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Serum NfL levels may predict 10-year deep gray matter volumes
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.
She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.
About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.
The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm3 in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm3 in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.
“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”
The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.
SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.
She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.
About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.
The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm3 in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm3 in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.
“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”
The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.
SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.
She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.
About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.
The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm3 in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm3 in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.
“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”
The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.
SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.
REPORTING FROM ACTRIMS FORUM 2020
Phase 2 remyelination trial yields ‘intriguing’ interim results
Placebo and CMN-Au8 help patients with relapsing MS, visual impairment
WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.
The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.
The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.
Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.
The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.
Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.
About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.
“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”
At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.
“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.
Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.
SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.
Placebo and CMN-Au8 help patients with relapsing MS, visual impairment
Placebo and CMN-Au8 help patients with relapsing MS, visual impairment
WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.
The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.
The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.
Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.
The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.
Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.
About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.
“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”
At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.
“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.
Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.
SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.
WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.
The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.
The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.
Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.
The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.
Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.
About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.
“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”
At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.
“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.
Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.
SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.
REPORTING FROM ACTRIMS FORUM 2020
Cancer increase observed in modern era of MS drugs
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
REPORTING FROM ACTRIMS FORUM 2020
Key differences found between pediatric- and adult-onset MS
WEST PALM BEACH, FLA. – , according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.
POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.
MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.
The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.
The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.
Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.
Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.
“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”
These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”
Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.
SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.
WEST PALM BEACH, FLA. – , according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.
POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.
MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.
The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.
The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.
Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.
Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.
“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”
These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”
Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.
SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.
WEST PALM BEACH, FLA. – , according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.
POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.
MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.
The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.
The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.
Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.
Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.
“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”
These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”
Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.
SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.
REPORTING FROM ACTRIMS FORUM 2020
Increased risk of infection seen in patients with MS
womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.
Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.
At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.
Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.
In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).
After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.
In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).
“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.
The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.
SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.
womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.
Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.
At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.
Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.
In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).
After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.
In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).
“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.
The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.
SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.
womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.
Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.
At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.
Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.
In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).
After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.
In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).
“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.
The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.
SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.
REPORTING FROM ACTRIMS FORUM 2020
Pregnancy linked to slowed MS progression
The effect increases with multiple children
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
The effect increases with multiple children
The effect increases with multiple children
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
REPORTING FROM ACTRIMS FORUM 2020
OCT may help predict disease activity in CIS
WEST PALM BEACH, FLA. – according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that optical coherence tomography (OCT) could support patient monitoring and the initiation of disease-modifying therapy.
“Treatment of early MS [multiple sclerosis] is crucial to prevent neuroaxonal damage and, thus, sustained disability,” said Hanna G. Zimmermann, PhD, a research associate at NeuroCure Clinical Research Center at Charité Universitätsmedizin in Berlin. The ability to identify patients at high risk of future disease activity shortly after disease onset could help optimize patient management and guide the initiation of disease-modifying therapy. Dr. Zimmermann and colleagues investigated whether retinal OCT could predict disease activity in patients with CIS.
The investigators included 97 patients (mean age, 33.6 years; 62.9% female) with CIS in a prospective, longitudinal cohort study. Diagnoses of CIS were based on the 2010 revisions to the McDonald criteria. Patients were enrolled from two German centers within 12 months after a first clinical event. The researchers performed a neurologic examination, cerebral MRI, and retinal OCT for each participant and followed the population for 729 days (median, 664 days).
The primary OCT predictor was ganglion cell and inner plexiform (GCIP) layer thickness, because this parameter is stable and reliable for quantifying neuronal visual system damage in MS, said Dr. Zimmermann. Secondary OCT predictors were peripapillary retinal nerve fiber layer (pRNFL) thickness and inner nuclear layer (INL) thickness. The investigators only included eyes without a history of optic neuritis in the analysis.
The study’s primary outcome was failing the no evidence of disease activity (NEDA-3) criteria (no relapses, no disability progression, and no MRI activity). The secondary outcomes were MS diagnosis (according to the 2010 McDonald criteria) and worsening of disability.
