ICYMI Multiple Sclerosis

Key clinical point: Serum neurofilament light chain (sNfL) could serve as an effective prognostic biomarker for long-term disability progression in patients with progressive multiple sclerosis (PMS).

Major finding: An sNfL value of >10.2 pg/mL at baseline differentiated long-term progressors and nonprogressors with a sensitivity of 75% and a specificity of 67% (adjusted odds ratio [aOR] 7.8; P = .01), and an increase of >5.1 pg/mL in the sNfL value from baseline to 6 years differentiated long-term progressors and nonprogressors with a sensitivity of 71% and a specificity of 86% (aOR 49.4; P = .008).

Study details: This was a 6-year prospective observational cohort study that included 51 patients with PMS who had participated in a 2-year phase 2, randomized, placebo-controlled trial of interferon-beta.

Disclosures: No external funding was received for this study. The authors declared no conflicts of interests.

Source: Comabella M et al. Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 (Apr 29). Doi: 10.1136/jnnp-2022-329020

Key clinical point: Serum neurofilament light chain (sNfL) could serve as an effective prognostic biomarker for long-term disability progression in patients with progressive multiple sclerosis (PMS).

Major finding: An sNfL value of >10.2 pg/mL at baseline differentiated long-term progressors and nonprogressors with a sensitivity of 75% and a specificity of 67% (adjusted odds ratio [aOR] 7.8; P = .01), and an increase of >5.1 pg/mL in the sNfL value from baseline to 6 years differentiated long-term progressors and nonprogressors with a sensitivity of 71% and a specificity of 86% (aOR 49.4; P = .008).

Study details: This was a 6-year prospective observational cohort study that included 51 patients with PMS who had participated in a 2-year phase 2, randomized, placebo-controlled trial of interferon-beta.

Disclosures: No external funding was received for this study. The authors declared no conflicts of interests.

Source: Comabella M et al. Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 (Apr 29). Doi: 10.1136/jnnp-2022-329020

Key clinical point: Serum neurofilament light chain (sNfL) could serve as an effective prognostic biomarker for long-term disability progression in patients with progressive multiple sclerosis (PMS).

Major finding: An sNfL value of >10.2 pg/mL at baseline differentiated long-term progressors and nonprogressors with a sensitivity of 75% and a specificity of 67% (adjusted odds ratio [aOR] 7.8; P = .01), and an increase of >5.1 pg/mL in the sNfL value from baseline to 6 years differentiated long-term progressors and nonprogressors with a sensitivity of 71% and a specificity of 86% (aOR 49.4; P = .008).

Study details: This was a 6-year prospective observational cohort study that included 51 patients with PMS who had participated in a 2-year phase 2, randomized, placebo-controlled trial of interferon-beta.

Disclosures: No external funding was received for this study. The authors declared no conflicts of interests.

Source: Comabella M et al. Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 (Apr 29). Doi: 10.1136/jnnp-2022-329020

Key clinical point: Switching to once every-6-weeks (QW6) dosing of natalizumab from a stable dosing of once every-4-weeks (QW4) was safe without any clinically meaningful loss of efficacy in most patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) vs 0.05 (95% CI 0.01-0.22) with natalizumab QW6 vs QW4 dosing regimen, with two patients developing ≥25 lesions contributing to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Study details: Findings are from a phase 3b NOVA trial including 499 patients with RRMS on stable intravenous natalizumab QW4 dosing who were randomly assigned to continue QW4 (n  = 248) or switch to QW6 (n = 251) natalizumab dosing.

Disclosures: This study was funded by Biogen. Five authors reported being current or former employees or holding stocks in Biogen, and some authors reported receiving consulting or speakers’ fees, personal compensation, or serving as a steering committee or advisory board member for various sources.

Source: Foley JF et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): A randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 (Apr 25). Doi: 10.1016/ S1474-4422(22)00143-0

Key clinical point: Switching to once every-6-weeks (QW6) dosing of natalizumab from a stable dosing of once every-4-weeks (QW4) was safe without any clinically meaningful loss of efficacy in most patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) vs 0.05 (95% CI 0.01-0.22) with natalizumab QW6 vs QW4 dosing regimen, with two patients developing ≥25 lesions contributing to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Study details: Findings are from a phase 3b NOVA trial including 499 patients with RRMS on stable intravenous natalizumab QW4 dosing who were randomly assigned to continue QW4 (n  = 248) or switch to QW6 (n = 251) natalizumab dosing.

