Pub Date : 2023-04-01DOI: 10.1177/20552173231169463
Gary Cutter, Richard A Rudick, Carl de Moor, Carol M Singh, Elizabeth Fisher, Thijs Koster, Fred D Lublin, Jerry S Wolinsky, Henry McFarland, Steven Jacobson, Maria L Naylor
Background: CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies.
Objective: This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse.
Methods: RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included. A linear mixed model compared sNfL values over time. Cox regression models analyzed baseline sNfL and gadolinium-enhancing (Gd+) lesions as predictors of relapse.
Results: In all treatment arms, the proportion of patients with sNfL ≥16 pg/mL decreased significantly from baseline to 6 months and was maintained at 36 months. A significantly higher percentage of patients with both baseline sNfL ≥16 pg/mL and ≥1 Gd+ lesion experienced relapses within 90 days compared to patients with sNfL <16 pg/mL and/or no Gd+ lesions.
Conclusion: sNfL levels were reduced within 6 months and remained low at 36 months. Results suggest that the combination of lesion activity and sNfL was a stronger predictor of relapse than either factor alone.
{"title":"Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial.","authors":"Gary Cutter, Richard A Rudick, Carl de Moor, Carol M Singh, Elizabeth Fisher, Thijs Koster, Fred D Lublin, Jerry S Wolinsky, Henry McFarland, Steven Jacobson, Maria L Naylor","doi":"10.1177/20552173231169463","DOIUrl":"https://doi.org/10.1177/20552173231169463","url":null,"abstract":"<p><strong>Background: </strong>CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies.</p><p><strong>Objective: </strong>This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse.</p><p><strong>Methods: </strong>RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included. A linear mixed model compared sNfL values over time. Cox regression models analyzed baseline sNfL and gadolinium-enhancing (Gd+) lesions as predictors of relapse.</p><p><strong>Results: </strong>In all treatment arms, the proportion of patients with sNfL ≥16 pg/mL decreased significantly from baseline to 6 months and was maintained at 36 months. A significantly higher percentage of patients with both baseline sNfL ≥16 pg/mL and ≥1 Gd+ lesion experienced relapses within 90 days compared to patients with sNfL <16 pg/mL and/or no Gd+ lesions.</p><p><strong>Conclusion: </strong>sNfL levels were reduced within 6 months and remained low at 36 months. Results suggest that the combination of lesion activity and sNfL was a stronger predictor of relapse than either factor alone.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 2","pages":"20552173231169463"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/f5/10.1177_20552173231169463.PMC10150429.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9410436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1177/20552173231167079
Amber Salter, Alexander Keenan, Hoa H Le, Kavita Gandhi, Maria Ait-Tihyaty, Samantha Lancia, Gary R Cutter, Robert J Fox, Ruth Ann Marrie
Background: Fatigue is associated with reduced quality of life and social participation, and poor employment outcomes. However, most studies examining fatigue are limited by small sample sizes or short follow-up periods.
Objective: To characterize the natural history of fatigue.
Methods: The North American Research Committee on Multiple Sclerosis Registry participants with ≥7 years of longitudinal data between 2004 and 2019 and a relapsing disease course were included. A subset of participants enrolled within 5 years of diagnosis was identified. The Fatigue Performance Scale assessed fatigue and ≥1-point increase in Fatigue Performance Scale sustained at the next survey defined fatigue worsening.
Results: Of 3057 participants with longitudinal data, 944 were within 5 years of multiple sclerosis diagnosis. Most participants (52%) reported fatigue worsening during follow-up. Median time to fatigue worsening ranged from 3.5 to 5 years at lower levels of index fatigue. Fatigue worsening was associated with lower annual income, increasing disability, lower initial fatigue level, taking injectable disease-modifying therapies and increasing depression levels in the relapsing multiple sclerosis participants.
Conclusion: Most multiple sclerosis participants early in their disease suffer from fatigue and at least half reported fatigue worsening over time. Understanding factors associated with fatigue may help to identify populations most at risk of fatigue worsening will be informative for the overall management of patients with multiple sclerosis.
