ICYMI Multiple Sclerosis

DALLAS – A battery of smartphone tests have been developed to help clinicians detect and monitor eye changes in MS patients.

At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, Randy H. Kardon, MD, PhD, said that there are two main high priority gaps to fill when it comes to better understanding the effects of MS on vision. “One, I think we need a way for early detection of visual pathway disturbances after either an acute clinical event or a subclinical event,” said Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City. “Two, we need to monitor changes in the visual pathway over time in MS patients and capture variations due to changes in nerve conduction. The idea is, can we have a suite of smartphone tests that you can use in the clinic, but the patient can also use at home unsupervised, to get a time domain, so if there are fluctuations of core body temperature due to myelination, or subclinical changes going on, could we detect it earlier and monitor these patients? That’s the motivation.”

Doug Brunk/MDedge News

Although use of smartphone technology and mobile devices are emerging in health care settings, most of this technology is used sparingly in vision testing, mostly due to a lack of rigorous calibration of instruments and validation, said Dr. Kardon, who also directs the Iowa City VA Center for Prevention and Treatment of Visual Loss. To make a visual smartphone test viable, he continued, the visual output of the device must match the intended input in terms of multiple parameters (technical validation). Important parameters for vision tests include brightness, luminance, spatial resolution, and temporal resolution. Confounding variables include ambient lighting and viewing distance.

In his work with researchers from Aalborg University in Denmark, Dr. Kardon has developed four smartphone visual tests intended to be intuitive for patients. “We didn’t want something that was going to take more than 15 seconds,” he said. The visual tests include:

1. Critical flicker fusion, a test of optic nerve conduction. “This tests how well you can see a light flickering at a given temporal frequency at different levels of contrast, or how fast it can flicker before you don’t see a flicker anymore,” Dr. Kardon said. “The user sees spots that are flickering and just touches the ones they perceive to be flickering; they eliminate them by touching them.” When the test ends, the software “brackets what they did to a finer scale, and it finds the contrast at which that flicker wasn’t perceived anymore.”

2. The Landolt C visual acuity test. For this, the user must indicate the direction of the gap in the ring in a forced-choice task. “The user touches which arrow on the screen is pointing to where the location of the break in the Landolt C is perceived,” Dr. Kardon said. The Landolt C becomes progressively smaller until the location of the break can no longer be seen. “It’s pretty simple, and it finds the smallest size of the ‘C’ at which you’re making mistakes about 50% of the time, which is the threshold value for visual acuity,” he said.

3. Contrast sensitivity test at a fixed spatial frequency. “In this test, we fix the size of the letter to a large size, so spatial frequency is not at play, and we vary the contrast,” he said. “Users push the arrow wherever they see the break.” The contrast between the “C” and the background is sequentially reduced until a threshold is determined for the lowest contrast at which the location of the break in the “C” can still be observed.

4. Contrast sensitivity test at different spatial frequencies. This measure, also known as a vanishing optotype, is a line drawing of an object on a smooth, diffuse grayscale background. By altering the line properties used to define the shape of the vanishing optotype, one can vary its spatial frequency and contrast independent of target size. “This makes it an easy test because what the patient is asked to do is to touch wherever they see an object on the screen to eliminate it from the series of optotypes on the screen,” Dr. Kardon said. “The test is very fast, very intuitive.”

The researchers piloted use of these tests in a study of 104 age-matched control subjects and 117 MS patients. Of the 117 MS patients, 74 had a history of optic neuritis and 43 did not. The four tests were used in conjunction with standardized assessments, including the near-contrast acuity card test at 2.5%, the distant Early Treatment Diabetic Retinopathy Study (ETDRS) acuity test, as well as optical coherence tomography (OCT) of the retinal nerve fiber layer and ganglion cell layer thickness. Dr. Kardon and his colleagues found that when clinicians used a large target and varied the contrast, the test “did very well at differentiating normal from eyes with either previous optic neuritis or no previous optic neuritis,” he said. “It also differentiated eyes with previous optic neuritis and those with no optic neuritis. The visual acuity test didn’t perform as well because this is a near test. What we discovered afterward is that even at a fixed distance, many people who are presbyopic, or don’t have their optimal near correction, don’t do so well, because you’re testing spatial acuity. That’s a warning sign for future tests. You have to be careful as to how these are interpreted if they don’t have their best correction at near.”

Results from the critical flicker fusions tests were significant, except that they didn’t differentiate eyes affected by optic neuritis from those that weren’t. “The reason is that conduction was down in all of those eyes, so the combination of using contrast sensitivity and flicker fusion may not only help you diagnose MS, but whether that eye had been involved with optic neuritis before,” Dr. Kardon said. To date, he and his colleagues have completed technical validation of temporal frequency and contrast parameters. They’ve also completed preliminary investigations for determining test-retest variability, blurring effects, binocular summation effects, and quantification of normative ranges and abnormal subject data.

“A benefit of smartphone testing in MS is that visual dysfunction can be detected, leading to earlier interventions,” Dr. Kardon concluded. “We can study this on a time scale that wasn’t previously available. Wouldn’t you like to know on a daily or even a weekly basis what the fluctuations are in a home environment for MS patients? It’s low-cost, large-scale, and enables you to study genotype-phenotype comparisons.”

Going forward, Dr. Kardon and his colleagues have developed video cameras that go around the periphery of the iPad that can assess pupil and ocular motility, as well as eyelid and facial features in real time. He disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

dbrunk@mdedge.com

DALLAS – A battery of smartphone tests have been developed to help clinicians detect and monitor eye changes in MS patients.

At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, Randy H. Kardon, MD, PhD, said that there are two main high priority gaps to fill when it comes to better understanding the effects of MS on vision. “One, I think we need a way for early detection of visual pathway disturbances after either an acute clinical event or a subclinical event,” said Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City. “Two, we need to monitor changes in the visual pathway over time in MS patients and capture variations due to changes in nerve conduction. The idea is, can we have a suite of smartphone tests that you can use in the clinic, but the patient can also use at home unsupervised, to get a time domain, so if there are fluctuations of core body temperature due to myelination, or subclinical changes going on, could we detect it earlier and monitor these patients? That’s the motivation.”

Doug Brunk/MDedge News

Although use of smartphone technology and mobile devices are emerging in health care settings, most of this technology is used sparingly in vision testing, mostly due to a lack of rigorous calibration of instruments and validation, said Dr. Kardon, who also directs the Iowa City VA Center for Prevention and Treatment of Visual Loss. To make a visual smartphone test viable, he continued, the visual output of the device must match the intended input in terms of multiple parameters (technical validation). Important parameters for vision tests include brightness, luminance, spatial resolution, and temporal resolution. Confounding variables include ambient lighting and viewing distance.

In his work with researchers from Aalborg University in Denmark, Dr. Kardon has developed four smartphone visual tests intended to be intuitive for patients. “We didn’t want something that was going to take more than 15 seconds,” he said. The visual tests include:

1. Critical flicker fusion, a test of optic nerve conduction. “This tests how well you can see a light flickering at a given temporal frequency at different levels of contrast, or how fast it can flicker before you don’t see a flicker anymore,” Dr. Kardon said. “The user sees spots that are flickering and just touches the ones they perceive to be flickering; they eliminate them by touching them.” When the test ends, the software “brackets what they did to a finer scale, and it finds the contrast at which that flicker wasn’t perceived anymore.”

2. The Landolt C visual acuity test. For this, the user must indicate the direction of the gap in the ring in a forced-choice task. “The user touches which arrow on the screen is pointing to where the location of the break in the Landolt C is perceived,” Dr. Kardon said. The Landolt C becomes progressively smaller until the location of the break can no longer be seen. “It’s pretty simple, and it finds the smallest size of the ‘C’ at which you’re making mistakes about 50% of the time, which is the threshold value for visual acuity,” he said.

3. Contrast sensitivity test at a fixed spatial frequency. “In this test, we fix the size of the letter to a large size, so spatial frequency is not at play, and we vary the contrast,” he said. “Users push the arrow wherever they see the break.” The contrast between the “C” and the background is sequentially reduced until a threshold is determined for the lowest contrast at which the location of the break in the “C” can still be observed.

4. Contrast sensitivity test at different spatial frequencies. This measure, also known as a vanishing optotype, is a line drawing of an object on a smooth, diffuse grayscale background. By altering the line properties used to define the shape of the vanishing optotype, one can vary its spatial frequency and contrast independent of target size. “This makes it an easy test because what the patient is asked to do is to touch wherever they see an object on the screen to eliminate it from the series of optotypes on the screen,” Dr. Kardon said. “The test is very fast, very intuitive.”

The researchers piloted use of these tests in a study of 104 age-matched control subjects and 117 MS patients. Of the 117 MS patients, 74 had a history of optic neuritis and 43 did not. The four tests were used in conjunction with standardized assessments, including the near-contrast acuity card test at 2.5%, the distant Early Treatment Diabetic Retinopathy Study (ETDRS) acuity test, as well as optical coherence tomography (OCT) of the retinal nerve fiber layer and ganglion cell layer thickness. Dr. Kardon and his colleagues found that when clinicians used a large target and varied the contrast, the test “did very well at differentiating normal from eyes with either previous optic neuritis or no previous optic neuritis,” he said. “It also differentiated eyes with previous optic neuritis and those with no optic neuritis. The visual acuity test didn’t perform as well because this is a near test. What we discovered afterward is that even at a fixed distance, many people who are presbyopic, or don’t have their optimal near correction, don’t do so well, because you’re testing spatial acuity. That’s a warning sign for future tests. You have to be careful as to how these are interpreted if they don’t have their best correction at near.”

Results from the critical flicker fusions tests were significant, except that they didn’t differentiate eyes affected by optic neuritis from those that weren’t. “The reason is that conduction was down in all of those eyes, so the combination of using contrast sensitivity and flicker fusion may not only help you diagnose MS, but whether that eye had been involved with optic neuritis before,” Dr. Kardon said. To date, he and his colleagues have completed technical validation of temporal frequency and contrast parameters. They’ve also completed preliminary investigations for determining test-retest variability, blurring effects, binocular summation effects, and quantification of normative ranges and abnormal subject data.

“A benefit of smartphone testing in MS is that visual dysfunction can be detected, leading to earlier interventions,” Dr. Kardon concluded. “We can study this on a time scale that wasn’t previously available. Wouldn’t you like to know on a daily or even a weekly basis what the fluctuations are in a home environment for MS patients? It’s low-cost, large-scale, and enables you to study genotype-phenotype comparisons.”

