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Multiple sclerosis: Reduced humoral response contributes to breakthrough SARS-CoV-2 infection in patients on DMTs
Key clinical point: Decreased SARS-CoV-2 antibody level is the major contributor to breakthrough SARS-CoV-2 infection in vaccinated patients with multiple sclerosis (MS) on various disease modifying therapies (DMT), with the third dose significantly reducing the risk for infection.
Major finding: After the second vaccine dose, the only significant factor associated with the risk for breakthrough infection was low antibody level (hazard ratio [HR] 0.51; P < .001), with the third dose reducing the risk for infection by 56% (HR 0.44; P = .025) during the Omicron wave.
Study details: Findings are from a prospective study of 1705 patients with MS on various DMT who received 2 doses of BNT162b2 (BioNTech-Pfizer) (n = 1391) or mRNA-1273 (Moderna) (n = 314) SARS-CoV-2 vaccine, with most receiving the third dose.
Disclosures: This study was funded by Fondazione Italiana Sclerosi Multipla. Some authors declared receiving grants, travel compensation, speaker honoraria, or advisory board/lecture and consulting fees from various sources.
Source: Sormani MP et al. Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy. EBioMedicine. 2022;80:104042 (May 4). Doi: 10.1016/j.ebiom.2022.104042
Key clinical point: Decreased SARS-CoV-2 antibody level is the major contributor to breakthrough SARS-CoV-2 infection in vaccinated patients with multiple sclerosis (MS) on various disease modifying therapies (DMT), with the third dose significantly reducing the risk for infection.
Major finding: After the second vaccine dose, the only significant factor associated with the risk for breakthrough infection was low antibody level (hazard ratio [HR] 0.51; P < .001), with the third dose reducing the risk for infection by 56% (HR 0.44; P = .025) during the Omicron wave.
Study details: Findings are from a prospective study of 1705 patients with MS on various DMT who received 2 doses of BNT162b2 (BioNTech-Pfizer) (n = 1391) or mRNA-1273 (Moderna) (n = 314) SARS-CoV-2 vaccine, with most receiving the third dose.
Disclosures: This study was funded by Fondazione Italiana Sclerosi Multipla. Some authors declared receiving grants, travel compensation, speaker honoraria, or advisory board/lecture and consulting fees from various sources.
Source: Sormani MP et al. Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy. EBioMedicine. 2022;80:104042 (May 4). Doi: 10.1016/j.ebiom.2022.104042
Key clinical point: Decreased SARS-CoV-2 antibody level is the major contributor to breakthrough SARS-CoV-2 infection in vaccinated patients with multiple sclerosis (MS) on various disease modifying therapies (DMT), with the third dose significantly reducing the risk for infection.
Major finding: After the second vaccine dose, the only significant factor associated with the risk for breakthrough infection was low antibody level (hazard ratio [HR] 0.51; P < .001), with the third dose reducing the risk for infection by 56% (HR 0.44; P = .025) during the Omicron wave.
Study details: Findings are from a prospective study of 1705 patients with MS on various DMT who received 2 doses of BNT162b2 (BioNTech-Pfizer) (n = 1391) or mRNA-1273 (Moderna) (n = 314) SARS-CoV-2 vaccine, with most receiving the third dose.
Disclosures: This study was funded by Fondazione Italiana Sclerosi Multipla. Some authors declared receiving grants, travel compensation, speaker honoraria, or advisory board/lecture and consulting fees from various sources.
Source: Sormani MP et al. Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy. EBioMedicine. 2022;80:104042 (May 4). Doi: 10.1016/j.ebiom.2022.104042
T-cell response after third SARS-CoV-2 vaccination in patients with MS on ocrelizumab
Key clinical point: In ocrelizumab-treated patients with multiple sclerosis (MS), a third SARS-CoV-2 vaccine boosted the T-cell response, but had no additive effect on the maximal T-cell response.
Major finding: SARS-CoV-2-specific T-cell response in patients treated with ocrelizumab was comparable to those not treated with disease modifying therapy (DMT) and healthy controls (HC) after the second SARS-CoV-2 vaccination; however, the third SARS-CoV-2 vaccination had no additive effect on T-cell response, but it did induce a booster response (P < .05).