At baseline, Dr. Zimmerman and colleagues found no differences in thickness of GCIP and pRNFL between patients and matched healthy controls. In all, 58 patients (59%) failed NEDA-3 criteria during follow-up. When Dr. Zimmermann and colleagues conducted Kaplan-Meier analysis, they found that patients with thinner GCIP thickness had a significantly higher risk of failing NEDA-3 criteria (thinnest vs. thickest tertile: hazard ratio, 3.33). A follow-up diagnosis of MS also was significantly more likely among patients with low GCIP thickness (thinnest vs. thickest tertile: HR, 4.05).
In addition, low pRNFL thickness indicated an increased risk of not meeting NEDA-3 criteria (thinnest vs. thickest tertile: HR, 2.46). However, neither INL thickness nor T2-weighted lesion count were associated with failing NEDA-3 criteria. Also, none of the OCT parameters were associated with future disability worsening.
Among the study’s limitations are its small sample size, the relatively short observation time, and the heterogeneity of patients between the two centers, which used different study protocols, said Dr. Zimmermann.
“OCT-assessed GCIP is promising for the early appraisal of future disease activity and might thus be helpful for risk-adjusted patient participation in clinical research,” she said. “It might also be helpful for clinicians for identifying CIS patients with worse prognosis and planning the care.” Dr. Zimmermann and colleagues plan to use advanced imaging techniques in future studies to understand the mechanisms behind the associations they identified. They hope to confirm their findings in a larger cohort and examine whether OCT can predict clinical outcomes such as relapses, disability worsening, and the extent of disease activity.
Dr. Zimmermann had no relevant disclosures and did not report a source of funding for the study.
SOURCE: Zimmermann HG et al. ACTRIMS Forum 2020, Abstract.
WEST PALM BEACH, FLA. – according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that optical coherence tomography (OCT) could support patient monitoring and the initiation of disease-modifying therapy.
“Treatment of early MS [multiple sclerosis] is crucial to prevent neuroaxonal damage and, thus, sustained disability,” said Hanna G. Zimmermann, PhD, a research associate at NeuroCure Clinical Research Center at Charité Universitätsmedizin in Berlin. The ability to identify patients at high risk of future disease activity shortly after disease onset could help optimize patient management and guide the initiation of disease-modifying therapy. Dr. Zimmermann and colleagues investigated whether retinal OCT could predict disease activity in patients with CIS.
The investigators included 97 patients (mean age, 33.6 years; 62.9% female) with CIS in a prospective, longitudinal cohort study. Diagnoses of CIS were based on the 2010 revisions to the McDonald criteria. Patients were enrolled from two German centers within 12 months after a first clinical event. The researchers performed a neurologic examination, cerebral MRI, and retinal OCT for each participant and followed the population for 729 days (median, 664 days).
The primary OCT predictor was ganglion cell and inner plexiform (GCIP) layer thickness, because this parameter is stable and reliable for quantifying neuronal visual system damage in MS, said Dr. Zimmermann. Secondary OCT predictors were peripapillary retinal nerve fiber layer (pRNFL) thickness and inner nuclear layer (INL) thickness. The investigators only included eyes without a history of optic neuritis in the analysis.
The study’s primary outcome was failing the no evidence of disease activity (NEDA-3) criteria (no relapses, no disability progression, and no MRI activity). The secondary outcomes were MS diagnosis (according to the 2010 McDonald criteria) and worsening of disability.
At baseline, Dr. Zimmerman and colleagues found no differences in thickness of GCIP and pRNFL between patients and matched healthy controls. In all, 58 patients (59%) failed NEDA-3 criteria during follow-up. When Dr. Zimmermann and colleagues conducted Kaplan-Meier analysis, they found that patients with thinner GCIP thickness had a significantly higher risk of failing NEDA-3 criteria (thinnest vs. thickest tertile: hazard ratio, 3.33). A follow-up diagnosis of MS also was significantly more likely among patients with low GCIP thickness (thinnest vs. thickest tertile: HR, 4.05).
In addition, low pRNFL thickness indicated an increased risk of not meeting NEDA-3 criteria (thinnest vs. thickest tertile: HR, 2.46). However, neither INL thickness nor T2-weighted lesion count were associated with failing NEDA-3 criteria. Also, none of the OCT parameters were associated with future disability worsening.