Disclosures: This study was funded by Biogen. Five authors reported being current or former employees or holding stocks in Biogen, and some authors reported receiving consulting or speakers’ fees, personal compensation, or serving as a steering committee or advisory board member for various sources.

Source: Foley JF et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): A randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 (Apr 25). Doi: 10.1016/ S1474-4422(22)00143-0

Key clinical point: Switching to once every-6-weeks (QW6) dosing of natalizumab from a stable dosing of once every-4-weeks (QW4) was safe without any clinically meaningful loss of efficacy in most patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) vs 0.05 (95% CI 0.01-0.22) with natalizumab QW6 vs QW4 dosing regimen, with two patients developing ≥25 lesions contributing to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Study details: Findings are from a phase 3b NOVA trial including 499 patients with RRMS on stable intravenous natalizumab QW4 dosing who were randomly assigned to continue QW4 (n  = 248) or switch to QW6 (n = 251) natalizumab dosing.

Disclosures: This study was funded by Biogen. Five authors reported being current or former employees or holding stocks in Biogen, and some authors reported receiving consulting or speakers’ fees, personal compensation, or serving as a steering committee or advisory board member for various sources.

Source: Foley JF et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): A randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 (Apr 25). Doi: 10.1016/ S1474-4422(22)00143-0

Portaccio and colleagues explored this issue and concluded that disease progression independent of relapse activity (PIRA) was a major contributor of confirmed disability accrual (CDA) in early relapse after the onset of MS, with age being a major determinant in the way that CDA occurs. In a retrospective cohort analysis of 5169 patients with either clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥ 5 years, PIRA accounted for 27.6% of disability-worsening events, whereas relapse-associated worsening accounted for 17.8% of events, with relapse-associated worsening being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients. Recognition of disease relapse or progression is not always simple in a complex disease, but failure to recognize these issues can result in long-term accumulation of economically important disability. Multiple other issues related to effective disease management also require effective juggling in routine care. Adherence to treatment, timing of DMT change, and interval between discontinuing a DMT and starting a different one continue to be critical concerns as well. Malpas and associates explored this issue and noted that the importance of adherence impact on disease control also relates to treatment interruption and timing of duration between stopping one DMT and starting another agent. The annualized relapse rate (ARR) and the rate of severe relapses was explored in a cohort of 685 people with MS and did not increase significantly after discontinuation of fingolimod in this population, but delaying the commencement of immunotherapy increased the risk for relapse. The ARR was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior to and after fingolimod cessation. However, delaying the recommencement of DMT, or if change in DMT was delayed from 2 to 4 months, vs beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse. Discontinuation of DMT or treatment interruption also relates to planned or unplanned pregnancy in people with MS. In another study Portaccio and colleagues continued treatment with natalizumab until conception and then restarted treatment within 1 month after delivery. This reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery in women with MS. No major developmental abnormalities were noted in the infants born of 72 pregnancies in 70 women with MS who were treated for at least 2 years. Specifically, relapses occurred in 29.4% of people with MS treated until conception vs 70.2% in those who discontinued prior to conception, after a mean follow-up of 6.1 years (P = .001), with timing of treatment cessation being the only predictor of relapses (HR 4.1; P = .003). No developmental abnormalities were observed in the infants.

Practical points for the treating clinician are many and continue to highlight the complexity of managing people with MS in the real world, with real issues from COVID-19 vaccination, SARS-CoV-2 infection, recognition or awareness of relapse, and the increased challenges of adherence and timing of DMT change and of DMT use relative to pregnancy. Data-driven, reliable, relevant information is critical to incorporate into routine care to enhance and optimize decision-making.

Portaccio and colleagues explored this issue and concluded that disease progression independent of relapse activity (PIRA) was a major contributor of confirmed disability accrual (CDA) in early relapse after the onset of MS, with age being a major determinant in the way that CDA occurs. In a retrospective cohort analysis of 5169 patients with either clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥ 5 years, PIRA accounted for 27.6% of disability-worsening events, whereas relapse-associated worsening accounted for 17.8% of events, with relapse-associated worsening being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients. Recognition of disease relapse or progression is not always simple in a complex disease, but failure to recognize these issues can result in long-term accumulation of economically important disability. Multiple other issues related to effective disease management also require effective juggling in routine care. Adherence to treatment, timing of DMT change, and interval between discontinuing a DMT and starting a different one continue to be critical concerns as well. Malpas and associates explored this issue and noted that the importance of adherence impact on disease control also relates to treatment interruption and timing of duration between stopping one DMT and starting another agent. The annualized relapse rate (ARR) and the rate of severe relapses was explored in a cohort of 685 people with MS and did not increase significantly after discontinuation of fingolimod in this population, but delaying the commencement of immunotherapy increased the risk for relapse. The ARR was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior to and after fingolimod cessation. However, delaying the recommencement of DMT, or if change in DMT was delayed from 2 to 4 months, vs beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse. Discontinuation of DMT or treatment interruption also relates to planned or unplanned pregnancy in people with MS. In another study Portaccio and colleagues continued treatment with natalizumab until conception and then restarted treatment within 1 month after delivery. This reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery in women with MS. No major developmental abnormalities were noted in the infants born of 72 pregnancies in 70 women with MS who were treated for at least 2 years. Specifically, relapses occurred in 29.4% of people with MS treated until conception vs 70.2% in those who discontinued prior to conception, after a mean follow-up of 6.1 years (P = .001), with timing of treatment cessation being the only predictor of relapses (HR 4.1; P = .003). No developmental abnormalities were observed in the infants.