Study details: This was a prospective longitudinal study including patients with MS treated with ocrelizumab (n = 24), fingolimod (n = 12), or no DMT (n = 10) and HC (n = 12) who received three SARS-CoV-2 vaccine doses (BNT162b2 [BioNTech-Pfizer] or CX-024414 [Moderna]).
Disclosures: This study was funded by The Netherlands Organisation for Health Research and Development. Some authors reported receiving consulting fees and research support from various sources.
Source: Cabeza VP et al. Longitudinal T-cell responses after a third SARS-CoV-2 vaccination in patients with multiple sclerosis on ocrelizumab or fingolimod. Neurol Neuroimmunol Neuroinflamm. 2022;9(4):e1178 (May 6). Doi: 10.1212/NXI.0000000000001178
Key clinical point: In ocrelizumab-treated patients with multiple sclerosis (MS), a third SARS-CoV-2 vaccine boosted the T-cell response, but had no additive effect on the maximal T-cell response.
Major finding: SARS-CoV-2-specific T-cell response in patients treated with ocrelizumab was comparable to those not treated with disease modifying therapy (DMT) and healthy controls (HC) after the second SARS-CoV-2 vaccination; however, the third SARS-CoV-2 vaccination had no additive effect on T-cell response, but it did induce a booster response (P < .05).
Study details: This was a prospective longitudinal study including patients with MS treated with ocrelizumab (n = 24), fingolimod (n = 12), or no DMT (n = 10) and HC (n = 12) who received three SARS-CoV-2 vaccine doses (BNT162b2 [BioNTech-Pfizer] or CX-024414 [Moderna]).
Disclosures: This study was funded by The Netherlands Organisation for Health Research and Development. Some authors reported receiving consulting fees and research support from various sources.
Source: Cabeza VP et al. Longitudinal T-cell responses after a third SARS-CoV-2 vaccination in patients with multiple sclerosis on ocrelizumab or fingolimod. Neurol Neuroimmunol Neuroinflamm. 2022;9(4):e1178 (May 6). Doi: 10.1212/NXI.0000000000001178
Key clinical point: In ocrelizumab-treated patients with multiple sclerosis (MS), a third SARS-CoV-2 vaccine boosted the T-cell response, but had no additive effect on the maximal T-cell response.
Major finding: SARS-CoV-2-specific T-cell response in patients treated with ocrelizumab was comparable to those not treated with disease modifying therapy (DMT) and healthy controls (HC) after the second SARS-CoV-2 vaccination; however, the third SARS-CoV-2 vaccination had no additive effect on T-cell response, but it did induce a booster response (P < .05).
Study details: This was a prospective longitudinal study including patients with MS treated with ocrelizumab (n = 24), fingolimod (n = 12), or no DMT (n = 10) and HC (n = 12) who received three SARS-CoV-2 vaccine doses (BNT162b2 [BioNTech-Pfizer] or CX-024414 [Moderna]).
Disclosures: This study was funded by The Netherlands Organisation for Health Research and Development. Some authors reported receiving consulting fees and research support from various sources.
Source: Cabeza VP et al. Longitudinal T-cell responses after a third SARS-CoV-2 vaccination in patients with multiple sclerosis on ocrelizumab or fingolimod. Neurol Neuroimmunol Neuroinflamm. 2022;9(4):e1178 (May 6). Doi: 10.1212/NXI.0000000000001178
Long-term treatment with siponimod is effective and safe in SPMS
Key clinical point: Continuous siponimod treatment for up to >5 years showed sustained efficacy and a consistent safety profile in patients with secondary progressive multiple sclerosis (SPMS).
Major finding: The risk for 6-month confirmed disability progression (CDP) was 22% lower (P = .0026) and confirmed worsening in cognitive processing speed was 23% lower (P = .0047) in patients who received continuous siponimod vs those who switched from placebo to siponimod. Siponimod had a manageable and consistent safety profile.
Study details: Findings are from the phase 3 EXPAND study including the extension phase that included 1220 of 1651 patients with SPMS from the core phase. In the extension phase, patients who had received placebo in the core phase switched to siponimod, whereas those who had received siponimod continued the same treatment.