Among the study’s limitations are its small sample size, the relatively short observation time, and the heterogeneity of patients between the two centers, which used different study protocols, said Dr. Zimmermann.
“OCT-assessed GCIP is promising for the early appraisal of future disease activity and might thus be helpful for risk-adjusted patient participation in clinical research,” she said. “It might also be helpful for clinicians for identifying CIS patients with worse prognosis and planning the care.” Dr. Zimmermann and colleagues plan to use advanced imaging techniques in future studies to understand the mechanisms behind the associations they identified. They hope to confirm their findings in a larger cohort and examine whether OCT can predict clinical outcomes such as relapses, disability worsening, and the extent of disease activity.
Dr. Zimmermann had no relevant disclosures and did not report a source of funding for the study.
SOURCE: Zimmermann HG et al. ACTRIMS Forum 2020, Abstract.
WEST PALM BEACH, FLA. – according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that optical coherence tomography (OCT) could support patient monitoring and the initiation of disease-modifying therapy.
“Treatment of early MS [multiple sclerosis] is crucial to prevent neuroaxonal damage and, thus, sustained disability,” said Hanna G. Zimmermann, PhD, a research associate at NeuroCure Clinical Research Center at Charité Universitätsmedizin in Berlin. The ability to identify patients at high risk of future disease activity shortly after disease onset could help optimize patient management and guide the initiation of disease-modifying therapy. Dr. Zimmermann and colleagues investigated whether retinal OCT could predict disease activity in patients with CIS.
The investigators included 97 patients (mean age, 33.6 years; 62.9% female) with CIS in a prospective, longitudinal cohort study. Diagnoses of CIS were based on the 2010 revisions to the McDonald criteria. Patients were enrolled from two German centers within 12 months after a first clinical event. The researchers performed a neurologic examination, cerebral MRI, and retinal OCT for each participant and followed the population for 729 days (median, 664 days).
The primary OCT predictor was ganglion cell and inner plexiform (GCIP) layer thickness, because this parameter is stable and reliable for quantifying neuronal visual system damage in MS, said Dr. Zimmermann. Secondary OCT predictors were peripapillary retinal nerve fiber layer (pRNFL) thickness and inner nuclear layer (INL) thickness. The investigators only included eyes without a history of optic neuritis in the analysis.
The study’s primary outcome was failing the no evidence of disease activity (NEDA-3) criteria (no relapses, no disability progression, and no MRI activity). The secondary outcomes were MS diagnosis (according to the 2010 McDonald criteria) and worsening of disability.
At baseline, Dr. Zimmerman and colleagues found no differences in thickness of GCIP and pRNFL between patients and matched healthy controls. In all, 58 patients (59%) failed NEDA-3 criteria during follow-up. When Dr. Zimmermann and colleagues conducted Kaplan-Meier analysis, they found that patients with thinner GCIP thickness had a significantly higher risk of failing NEDA-3 criteria (thinnest vs. thickest tertile: hazard ratio, 3.33). A follow-up diagnosis of MS also was significantly more likely among patients with low GCIP thickness (thinnest vs. thickest tertile: HR, 4.05).
In addition, low pRNFL thickness indicated an increased risk of not meeting NEDA-3 criteria (thinnest vs. thickest tertile: HR, 2.46). However, neither INL thickness nor T2-weighted lesion count were associated with failing NEDA-3 criteria. Also, none of the OCT parameters were associated with future disability worsening.
Among the study’s limitations are its small sample size, the relatively short observation time, and the heterogeneity of patients between the two centers, which used different study protocols, said Dr. Zimmermann.
“OCT-assessed GCIP is promising for the early appraisal of future disease activity and might thus be helpful for risk-adjusted patient participation in clinical research,” she said. “It might also be helpful for clinicians for identifying CIS patients with worse prognosis and planning the care.” Dr. Zimmermann and colleagues plan to use advanced imaging techniques in future studies to understand the mechanisms behind the associations they identified. They hope to confirm their findings in a larger cohort and examine whether OCT can predict clinical outcomes such as relapses, disability worsening, and the extent of disease activity.
Dr. Zimmermann had no relevant disclosures and did not report a source of funding for the study.