{"title":"Severity and worsening of fatigue among individuals with multiple sclerosis.","authors":"Amber Salter, Alexander Keenan, Hoa H Le, Kavita Gandhi, Maria Ait-Tihyaty, Samantha Lancia, Gary R Cutter, Robert J Fox, Ruth Ann Marrie","doi":"10.1177/20552173231167079","DOIUrl":"https://doi.org/10.1177/20552173231167079","url":null,"abstract":"<p><strong>Background: </strong>Fatigue is associated with reduced quality of life and social participation, and poor employment outcomes. However, most studies examining fatigue are limited by small sample sizes or short follow-up periods.</p><p><strong>Objective: </strong>To characterize the natural history of fatigue.</p><p><strong>Methods: </strong>The North American Research Committee on Multiple Sclerosis Registry participants with ≥7 years of longitudinal data between 2004 and 2019 and a relapsing disease course were included. A subset of participants enrolled within 5 years of diagnosis was identified. The Fatigue Performance Scale assessed fatigue and ≥1-point increase in Fatigue Performance Scale sustained at the next survey defined fatigue worsening.</p><p><strong>Results: </strong>Of 3057 participants with longitudinal data, 944 were within 5 years of multiple sclerosis diagnosis. Most participants (52%) reported fatigue worsening during follow-up. Median time to fatigue worsening ranged from 3.5 to 5 years at lower levels of index fatigue. Fatigue worsening was associated with lower annual income, increasing disability, lower initial fatigue level, taking injectable disease-modifying therapies and increasing depression levels in the relapsing multiple sclerosis participants.</p><p><strong>Conclusion: </strong>Most multiple sclerosis participants early in their disease suffer from fatigue and at least half reported fatigue worsening over time. Understanding factors associated with fatigue may help to identify populations most at risk of fatigue worsening will be informative for the overall management of patients with multiple sclerosis.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 2","pages":"20552173231167079"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cf/d1/10.1177_20552173231167079.PMC10123908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9726263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1177/20552173231178441
A Heather, E Goodwin, C Green, N Morrish, O C Ukoumunne, R M Middleton, A Hawton
Background: New interventions for multiple sclerosis (MS) commonly require a demonstration of cost-effectiveness using health-related quality of life (HRQoL) utility values. The EQ-5D is the utility measure approved for use in the UK NHS funding decision-making. There are also MS-specific utility measures - e.g., MS Impact Scale Eight Dimensions (MSIS-8D) and MSIS-8D-Patient (MSIS-8D-P).
Objectives: Provide EQ-5D, MSIS-8D and MSIS-8D-P utility values from a large UK MS cohort and investigate their association with demographic/clinical characteristics.
Methods: UK MS Register data from 14,385 respondents (2011 to 2019) were analysed descriptively and using multivariable linear regression, with self-report Expanded Disability Status Scale (EDSS) scores.
Results: The EQ-5D and MSIS-8D were both sensitive to differences in demographic/clinical characteristics. An inconsistency found in previous studies whereby mean EQ-5D values were higher for an EDSS score of 4 rather than 3 was not observed. Similar utility values were observed between MS types at each EDSS score. Regression showed EDSS score and age were associated with utility values from all three measures.
Conclusions: This study provides generic and MS-specific utility values for a large UK MS sample, with the potential for use in cost-effectiveness analyses of treatments for MS.
{"title":"Multiple sclerosis health-related quality of life utility values from the UK MS register.","authors":"A Heather, E Goodwin, C Green, N Morrish, O C Ukoumunne, R M Middleton, A Hawton","doi":"10.1177/20552173231178441","DOIUrl":"https://doi.org/10.1177/20552173231178441","url":null,"abstract":"<p><strong>Background: </strong>New interventions for multiple sclerosis (MS) commonly require a demonstration of cost-effectiveness using health-related quality of life (HRQoL) utility values. The EQ-5D is the utility measure approved for use in the UK NHS funding decision-making. There are also MS-specific utility measures - e.g., MS Impact Scale Eight Dimensions (MSIS-8D) and MSIS-8D-Patient (MSIS-8D-P).</p><p><strong>Objectives: </strong>Provide EQ-5D, MSIS-8D and MSIS-8D-P utility values from a large UK MS cohort and investigate their association with demographic/clinical characteristics.</p><p><strong>Methods: </strong>UK MS Register data from 14,385 respondents (2011 to 2019) were analysed descriptively and using multivariable linear regression, with self-report Expanded Disability Status Scale (EDSS) scores.</p><p><strong>Results: </strong>The EQ-5D and MSIS-8D were both sensitive to differences in demographic/clinical characteristics. An inconsistency found in previous studies whereby mean EQ-5D values were higher for an EDSS score of 4 rather than 3 was not observed. Similar utility values were observed between MS types at each EDSS score. Regression showed EDSS score and age were associated with utility values from all three measures.</p><p><strong>Conclusions: </strong>This study provides generic and MS-specific utility values for a large UK MS sample, with the potential for use in cost-effectiveness analyses of treatments for MS.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 2","pages":"20552173231178441"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1177/20552173231165196
Sarah Conway, Shrishti Saxena, Clare Baecher-Allan, Rajesh Krishnan, Maria Houtchens, Bonnie Glanz, Taylor J Saraceno, Mariann Polgar-Turcsanyi, Gauruv Bose, Rohit Bakshi, Shamik Bhattacharyya, Kristin Galetta, Tamara Kaplan, Christopher Severson, Tarun Singhal, Lynn Stazzone, Jonathan Zurawski, Anu Paul, Howard L Weiner, Brian C Healy, Tanuja Chitnis
Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine.
Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination.
Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab.
Results: After 2-vax, 8/33 (24.2%) patients in ocrelizumab group, 5/7 (71.4%) in fingolimod group, and 29/29 (100%) in HC group (P = 5.7 × 10-11) seroconverted. After 3-vax, 9/22 (40.9%) patients in ocrelizumab group, 19/21 (90.5%) in fingolimod group, and 7/7 (100%) in HC group seroconverted (P = 0.0003). The percentage of SARS-CoV-2 peptide reactive total CD4+ T cells increased in HC and ocrelizumab group but not in fingolimod group after 2-vax and 3-vax (P < 0.0001). The percentage of IFNγ and TNFα producing total CD4+ and CD8+ T cells increased in fingolimod group as compared to HC and ocrelizumab group after 2-vax and 3-vax (P < 0.0001).
Conclusions: MS patients on ocrelizumab and fingolimod had attenuated humoral responses, but preserved cytokine producing T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination.
{"title":"Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.","authors":"Sarah Conway, Shrishti Saxena, Clare Baecher-Allan, Rajesh Krishnan, Maria Houtchens, Bonnie Glanz, Taylor J Saraceno, Mariann Polgar-Turcsanyi, Gauruv Bose, Rohit Bakshi, Shamik Bhattacharyya, Kristin Galetta, Tamara Kaplan, Christopher Severson, Tarun Singhal, Lynn Stazzone, Jonathan Zurawski, Anu Paul, Howard L Weiner, Brian C Healy, Tanuja Chitnis","doi":"10.1177/20552173231165196","DOIUrl":"https://doi.org/10.1177/20552173231165196","url":null,"abstract":"<p><strong>Background: </strong>There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine.</p><p><strong>Objectives: </strong>Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination.</p><p><strong>Methods: </strong>We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab.</p><p><strong>Results: </strong>After 2-vax, 8/33 (24.2%) patients in ocrelizumab group, 5/7 (71.4%) in fingolimod group, and 29/29 (100%) in HC group (<i>P</i> = 5.7 × 10<sup>-11</sup>) seroconverted. After 3-vax, 9/22 (40.9%) patients in ocrelizumab group, 19/21 (90.5%) in fingolimod group, and 7/7 (100%) in HC group seroconverted (<i>P </i>= 0.0003). The percentage of SARS-CoV-2 peptide reactive total CD4+ T cells increased in HC and ocrelizumab group but not in fingolimod group after 2-vax and 3-vax (<i>P </i>< 0.0001). The percentage of IFNγ and TNFα producing total CD4+ and CD8+ T cells increased in fingolimod group as compared to HC and ocrelizumab group after 2-vax and 3-vax (<i>P </i>< 0.0001).</p><p><strong>Conclusions: </strong>MS patients on ocrelizumab and fingolimod had attenuated humoral responses, but preserved cytokine producing T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination.</p><p><strong>Clinical trials registration: </strong>NCT05060354.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 2","pages":"20552173231165196"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/fb/10.1177_20552173231165196.PMC10086198.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9311232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1177/20552173231169475
Susana Sainz de la Maza, Rocío Gómez-Ballesteros, Mónica Borges, Jesús Martín-Martínez, Javier Sotoca, Ana Alonso, Ana B Caminero, Laura Borrega, José L Sánchez-Menoyo, Francisco J Barrero-Hernández, Carmen Calles, Luis Brieva, María R Blasco-Quílez, Julio Dotor García-Soto, María Del Campo-Amigo, Laura Navarro-Cantó, Eduardo Agüera, Moisés Garcés-Redondo, Olga Carmona, Laura Gabaldón-Torres, Lucía Forero, Mariona Hervàs, Nicolás Medrano, Jorge Maurino, Tamara Castillo-Triviño