Practical points for the treating clinician are many and continue to highlight the complexity of managing people with MS in the real world, with real issues from COVID-19 vaccination, SARS-CoV-2 infection, recognition or awareness of relapse, and the increased challenges of adherence and timing of DMT change and of DMT use relative to pregnancy. Data-driven, reliable, relevant information is critical to incorporate into routine care to enhance and optimize decision-making.

Portaccio and colleagues explored this issue and concluded that disease progression independent of relapse activity (PIRA) was a major contributor of confirmed disability accrual (CDA) in early relapse after the onset of MS, with age being a major determinant in the way that CDA occurs. In a retrospective cohort analysis of 5169 patients with either clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥ 5 years, PIRA accounted for 27.6% of disability-worsening events, whereas relapse-associated worsening accounted for 17.8% of events, with relapse-associated worsening being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients. Recognition of disease relapse or progression is not always simple in a complex disease, but failure to recognize these issues can result in long-term accumulation of economically important disability. Multiple other issues related to effective disease management also require effective juggling in routine care. Adherence to treatment, timing of DMT change, and interval between discontinuing a DMT and starting a different one continue to be critical concerns as well. Malpas and associates explored this issue and noted that the importance of adherence impact on disease control also relates to treatment interruption and timing of duration between stopping one DMT and starting another agent. The annualized relapse rate (ARR) and the rate of severe relapses was explored in a cohort of 685 people with MS and did not increase significantly after discontinuation of fingolimod in this population, but delaying the commencement of immunotherapy increased the risk for relapse. The ARR was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior to and after fingolimod cessation. However, delaying the recommencement of DMT, or if change in DMT was delayed from 2 to 4 months, vs beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse. Discontinuation of DMT or treatment interruption also relates to planned or unplanned pregnancy in people with MS. In another study Portaccio and colleagues continued treatment with natalizumab until conception and then restarted treatment within 1 month after delivery. This reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery in women with MS. No major developmental abnormalities were noted in the infants born of 72 pregnancies in 70 women with MS who were treated for at least 2 years. Specifically, relapses occurred in 29.4% of people with MS treated until conception vs 70.2% in those who discontinued prior to conception, after a mean follow-up of 6.1 years (P = .001), with timing of treatment cessation being the only predictor of relapses (HR 4.1; P = .003). No developmental abnormalities were observed in the infants.

Practical points for the treating clinician are many and continue to highlight the complexity of managing people with MS in the real world, with real issues from COVID-19 vaccination, SARS-CoV-2 infection, recognition or awareness of relapse, and the increased challenges of adherence and timing of DMT change and of DMT use relative to pregnancy. Data-driven, reliable, relevant information is critical to incorporate into routine care to enhance and optimize decision-making.

Key clinical point: Hormone therapy with Duavee®, containing conjugated estrogens (0.45 mg) and bazedoxifene (20 mg), yielded a favorable study retention and treatment satisfaction in menopausal women with multiple sclerosis (MS).

Major finding: Patients receiving Duavee® vs. placebo had a fewer missed doses (median, interquartile range [IQR] 0 [0-0] vs. 1 [0-9]), a greater Global Satisfaction on the Treatment Satisfaction Questionnaire for Medication (median, IQR 65.9 [52.8-100] vs. 62.5 [11.1-93.0]), and lesser side effects (20% vs. 13%), with none of the patients reporting a clinical relapse.

Study details: Findings are from a double-blind phase 1b/2a trial involving 21 peri/postmenopausal women with MS who were randomly assigned to parallel groups of Duavee® or equivalent placebo for 8 weeks.