Disclosures: This study was supported by Novartis Pharma AG, Basel, Switzerland. Five authors reported being employees of Novartis. Some authors reported receiving consulting or speakers’ fees or personal compensation or serving as a steering committee member or on an advisory board for various sources.
Source: Cree BAC et al. Long-term efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis: Analysis of EXPAND core and extension data up to >5 years. Mult Scler. 2022 (Apr 5). Doi: 10.1177/13524585221083194
Key clinical point: Continuous siponimod treatment for up to >5 years showed sustained efficacy and a consistent safety profile in patients with secondary progressive multiple sclerosis (SPMS).
Major finding: The risk for 6-month confirmed disability progression (CDP) was 22% lower (P = .0026) and confirmed worsening in cognitive processing speed was 23% lower (P = .0047) in patients who received continuous siponimod vs those who switched from placebo to siponimod. Siponimod had a manageable and consistent safety profile.
Study details: Findings are from the phase 3 EXPAND study including the extension phase that included 1220 of 1651 patients with SPMS from the core phase. In the extension phase, patients who had received placebo in the core phase switched to siponimod, whereas those who had received siponimod continued the same treatment.
Disclosures: This study was supported by Novartis Pharma AG, Basel, Switzerland. Five authors reported being employees of Novartis. Some authors reported receiving consulting or speakers’ fees or personal compensation or serving as a steering committee member or on an advisory board for various sources.
Source: Cree BAC et al. Long-term efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis: Analysis of EXPAND core and extension data up to >5 years. Mult Scler. 2022 (Apr 5). Doi: 10.1177/13524585221083194
Key clinical point: Continuous siponimod treatment for up to >5 years showed sustained efficacy and a consistent safety profile in patients with secondary progressive multiple sclerosis (SPMS).
Major finding: The risk for 6-month confirmed disability progression (CDP) was 22% lower (P = .0026) and confirmed worsening in cognitive processing speed was 23% lower (P = .0047) in patients who received continuous siponimod vs those who switched from placebo to siponimod. Siponimod had a manageable and consistent safety profile.
Study details: Findings are from the phase 3 EXPAND study including the extension phase that included 1220 of 1651 patients with SPMS from the core phase. In the extension phase, patients who had received placebo in the core phase switched to siponimod, whereas those who had received siponimod continued the same treatment.
Disclosures: This study was supported by Novartis Pharma AG, Basel, Switzerland. Five authors reported being employees of Novartis. Some authors reported receiving consulting or speakers’ fees or personal compensation or serving as a steering committee member or on an advisory board for various sources.
Source: Cree BAC et al. Long-term efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis: Analysis of EXPAND core and extension data up to >5 years. Mult Scler. 2022 (Apr 5). Doi: 10.1177/13524585221083194
Teriflunomide effective and well-tolerated in patients with RRMS
Key clinical point: Teriflunomide is effective and well-tolerated in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS), with females with mild disease activity and lesser disability most likely to benefit.
Major finding: Overall, 79% of patients achieved No Evidence of Disease Activity 3 (NEDA) at 12 months, with the mean annualized relapse rate reducing significantly (P < .001), the mean Expanded Disability Status Scale (EDSS) score remaining stable (P = .658), and only 8.3% of patients discontinuing treatment because of adverse events. Male sex (hazard ratio [HR] 1.856; P < .017), frequent relapses before treatment (HR 3.056; P < .000), and a baseline EDSS score of ≥4 (HR 2.682; P < .004) were associated with the failure to achieve NEDA 3.
Study details: This was an observational cohort study including 217 treatment-naive patients with RRMS who were treated with teriflunomide.
Disclosures: This study was supported by the National Key Research and Development Program of China, CAMS Innovation Fund for Medical Sciences, and others. The authors declared no conflicts of interests.
Source: Zhang Y et al. Real-world outcomes of teriflunomide in relapsing–remitting multiple sclerosis: A prospective cohort study. J Neurol. 2022 (Apr 11). Doi: 10.1007/s00415-022-11118-7
Key clinical point: Teriflunomide is effective and well-tolerated in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS), with females with mild disease activity and lesser disability most likely to benefit.