Going forward, Dr. Kardon and his colleagues have developed video cameras that go around the periphery of the iPad that can assess pupil and ocular motility, as well as eyelid and facial features in real time. He disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

dbrunk@mdedge.com

DALLAS – A battery of smartphone tests have been developed to help clinicians detect and monitor eye changes in MS patients.

At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, Randy H. Kardon, MD, PhD, said that there are two main high priority gaps to fill when it comes to better understanding the effects of MS on vision. “One, I think we need a way for early detection of visual pathway disturbances after either an acute clinical event or a subclinical event,” said Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City. “Two, we need to monitor changes in the visual pathway over time in MS patients and capture variations due to changes in nerve conduction. The idea is, can we have a suite of smartphone tests that you can use in the clinic, but the patient can also use at home unsupervised, to get a time domain, so if there are fluctuations of core body temperature due to myelination, or subclinical changes going on, could we detect it earlier and monitor these patients? That’s the motivation.”

Doug Brunk/MDedge News

Although use of smartphone technology and mobile devices are emerging in health care settings, most of this technology is used sparingly in vision testing, mostly due to a lack of rigorous calibration of instruments and validation, said Dr. Kardon, who also directs the Iowa City VA Center for Prevention and Treatment of Visual Loss. To make a visual smartphone test viable, he continued, the visual output of the device must match the intended input in terms of multiple parameters (technical validation). Important parameters for vision tests include brightness, luminance, spatial resolution, and temporal resolution. Confounding variables include ambient lighting and viewing distance.

In his work with researchers from Aalborg University in Denmark, Dr. Kardon has developed four smartphone visual tests intended to be intuitive for patients. “We didn’t want something that was going to take more than 15 seconds,” he said. The visual tests include:

1. Critical flicker fusion, a test of optic nerve conduction. “This tests how well you can see a light flickering at a given temporal frequency at different levels of contrast, or how fast it can flicker before you don’t see a flicker anymore,” Dr. Kardon said. “The user sees spots that are flickering and just touches the ones they perceive to be flickering; they eliminate them by touching them.” When the test ends, the software “brackets what they did to a finer scale, and it finds the contrast at which that flicker wasn’t perceived anymore.”

2. The Landolt C visual acuity test. For this, the user must indicate the direction of the gap in the ring in a forced-choice task. “The user touches which arrow on the screen is pointing to where the location of the break in the Landolt C is perceived,” Dr. Kardon said. The Landolt C becomes progressively smaller until the location of the break can no longer be seen. “It’s pretty simple, and it finds the smallest size of the ‘C’ at which you’re making mistakes about 50% of the time, which is the threshold value for visual acuity,” he said.

3. Contrast sensitivity test at a fixed spatial frequency. “In this test, we fix the size of the letter to a large size, so spatial frequency is not at play, and we vary the contrast,” he said. “Users push the arrow wherever they see the break.” The contrast between the “C” and the background is sequentially reduced until a threshold is determined for the lowest contrast at which the location of the break in the “C” can still be observed.

4. Contrast sensitivity test at different spatial frequencies. This measure, also known as a vanishing optotype, is a line drawing of an object on a smooth, diffuse grayscale background. By altering the line properties used to define the shape of the vanishing optotype, one can vary its spatial frequency and contrast independent of target size. “This makes it an easy test because what the patient is asked to do is to touch wherever they see an object on the screen to eliminate it from the series of optotypes on the screen,” Dr. Kardon said. “The test is very fast, very intuitive.”

The researchers piloted use of these tests in a study of 104 age-matched control subjects and 117 MS patients. Of the 117 MS patients, 74 had a history of optic neuritis and 43 did not. The four tests were used in conjunction with standardized assessments, including the near-contrast acuity card test at 2.5%, the distant Early Treatment Diabetic Retinopathy Study (ETDRS) acuity test, as well as optical coherence tomography (OCT) of the retinal nerve fiber layer and ganglion cell layer thickness. Dr. Kardon and his colleagues found that when clinicians used a large target and varied the contrast, the test “did very well at differentiating normal from eyes with either previous optic neuritis or no previous optic neuritis,” he said. “It also differentiated eyes with previous optic neuritis and those with no optic neuritis. The visual acuity test didn’t perform as well because this is a near test. What we discovered afterward is that even at a fixed distance, many people who are presbyopic, or don’t have their optimal near correction, don’t do so well, because you’re testing spatial acuity. That’s a warning sign for future tests. You have to be careful as to how these are interpreted if they don’t have their best correction at near.”

Results from the critical flicker fusions tests were significant, except that they didn’t differentiate eyes affected by optic neuritis from those that weren’t. “The reason is that conduction was down in all of those eyes, so the combination of using contrast sensitivity and flicker fusion may not only help you diagnose MS, but whether that eye had been involved with optic neuritis before,” Dr. Kardon said. To date, he and his colleagues have completed technical validation of temporal frequency and contrast parameters. They’ve also completed preliminary investigations for determining test-retest variability, blurring effects, binocular summation effects, and quantification of normative ranges and abnormal subject data.

“A benefit of smartphone testing in MS is that visual dysfunction can be detected, leading to earlier interventions,” Dr. Kardon concluded. “We can study this on a time scale that wasn’t previously available. Wouldn’t you like to know on a daily or even a weekly basis what the fluctuations are in a home environment for MS patients? It’s low-cost, large-scale, and enables you to study genotype-phenotype comparisons.”

Going forward, Dr. Kardon and his colleagues have developed video cameras that go around the periphery of the iPad that can assess pupil and ocular motility, as well as eyelid and facial features in real time. He disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

dbrunk@mdedge.com

DALLAS – An analysis of two large cohorts treated with rituximab (Rituxan) showed that the rate of serious infections was 8.1%, yet no life-threatening infusion reactions occurred.

The finding comes from a retrospective chart review of 500 patients treated at the Rocky Mountain Multiple Sclerosis Center at the University of Colorado at Denver, Aurora, and 269 treated at the New York University Multiple Sclerosis Comprehensive Care Center.

Doug Brunk/MDedge News

At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, one of the study authors, Brandi L. Vollmer, MPH, noted that while rituximab is used off-label to treat multiple sclerosis (MS) and related disorders, limited long-term data for MS patients exist. Ms. Vollmer, a professional research assistant in the department of neurology in the division of neuroimmunology at the University of Colorado at Denver, and her associates identified all patients at the two MS centers who received at least one dose of rituximab. They reviewed patient charts from rituximab start date until 12 months after the last rituximab end date, or last ocrelizumab (Ocrevus) infusion in cases where patients switched to ocrelizumab without interruption with any other disease-modifying therapy. Data were abstracted from each chart using a case report form that systematically queried for demographic and clinical characteristics, serious adverse events, and significant laboratory abnormalities. The researchers used descriptive statistics to describe the sample group.

Key outcomes of interest were infusion reactions that were life-threatening or resulted in a hospitalization; infections that resulted in hospitalization, the need for IV antibiotics, or extended antibiotics; abnormal lab values; new diagnosis of malignant cancer; new diagnosis of autoimmune disease; diagnosis of serious thromboembolism; and mortality within 12 months of last infusion. At baseline, the mean age of the 769 patients was 43 years, 69% were female, 64% were white, and 16% were black. More than half (58%) had a diagnosis of relapsing-remitting MS, followed by secondary progressive MS (20%), primary progressive MS (11%), neuromyelitis optica spectrum disorder (9%), or other, and their mean disease duration was 8 years.

The researchers reported that the mean cumulative rituximab dose was 4,124 mg (median of 3,000 mg), the mean dose of ocrelizumab for ocrelizumab-switchers was 1,087 mg, and the mean time of follow-up was 33 months. Infections while on rituximab/ocrelizumab resulting in a hospitalization were observed in 50 patients (6.5%), which were primarily urinary tract infections (UTIs; 19 cases), pneumonia (12 cases), and sepsis (12 cases), while 7 patients (0.9%) experienced an infection that resulted in extended dosing antibiotics, including 5 recurrent UTIs, 1 case of bacteremia, and 1 case of osteomyelitis.

Ms. Vollmer and her colleagues also found that five patients (0.7%) experienced an infection that resulted in IV antibiotics without hospitalization, including one case each of pneumonia, cellulitis, UTI, infected wound, and aspiration pneumonia with respiratory syncytial virus. Serious de novo diagnoses while on rituximab were reported for 18 patients (2%), including autoimmune disease in 4, non-skin neoplasm in 7, and serious thromboembolic events in 7.

No patient experienced an infusion reaction requiring hospitalization. However, one patient received epinephrine after seeking care at an emergency department post infusion. Twelve patients (2%) died within 12 months of their last rituximab dose, although none were deemed by the treating clinician to be related to rituximab. Significant neutropenia was observed in 12 (2%), lymphopenia in 46 (6%), and IgG values below 500 mg/dL in 28 (4%).

“So far, this is just a descriptive analysis,” Ms. Vollmer said. “We want to look further into how abnormal lab values correlate with serious infections in particular.”

She acknowledged certain limitations of the study, including its retrospective design. Ms. Vollmer reported having no financial disclosures. Many of her coauthors reporting having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

SOURCE: Vollmer B et al. ACTRIMS Forum 2019, Poster 113

DALLAS – An analysis of two large cohorts treated with rituximab (Rituxan) showed that the rate of serious infections was 8.1%, yet no life-threatening infusion reactions occurred.

The finding comes from a retrospective chart review of 500 patients treated at the Rocky Mountain Multiple Sclerosis Center at the University of Colorado at Denver, Aurora, and 269 treated at the New York University Multiple Sclerosis Comprehensive Care Center.

Doug Brunk/MDedge News

At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, one of the study authors, Brandi L. Vollmer, MPH, noted that while rituximab is used off-label to treat multiple sclerosis (MS) and related disorders, limited long-term data for MS patients exist. Ms. Vollmer, a professional research assistant in the department of neurology in the division of neuroimmunology at the University of Colorado at Denver, and her associates identified all patients at the two MS centers who received at least one dose of rituximab. They reviewed patient charts from rituximab start date until 12 months after the last rituximab end date, or last ocrelizumab (Ocrevus) infusion in cases where patients switched to ocrelizumab without interruption with any other disease-modifying therapy. Data were abstracted from each chart using a case report form that systematically queried for demographic and clinical characteristics, serious adverse events, and significant laboratory abnormalities. The researchers used descriptive statistics to describe the sample group.