Disclosures: This study was funded the National Multiple Sclerosis Society pilot grant and CTSI grant. Some authors declared receiving research support, personal compensation, speaker fees, or nonfinancial support from various sources, including Wyeth/Pfizer, the manufacturer of Duavee®. Several authors are provisional patent holders for the use of bazedoxifene in remyelination therapy.

Source: Bove R et al. A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial. Mult Scler Relat Disord. 2022;67:103747 (Mar 19). Doi:  10.1016/j.msard.2022.103747

Key clinical point: Hormone therapy with Duavee®, containing conjugated estrogens (0.45 mg) and bazedoxifene (20 mg), yielded a favorable study retention and treatment satisfaction in menopausal women with multiple sclerosis (MS).

Major finding: Patients receiving Duavee® vs. placebo had a fewer missed doses (median, interquartile range [IQR] 0 [0-0] vs. 1 [0-9]), a greater Global Satisfaction on the Treatment Satisfaction Questionnaire for Medication (median, IQR 65.9 [52.8-100] vs. 62.5 [11.1-93.0]), and lesser side effects (20% vs. 13%), with none of the patients reporting a clinical relapse.

Study details: Findings are from a double-blind phase 1b/2a trial involving 21 peri/postmenopausal women with MS who were randomly assigned to parallel groups of Duavee® or equivalent placebo for 8 weeks.

Disclosures: This study was funded the National Multiple Sclerosis Society pilot grant and CTSI grant. Some authors declared receiving research support, personal compensation, speaker fees, or nonfinancial support from various sources, including Wyeth/Pfizer, the manufacturer of Duavee®. Several authors are provisional patent holders for the use of bazedoxifene in remyelination therapy.

Source: Bove R et al. A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial. Mult Scler Relat Disord. 2022;67:103747 (Mar 19). Doi:  10.1016/j.msard.2022.103747

Key clinical point: Hormone therapy with Duavee®, containing conjugated estrogens (0.45 mg) and bazedoxifene (20 mg), yielded a favorable study retention and treatment satisfaction in menopausal women with multiple sclerosis (MS).

Major finding: Patients receiving Duavee® vs. placebo had a fewer missed doses (median, interquartile range [IQR] 0 [0-0] vs. 1 [0-9]), a greater Global Satisfaction on the Treatment Satisfaction Questionnaire for Medication (median, IQR 65.9 [52.8-100] vs. 62.5 [11.1-93.0]), and lesser side effects (20% vs. 13%), with none of the patients reporting a clinical relapse.

Study details: Findings are from a double-blind phase 1b/2a trial involving 21 peri/postmenopausal women with MS who were randomly assigned to parallel groups of Duavee® or equivalent placebo for 8 weeks.

Disclosures: This study was funded the National Multiple Sclerosis Society pilot grant and CTSI grant. Some authors declared receiving research support, personal compensation, speaker fees, or nonfinancial support from various sources, including Wyeth/Pfizer, the manufacturer of Duavee®. Several authors are provisional patent holders for the use of bazedoxifene in remyelination therapy.

Source: Bove R et al. A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial. Mult Scler Relat Disord. 2022;67:103747 (Mar 19). Doi:  10.1016/j.msard.2022.103747

Key clinical point: Pregnancy may have a protective effect on the risk of developing multiple sclerosis (MS) in addition to a hypothesized reverse causality.

Major finding: Women with MS vs. women without any autoimmune disease were less likely to record the 18 pregnancy-related gynecological International Classification of Diseases 10th Revision codes, with strongest negative correlation observed for the supervision of normal pregnancy (adjusted P = 9.12 × 10⁻²⁷) and high-risk pregnancy (adjusted P = 2.49 × 10⁻¹²).

Study details: Findings are from a retrospective case-control study including women with newly diagnosed MS (n = 5720) and three control cohorts of women with newly diagnosed Crohn’s Disease (n = 6280), psoriasis (n = 26,729), and women without any of the three autoimmune diseases (n = 40,555).

Disclosures: The study was funded by European Union’s Horizon 2020 Research and Innovation Program, Hertie Foundation, and the Hans and Klementia Langmatz Stiftung, among others. B Hemmer declared serving on scientific advisory boards and receiving speaker honoraria and research funding from various sources. The other authors declared no conflicts of interest.

Citation: Gasperi C et al. Association of pregnancies with risk of multiple sclerosis. Mult Scler. 2022 (Mar 18). Doi: 10.1177/13524585221080542

Key clinical point: Pregnancy may have a protective effect on the risk of developing multiple sclerosis (MS) in addition to a hypothesized reverse causality.