Major finding: Overall, 79% of patients achieved No Evidence of Disease Activity 3 (NEDA) at 12 months, with the mean annualized relapse rate reducing significantly (P < .001), the mean Expanded Disability Status Scale (EDSS) score remaining stable (P = .658), and only 8.3% of patients discontinuing treatment because of adverse events. Male sex (hazard ratio [HR] 1.856; P < .017), frequent relapses before treatment (HR 3.056; P < .000), and a baseline EDSS score of ≥4 (HR 2.682; P < .004) were associated with the failure to achieve NEDA 3.
Study details: This was an observational cohort study including 217 treatment-naive patients with RRMS who were treated with teriflunomide.
Disclosures: This study was supported by the National Key Research and Development Program of China, CAMS Innovation Fund for Medical Sciences, and others. The authors declared no conflicts of interests.
Source: Zhang Y et al. Real-world outcomes of teriflunomide in relapsing–remitting multiple sclerosis: A prospective cohort study. J Neurol. 2022 (Apr 11). Doi: 10.1007/s00415-022-11118-7
Key clinical point: Teriflunomide is effective and well-tolerated in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS), with females with mild disease activity and lesser disability most likely to benefit.
Major finding: Overall, 79% of patients achieved No Evidence of Disease Activity 3 (NEDA) at 12 months, with the mean annualized relapse rate reducing significantly (P < .001), the mean Expanded Disability Status Scale (EDSS) score remaining stable (P = .658), and only 8.3% of patients discontinuing treatment because of adverse events. Male sex (hazard ratio [HR] 1.856; P < .017), frequent relapses before treatment (HR 3.056; P < .000), and a baseline EDSS score of ≥4 (HR 2.682; P < .004) were associated with the failure to achieve NEDA 3.
Study details: This was an observational cohort study including 217 treatment-naive patients with RRMS who were treated with teriflunomide.
Disclosures: This study was supported by the National Key Research and Development Program of China, CAMS Innovation Fund for Medical Sciences, and others. The authors declared no conflicts of interests.
Source: Zhang Y et al. Real-world outcomes of teriflunomide in relapsing–remitting multiple sclerosis: A prospective cohort study. J Neurol. 2022 (Apr 11). Doi: 10.1007/s00415-022-11118-7
Multiple sclerosis: Greater prevalence of disease activity in women and disability accrual in men
Key clinical point: Women vs men with multiple sclerosis (MS) showed greater inflammatory disease activity up to menopausal age, whereas men vs women with MS showed greater disability accrual.
Major finding: Women vs men had a 16% higher relapse rate and a higher estimated marginal mean of annualized relapse rate (0.32 vs 0.28; P < .001); however, the difference disappeared after the age of 50 years. The deterioration in the Expanded Disability Status Scale (EDSS) points was higher in men vs women (0.065 vs 0.049 EDSS points per year; P = .0017), with men at a higher risk of reaching EDSS 4 (P < .001).
Study details: Findings are from an analysis of 9647 patients (3028 men and 6619 women) with MS from the Danish MS registry (DMSR) who received disease-modifying therapy and were followed-up for at least 1 year and two control visits.
Disclosures: The DMSR was funded by the Danish MS Society. M Magyari declared receiving consulting and speakers’ fees and serving on scientific advisory boards for various sources.
Source: Magyari M et al. Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 (Apr 7). Doi: 10.1136/jnnp-2022-328994
Key clinical point: Women vs men with multiple sclerosis (MS) showed greater inflammatory disease activity up to menopausal age, whereas men vs women with MS showed greater disability accrual.
Major finding: Women vs men had a 16% higher relapse rate and a higher estimated marginal mean of annualized relapse rate (0.32 vs 0.28; P < .001); however, the difference disappeared after the age of 50 years. The deterioration in the Expanded Disability Status Scale (EDSS) points was higher in men vs women (0.065 vs 0.049 EDSS points per year; P = .0017), with men at a higher risk of reaching EDSS 4 (P < .001).
Study details: Findings are from an analysis of 9647 patients (3028 men and 6619 women) with MS from the Danish MS registry (DMSR) who received disease-modifying therapy and were followed-up for at least 1 year and two control visits.
Disclosures: The DMSR was funded by the Danish MS Society. M Magyari declared receiving consulting and speakers’ fees and serving on scientific advisory boards for various sources.