Key outcomes of interest were infusion reactions that were life-threatening or resulted in a hospitalization; infections that resulted in hospitalization, the need for IV antibiotics, or extended antibiotics; abnormal lab values; new diagnosis of malignant cancer; new diagnosis of autoimmune disease; diagnosis of serious thromboembolism; and mortality within 12 months of last infusion. At baseline, the mean age of the 769 patients was 43 years, 69% were female, 64% were white, and 16% were black. More than half (58%) had a diagnosis of relapsing-remitting MS, followed by secondary progressive MS (20%), primary progressive MS (11%), neuromyelitis optica spectrum disorder (9%), or other, and their mean disease duration was 8 years.

The researchers reported that the mean cumulative rituximab dose was 4,124 mg (median of 3,000 mg), the mean dose of ocrelizumab for ocrelizumab-switchers was 1,087 mg, and the mean time of follow-up was 33 months. Infections while on rituximab/ocrelizumab resulting in a hospitalization were observed in 50 patients (6.5%), which were primarily urinary tract infections (UTIs; 19 cases), pneumonia (12 cases), and sepsis (12 cases), while 7 patients (0.9%) experienced an infection that resulted in extended dosing antibiotics, including 5 recurrent UTIs, 1 case of bacteremia, and 1 case of osteomyelitis.

Ms. Vollmer and her colleagues also found that five patients (0.7%) experienced an infection that resulted in IV antibiotics without hospitalization, including one case each of pneumonia, cellulitis, UTI, infected wound, and aspiration pneumonia with respiratory syncytial virus. Serious de novo diagnoses while on rituximab were reported for 18 patients (2%), including autoimmune disease in 4, non-skin neoplasm in 7, and serious thromboembolic events in 7.

No patient experienced an infusion reaction requiring hospitalization. However, one patient received epinephrine after seeking care at an emergency department post infusion. Twelve patients (2%) died within 12 months of their last rituximab dose, although none were deemed by the treating clinician to be related to rituximab. Significant neutropenia was observed in 12 (2%), lymphopenia in 46 (6%), and IgG values below 500 mg/dL in 28 (4%).

“So far, this is just a descriptive analysis,” Ms. Vollmer said. “We want to look further into how abnormal lab values correlate with serious infections in particular.”

She acknowledged certain limitations of the study, including its retrospective design. Ms. Vollmer reported having no financial disclosures. Many of her coauthors reporting having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

SOURCE: Vollmer B et al. ACTRIMS Forum 2019, Poster 113

DALLAS – An analysis of two large cohorts treated with rituximab (Rituxan) showed that the rate of serious infections was 8.1%, yet no life-threatening infusion reactions occurred.

The finding comes from a retrospective chart review of 500 patients treated at the Rocky Mountain Multiple Sclerosis Center at the University of Colorado at Denver, Aurora, and 269 treated at the New York University Multiple Sclerosis Comprehensive Care Center.

Doug Brunk/MDedge News

At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, one of the study authors, Brandi L. Vollmer, MPH, noted that while rituximab is used off-label to treat multiple sclerosis (MS) and related disorders, limited long-term data for MS patients exist. Ms. Vollmer, a professional research assistant in the department of neurology in the division of neuroimmunology at the University of Colorado at Denver, and her associates identified all patients at the two MS centers who received at least one dose of rituximab. They reviewed patient charts from rituximab start date until 12 months after the last rituximab end date, or last ocrelizumab (Ocrevus) infusion in cases where patients switched to ocrelizumab without interruption with any other disease-modifying therapy. Data were abstracted from each chart using a case report form that systematically queried for demographic and clinical characteristics, serious adverse events, and significant laboratory abnormalities. The researchers used descriptive statistics to describe the sample group.

Key outcomes of interest were infusion reactions that were life-threatening or resulted in a hospitalization; infections that resulted in hospitalization, the need for IV antibiotics, or extended antibiotics; abnormal lab values; new diagnosis of malignant cancer; new diagnosis of autoimmune disease; diagnosis of serious thromboembolism; and mortality within 12 months of last infusion. At baseline, the mean age of the 769 patients was 43 years, 69% were female, 64% were white, and 16% were black. More than half (58%) had a diagnosis of relapsing-remitting MS, followed by secondary progressive MS (20%), primary progressive MS (11%), neuromyelitis optica spectrum disorder (9%), or other, and their mean disease duration was 8 years.

The researchers reported that the mean cumulative rituximab dose was 4,124 mg (median of 3,000 mg), the mean dose of ocrelizumab for ocrelizumab-switchers was 1,087 mg, and the mean time of follow-up was 33 months. Infections while on rituximab/ocrelizumab resulting in a hospitalization were observed in 50 patients (6.5%), which were primarily urinary tract infections (UTIs; 19 cases), pneumonia (12 cases), and sepsis (12 cases), while 7 patients (0.9%) experienced an infection that resulted in extended dosing antibiotics, including 5 recurrent UTIs, 1 case of bacteremia, and 1 case of osteomyelitis.

Ms. Vollmer and her colleagues also found that five patients (0.7%) experienced an infection that resulted in IV antibiotics without hospitalization, including one case each of pneumonia, cellulitis, UTI, infected wound, and aspiration pneumonia with respiratory syncytial virus. Serious de novo diagnoses while on rituximab were reported for 18 patients (2%), including autoimmune disease in 4, non-skin neoplasm in 7, and serious thromboembolic events in 7.

No patient experienced an infusion reaction requiring hospitalization. However, one patient received epinephrine after seeking care at an emergency department post infusion. Twelve patients (2%) died within 12 months of their last rituximab dose, although none were deemed by the treating clinician to be related to rituximab. Significant neutropenia was observed in 12 (2%), lymphopenia in 46 (6%), and IgG values below 500 mg/dL in 28 (4%).

“So far, this is just a descriptive analysis,” Ms. Vollmer said. “We want to look further into how abnormal lab values correlate with serious infections in particular.”

She acknowledged certain limitations of the study, including its retrospective design. Ms. Vollmer reported having no financial disclosures. Many of her coauthors reporting having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

SOURCE: Vollmer B et al. ACTRIMS Forum 2019, Poster 113

DALLAS – Optical coherence tomography (OCT) has emerged as a promising biomarker in multiple sclerosis.

Doug Brunk/MDedge News

Thanks to OCT, clinicians are gaining an improved understanding of how MS affects certain eye structures. An optical analogue of ultrasound B mode imaging, OCT achieves a resolution of about 3-6 microns with commercially available devices. “That allows us to quantify the layers of the retina with quite a degree of accuracy,” Shiv Saidha, MD, said at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

At postmortem, up to 99% of MS patients have demyelinated plaques in their optic nerves. “This implies that optic neuropathy is an ubiquitous phenomenon as part of the MS disease process,” said Dr. Saidha, a neurologist at Johns Hopkins University, Baltimore. “The prevailing hypothesis is that there is demyelination or axonal transection related to acute inflammation that occurs within the optic nerve. There’s a retrograde degeneration of its constituent axons, and that results in thinning of the inner retinal nerve fiber layer as well as the neuronal derivative of this layer called the ganglion cell layer. In addition to neurodegenerative mechanisms in the retina, there is also perivascular inflammation, called retinal periphlebitis, which we know occurs in about 20% of MS patients. At postmortem, there are also activate microglia present within the retina of MS patients.”


One of the principal findings of OCT in MS to date is that the retinal nerve fiber layer (RNFL) and ganglion cell plus inner plexiform layer (GCIP) thinning reflects MS-related optic nerve neurodegeneration. In addition, RNFL and GCIP thinning occur after optic neuritis and also as part of the MS disease course in eyes without a history of optic neuritis. “RNFL and GCIP thinning in MS are clinically relevant and correlate with visual function, global disability, and brain atrophy,” Dr. Saidha said. Researchers have also found that rates of GCIP thinning are accelerated in MS patients exhibiting clinical and/or radiological disease activity and are altered by disease-modifying therapies, and that increased inner nuclear layer (INL) thickness correlates with T2 lesion volume and predicts clinical and radiological disease activity. “In numerous trials of putatively neuroprotective and restorative treatments, we see OCT incorporated more and more, either as a secondary or a primary outcome,” he said.

Predicting disability and brain atrophy

In a study expected to be appear in a forthcoming issue of the Annals of Translational and Clinical Neurology, colleagues of Dr. Saidha found that OCT derived retinal layer measurements and visual function predict disability at 10 years in patients with MS. The researchers used an earlier generation, lower quality OCT device to examine tertiles of total macular volume, “an old, nonspecific composite measure of all of the retinal components,” he explained. “Even with inferior technology, a single measurement at a point in time not only could predict the change in EDSS [Expanded Disability Status Scale] scores from baseline to 10 years, but the accumulation of meaningful disability.”

In an earlier study, Dr. Saidha and his colleagues conducted a 4-year study of OCT and MRI in MS (Ann Neurol 2015; 78[5]:801-13). It consisted of six monthly spectral domain OCT scans (including automated intra-retinal segmentation) and baseline and annual 3 T brain MRI (including substructure volumetrics). Patients with ocular relapses (optic neuritis) during the study were excluded. The researchers correlated individual-specific rates of change in retinal and brain measurements, adjusting for age, sex, disease duration, and optic neuritis history. They found that cerebral volume fraction (analogous to whole brain volume) “had a decent correlation between rates of GCIP atrophy and rates of whole brain volume loss,” he said. “That was predominately driven by cortical gray matter atrophy.”

Measuring effects of disease-modifying therapies

What about the effects of disease-modifying therapies? According to Dr. Saidha, there has been a paucity of studies assessing the effects of DMTs on retinal layer thickness, and they are limited by small patient numbers, cross-sectional design, and/or short periods of observation. In a retrospective analysis, he and his associates examined the effects of treatments in relapsing-remitting MS patients at his center who underwent OCT (Neurology. 2017;88[6]:525-32). Over a mean 3 years of follow-up, they examined the effects of glatiramer acetate (Copaxone), natalizumab (Tysabri), and interferon beta-1a subcutaneously (Rebif) and intramuscularly (Avonex). They adjusted for gap time, which is the interval between when a patient started a treatment and when they started to undergo retinal observation with OCT. “This is to try to account for some of the biological changes that might have occurred during that period of time,” he explained. The researchers observed that rates of GCIP atrophy as well as other retinal measures were significantly lower in people treated with natalizumab, relative to all other DMTs. “What I found fascinating was the rate of GCIP atrophy of those on natalizumab was basically the same as healthy controls,” Dr. Saidha said. “It didn’t differ.”