Major finding: Women with MS vs. women without any autoimmune disease were less likely to record the 18 pregnancy-related gynecological International Classification of Diseases 10th Revision codes, with strongest negative correlation observed for the supervision of normal pregnancy (adjusted P = 9.12 × 10⁻²⁷) and high-risk pregnancy (adjusted P = 2.49 × 10⁻¹²).

Study details: Findings are from a retrospective case-control study including women with newly diagnosed MS (n = 5720) and three control cohorts of women with newly diagnosed Crohn’s Disease (n = 6280), psoriasis (n = 26,729), and women without any of the three autoimmune diseases (n = 40,555).

Disclosures: The study was funded by European Union’s Horizon 2020 Research and Innovation Program, Hertie Foundation, and the Hans and Klementia Langmatz Stiftung, among others. B Hemmer declared serving on scientific advisory boards and receiving speaker honoraria and research funding from various sources. The other authors declared no conflicts of interest.

Citation: Gasperi C et al. Association of pregnancies with risk of multiple sclerosis. Mult Scler. 2022 (Mar 18). Doi: 10.1177/13524585221080542

Key clinical point: Pregnancy may have a protective effect on the risk of developing multiple sclerosis (MS) in addition to a hypothesized reverse causality.

Major finding: Women with MS vs. women without any autoimmune disease were less likely to record the 18 pregnancy-related gynecological International Classification of Diseases 10th Revision codes, with strongest negative correlation observed for the supervision of normal pregnancy (adjusted P = 9.12 × 10⁻²⁷) and high-risk pregnancy (adjusted P = 2.49 × 10⁻¹²).

Study details: Findings are from a retrospective case-control study including women with newly diagnosed MS (n = 5720) and three control cohorts of women with newly diagnosed Crohn’s Disease (n = 6280), psoriasis (n = 26,729), and women without any of the three autoimmune diseases (n = 40,555).

Disclosures: The study was funded by European Union’s Horizon 2020 Research and Innovation Program, Hertie Foundation, and the Hans and Klementia Langmatz Stiftung, among others. B Hemmer declared serving on scientific advisory boards and receiving speaker honoraria and research funding from various sources. The other authors declared no conflicts of interest.

Citation: Gasperi C et al. Association of pregnancies with risk of multiple sclerosis. Mult Scler. 2022 (Mar 18). Doi: 10.1177/13524585221080542

Key clinical point: Genetic liability to multiple sclerosis (MS) was associated with an increased risk for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), all-cause stroke (AS), and any ischemic stroke (AIS), but not atrial fibrillation (AF) or other stroke subtypes.

Major finding: Genetic liability to MS was associated with an increased risk for CAD (odds ratio [OR] 1.02; P = .03), MI (OR 1.03; P = .01), HF (OR 1.02; P = .02), AS (OR 1.02; P = .02), and AIS (OR 1.02; P = .04), but not with AF or other stroke subtypes.

Study details: This was a two-sample Mendelian randomization analysis of genetic summary data for 47,429 MS (68,374 healthy controls [HC]), 60,801 CAD (123,504 HC), and 43,676 MI (128,199 HC), 60,620 AF (970,216 HC), and 47,309 HF (930,014 HC) cases from large-scale genome-wide association studies.

Disclosures: The study was supported by grants from Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang, China, the Major Project of Science and Technology Innovation 2025 in Ningbo, and others. The authors declared no conflicts of interest.

Source: Yang F et al. Multiple sclerosis and the risk of cardiovascular diseases: A Mendelian randomization study. Front Immunol. 2022;13:861885 (Mar 15). Doi: 10.3389/fimmu.2022.861885

Key clinical point: Genetic liability to multiple sclerosis (MS) was associated with an increased risk for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), all-cause stroke (AS), and any ischemic stroke (AIS), but not atrial fibrillation (AF) or other stroke subtypes.

Major finding: Genetic liability to MS was associated with an increased risk for CAD (odds ratio [OR] 1.02; P = .03), MI (OR 1.03; P = .01), HF (OR 1.02; P = .02), AS (OR 1.02; P = .02), and AIS (OR 1.02; P = .04), but not with AF or other stroke subtypes.

Study details: This was a two-sample Mendelian randomization analysis of genetic summary data for 47,429 MS (68,374 healthy controls [HC]), 60,801 CAD (123,504 HC), and 43,676 MI (128,199 HC), 60,620 AF (970,216 HC), and 47,309 HF (930,014 HC) cases from large-scale genome-wide association studies.