Disability accrual is mainly driven by progression independent of relapse activity, which is present even in early stages of relapsing-remitting multiple sclerosis (RRMS) and sometimes overlooked. This multicenter, non-interventional study evaluated whether patient-reported outcomes measures (PROMs) could capture disability in 189 early-stage RRMS patients (mean age: 36.1 ± 9.4 years, 71.4% female, mean disease duration: 1.4 ± 0.8 years, median EDSS: 1.0). The 9-Hole Peg Test (9-HPT), NeuroQoL Upper Extremity (NeuroQoL-UE), Timed 25-Foot Walk (T25-FW), Multiple Sclerosis Walking Scale (MSWS-12), Symbol Digit Modalities Test (SDMT), and Perceived Deficits Questionnaire (PDQ-5) were used to assess hand function, gait, and cognition, respectively. These functions were at least mildly affected in this early-stage population, finding significant correlations between PROMs and clinical assessments. PROMs could enable early-stage RRMS patients to communicate their perceived disability in different domains, assisting clinicians in disease monitoring and decision making.
{"title":"Detecting disability using self-reported and clinical assessments in early-stage relapsing-remitting multiple sclerosis: Looking for a complementary approach.","authors":"Susana Sainz de la Maza, Rocío Gómez-Ballesteros, Mónica Borges, Jesús Martín-Martínez, Javier Sotoca, Ana Alonso, Ana B Caminero, Laura Borrega, José L Sánchez-Menoyo, Francisco J Barrero-Hernández, Carmen Calles, Luis Brieva, María R Blasco-Quílez, Julio Dotor García-Soto, María Del Campo-Amigo, Laura Navarro-Cantó, Eduardo Agüera, Moisés Garcés-Redondo, Olga Carmona, Laura Gabaldón-Torres, Lucía Forero, Mariona Hervàs, Nicolás Medrano, Jorge Maurino, Tamara Castillo-Triviño","doi":"10.1177/20552173231169475","DOIUrl":"https://doi.org/10.1177/20552173231169475","url":null,"abstract":"<p><p>Disability accrual is mainly driven by progression independent of relapse activity, which is present even in early stages of relapsing-remitting multiple sclerosis (RRMS) and sometimes overlooked. This multicenter, non-interventional study evaluated whether patient-reported outcomes measures (PROMs) could capture disability in 189 early-stage RRMS patients (mean age: 36.1 ± 9.4 years, 71.4% female, mean disease duration: 1.4 ± 0.8 years, median EDSS: 1.0). The 9-Hole Peg Test (9-HPT), NeuroQoL Upper Extremity (NeuroQoL-UE), Timed 25-Foot Walk (T25-FW), Multiple Sclerosis Walking Scale (MSWS-12), Symbol Digit Modalities Test (SDMT), and Perceived Deficits Questionnaire (PDQ-5) were used to assess hand function, gait, and cognition, respectively. These functions were at least mildly affected in this early-stage population, finding significant correlations between PROMs and clinical assessments. PROMs could enable early-stage RRMS patients to communicate their perceived disability in different domains, assisting clinicians in disease monitoring and decision making.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 2","pages":"20552173231169475"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/ab/10.1177_20552173231169475.PMC10176560.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-16eCollection Date: 2023-01-01DOI: 10.1177/20552173221147620
Eva A Krijnen, Chanon Ngamsombat, Ilena C George, Fang F Yu, Qiuyun Fan, Qiyuan Tian, Susie Y Huang, Eric C Klawiter
Background: The imaging g-ratio, estimated from axonal volume fraction (AVF) and myelin volume fraction (MVF), is a novel biomarker of microstructural tissue integrity in multiple sclerosis (MS).