Retinal inflammation and treatment’s impact

Significant inflammation in the unmyelinated retina may inform clinicians about other aspects of MS, he continued. For example, retinal periphlebitis occurs in about 20% of MS patients and may be a marker of CNS inflammation. In addition, intermediate uveitis occurs in about 16% of MS patients, and postmortem studies reveal retinal inflammation with microglia. Specifically, macular microcystoid changes occur in the eyes of about 5% of MS patients and may represent a breakdown of the blood-retinal barrier and inflammation. “Since it’s a dynamic process, increased thickness of the INL in the absence of visible microcystoid changes might occur,” Dr. Saidha said. “We found that baseline INL thickness is predictive of clinico-radiologic disease activity.”

In a separate analysis of 108 MS patients and 40 healthy controls, German researchers evaluated the impact of DMTs on INL volume (Brain. 2016;11[1]:2855-63). They found that higher baseline INL volume correlated with new T2 and GAD lesions over 1 year. The reduction in INL volume was significantly associated with reduced activity, and overall, DMTs reduced INL volume over 6 months. Patients who were not treated, or who were treated and did not achieve NEDA-3 (no evidence of disease activity) did not show reductions in INL volume. They concluded that INL volume might be a novel outcome of DMT treatment.

Finding prognostic and diagnostic biomarkers

In an ongoing multisite study, Dr. Saidha and his colleagues are assessing the use of OCT in patients with progressive MS (including 186 patients from Johns Hopkins), and also determining if OCT changes differ over time between relapsing-remitting MS and different subtypes of progressive MS. So far, they have found that progressive MS is associated with accelerated inner and in particular outer layer retinal atrophy. “Although this is a decent-sized cohort, at this stage I’m not sure I would definitively say that these novel retinal biomarkers have utility specific to progressive MS, but I’m very excited about it,” he said. “The goal is to take a much deeper look at this.”

Findings from a large collaborative IMSVISUAL inter-eye asymmetry study showed that peripapillary RNFL and ganglion cell–inner plexiform layer inter-eye differences of 5 microns, respectively, were optimal for identifying patients with prior unilateral optic neuritis in the MS cohort. “In the future, the possibility of using OCT to identify subclinical optic neuropathy so we can define when a lesion is present in the optic nerve has huge diagnostic implications for MS, because the optic nerve is not currently recognized as a lesion site in current MS diagnostic criteria,” Dr. Saidha said.

Dr. Saidha disclosed that he has served on scientific advisory boards for Biogen, Genzyme, Genentech, EMD Serono, and Novartis. He has also received consulting fees from JuneBrain LLC and is the site investigator of a trial sponsored by MedDay Pharmaceuticals.

dbrunk@mdedge.com

DALLAS – Optical coherence tomography (OCT) has emerged as a promising biomarker in multiple sclerosis.

Doug Brunk/MDedge News

Thanks to OCT, clinicians are gaining an improved understanding of how MS affects certain eye structures. An optical analogue of ultrasound B mode imaging, OCT achieves a resolution of about 3-6 microns with commercially available devices. “That allows us to quantify the layers of the retina with quite a degree of accuracy,” Shiv Saidha, MD, said at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

At postmortem, up to 99% of MS patients have demyelinated plaques in their optic nerves. “This implies that optic neuropathy is an ubiquitous phenomenon as part of the MS disease process,” said Dr. Saidha, a neurologist at Johns Hopkins University, Baltimore. “The prevailing hypothesis is that there is demyelination or axonal transection related to acute inflammation that occurs within the optic nerve. There’s a retrograde degeneration of its constituent axons, and that results in thinning of the inner retinal nerve fiber layer as well as the neuronal derivative of this layer called the ganglion cell layer. In addition to neurodegenerative mechanisms in the retina, there is also perivascular inflammation, called retinal periphlebitis, which we know occurs in about 20% of MS patients. At postmortem, there are also activate microglia present within the retina of MS patients.”


One of the principal findings of OCT in MS to date is that the retinal nerve fiber layer (RNFL) and ganglion cell plus inner plexiform layer (GCIP) thinning reflects MS-related optic nerve neurodegeneration. In addition, RNFL and GCIP thinning occur after optic neuritis and also as part of the MS disease course in eyes without a history of optic neuritis. “RNFL and GCIP thinning in MS are clinically relevant and correlate with visual function, global disability, and brain atrophy,” Dr. Saidha said. Researchers have also found that rates of GCIP thinning are accelerated in MS patients exhibiting clinical and/or radiological disease activity and are altered by disease-modifying therapies, and that increased inner nuclear layer (INL) thickness correlates with T2 lesion volume and predicts clinical and radiological disease activity. “In numerous trials of putatively neuroprotective and restorative treatments, we see OCT incorporated more and more, either as a secondary or a primary outcome,” he said.

Predicting disability and brain atrophy

In a study expected to be appear in a forthcoming issue of the Annals of Translational and Clinical Neurology, colleagues of Dr. Saidha found that OCT derived retinal layer measurements and visual function predict disability at 10 years in patients with MS. The researchers used an earlier generation, lower quality OCT device to examine tertiles of total macular volume, “an old, nonspecific composite measure of all of the retinal components,” he explained. “Even with inferior technology, a single measurement at a point in time not only could predict the change in EDSS [Expanded Disability Status Scale] scores from baseline to 10 years, but the accumulation of meaningful disability.”

In an earlier study, Dr. Saidha and his colleagues conducted a 4-year study of OCT and MRI in MS (Ann Neurol 2015; 78[5]:801-13). It consisted of six monthly spectral domain OCT scans (including automated intra-retinal segmentation) and baseline and annual 3 T brain MRI (including substructure volumetrics). Patients with ocular relapses (optic neuritis) during the study were excluded. The researchers correlated individual-specific rates of change in retinal and brain measurements, adjusting for age, sex, disease duration, and optic neuritis history. They found that cerebral volume fraction (analogous to whole brain volume) “had a decent correlation between rates of GCIP atrophy and rates of whole brain volume loss,” he said. “That was predominately driven by cortical gray matter atrophy.”

Measuring effects of disease-modifying therapies

What about the effects of disease-modifying therapies? According to Dr. Saidha, there has been a paucity of studies assessing the effects of DMTs on retinal layer thickness, and they are limited by small patient numbers, cross-sectional design, and/or short periods of observation. In a retrospective analysis, he and his associates examined the effects of treatments in relapsing-remitting MS patients at his center who underwent OCT (Neurology. 2017;88[6]:525-32). Over a mean 3 years of follow-up, they examined the effects of glatiramer acetate (Copaxone), natalizumab (Tysabri), and interferon beta-1a subcutaneously (Rebif) and intramuscularly (Avonex). They adjusted for gap time, which is the interval between when a patient started a treatment and when they started to undergo retinal observation with OCT. “This is to try to account for some of the biological changes that might have occurred during that period of time,” he explained. The researchers observed that rates of GCIP atrophy as well as other retinal measures were significantly lower in people treated with natalizumab, relative to all other DMTs. “What I found fascinating was the rate of GCIP atrophy of those on natalizumab was basically the same as healthy controls,” Dr. Saidha said. “It didn’t differ.”

Retinal inflammation and treatment’s impact

Significant inflammation in the unmyelinated retina may inform clinicians about other aspects of MS, he continued. For example, retinal periphlebitis occurs in about 20% of MS patients and may be a marker of CNS inflammation. In addition, intermediate uveitis occurs in about 16% of MS patients, and postmortem studies reveal retinal inflammation with microglia. Specifically, macular microcystoid changes occur in the eyes of about 5% of MS patients and may represent a breakdown of the blood-retinal barrier and inflammation. “Since it’s a dynamic process, increased thickness of the INL in the absence of visible microcystoid changes might occur,” Dr. Saidha said. “We found that baseline INL thickness is predictive of clinico-radiologic disease activity.”

In a separate analysis of 108 MS patients and 40 healthy controls, German researchers evaluated the impact of DMTs on INL volume (Brain. 2016;11[1]:2855-63). They found that higher baseline INL volume correlated with new T2 and GAD lesions over 1 year. The reduction in INL volume was significantly associated with reduced activity, and overall, DMTs reduced INL volume over 6 months. Patients who were not treated, or who were treated and did not achieve NEDA-3 (no evidence of disease activity) did not show reductions in INL volume. They concluded that INL volume might be a novel outcome of DMT treatment.

Finding prognostic and diagnostic biomarkers

In an ongoing multisite study, Dr. Saidha and his colleagues are assessing the use of OCT in patients with progressive MS (including 186 patients from Johns Hopkins), and also determining if OCT changes differ over time between relapsing-remitting MS and different subtypes of progressive MS. So far, they have found that progressive MS is associated with accelerated inner and in particular outer layer retinal atrophy. “Although this is a decent-sized cohort, at this stage I’m not sure I would definitively say that these novel retinal biomarkers have utility specific to progressive MS, but I’m very excited about it,” he said. “The goal is to take a much deeper look at this.”

Findings from a large collaborative IMSVISUAL inter-eye asymmetry study showed that peripapillary RNFL and ganglion cell–inner plexiform layer inter-eye differences of 5 microns, respectively, were optimal for identifying patients with prior unilateral optic neuritis in the MS cohort. “In the future, the possibility of using OCT to identify subclinical optic neuropathy so we can define when a lesion is present in the optic nerve has huge diagnostic implications for MS, because the optic nerve is not currently recognized as a lesion site in current MS diagnostic criteria,” Dr. Saidha said.

Dr. Saidha disclosed that he has served on scientific advisory boards for Biogen, Genzyme, Genentech, EMD Serono, and Novartis. He has also received consulting fees from JuneBrain LLC and is the site investigator of a trial sponsored by MedDay Pharmaceuticals.

dbrunk@mdedge.com

DALLAS – Optical coherence tomography (OCT) has emerged as a promising biomarker in multiple sclerosis.