Disclosures: The study was supported by grants from Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang, China, the Major Project of Science and Technology Innovation 2025 in Ningbo, and others. The authors declared no conflicts of interest.

Source: Yang F et al. Multiple sclerosis and the risk of cardiovascular diseases: A Mendelian randomization study. Front Immunol. 2022;13:861885 (Mar 15). Doi: 10.3389/fimmu.2022.861885

Key clinical point: Genetic liability to multiple sclerosis (MS) was associated with an increased risk for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), all-cause stroke (AS), and any ischemic stroke (AIS), but not atrial fibrillation (AF) or other stroke subtypes.

Major finding: Genetic liability to MS was associated with an increased risk for CAD (odds ratio [OR] 1.02; P = .03), MI (OR 1.03; P = .01), HF (OR 1.02; P = .02), AS (OR 1.02; P = .02), and AIS (OR 1.02; P = .04), but not with AF or other stroke subtypes.

Study details: This was a two-sample Mendelian randomization analysis of genetic summary data for 47,429 MS (68,374 healthy controls [HC]), 60,801 CAD (123,504 HC), and 43,676 MI (128,199 HC), 60,620 AF (970,216 HC), and 47,309 HF (930,014 HC) cases from large-scale genome-wide association studies.

Disclosures: The study was supported by grants from Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang, China, the Major Project of Science and Technology Innovation 2025 in Ningbo, and others. The authors declared no conflicts of interest.

Source: Yang F et al. Multiple sclerosis and the risk of cardiovascular diseases: A Mendelian randomization study. Front Immunol. 2022;13:861885 (Mar 15). Doi: 10.3389/fimmu.2022.861885

Key clinical point: Maintaining natalizumab until conception and restarting within 1 month after delivery (treatment approach [TA]) reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery (conservative approach [CA]) in women with multiple sclerosis (MS), with no major development abnormalities noted in infants.

Major finding: Relapses occurred in 29.4% vs. 70.2% (P = .001) of patients in TA vs. CA after a mean follow-up of 6.1 years, with the CA being the only predictor of relapses (hazard ratio 4.1; P = .003). No developmental abnormalities were observed in infants.

Study details: Findings are from a cohort study of 72 pregnancies in 70 women with MS who were treated with natalizumab and were followed-up for at least 2 years.

Disclosures: No financial support was received. The authors declared receiving research support, travel, consulting, and speaker fees or personal compensation or serving on advisory boards for various sources.

Citation: Portaccio E et al. Natalizumab treatment and pregnancy in multiple sclerosis: A reappraisal of maternal and infant outcomes after 6 years. Mult Scler. 2022 (Mar 16). Doi: 10.1177/13524585221079598

Key clinical point: Maintaining natalizumab until conception and restarting within 1 month after delivery (treatment approach [TA]) reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery (conservative approach [CA]) in women with multiple sclerosis (MS), with no major development abnormalities noted in infants.

Major finding: Relapses occurred in 29.4% vs. 70.2% (P = .001) of patients in TA vs. CA after a mean follow-up of 6.1 years, with the CA being the only predictor of relapses (hazard ratio 4.1; P = .003). No developmental abnormalities were observed in infants.

Study details: Findings are from a cohort study of 72 pregnancies in 70 women with MS who were treated with natalizumab and were followed-up for at least 2 years.

Disclosures: No financial support was received. The authors declared receiving research support, travel, consulting, and speaker fees or personal compensation or serving on advisory boards for various sources.

Citation: Portaccio E et al. Natalizumab treatment and pregnancy in multiple sclerosis: A reappraisal of maternal and infant outcomes after 6 years. Mult Scler. 2022 (Mar 16). Doi: 10.1177/13524585221079598

Key clinical point: Maintaining natalizumab until conception and restarting within 1 month after delivery (treatment approach [TA]) reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery (conservative approach [CA]) in women with multiple sclerosis (MS), with no major development abnormalities noted in infants.

Major finding: Relapses occurred in 29.4% vs. 70.2% (P = .001) of patients in TA vs. CA after a mean follow-up of 6.1 years, with the CA being the only predictor of relapses (hazard ratio 4.1; P = .003). No developmental abnormalities were observed in infants.

Study details: Findings are from a cohort study of 72 pregnancies in 70 women with MS who were treated with natalizumab and were followed-up for at least 2 years.

Disclosures: No financial support was received. The authors declared receiving research support, travel, consulting, and speaker fees or personal compensation or serving on advisory boards for various sources.