Objective: To assess axonal and myelin changes and their inter-relationship as measured by g-ratio in the optic radiations (OR) in people with MS (pwMS) with and without previous optic neuritis (ON) compared to healthy controls (HC).
Methods: Thirty pwMS and 17 HCs were scanned on a 3Tesla Connectom scanner. AVF and MVF, derived from a multi-shell diffusion protocol and macromolecular tissue volume, respectively, were measured in normal-appearing white matter (NAWM) and lesions within the OR and used to calculate imaging g-ratio.
Results: OR AVF and MVF were decreased in pwMS compared to HC, and in OR lesions compared to NAWM, whereas the g-ratio was not different. Compared to pwMS with previous ON, AVF and g-ratio tended to be higher in pwMS without prior ON. AVF and MVF, particularly in NAWM, were positively correlated with retinal thickness, which was more pronounced in pwMS with prior ON.
Conclusion: Axonal measures reflect microstructural tissue damage in the OR, particularly in the setting of remote ON, and correlate with established metrics of visual health in MS.
{"title":"Axonal and myelin changes and their inter-relationship in the optic radiations in people with multiple sclerosis.","authors":"Eva A Krijnen, Chanon Ngamsombat, Ilena C George, Fang F Yu, Qiuyun Fan, Qiyuan Tian, Susie Y Huang, Eric C Klawiter","doi":"10.1177/20552173221147620","DOIUrl":"10.1177/20552173221147620","url":null,"abstract":"<p><strong>Background: </strong>The imaging g-ratio, estimated from axonal volume fraction (AVF) and myelin volume fraction (MVF), is a novel biomarker of microstructural tissue integrity in multiple sclerosis (MS).</p><p><strong>Objective: </strong>To assess axonal and myelin changes and their inter-relationship as measured by g-ratio in the optic radiations (OR) in people with MS (pwMS) with and without previous optic neuritis (ON) compared to healthy controls (HC).</p><p><strong>Methods: </strong>Thirty pwMS and 17 HCs were scanned on a 3Tesla Connectom scanner. AVF and MVF, derived from a multi-shell diffusion protocol and macromolecular tissue volume, respectively, were measured in normal-appearing white matter (NAWM) and lesions within the OR and used to calculate imaging g-ratio.</p><p><strong>Results: </strong>OR AVF and MVF were decreased in pwMS compared to HC, and in OR lesions compared to NAWM, whereas the g-ratio was not different. Compared to pwMS with previous ON, AVF and g-ratio tended to be higher in pwMS without prior ON. AVF and MVF, particularly in NAWM, were positively correlated with retinal thickness, which was more pronounced in pwMS with prior ON.</p><p><strong>Conclusion: </strong>Axonal measures reflect microstructural tissue damage in the OR, particularly in the setting of remote ON, and correlate with established metrics of visual health in MS.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 1","pages":"20552173221147620"},"PeriodicalIF":2.8,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/84/10.1177_20552173221147620.PMC9940187.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9313988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1177/20552173221151127
Shay Menascu, Michal Siegel-Kirshenbaum, Sapir Dreyer-Alster, Yehuda Warszawer, David Magalashvili, Mark Dolev, Mathilda Mandel, Gil Harari, Anat Achiron
Background: Relapsing-remitting multiple sclerosis (RRMS) affects predominantly young women within reproductive years. As an increased risk of relapses is known to occur during the post-partum period, it is important to consider treatment options.
Aim: Evaluate the effects of intravenous immunoglobulins (IVIg) to prevent post-partum relapses.
Methods: We prospectively followed 198 pregnant female RRMS patients, 67 treated with IVIg during pregnancy and the three months post-partum, and 131 untreated patients that served as controls.
Results: During the pre-gestation year, 41.4% were treated with immunomodulatory drugs, and 28.3% experienced a relapse. During pregnancy and the post-partum period, the number of relapsing patients significantly decreased in the IVIg group (37.3%, 10.4%, 8.9%, respectively, p = 0.0003), while no significant change was observed in the untreated group (23.7%, 17.6%, and 22.1%). During the three-month post-partum period, there were only mild and moderate relapses in the IVIg group, while in the untreated group, there were also severe relapses. Stepwise logistic regression that assessed the relation between three-month post-partum relapse and explanatory variables demonstrated that untreated patients had increased risk for post-partum relapse (odds ratio = 4.6, 95% CI [1.69, 12.78], p = 0.033).