Doug Brunk/MDedge News

Thanks to OCT, clinicians are gaining an improved understanding of how MS affects certain eye structures. An optical analogue of ultrasound B mode imaging, OCT achieves a resolution of about 3-6 microns with commercially available devices. “That allows us to quantify the layers of the retina with quite a degree of accuracy,” Shiv Saidha, MD, said at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

At postmortem, up to 99% of MS patients have demyelinated plaques in their optic nerves. “This implies that optic neuropathy is an ubiquitous phenomenon as part of the MS disease process,” said Dr. Saidha, a neurologist at Johns Hopkins University, Baltimore. “The prevailing hypothesis is that there is demyelination or axonal transection related to acute inflammation that occurs within the optic nerve. There’s a retrograde degeneration of its constituent axons, and that results in thinning of the inner retinal nerve fiber layer as well as the neuronal derivative of this layer called the ganglion cell layer. In addition to neurodegenerative mechanisms in the retina, there is also perivascular inflammation, called retinal periphlebitis, which we know occurs in about 20% of MS patients. At postmortem, there are also activate microglia present within the retina of MS patients.”


One of the principal findings of OCT in MS to date is that the retinal nerve fiber layer (RNFL) and ganglion cell plus inner plexiform layer (GCIP) thinning reflects MS-related optic nerve neurodegeneration. In addition, RNFL and GCIP thinning occur after optic neuritis and also as part of the MS disease course in eyes without a history of optic neuritis. “RNFL and GCIP thinning in MS are clinically relevant and correlate with visual function, global disability, and brain atrophy,” Dr. Saidha said. Researchers have also found that rates of GCIP thinning are accelerated in MS patients exhibiting clinical and/or radiological disease activity and are altered by disease-modifying therapies, and that increased inner nuclear layer (INL) thickness correlates with T2 lesion volume and predicts clinical and radiological disease activity. “In numerous trials of putatively neuroprotective and restorative treatments, we see OCT incorporated more and more, either as a secondary or a primary outcome,” he said.

Predicting disability and brain atrophy

In a study expected to be appear in a forthcoming issue of the Annals of Translational and Clinical Neurology, colleagues of Dr. Saidha found that OCT derived retinal layer measurements and visual function predict disability at 10 years in patients with MS. The researchers used an earlier generation, lower quality OCT device to examine tertiles of total macular volume, “an old, nonspecific composite measure of all of the retinal components,” he explained. “Even with inferior technology, a single measurement at a point in time not only could predict the change in EDSS [Expanded Disability Status Scale] scores from baseline to 10 years, but the accumulation of meaningful disability.”

In an earlier study, Dr. Saidha and his colleagues conducted a 4-year study of OCT and MRI in MS (Ann Neurol 2015; 78[5]:801-13). It consisted of six monthly spectral domain OCT scans (including automated intra-retinal segmentation) and baseline and annual 3 T brain MRI (including substructure volumetrics). Patients with ocular relapses (optic neuritis) during the study were excluded. The researchers correlated individual-specific rates of change in retinal and brain measurements, adjusting for age, sex, disease duration, and optic neuritis history. They found that cerebral volume fraction (analogous to whole brain volume) “had a decent correlation between rates of GCIP atrophy and rates of whole brain volume loss,” he said. “That was predominately driven by cortical gray matter atrophy.”

Measuring effects of disease-modifying therapies

What about the effects of disease-modifying therapies? According to Dr. Saidha, there has been a paucity of studies assessing the effects of DMTs on retinal layer thickness, and they are limited by small patient numbers, cross-sectional design, and/or short periods of observation. In a retrospective analysis, he and his associates examined the effects of treatments in relapsing-remitting MS patients at his center who underwent OCT (Neurology. 2017;88[6]:525-32). Over a mean 3 years of follow-up, they examined the effects of glatiramer acetate (Copaxone), natalizumab (Tysabri), and interferon beta-1a subcutaneously (Rebif) and intramuscularly (Avonex). They adjusted for gap time, which is the interval between when a patient started a treatment and when they started to undergo retinal observation with OCT. “This is to try to account for some of the biological changes that might have occurred during that period of time,” he explained. The researchers observed that rates of GCIP atrophy as well as other retinal measures were significantly lower in people treated with natalizumab, relative to all other DMTs. “What I found fascinating was the rate of GCIP atrophy of those on natalizumab was basically the same as healthy controls,” Dr. Saidha said. “It didn’t differ.”

Retinal inflammation and treatment’s impact

Significant inflammation in the unmyelinated retina may inform clinicians about other aspects of MS, he continued. For example, retinal periphlebitis occurs in about 20% of MS patients and may be a marker of CNS inflammation. In addition, intermediate uveitis occurs in about 16% of MS patients, and postmortem studies reveal retinal inflammation with microglia. Specifically, macular microcystoid changes occur in the eyes of about 5% of MS patients and may represent a breakdown of the blood-retinal barrier and inflammation. “Since it’s a dynamic process, increased thickness of the INL in the absence of visible microcystoid changes might occur,” Dr. Saidha said. “We found that baseline INL thickness is predictive of clinico-radiologic disease activity.”

In a separate analysis of 108 MS patients and 40 healthy controls, German researchers evaluated the impact of DMTs on INL volume (Brain. 2016;11[1]:2855-63). They found that higher baseline INL volume correlated with new T2 and GAD lesions over 1 year. The reduction in INL volume was significantly associated with reduced activity, and overall, DMTs reduced INL volume over 6 months. Patients who were not treated, or who were treated and did not achieve NEDA-3 (no evidence of disease activity) did not show reductions in INL volume. They concluded that INL volume might be a novel outcome of DMT treatment.

Finding prognostic and diagnostic biomarkers

In an ongoing multisite study, Dr. Saidha and his colleagues are assessing the use of OCT in patients with progressive MS (including 186 patients from Johns Hopkins), and also determining if OCT changes differ over time between relapsing-remitting MS and different subtypes of progressive MS. So far, they have found that progressive MS is associated with accelerated inner and in particular outer layer retinal atrophy. “Although this is a decent-sized cohort, at this stage I’m not sure I would definitively say that these novel retinal biomarkers have utility specific to progressive MS, but I’m very excited about it,” he said. “The goal is to take a much deeper look at this.”

Findings from a large collaborative IMSVISUAL inter-eye asymmetry study showed that peripapillary RNFL and ganglion cell–inner plexiform layer inter-eye differences of 5 microns, respectively, were optimal for identifying patients with prior unilateral optic neuritis in the MS cohort. “In the future, the possibility of using OCT to identify subclinical optic neuropathy so we can define when a lesion is present in the optic nerve has huge diagnostic implications for MS, because the optic nerve is not currently recognized as a lesion site in current MS diagnostic criteria,” Dr. Saidha said.

Dr. Saidha disclosed that he has served on scientific advisory boards for Biogen, Genzyme, Genentech, EMD Serono, and Novartis. He has also received consulting fees from JuneBrain LLC and is the site investigator of a trial sponsored by MedDay Pharmaceuticals.

dbrunk@mdedge.com

DALLAS – Latitude continues to be associated with the prevalence of multiple sclerosis (MS), according to an updated meta-analysis presented at ACTRIMS Forum 2019, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

For every degree of latitude increase, prevalence of MS per 100,000 people (i.e., the slope) increased by 3.64 in a fully adjusted, age-standardized model. The researchers’ original study, published in 2011, found a slope of 2.68.

Latitudinal variations in MS prevalence have given credence to the theory that sun exposure and vitamin D may play a role in MS onset. The researchers’ original meta-analysis – based on 650 prevalence estimates from 321 studies – “confirmed the existence of a robust latitudinal gradient,” they said. To examine whether the gradient has changed, the researchers identified relevant studies published between 2010 and 2018.

They included complete, peer-reviewed articles in their analysis and extracted data about the study area, prevalence year, MS diagnostic criteria used, sample size, source population, crude prevalence, and age-specific prevalence. They combined the new prevalence estimates with those from their original study. The estimates were log-transformed and weighted with the inverse of the variance. In addition, the researchers used random-effects meta-regression models that adjusted for prevalence year and method of case ascertainment.

Their literature review identified 126 new studies, 94 of which met inclusion criteria. The new studies yielded 230 additional prevalence points, predominantly in Scandinavia, France, and the Middle East.

“Latitude was consistently and significantly associated with MS prevalence in all analyses, increasing in magnitude on adjustment and persisting on age-standardization,” Dr. Simpson and his colleagues reported.

By region, strong and significant positive gradients continue to exist in Australasia, the United Kingdom/Ireland, and North America. Meanwhile, a significant inverse gradient continues to exist in the Italian region, which the researchers have said relates to the frequency of an MS-related HLA-DRB1 allele there. A negative gradient in the Scandinavian/North Atlantic region in the original meta-analysis, considered potentially related to dietary differences, was “markedly reduced” and no longer statistically significant in the updated meta-analysis.

“While there are potential intra-regional effects contributing to the latitudinal variation in MS prevalence, these results and the relative consistency across the whole of the globe continue to provide indirect evidence in support of the role of sun and vitamin D in MS etiology,” Dr. Simpson and his colleagues concluded.

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Simpson S Jr et al. ACTRIMS Forum 2019, Abstract 126.

DALLAS – Latitude continues to be associated with the prevalence of multiple sclerosis (MS), according to an updated meta-analysis presented at ACTRIMS Forum 2019, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

For every degree of latitude increase, prevalence of MS per 100,000 people (i.e., the slope) increased by 3.64 in a fully adjusted, age-standardized model. The researchers’ original study, published in 2011, found a slope of 2.68.

Latitudinal variations in MS prevalence have given credence to the theory that sun exposure and vitamin D may play a role in MS onset. The researchers’ original meta-analysis – based on 650 prevalence estimates from 321 studies – “confirmed the existence of a robust latitudinal gradient,” they said. To examine whether the gradient has changed, the researchers identified relevant studies published between 2010 and 2018.

They included complete, peer-reviewed articles in their analysis and extracted data about the study area, prevalence year, MS diagnostic criteria used, sample size, source population, crude prevalence, and age-specific prevalence. They combined the new prevalence estimates with those from their original study. The estimates were log-transformed and weighted with the inverse of the variance. In addition, the researchers used random-effects meta-regression models that adjusted for prevalence year and method of case ascertainment.

Their literature review identified 126 new studies, 94 of which met inclusion criteria. The new studies yielded 230 additional prevalence points, predominantly in Scandinavia, France, and the Middle East.