SOURCE: Zimmermann HG et al. ACTRIMS Forum 2020, Abstract.
REPORTING FROM ACTRIMS FORUM 2020
Amyloid PET Findings Correlate With Cognitive Decline in MS
Key clinical point: Lower amyloid positron imaging tomography (PET) uptake in normal-appearing white matter (NAWM) is associated with cognitive decline and an increase in white matter lesion volume.
Major finding: Cognitive decline was associated with lower standardized uptake value relative to cerebellum in NAWM (1.52 in the cognitive decline group vs. 1.67 in the cognitively stable group; Mann-Whitney U test [U] = 42.0; P = .011), lower thalamic volume (13.84 vs. 15.61; U = 55.0; P = .059), and higher white matter lesion burden (15.25 vs. 9.17; U = 49.0; P = .029).
Study details: A prospective longitudinal PET study using 18F-florbetaben included 29 patients diagnosed with MS; the mean follow-up period was 18.00 ± 3.31 months.
Disclosures: The authors declared no conflicts of interest.
Citation: Pytel V et al. Mult Scler Relat Disord. 2020 Jan 2. doi: 10.1016/j.msard.2020.101926.
Key clinical point: Lower amyloid positron imaging tomography (PET) uptake in normal-appearing white matter (NAWM) is associated with cognitive decline and an increase in white matter lesion volume.
Major finding: Cognitive decline was associated with lower standardized uptake value relative to cerebellum in NAWM (1.52 in the cognitive decline group vs. 1.67 in the cognitively stable group; Mann-Whitney U test [U] = 42.0; P = .011), lower thalamic volume (13.84 vs. 15.61; U = 55.0; P = .059), and higher white matter lesion burden (15.25 vs. 9.17; U = 49.0; P = .029).
Study details: A prospective longitudinal PET study using 18F-florbetaben included 29 patients diagnosed with MS; the mean follow-up period was 18.00 ± 3.31 months.
Disclosures: The authors declared no conflicts of interest.
Citation: Pytel V et al. Mult Scler Relat Disord. 2020 Jan 2. doi: 10.1016/j.msard.2020.101926.
Key clinical point: Lower amyloid positron imaging tomography (PET) uptake in normal-appearing white matter (NAWM) is associated with cognitive decline and an increase in white matter lesion volume.
Major finding: Cognitive decline was associated with lower standardized uptake value relative to cerebellum in NAWM (1.52 in the cognitive decline group vs. 1.67 in the cognitively stable group; Mann-Whitney U test [U] = 42.0; P = .011), lower thalamic volume (13.84 vs. 15.61; U = 55.0; P = .059), and higher white matter lesion burden (15.25 vs. 9.17; U = 49.0; P = .029).
Study details: A prospective longitudinal PET study using 18F-florbetaben included 29 patients diagnosed with MS; the mean follow-up period was 18.00 ± 3.31 months.
Disclosures: The authors declared no conflicts of interest.
Citation: Pytel V et al. Mult Scler Relat Disord. 2020 Jan 2. doi: 10.1016/j.msard.2020.101926.
Mothers of Children With MS More Likely to Use Mental Health Services
Key clinical point: Mothers of children with MS are more likely to use mental health services before and after their child’s diagnosis with multiple sclerosis (MS) than mothers of children without MS.
Major finding: The prevalence of any physical condition and mood or anxiety disorder was higher in MS-mothers vs. non-MS-mothers. The odds of having any psychiatry visit was significantly increased in MS-mothers (odds ratio, 1.60; 95% confidence interval [CI], 1.10-2.31). The annual rate of psychiatry visits did not differ between MS-mothers and non-MS-mothers (rate ratio, 0.66; 95% CI, 0.33-1.30).
Study details: A population-based retrospective matched cohort study of 156 MS-mothers and 624 non-MS mothers.
Disclosures: This study was funded by the Multiple Sclerosis Scientific Research Foundation. Dr. Marrie received research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, and CMSC and was supported by the Waugh Family Chair in Multiple Sclerosis.
Citation: Marrie RA et al. Neurology. 2020 Jan 9. doi: 10.1212/WNL.0000000000008871.