Conclusions: IVIg treatment proved efficient to reduce the rate and severity of relapses during pregnancy and the three-month post-partum.
背景:复发缓解型多发性硬化症(RRMS)主要影响育龄期的年轻女性。由于已知在产后期间复发的风险增加,因此考虑治疗方案很重要。目的:评价静脉注射免疫球蛋白(IVIg)预防产后复发的效果。方法:对198例妊娠期女性RRMS患者进行前瞻性随访,其中67例在妊娠期及产后3个月接受IVIg治疗,131例未接受IVIg治疗的患者作为对照。结果:孕前一年,41.4%的患者接受免疫调节药物治疗,28.3%的患者复发。在妊娠期和产后,IVIg组复发率显著降低(分别为37.3%、10.4%、8.9%,p = 0.0003),而未治疗组复发率无显著变化(分别为23.7%、17.6%、22.1%)。在产后3个月期间,IVIg组仅有轻、中度复发,而未治疗组也有重度复发。逐步logistic回归评估了产后3个月复发与解释变量之间的关系,结果显示未经治疗的患者产后复发的风险增加(优势比= 4.6,95% CI [1.69, 12.78], p = 0.033)。结论:IVIg治疗可有效降低妊娠期及产后3个月的复发率和严重程度。
{"title":"Intravenous immunoglobulin treatment during pregnancy and the post-partum period in women with multiple sclerosis: A prospective analysis.","authors":"Shay Menascu, Michal Siegel-Kirshenbaum, Sapir Dreyer-Alster, Yehuda Warszawer, David Magalashvili, Mark Dolev, Mathilda Mandel, Gil Harari, Anat Achiron","doi":"10.1177/20552173221151127","DOIUrl":"https://doi.org/10.1177/20552173221151127","url":null,"abstract":"<p><strong>Background: </strong>Relapsing-remitting multiple sclerosis (RRMS) affects predominantly young women within reproductive years. As an increased risk of relapses is known to occur during the post-partum period, it is important to consider treatment options.</p><p><strong>Aim: </strong>Evaluate the effects of intravenous immunoglobulins (IVIg) to prevent post-partum relapses.</p><p><strong>Methods: </strong>We prospectively followed 198 pregnant female RRMS patients, 67 treated with IVIg during pregnancy and the three months post-partum, and 131 untreated patients that served as controls.</p><p><strong>Results: </strong>During the pre-gestation year, 41.4% were treated with immunomodulatory drugs, and 28.3% experienced a relapse. During pregnancy and the post-partum period, the number of relapsing patients significantly decreased in the IVIg group (37.3%, 10.4%, 8.9%, respectively, <i>p</i> = 0.0003), while no significant change was observed in the untreated group (23.7%, 17.6%, and 22.1%). During the three-month post-partum period, there were only mild and moderate relapses in the IVIg group, while in the untreated group, there were also severe relapses. Stepwise logistic regression that assessed the relation between three-month post-partum relapse and explanatory variables demonstrated that untreated patients had increased risk for post-partum relapse (odds ratio = 4.6, 95% CI [1.69, 12.78], <i>p</i> = 0.033).</p><p><strong>Conclusions: </strong>IVIg treatment proved efficient to reduce the rate and severity of relapses during pregnancy and the three-month post-partum.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 1","pages":"20552173221151127"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/88/03/10.1177_20552173221151127.PMC9853871.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9134260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1177/20552173221144229
Giancarlo Comi, Letizia Leocani, Luigi Ferini-Strambi, Marta Radaelli, Gloria D Costa, Roberta Lanzillo, Giacomo Lus, Valentina Bianchi, Sebastiano Traccis, Fioravante Capone, Luigi Me Grimaldi, Giuseppe Salemi, Alessandra Cardillo, Valentina Zipoli
Background: Sleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression.
Objective: To evaluate the effect of treatment with oral dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis.
Methods: This was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate (n=177) or beta interferon (n=46). All patients underwent subjective (Pittsburgh Sleep Quality Index) and objective (wearable tracker) measurements of quality of sleep. Fatigue, depression, and quality of life were also investigated and physical activity was monitored.