“Latitude was consistently and significantly associated with MS prevalence in all analyses, increasing in magnitude on adjustment and persisting on age-standardization,” Dr. Simpson and his colleagues reported.

By region, strong and significant positive gradients continue to exist in Australasia, the United Kingdom/Ireland, and North America. Meanwhile, a significant inverse gradient continues to exist in the Italian region, which the researchers have said relates to the frequency of an MS-related HLA-DRB1 allele there. A negative gradient in the Scandinavian/North Atlantic region in the original meta-analysis, considered potentially related to dietary differences, was “markedly reduced” and no longer statistically significant in the updated meta-analysis.

“While there are potential intra-regional effects contributing to the latitudinal variation in MS prevalence, these results and the relative consistency across the whole of the globe continue to provide indirect evidence in support of the role of sun and vitamin D in MS etiology,” Dr. Simpson and his colleagues concluded.

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Simpson S Jr et al. ACTRIMS Forum 2019, Abstract 126.

DALLAS – Latitude continues to be associated with the prevalence of multiple sclerosis (MS), according to an updated meta-analysis presented at ACTRIMS Forum 2019, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

For every degree of latitude increase, prevalence of MS per 100,000 people (i.e., the slope) increased by 3.64 in a fully adjusted, age-standardized model. The researchers’ original study, published in 2011, found a slope of 2.68.

Latitudinal variations in MS prevalence have given credence to the theory that sun exposure and vitamin D may play a role in MS onset. The researchers’ original meta-analysis – based on 650 prevalence estimates from 321 studies – “confirmed the existence of a robust latitudinal gradient,” they said. To examine whether the gradient has changed, the researchers identified relevant studies published between 2010 and 2018.

They included complete, peer-reviewed articles in their analysis and extracted data about the study area, prevalence year, MS diagnostic criteria used, sample size, source population, crude prevalence, and age-specific prevalence. They combined the new prevalence estimates with those from their original study. The estimates were log-transformed and weighted with the inverse of the variance. In addition, the researchers used random-effects meta-regression models that adjusted for prevalence year and method of case ascertainment.

Their literature review identified 126 new studies, 94 of which met inclusion criteria. The new studies yielded 230 additional prevalence points, predominantly in Scandinavia, France, and the Middle East.

“Latitude was consistently and significantly associated with MS prevalence in all analyses, increasing in magnitude on adjustment and persisting on age-standardization,” Dr. Simpson and his colleagues reported.

By region, strong and significant positive gradients continue to exist in Australasia, the United Kingdom/Ireland, and North America. Meanwhile, a significant inverse gradient continues to exist in the Italian region, which the researchers have said relates to the frequency of an MS-related HLA-DRB1 allele there. A negative gradient in the Scandinavian/North Atlantic region in the original meta-analysis, considered potentially related to dietary differences, was “markedly reduced” and no longer statistically significant in the updated meta-analysis.

“While there are potential intra-regional effects contributing to the latitudinal variation in MS prevalence, these results and the relative consistency across the whole of the globe continue to provide indirect evidence in support of the role of sun and vitamin D in MS etiology,” Dr. Simpson and his colleagues concluded.

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Simpson S Jr et al. ACTRIMS Forum 2019, Abstract 126.

DALLAS – Genetic and molecular studies are coming closer to pinpointing just when multiple sclerosis really starts, Philip De Jager, MD, PhD, said in a precision medicine–focused session at the meeting of the Americas Committee on Treatment and Research in Multiple Sclerosis.

“MS remains a diagnosis of exclusion ... But we’re now beginning to understand a lot more about the earliest stages of the disease, and we’re constantly redefining the disease in terms of when it starts, and what it consists of,” said Dr. De Jager, professor of neurology and chief of neuroimmunology at Columbia University, New York, in an interview.

For example, physicians are now starting to treat asymptomatic individuals with radiologically isolated syndrome, he said. “Is that part of the disease? Well, a lot of us think so, and we’re currently doing the studies to see whether treating them has an impact on long-term disability.”

“In this effort to redefine this disease and when it starts, these molecular and cellular studies are becoming very important,” Dr. De Jager said. Both individuals in the general population and high-risk individuals, such as family members of people with MS, will benefit from these research approaches, he said.

Right now, it’s hard to know who could benefit most from future preventive therapies, or who should have the most rigorous surveillance.

Dr. De Jager pointed to a presentation by his collaborator, Nikolaos Patsopoulos, MD, PhD, of Brigham and Women’s Hospital, Boston, who reported on the activities of the International MS Genetics Consortium. The consortium has collected and is nearing publication of data from more than 45,000 people with MS and 65,000 control participants to identify the genetic architecture of MS onset.

“We’re going to be reporting that there are over 234 genetic variations” that contribute to the onset of MS, Dr. De Jager said. “There are more to be found, but that’s a large number,” he said. The data point toward a genetic fingerprint that’s close to lupus, type 1 diabetes, and other inflammatory diseases. This shared genetic architecture means that there’s overlapping susceptibility for many diseases in this spectrum.

koakes@mdedge.com

DALLAS – Genetic and molecular studies are coming closer to pinpointing just when multiple sclerosis really starts, Philip De Jager, MD, PhD, said in a precision medicine–focused session at the meeting of the Americas Committee on Treatment and Research in Multiple Sclerosis.

“MS remains a diagnosis of exclusion ... But we’re now beginning to understand a lot more about the earliest stages of the disease, and we’re constantly redefining the disease in terms of when it starts, and what it consists of,” said Dr. De Jager, professor of neurology and chief of neuroimmunology at Columbia University, New York, in an interview.

For example, physicians are now starting to treat asymptomatic individuals with radiologically isolated syndrome, he said. “Is that part of the disease? Well, a lot of us think so, and we’re currently doing the studies to see whether treating them has an impact on long-term disability.”

“In this effort to redefine this disease and when it starts, these molecular and cellular studies are becoming very important,” Dr. De Jager said. Both individuals in the general population and high-risk individuals, such as family members of people with MS, will benefit from these research approaches, he said.

Right now, it’s hard to know who could benefit most from future preventive therapies, or who should have the most rigorous surveillance.

Dr. De Jager pointed to a presentation by his collaborator, Nikolaos Patsopoulos, MD, PhD, of Brigham and Women’s Hospital, Boston, who reported on the activities of the International MS Genetics Consortium. The consortium has collected and is nearing publication of data from more than 45,000 people with MS and 65,000 control participants to identify the genetic architecture of MS onset.

“We’re going to be reporting that there are over 234 genetic variations” that contribute to the onset of MS, Dr. De Jager said. “There are more to be found, but that’s a large number,” he said. The data point toward a genetic fingerprint that’s close to lupus, type 1 diabetes, and other inflammatory diseases. This shared genetic architecture means that there’s overlapping susceptibility for many diseases in this spectrum.

koakes@mdedge.com

DALLAS – Genetic and molecular studies are coming closer to pinpointing just when multiple sclerosis really starts, Philip De Jager, MD, PhD, said in a precision medicine–focused session at the meeting of the Americas Committee on Treatment and Research in Multiple Sclerosis.

“MS remains a diagnosis of exclusion ... But we’re now beginning to understand a lot more about the earliest stages of the disease, and we’re constantly redefining the disease in terms of when it starts, and what it consists of,” said Dr. De Jager, professor of neurology and chief of neuroimmunology at Columbia University, New York, in an interview.

For example, physicians are now starting to treat asymptomatic individuals with radiologically isolated syndrome, he said. “Is that part of the disease? Well, a lot of us think so, and we’re currently doing the studies to see whether treating them has an impact on long-term disability.”

“In this effort to redefine this disease and when it starts, these molecular and cellular studies are becoming very important,” Dr. De Jager said. Both individuals in the general population and high-risk individuals, such as family members of people with MS, will benefit from these research approaches, he said.

Right now, it’s hard to know who could benefit most from future preventive therapies, or who should have the most rigorous surveillance.

Dr. De Jager pointed to a presentation by his collaborator, Nikolaos Patsopoulos, MD, PhD, of Brigham and Women’s Hospital, Boston, who reported on the activities of the International MS Genetics Consortium. The consortium has collected and is nearing publication of data from more than 45,000 people with MS and 65,000 control participants to identify the genetic architecture of MS onset.

“We’re going to be reporting that there are over 234 genetic variations” that contribute to the onset of MS, Dr. De Jager said. “There are more to be found, but that’s a large number,” he said. The data point toward a genetic fingerprint that’s close to lupus, type 1 diabetes, and other inflammatory diseases. This shared genetic architecture means that there’s overlapping susceptibility for many diseases in this spectrum.

koakes@mdedge.com

Subjective cognitive concern in multiple sclerosis (MS) is associated with reduced thalamic and cortical gray matter volumes, areas of the brain that have been implicated in objective cognitive impairment, according to a recent study. These findings may lend neuroanatomical significance to subjective cognitive concerns and patient-reported outcomes as measured by the Quality of Life in Neurologic Disorders Measures (Neuro-QoL). A total of 158 patients with MS completed the Neuro-QoL short forms to assess subjective cognitive concerns and underwent brain magnetic resonance imaging. Regional brain volumes from regions of interest implicated in cognitive dysfunction were measured using NeuroQuant automated volumetric quantitation. Linear regression was used to analyze the relationship between subjective cognitive concerns and brain volume. Researchers found:

• Controlling for age, disease duration, gender, depression and fatigue, increased subjective cognitive concerns were associated with reduced thalamic volume (standardized β = 0.223, t₁₅₀ =2.406) and reduced cortical gray matter volume (standardized β = 0.240, t₁₅₀ = 2.777).
• Increased subjective cognitive concerns were not associated with any other regions of interest that were analyzed.

Kletenik I, Alvarez E, Honce JM, Valdez B, Vollmer TL. Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes. Mult Scler J Exp Transl Clin. 2019;5(1); doi:10.1177/2055217319827618.