Key clinical point: Mothers of children with MS are more likely to use mental health services before and after their child’s diagnosis with multiple sclerosis (MS) than mothers of children without MS.
Major finding: The prevalence of any physical condition and mood or anxiety disorder was higher in MS-mothers vs. non-MS-mothers. The odds of having any psychiatry visit was significantly increased in MS-mothers (odds ratio, 1.60; 95% confidence interval [CI], 1.10-2.31). The annual rate of psychiatry visits did not differ between MS-mothers and non-MS-mothers (rate ratio, 0.66; 95% CI, 0.33-1.30).
Study details: A population-based retrospective matched cohort study of 156 MS-mothers and 624 non-MS mothers.
Disclosures: This study was funded by the Multiple Sclerosis Scientific Research Foundation. Dr. Marrie received research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, and CMSC and was supported by the Waugh Family Chair in Multiple Sclerosis.
Citation: Marrie RA et al. Neurology. 2020 Jan 9. doi: 10.1212/WNL.0000000000008871.
Key clinical point: Mothers of children with MS are more likely to use mental health services before and after their child’s diagnosis with multiple sclerosis (MS) than mothers of children without MS.
Major finding: The prevalence of any physical condition and mood or anxiety disorder was higher in MS-mothers vs. non-MS-mothers. The odds of having any psychiatry visit was significantly increased in MS-mothers (odds ratio, 1.60; 95% confidence interval [CI], 1.10-2.31). The annual rate of psychiatry visits did not differ between MS-mothers and non-MS-mothers (rate ratio, 0.66; 95% CI, 0.33-1.30).
Study details: A population-based retrospective matched cohort study of 156 MS-mothers and 624 non-MS mothers.
Disclosures: This study was funded by the Multiple Sclerosis Scientific Research Foundation. Dr. Marrie received research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, and CMSC and was supported by the Waugh Family Chair in Multiple Sclerosis.
Citation: Marrie RA et al. Neurology. 2020 Jan 9. doi: 10.1212/WNL.0000000000008871.
Low Vitamin D and BMI Are Causal Factors for MS
Key clinical point: Vitamin D and body mass index (BMI) are independent causal risk factors for multiple sclerosis (MS) in adulthood and childhood.
Major finding: Genetically determined increased childhood BMI and adult BMI were associated with a 24% and 14% higher risk of MS, respectively. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% reduction in the MS risk.
Study details: A 2-sample Mendelian randomization study estimated the effect of BMI and vitamin D status on MS risk; associations of single-nucleotide polymorphisms with both the risk factors of interest were obtained from the relevant consortia.
Disclosures: This study was funded through a grant from the Barts Charity. The authors declared no conflicts of interest.
Citation: Jacobs BM et al. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 14. doi: 10.1212/NXI.0000000000000662.
Key clinical point: Vitamin D and body mass index (BMI) are independent causal risk factors for multiple sclerosis (MS) in adulthood and childhood.
Major finding: Genetically determined increased childhood BMI and adult BMI were associated with a 24% and 14% higher risk of MS, respectively. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% reduction in the MS risk.
Study details: A 2-sample Mendelian randomization study estimated the effect of BMI and vitamin D status on MS risk; associations of single-nucleotide polymorphisms with both the risk factors of interest were obtained from the relevant consortia.
Disclosures: This study was funded through a grant from the Barts Charity. The authors declared no conflicts of interest.
Citation: Jacobs BM et al. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 14. doi: 10.1212/NXI.0000000000000662.
Key clinical point: Vitamin D and body mass index (BMI) are independent causal risk factors for multiple sclerosis (MS) in adulthood and childhood.
Major finding: Genetically determined increased childhood BMI and adult BMI were associated with a 24% and 14% higher risk of MS, respectively. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% reduction in the MS risk.
Study details: A 2-sample Mendelian randomization study estimated the effect of BMI and vitamin D status on MS risk; associations of single-nucleotide polymorphisms with both the risk factors of interest were obtained from the relevant consortia.
Disclosures: This study was funded through a grant from the Barts Charity. The authors declared no conflicts of interest.
Citation: Jacobs BM et al. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 14. doi: 10.1212/NXI.0000000000000662.