Results: Patients treated with dimethyl fumarate had significant improvement in the quality of sleep as measured with the Pittsburgh Sleep Quality Index (p<0.001). At all-time points, no significant changes in Pittsburgh Sleep Quality Index score were observed in the interferon group. Total and deep sleep measured by wearable tracker decreased at week 12 with both treatments, then remained stable for the total study duration. Depression significantly improved in patients treated with dimethyl fumarate. No significant changes were observed in mobility, fatigue and quality of life.
Conclusion: In patients with relapsing-remitting multiple sclerosis, the treatment with dimethyl fumarate was associated with improvements in patient-reported quality of sleep. Further randomised clinical trials are needed to confirm the benefits of long-term treatment with dimethyl fumarate.
{"title":"Impact of treatment with dimethyl fumarate on sleep quality in patients with relapsing-remitting multiple sclerosis: A multicentre Italian wearable tracker study.","authors":"Giancarlo Comi, Letizia Leocani, Luigi Ferini-Strambi, Marta Radaelli, Gloria D Costa, Roberta Lanzillo, Giacomo Lus, Valentina Bianchi, Sebastiano Traccis, Fioravante Capone, Luigi Me Grimaldi, Giuseppe Salemi, Alessandra Cardillo, Valentina Zipoli","doi":"10.1177/20552173221144229","DOIUrl":"https://doi.org/10.1177/20552173221144229","url":null,"abstract":"<p><strong>Background: </strong>Sleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression.</p><p><strong>Objective: </strong>To evaluate the effect of treatment with oral dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis.</p><p><strong>Methods: </strong>This was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate (<i>n</i>=177) or beta interferon (<i>n</i>=46). All patients underwent subjective (Pittsburgh Sleep Quality Index) and objective (wearable tracker) measurements of quality of sleep. Fatigue, depression, and quality of life were also investigated and physical activity was monitored.</p><p><strong>Results: </strong>Patients treated with dimethyl fumarate had significant improvement in the quality of sleep as measured with the Pittsburgh Sleep Quality Index (<i>p</i><0.001). At all-time points, no significant changes in Pittsburgh Sleep Quality Index score were observed in the interferon group. Total and deep sleep measured by wearable tracker decreased at week 12 with both treatments, then remained stable for the total study duration. Depression significantly improved in patients treated with dimethyl fumarate. No significant changes were observed in mobility, fatigue and quality of life.</p><p><strong>Conclusion: </strong>In patients with relapsing-remitting multiple sclerosis, the treatment with dimethyl fumarate was associated with improvements in patient-reported quality of sleep. Further randomised clinical trials are needed to confirm the benefits of long-term treatment with dimethyl fumarate.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 1","pages":"20552173221144229"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/f2/10.1177_20552173221144229.PMC9912562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10707862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years.
Methods: This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs.
Results: In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (p < 0.01) and a shorter time between first treatment and current treatment (p = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (p < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, p < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, p 0.57).
Conclusion: We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.
背景:我们的目的是确定在高效治疗(HETs)下,在1年和2年达到无疾病活动证据3 (NEDA-3)的高活性多发性硬化症患者的比例,并确定在2年未能达到无疾病活动证据3的相关因素。方法:本回顾性队列研究基于阿根廷多发性硬化症患者登记处(RelevarEM),包括接受HETs治疗的高度活跃的多发性硬化症患者。结果:254例(78.51%)患者在1年达到NEDA-3, 220例(68.12%)患者在2年达到NEDA-3。2年达到NEDA-3的患者多发性硬化症持续时间较短(p p = 0.01)。早期高效策略患者达到NEDA-3的频率更高(p < p < 0.57)。结论:我们发现在1年和2年达到NEDA-3的患者比例很高。早期高效策略患者在2年时达到NEDA-3的概率更高。