Subjective cognitive concern in multiple sclerosis (MS) is associated with reduced thalamic and cortical gray matter volumes, areas of the brain that have been implicated in objective cognitive impairment, according to a recent study. These findings may lend neuroanatomical significance to subjective cognitive concerns and patient-reported outcomes as measured by the Quality of Life in Neurologic Disorders Measures (Neuro-QoL). A total of 158 patients with MS completed the Neuro-QoL short forms to assess subjective cognitive concerns and underwent brain magnetic resonance imaging. Regional brain volumes from regions of interest implicated in cognitive dysfunction were measured using NeuroQuant automated volumetric quantitation. Linear regression was used to analyze the relationship between subjective cognitive concerns and brain volume. Researchers found:

• Controlling for age, disease duration, gender, depression and fatigue, increased subjective cognitive concerns were associated with reduced thalamic volume (standardized β = 0.223, t₁₅₀ =2.406) and reduced cortical gray matter volume (standardized β = 0.240, t₁₅₀ = 2.777).
• Increased subjective cognitive concerns were not associated with any other regions of interest that were analyzed.

Kletenik I, Alvarez E, Honce JM, Valdez B, Vollmer TL. Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes. Mult Scler J Exp Transl Clin. 2019;5(1); doi:10.1177/2055217319827618.

Subjective cognitive concern in multiple sclerosis (MS) is associated with reduced thalamic and cortical gray matter volumes, areas of the brain that have been implicated in objective cognitive impairment, according to a recent study. These findings may lend neuroanatomical significance to subjective cognitive concerns and patient-reported outcomes as measured by the Quality of Life in Neurologic Disorders Measures (Neuro-QoL). A total of 158 patients with MS completed the Neuro-QoL short forms to assess subjective cognitive concerns and underwent brain magnetic resonance imaging. Regional brain volumes from regions of interest implicated in cognitive dysfunction were measured using NeuroQuant automated volumetric quantitation. Linear regression was used to analyze the relationship between subjective cognitive concerns and brain volume. Researchers found:

• Controlling for age, disease duration, gender, depression and fatigue, increased subjective cognitive concerns were associated with reduced thalamic volume (standardized β = 0.223, t₁₅₀ =2.406) and reduced cortical gray matter volume (standardized β = 0.240, t₁₅₀ = 2.777).
• Increased subjective cognitive concerns were not associated with any other regions of interest that were analyzed.

Kletenik I, Alvarez E, Honce JM, Valdez B, Vollmer TL. Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes. Mult Scler J Exp Transl Clin. 2019;5(1); doi:10.1177/2055217319827618.

Most patients with multiple sclerosis (MS) aged >60 who discontinued disease modifying therapy (DMT) remained off treatment, a recent study found. Among the outcomes, only the European Quality of Life 5 Dimensions (EQ-5D) index demonstrated significant differences over time, with continuers having lower quality of life scores compared to discontinuers before discontinuation (DBD). Researchers conducted a retrospective, observational study in which they identified patients from MS clinics aged ≥60 years who had been on DMT ≥2 years. They compared outcome evolution over time among treatment groups (continuers, DBD), and discontinuers after discontinuation [DAD]), by creating separate mixed-effects linear regression models that included an interaction term between time from age 60 and treatment group to study outcome trajectories. They found:

• 178 of 600 patients discontinued DMT, and 89.3% (n=159) of those who discontinued remained off DMT.
• Only the EQ-5D mixed-effects linear regression model with the interaction term was statistically significant.
• The slope relating time to EQ-5D was significantly different when comparing continuers to DBD.
• The slopes were not significantly different when comparing continuers to DAD, or when comparing the before and after discontinuation slopes among the discontinuers.

Hua LH, Harris H, Conway D, Thompson NR. Changes in patient-reported outcomes between continuers and discontinuers of disease modifying therapy in patients with multiple sclerosis over age 60. [Published online ahead of print March 1, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.02.028.

Most patients with multiple sclerosis (MS) aged >60 who discontinued disease modifying therapy (DMT) remained off treatment, a recent study found. Among the outcomes, only the European Quality of Life 5 Dimensions (EQ-5D) index demonstrated significant differences over time, with continuers having lower quality of life scores compared to discontinuers before discontinuation (DBD). Researchers conducted a retrospective, observational study in which they identified patients from MS clinics aged ≥60 years who had been on DMT ≥2 years. They compared outcome evolution over time among treatment groups (continuers, DBD), and discontinuers after discontinuation [DAD]), by creating separate mixed-effects linear regression models that included an interaction term between time from age 60 and treatment group to study outcome trajectories. They found:

• 178 of 600 patients discontinued DMT, and 89.3% (n=159) of those who discontinued remained off DMT.
• Only the EQ-5D mixed-effects linear regression model with the interaction term was statistically significant.
• The slope relating time to EQ-5D was significantly different when comparing continuers to DBD.
• The slopes were not significantly different when comparing continuers to DAD, or when comparing the before and after discontinuation slopes among the discontinuers.

Hua LH, Harris H, Conway D, Thompson NR. Changes in patient-reported outcomes between continuers and discontinuers of disease modifying therapy in patients with multiple sclerosis over age 60. [Published online ahead of print March 1, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.02.028.

Most patients with multiple sclerosis (MS) aged >60 who discontinued disease modifying therapy (DMT) remained off treatment, a recent study found. Among the outcomes, only the European Quality of Life 5 Dimensions (EQ-5D) index demonstrated significant differences over time, with continuers having lower quality of life scores compared to discontinuers before discontinuation (DBD). Researchers conducted a retrospective, observational study in which they identified patients from MS clinics aged ≥60 years who had been on DMT ≥2 years. They compared outcome evolution over time among treatment groups (continuers, DBD), and discontinuers after discontinuation [DAD]), by creating separate mixed-effects linear regression models that included an interaction term between time from age 60 and treatment group to study outcome trajectories. They found:

• 178 of 600 patients discontinued DMT, and 89.3% (n=159) of those who discontinued remained off DMT.
• Only the EQ-5D mixed-effects linear regression model with the interaction term was statistically significant.
• The slope relating time to EQ-5D was significantly different when comparing continuers to DBD.
• The slopes were not significantly different when comparing continuers to DAD, or when comparing the before and after discontinuation slopes among the discontinuers.

Hua LH, Harris H, Conway D, Thompson NR. Changes in patient-reported outcomes between continuers and discontinuers of disease modifying therapy in patients with multiple sclerosis over age 60. [Published online ahead of print March 1, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.02.028.

Recent findings support previous studies on the activities of daily living in people with multiple sclerosis (MS) and the effect of aerobic exercise on independence regarding instrumental activities of daily living (IADLs) in this population. 62 adults with MS completed an incremental exercise test as a measure of aerobic fitness (peak oxygen consumption), a demographic questionnaire, and an IADL scale and underwent a neurologic examination for characterization of disability level (ie, Expanded Disability Status Scale) in a single session. Researchers found:

• The analysis revealed a weak but significant association between aerobic fitness and total IADL score (r=0.28).
• Those reporting dependence in different IADL categories (eg, shopping, food preparation, housekeeping, laundry, and responsibility for own medication) presented with lower aerobic fitness compared with those reporting independence, although the difference was not statistically significant.

Sebastião E, Pilutti LA, Motl RW. Aerobic fitness and instrumental activities of daily living in people with multiple sclerosis. A cross-sectional study. Int J MS Care. 2019;21(1):23-28. doi:10.7224/1537-2073.2017-078.

Recent findings support previous studies on the activities of daily living in people with multiple sclerosis (MS) and the effect of aerobic exercise on independence regarding instrumental activities of daily living (IADLs) in this population. 62 adults with MS completed an incremental exercise test as a measure of aerobic fitness (peak oxygen consumption), a demographic questionnaire, and an IADL scale and underwent a neurologic examination for characterization of disability level (ie, Expanded Disability Status Scale) in a single session. Researchers found:

• The analysis revealed a weak but significant association between aerobic fitness and total IADL score (r=0.28).
• Those reporting dependence in different IADL categories (eg, shopping, food preparation, housekeeping, laundry, and responsibility for own medication) presented with lower aerobic fitness compared with those reporting independence, although the difference was not statistically significant.

Sebastião E, Pilutti LA, Motl RW. Aerobic fitness and instrumental activities of daily living in people with multiple sclerosis. A cross-sectional study. Int J MS Care. 2019;21(1):23-28. doi:10.7224/1537-2073.2017-078.

Recent findings support previous studies on the activities of daily living in people with multiple sclerosis (MS) and the effect of aerobic exercise on independence regarding instrumental activities of daily living (IADLs) in this population. 62 adults with MS completed an incremental exercise test as a measure of aerobic fitness (peak oxygen consumption), a demographic questionnaire, and an IADL scale and underwent a neurologic examination for characterization of disability level (ie, Expanded Disability Status Scale) in a single session. Researchers found:

• The analysis revealed a weak but significant association between aerobic fitness and total IADL score (r=0.28).
• Those reporting dependence in different IADL categories (eg, shopping, food preparation, housekeeping, laundry, and responsibility for own medication) presented with lower aerobic fitness compared with those reporting independence, although the difference was not statistically significant.

Sebastião E, Pilutti LA, Motl RW. Aerobic fitness and instrumental activities of daily living in people with multiple sclerosis. A cross-sectional study. Int J MS Care. 2019;21(1):23-28. doi:10.7224/1537-2073.2017-078.

DALLAS – Systemic lupus erythematosus, depression, hyperthyroidism, and anxiety are among the comorbidities that most affect health-related quality of life in patients with multiple sclerosis (MS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. In addition, comorbidities account for about 18% of the variance in health-related quality of life, and a higher number of comorbidities correlates with lower health-related quality of life in a “clear dose–response” manner, the researchers said.

The “magnitude of effect emphasizes the need for recognition and appropriate management of comorbidities,” said presenting author Lara Marie Pangan Lo, a researcher at Menzies Institute for Medical Research at the University of Tasmania, Australia, and her research colleagues. “The individual effect sizes may assist with the prioritizing of comorbidities that require more or less aggressive treatment in order to minimize” their impact.

Prior studies have found that patients with MS have lower health-related quality of life, compared with the general population, and that comorbidities affect patients’ quality of life, but few studies have looked at the effects of individual comorbidities on quality of life, Ms. Lo and her colleagues said. To examine the total impact and relative importance of comorbidities on psychosocial, physical, and overall health-related quality of life in people with MS, the investigators analyzed survey data from 902 participants in the survey-based Australian MS Longitudinal Study. They used linear regression and dominance analysis to assess relationships between comorbidities and participants’ Assessment of Quality of Life-8 Dimensions scores, which can range from 0 (death) to 1 (perfect health).

