investigators analyzed did not include this information.

Because CSF NfL level did not differ significantly between relapsing/remitting MS, secondary progressive MS, and primary progressive MS, this biomarker “may not differentiate acute inflammation-induced neuronal damage in the context of relapses from progressive neurodegeneration if the consequences of recent relapses or novel lesion formation are not considered,” said Dr. Bridel and colleagues. The findings do suggest, however, that CSF level of NfL can distinguish FTD from other dementias, as well as Parkinson’s disease from atypical parkinsonian syndromes. Furthermore, it is possible that the findings of this study can be translated to serum level of NfL, said the authors.

One of the study’s limitations was that diagnosis was based on clinical criteria, said Dr. Bridel and colleagues. In addition, the authors were unable to identify dementia of multifactorial origin, which might have reduced the differences in CSF NfL level distributions between dementia subtypes. Finally, the authors only analyzed studies that relied on a specific immunoassay for CSF NfL level.

The authors reported receiving funding from various pharmaceutical and biopharmaceutical companies, as well as from grants and research foundations. The funders did not influence the study design, data analysis, or interpretation, however.

[email protected]

SOURCE: Bridel C et al. JAMA Neurol. 2019 June 17. doi: 10.1001/jamaneurol.2019.1534.

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.