{"title":"Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies.","authors":"Ricardo Alonso, Magdalena Casas, Luciana Lazaro, Nora Fernandez Liguori, Cecilia Pita, Leila Cohen, Juan Ignacio Rojas, Agustín Pappolla, Liliana Patrucco, Edgardo Cristiano, Marcos Burgos, Carlos Vrech, Raul Piedrabuena, Lopez Pablo, Norma Deri, Geraldine Luetic, Jimena Miguez, Mariela Cabrera, Alejandra Martinez, Gisela Zanga, Verónica Tkachuk, Santiago Tizio, Edgar Carnero Contentti, Eduardo Knorre, Felisa Leguizamon, Carolina Mainella, Pedro Nofal, Susana Liwacki, Javier Hryb, Maria Menichini, Claudia Pestchanker, Marina Alonso, Orlando Garcea, Berenice Silva","doi":"10.1177/20552173231154712","DOIUrl":"https://doi.org/10.1177/20552173231154712","url":null,"abstract":"<p><strong>Background: </strong>We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years.</p><p><strong>Methods: </strong>This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs.</p><p><strong>Results: </strong>In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (<i>p</i> < 0.01) and a shorter time between first treatment and current treatment (<i>p</i> = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (<i>p</i> < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, <i>p</i> < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, <i>p</i> 0.57).</p><p><strong>Conclusion: </strong>We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 1","pages":"20552173231154712"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/18/10.1177_20552173231154712.PMC9950613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9341901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1177/20552173231159560
Peter V Sguigna, Sabeen Toranian, Lauren M Tardo, Kyle M Blackburn, Lindsay A Horton, Darrel Conger, Ethan Meltzer, R Nick Hogan, Morgan C McCreary, Phyllis C Zee, Joseph S Takahashi, Benjamin M Greenberg
Background: Excessive daytime sleepiness (EDS) in multiple sclerosis (MS) can be a significant source of disability. Despite this, its prevalence as a patient-reported outcome in this condition has not been well established, and its causes are not well understood.
Methods: We prospectively assessed EDS as part of an observational study for patients referred for diagnostic neuro-ophthalmological testing. EDS was evaluated by the Epworth Sleepiness Scale (ESS), and visual data were also collected as part of a research protocol. Analysis with patient data was performed following the exclusion of patients with known primary sleep disorders.
Results: A total of 69 patients with MS were included in the analysis. The mean ESS was 6.5 with a SD of 4.3. ESS ≥ 10 was present in 23% of the cohort even in the presence of minimal mean neurological disability (Patient Determined Disease Steps (PDDS) = 1.5). The ESS score was not associated with age, sex, disease-related disability, retinal nerve fiber layer (RNFL), or optic neuritis (ON), but displayed an association with visual dysfunction.
Conclusions: There is an increased prevalence of EDS in MS. The increased values of the ESS are not explained by other sleep disorders, suggesting separate mechanisms. Further study of the underlying mechanisms is warranted.
{"title":"Disease associations of excessive daytime sleepiness in multiple sclerosis: A prospective study.","authors":"Peter V Sguigna, Sabeen Toranian, Lauren M Tardo, Kyle M Blackburn, Lindsay A Horton, Darrel Conger, Ethan Meltzer, R Nick Hogan, Morgan C McCreary, Phyllis C Zee, Joseph S Takahashi, Benjamin M Greenberg","doi":"10.1177/20552173231159560","DOIUrl":"https://doi.org/10.1177/20552173231159560","url":null,"abstract":"<p><strong>Background: </strong>Excessive daytime sleepiness (EDS) in multiple sclerosis (MS) can be a significant source of disability. Despite this, its prevalence as a patient-reported outcome in this condition has not been well established, and its causes are not well understood.</p><p><strong>Methods: </strong>We prospectively assessed EDS as part of an observational study for patients referred for diagnostic neuro-ophthalmological testing. EDS was evaluated by the Epworth Sleepiness Scale (ESS), and visual data were also collected as part of a research protocol. Analysis with patient data was performed following the exclusion of patients with known primary sleep disorders.</p><p><strong>Results: </strong>A total of 69 patients with MS were included in the analysis. The mean ESS was 6.5 with a SD of 4.3. ESS ≥ 10 was present in 23% of the cohort even in the presence of minimal mean neurological disability (Patient Determined Disease Steps (PDDS) = 1.5). The ESS score was not associated with age, sex, disease-related disability, retinal nerve fiber layer (RNFL), or optic neuritis (ON), but displayed an association with visual dysfunction.</p><p><strong>Conclusions: </strong>There is an increased prevalence of EDS in MS. The increased values of the ESS are not explained by other sleep disorders, suggesting separate mechanisms. Further study of the underlying mechanisms is warranted.</p>","PeriodicalId":18961,"journal":{"name":"Multiple Sclerosis Journal - Experimental, Translational and Clinical","volume":"9 1","pages":"20552173231159560"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/59/10.1177_20552173231159560.PMC10017949.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}