Citation: Portaccio E et al. Natalizumab treatment and pregnancy in multiple sclerosis: A reappraisal of maternal and infant outcomes after 6 years. Mult Scler. 2022 (Mar 16). Doi: 10.1177/13524585221079598

Key clinical point: Progression independent of relapse activity (PIRA) is a major contributor of confirmed disability accrual (CDA) in early relapsing-onset multiple sclerosis (MS), with age being a major determinant of the way CDA occurs.

Major finding: PIRA accounted for 27.6% of disability worsening events, whereas relapse-associated worsening (RAW) accounted for 17.8% of events, with RAW being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients.

Study details: Findings are from a retrospective cohort analysis of 5169 patients with clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥5 years.

Disclosures: No source of funding was declared. Some authors declared serving on advisory boards or receiving grants, travel compensation, speaker honoraria, or lecture and consulting fees from various sources.

Source: Portaccio E et al. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study. Brain. 2022 (Mar 24). Doi: 10.1093/brain/awac111

Key clinical point: Progression independent of relapse activity (PIRA) is a major contributor of confirmed disability accrual (CDA) in early relapsing-onset multiple sclerosis (MS), with age being a major determinant of the way CDA occurs.

Major finding: PIRA accounted for 27.6% of disability worsening events, whereas relapse-associated worsening (RAW) accounted for 17.8% of events, with RAW being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients.

Study details: Findings are from a retrospective cohort analysis of 5169 patients with clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥5 years.

Disclosures: No source of funding was declared. Some authors declared serving on advisory boards or receiving grants, travel compensation, speaker honoraria, or lecture and consulting fees from various sources.

Source: Portaccio E et al. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study. Brain. 2022 (Mar 24). Doi: 10.1093/brain/awac111

Key clinical point: Progression independent of relapse activity (PIRA) is a major contributor of confirmed disability accrual (CDA) in early relapsing-onset multiple sclerosis (MS), with age being a major determinant of the way CDA occurs.

Major finding: PIRA accounted for 27.6% of disability worsening events, whereas relapse-associated worsening (RAW) accounted for 17.8% of events, with RAW being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients.

Study details: Findings are from a retrospective cohort analysis of 5169 patients with clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥5 years.

Disclosures: No source of funding was declared. Some authors declared serving on advisory boards or receiving grants, travel compensation, speaker honoraria, or lecture and consulting fees from various sources.

Source: Portaccio E et al. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study. Brain. 2022 (Mar 24). Doi: 10.1093/brain/awac111

Key clinical point: Patients with multiple sclerosis (MS) show reduced neutralizing antibody (nAb) response to SARS-CoV-2 mRNA vaccine, with B-cell depleting therapies having a significant effect on vaccine efficacy.

Major finding: Patients with MS treated with B-cell depleting therapies vs. other or no therapy showed a >9-fold decrease in the nAb response (P < .001), with 61.5% of patients showing no detectable levels of nAb. B-cell depleting therapy (P < .0001) was associated with significantly reduced neutralization titer 50% values.

Study details: This was a prospective longitudinal study including 51 patients with MS who completed the vaccination course of BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or Ad26.COV2 (Johnson and Johnson) SARS-CoV-2 vaccine.

Disclosures: No source of funding was declared. TV Gyang reported serving as consultant and BM Segal reported serving as a consultant, moderator, and speaker and on data safety monitoring boards for various sources. The other authors declared no conflicts of interest.

Source: Gyang TV et al. Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis. Mult Scler J Exp Transl Clin. 2022;8(1):1-9 (Mar 22). Doi: 10.1177/20552173221087357

Key clinical point: Patients with multiple sclerosis (MS) show reduced neutralizing antibody (nAb) response to SARS-CoV-2 mRNA vaccine, with B-cell depleting therapies having a significant effect on vaccine efficacy.

Major finding: Patients with MS treated with B-cell depleting therapies vs. other or no therapy showed a >9-fold decrease in the nAb response (P < .001), with 61.5% of patients showing no detectable levels of nAb. B-cell depleting therapy (P < .0001) was associated with significantly reduced neutralization titer 50% values.

Study details: This was a prospective longitudinal study including 51 patients with MS who completed the vaccination course of BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or Ad26.COV2 (Johnson and Johnson) SARS-CoV-2 vaccine.

Disclosures: No source of funding was declared. TV Gyang reported serving as consultant and BM Segal reported serving as a consultant, moderator, and speaker and on data safety monitoring boards for various sources. The other authors declared no conflicts of interest.