The predicted health-related quality of life for patients without comorbidities was 0.74. After the researchers adjusted for age, sex, and education, they found that systemic lupus erythematosus (reported by 1.56% of patients), depression (41.25%), hyperthyroidism (3.01%), and anxiety (38.35%) were associated with the greatest estimated decreases in health-related quality of life (–0.16, –0.15, –0.12, and –0.11, respectively). Depression and anxiety had the largest effect on psychosocial health–related quality of life, whereas systemic lupus erythematosus, rheumatoid arthritis, and hyperthyroidism had the largest impact on physical health–related quality of life. Other comorbidities that significantly correlated with quality of life included osteoporosis, type 2 diabetes, migraine, and inflammatory bowel disease.

The study was supported by Multiple Sclerosis Research Australia. The authors had no relevant disclosures.

jremaly@mdedge.com

SOURCE: Lo LMP et al. ACTRIMS Forum 2019, Abstract 80.

DALLAS – Systemic lupus erythematosus, depression, hyperthyroidism, and anxiety are among the comorbidities that most affect health-related quality of life in patients with multiple sclerosis (MS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. In addition, comorbidities account for about 18% of the variance in health-related quality of life, and a higher number of comorbidities correlates with lower health-related quality of life in a “clear dose–response” manner, the researchers said.

The “magnitude of effect emphasizes the need for recognition and appropriate management of comorbidities,” said presenting author Lara Marie Pangan Lo, a researcher at Menzies Institute for Medical Research at the University of Tasmania, Australia, and her research colleagues. “The individual effect sizes may assist with the prioritizing of comorbidities that require more or less aggressive treatment in order to minimize” their impact.

Prior studies have found that patients with MS have lower health-related quality of life, compared with the general population, and that comorbidities affect patients’ quality of life, but few studies have looked at the effects of individual comorbidities on quality of life, Ms. Lo and her colleagues said. To examine the total impact and relative importance of comorbidities on psychosocial, physical, and overall health-related quality of life in people with MS, the investigators analyzed survey data from 902 participants in the survey-based Australian MS Longitudinal Study. They used linear regression and dominance analysis to assess relationships between comorbidities and participants’ Assessment of Quality of Life-8 Dimensions scores, which can range from 0 (death) to 1 (perfect health).

The predicted health-related quality of life for patients without comorbidities was 0.74. After the researchers adjusted for age, sex, and education, they found that systemic lupus erythematosus (reported by 1.56% of patients), depression (41.25%), hyperthyroidism (3.01%), and anxiety (38.35%) were associated with the greatest estimated decreases in health-related quality of life (–0.16, –0.15, –0.12, and –0.11, respectively). Depression and anxiety had the largest effect on psychosocial health–related quality of life, whereas systemic lupus erythematosus, rheumatoid arthritis, and hyperthyroidism had the largest impact on physical health–related quality of life. Other comorbidities that significantly correlated with quality of life included osteoporosis, type 2 diabetes, migraine, and inflammatory bowel disease.

The study was supported by Multiple Sclerosis Research Australia. The authors had no relevant disclosures.

jremaly@mdedge.com

SOURCE: Lo LMP et al. ACTRIMS Forum 2019, Abstract 80.

DALLAS – Systemic lupus erythematosus, depression, hyperthyroidism, and anxiety are among the comorbidities that most affect health-related quality of life in patients with multiple sclerosis (MS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. In addition, comorbidities account for about 18% of the variance in health-related quality of life, and a higher number of comorbidities correlates with lower health-related quality of life in a “clear dose–response” manner, the researchers said.

The “magnitude of effect emphasizes the need for recognition and appropriate management of comorbidities,” said presenting author Lara Marie Pangan Lo, a researcher at Menzies Institute for Medical Research at the University of Tasmania, Australia, and her research colleagues. “The individual effect sizes may assist with the prioritizing of comorbidities that require more or less aggressive treatment in order to minimize” their impact.

Prior studies have found that patients with MS have lower health-related quality of life, compared with the general population, and that comorbidities affect patients’ quality of life, but few studies have looked at the effects of individual comorbidities on quality of life, Ms. Lo and her colleagues said. To examine the total impact and relative importance of comorbidities on psychosocial, physical, and overall health-related quality of life in people with MS, the investigators analyzed survey data from 902 participants in the survey-based Australian MS Longitudinal Study. They used linear regression and dominance analysis to assess relationships between comorbidities and participants’ Assessment of Quality of Life-8 Dimensions scores, which can range from 0 (death) to 1 (perfect health).

The predicted health-related quality of life for patients without comorbidities was 0.74. After the researchers adjusted for age, sex, and education, they found that systemic lupus erythematosus (reported by 1.56% of patients), depression (41.25%), hyperthyroidism (3.01%), and anxiety (38.35%) were associated with the greatest estimated decreases in health-related quality of life (–0.16, –0.15, –0.12, and –0.11, respectively). Depression and anxiety had the largest effect on psychosocial health–related quality of life, whereas systemic lupus erythematosus, rheumatoid arthritis, and hyperthyroidism had the largest impact on physical health–related quality of life. Other comorbidities that significantly correlated with quality of life included osteoporosis, type 2 diabetes, migraine, and inflammatory bowel disease.

The study was supported by Multiple Sclerosis Research Australia. The authors had no relevant disclosures.

jremaly@mdedge.com

SOURCE: Lo LMP et al. ACTRIMS Forum 2019, Abstract 80.

DALLAS – MRI has long been important in both diagnosis and management of multiple sclerosis (MS). It’s more important than ever though, as perivenular demyelinating lesions emerge as a potential biomarker of the disease, and a key tool in precision medicine initiatives that target MS.

“The central vein sign is at the current time still a research tool that is being touted as an imaging finding that may be a very useful biomarker for diagnosis in MS,” said Jiwon Oh, MD, PhD, in an interview at the meeting presented by the Americas Committee for Treatment and Research in Multiple Sclerosis.

It’s almost ready for “prime time,” she said, “because it can easily be acquired on most conventional 3 Tesla MRI scanners, the sequences that you use don’t require an inordinate amount of time [and] it doesn’t take too much training to be able to easily identify the sign.”

A number of groups have evaluated the central vein sign and are finding it “a very specific biomarker” for MS, Dr. Oh said.

“It would be very useful in very early stages of diagnosis because it would prevent people from being misdiagnosed” and being treated unnecessarily, she said.

In her own work, Dr. Oh and her collaborators are following a cohort of people with radiologically isolated syndrome (RIS) discovered incidentally on brain imaging. “It’s a very valuable patient population to study because it may give us insight into the very earliest stages of MS,” as the lesions were not accompanied by any symptoms when they were first noticed.

Dr. Oh and her colleagues are finding that, among RIS patients, “the vast, vast majority of people have lesions with central veins; in our cohort, over 90% of patients met the 40% threshold that has been proposed to distinguish MS from other white matter changes.”

Dr. Oh said that the central vein sign may prove to be prognostic among RIS patients; they continue to follow the cohort being studied at the University of Toronto, where Dr. Oh is a neurologist.

koakes@mdedge.com

DALLAS – MRI has long been important in both diagnosis and management of multiple sclerosis (MS). It’s more important than ever though, as perivenular demyelinating lesions emerge as a potential biomarker of the disease, and a key tool in precision medicine initiatives that target MS.

“The central vein sign is at the current time still a research tool that is being touted as an imaging finding that may be a very useful biomarker for diagnosis in MS,” said Jiwon Oh, MD, PhD, in an interview at the meeting presented by the Americas Committee for Treatment and Research in Multiple Sclerosis.

It’s almost ready for “prime time,” she said, “because it can easily be acquired on most conventional 3 Tesla MRI scanners, the sequences that you use don’t require an inordinate amount of time [and] it doesn’t take too much training to be able to easily identify the sign.”

A number of groups have evaluated the central vein sign and are finding it “a very specific biomarker” for MS, Dr. Oh said.

“It would be very useful in very early stages of diagnosis because it would prevent people from being misdiagnosed” and being treated unnecessarily, she said.

In her own work, Dr. Oh and her collaborators are following a cohort of people with radiologically isolated syndrome (RIS) discovered incidentally on brain imaging. “It’s a very valuable patient population to study because it may give us insight into the very earliest stages of MS,” as the lesions were not accompanied by any symptoms when they were first noticed.

Dr. Oh and her colleagues are finding that, among RIS patients, “the vast, vast majority of people have lesions with central veins; in our cohort, over 90% of patients met the 40% threshold that has been proposed to distinguish MS from other white matter changes.”

Dr. Oh said that the central vein sign may prove to be prognostic among RIS patients; they continue to follow the cohort being studied at the University of Toronto, where Dr. Oh is a neurologist.

koakes@mdedge.com

DALLAS – MRI has long been important in both diagnosis and management of multiple sclerosis (MS). It’s more important than ever though, as perivenular demyelinating lesions emerge as a potential biomarker of the disease, and a key tool in precision medicine initiatives that target MS.

“The central vein sign is at the current time still a research tool that is being touted as an imaging finding that may be a very useful biomarker for diagnosis in MS,” said Jiwon Oh, MD, PhD, in an interview at the meeting presented by the Americas Committee for Treatment and Research in Multiple Sclerosis.

It’s almost ready for “prime time,” she said, “because it can easily be acquired on most conventional 3 Tesla MRI scanners, the sequences that you use don’t require an inordinate amount of time [and] it doesn’t take too much training to be able to easily identify the sign.”

A number of groups have evaluated the central vein sign and are finding it “a very specific biomarker” for MS, Dr. Oh said.

“It would be very useful in very early stages of diagnosis because it would prevent people from being misdiagnosed” and being treated unnecessarily, she said.

In her own work, Dr. Oh and her collaborators are following a cohort of people with radiologically isolated syndrome (RIS) discovered incidentally on brain imaging. “It’s a very valuable patient population to study because it may give us insight into the very earliest stages of MS,” as the lesions were not accompanied by any symptoms when they were first noticed.

Dr. Oh and her colleagues are finding that, among RIS patients, “the vast, vast majority of people have lesions with central veins; in our cohort, over 90% of patients met the 40% threshold that has been proposed to distinguish MS from other white matter changes.”

Dr. Oh said that the central vein sign may prove to be prognostic among RIS patients; they continue to follow the cohort being studied at the University of Toronto, where Dr. Oh is a neurologist.

koakes@mdedge.com