Source: Gyang TV et al. Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis. Mult Scler J Exp Transl Clin. 2022;8(1):1-9 (Mar 22). Doi: 10.1177/20552173221087357

Key clinical point: Patients with multiple sclerosis (MS) show reduced neutralizing antibody (nAb) response to SARS-CoV-2 mRNA vaccine, with B-cell depleting therapies having a significant effect on vaccine efficacy.

Major finding: Patients with MS treated with B-cell depleting therapies vs. other or no therapy showed a >9-fold decrease in the nAb response (P < .001), with 61.5% of patients showing no detectable levels of nAb. B-cell depleting therapy (P < .0001) was associated with significantly reduced neutralization titer 50% values.

Study details: This was a prospective longitudinal study including 51 patients with MS who completed the vaccination course of BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or Ad26.COV2 (Johnson and Johnson) SARS-CoV-2 vaccine.

Disclosures: No source of funding was declared. TV Gyang reported serving as consultant and BM Segal reported serving as a consultant, moderator, and speaker and on data safety monitoring boards for various sources. The other authors declared no conflicts of interest.

Source: Gyang TV et al. Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis. Mult Scler J Exp Transl Clin. 2022;8(1):1-9 (Mar 22). Doi: 10.1177/20552173221087357

Key clinical point: A favorable benefit-risk profile of ofatumumab vs. teriflunomide in recently diagnosed treatment-naive (RDTN) patients with relapsing multiple sclerosis (MS) highlights the possibility of ofatumumab being considered the first-line therapy in these patients.

Major finding: Ofatumumab vs. teriflunomide reduced the annual relapse rate (ARR), confirmed disability worsening at 6 months, and mean number of gadolinium-enhanced T1 lesions/magnetic resonance imaging scan by 50% (P < .001), 46% (P = .044), and 95% (P < .001), respectively, with a manageable and consistent safety profile.

Study details: This was a post hoc analysis of ASCLEPIOS I and II studies including 615 RDTN patients with relapsing MS who were randomly assigned to receive ofatumumab or teriflunomide for up to 30 months.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. The authors declared receiving lecture, consultancy, or speaker fees; travel grants; or personal compensation or serving as a steering committee members and on advisory boards for various sources, including Novartis Pharma AG. Some authors declared being employees of Novartis Pharma AG.

Citation: Gärtner J et al. Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Mult Scler. 2022 (Mar 10). Doi: 10.1177/13524585221078825

Key clinical point: A favorable benefit-risk profile of ofatumumab vs. teriflunomide in recently diagnosed treatment-naive (RDTN) patients with relapsing multiple sclerosis (MS) highlights the possibility of ofatumumab being considered the first-line therapy in these patients.

Major finding: Ofatumumab vs. teriflunomide reduced the annual relapse rate (ARR), confirmed disability worsening at 6 months, and mean number of gadolinium-enhanced T1 lesions/magnetic resonance imaging scan by 50% (P < .001), 46% (P = .044), and 95% (P < .001), respectively, with a manageable and consistent safety profile.

Study details: This was a post hoc analysis of ASCLEPIOS I and II studies including 615 RDTN patients with relapsing MS who were randomly assigned to receive ofatumumab or teriflunomide for up to 30 months.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. The authors declared receiving lecture, consultancy, or speaker fees; travel grants; or personal compensation or serving as a steering committee members and on advisory boards for various sources, including Novartis Pharma AG. Some authors declared being employees of Novartis Pharma AG.

Citation: Gärtner J et al. Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Mult Scler. 2022 (Mar 10). Doi: 10.1177/13524585221078825

Key clinical point: A favorable benefit-risk profile of ofatumumab vs. teriflunomide in recently diagnosed treatment-naive (RDTN) patients with relapsing multiple sclerosis (MS) highlights the possibility of ofatumumab being considered the first-line therapy in these patients.

Major finding: Ofatumumab vs. teriflunomide reduced the annual relapse rate (ARR), confirmed disability worsening at 6 months, and mean number of gadolinium-enhanced T1 lesions/magnetic resonance imaging scan by 50% (P < .001), 46% (P = .044), and 95% (P < .001), respectively, with a manageable and consistent safety profile.

Study details: This was a post hoc analysis of ASCLEPIOS I and II studies including 615 RDTN patients with relapsing MS who were randomly assigned to receive ofatumumab or teriflunomide for up to 30 months.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. The authors declared receiving lecture, consultancy, or speaker fees; travel grants; or personal compensation or serving as a steering committee members and on advisory boards for various sources, including Novartis Pharma AG. Some authors declared being employees of Novartis Pharma AG.

Citation: Gärtner J et al. Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Mult Scler. 2022 (Mar 10). Doi: 10.1177/13524585221078825