Source: Magyari M et al. Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 (Apr 7). Doi: 10.1136/jnnp-2022-328994
Key clinical point: Women vs men with multiple sclerosis (MS) showed greater inflammatory disease activity up to menopausal age, whereas men vs women with MS showed greater disability accrual.
Major finding: Women vs men had a 16% higher relapse rate and a higher estimated marginal mean of annualized relapse rate (0.32 vs 0.28; P < .001); however, the difference disappeared after the age of 50 years. The deterioration in the Expanded Disability Status Scale (EDSS) points was higher in men vs women (0.065 vs 0.049 EDSS points per year; P = .0017), with men at a higher risk of reaching EDSS 4 (P < .001).
Study details: Findings are from an analysis of 9647 patients (3028 men and 6619 women) with MS from the Danish MS registry (DMSR) who received disease-modifying therapy and were followed-up for at least 1 year and two control visits.
Disclosures: The DMSR was funded by the Danish MS Society. M Magyari declared receiving consulting and speakers’ fees and serving on scientific advisory boards for various sources.
Source: Magyari M et al. Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 (Apr 7). Doi: 10.1136/jnnp-2022-328994
RRMS: Long-term fingolimod shows positive benefit-risk profile in real-life settings
Key clinical point: This real-world analysis of patients with relapsing-remitting multiple sclerosis (RRMS) showed a favorable benefit-risk profile for up to 5 years of fingolimod treatment, with a sustained efficacy and manageable safety profile.
Major finding: Overall, 69.6% of the patients remained relapse free after 5 years of treatment with fingolimod, with the annualized relapse rate reducing significantly from 0.804 at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (P < .001) after 1, 2, 3, 4, and 5 years of fingolimod treatment, respectively. Overall, 65.5% and 12.5% of the patients reported any adverse and serious adverse events, respectively.
Study details: This was a 5-year prospective, cross-sectional, observational study including 570 patients with RRMS who were on fingolimod treatment for at least 1 year.
Disclosures: This study was supported by Novartis Pharma AG, Basel, Switzerland. The authors declared no conflicts of interests.
Source: Biernacki T et al. The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary. PLoS One. 2022;17(4): e0267346 (Apr 22). Doi: 10.1371/journal.pone.0267346
Key clinical point: This real-world analysis of patients with relapsing-remitting multiple sclerosis (RRMS) showed a favorable benefit-risk profile for up to 5 years of fingolimod treatment, with a sustained efficacy and manageable safety profile.
Major finding: Overall, 69.6% of the patients remained relapse free after 5 years of treatment with fingolimod, with the annualized relapse rate reducing significantly from 0.804 at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (P < .001) after 1, 2, 3, 4, and 5 years of fingolimod treatment, respectively. Overall, 65.5% and 12.5% of the patients reported any adverse and serious adverse events, respectively.
Study details: This was a 5-year prospective, cross-sectional, observational study including 570 patients with RRMS who were on fingolimod treatment for at least 1 year.
Disclosures: This study was supported by Novartis Pharma AG, Basel, Switzerland. The authors declared no conflicts of interests.
Source: Biernacki T et al. The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary. PLoS One. 2022;17(4): e0267346 (Apr 22). Doi: 10.1371/journal.pone.0267346
Key clinical point: This real-world analysis of patients with relapsing-remitting multiple sclerosis (RRMS) showed a favorable benefit-risk profile for up to 5 years of fingolimod treatment, with a sustained efficacy and manageable safety profile.
Major finding: Overall, 69.6% of the patients remained relapse free after 5 years of treatment with fingolimod, with the annualized relapse rate reducing significantly from 0.804 at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (P < .001) after 1, 2, 3, 4, and 5 years of fingolimod treatment, respectively. Overall, 65.5% and 12.5% of the patients reported any adverse and serious adverse events, respectively.
Study details: This was a 5-year prospective, cross-sectional, observational study including 570 patients with RRMS who were on fingolimod treatment for at least 1 year.
Disclosures: This study was supported by Novartis Pharma AG, Basel, Switzerland. The authors declared no conflicts of interests.
Source: Biernacki T et al. The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary. PLoS One. 2022;17(4): e0267346 (Apr 22). Doi: 10.1371/journal.pone.0267346
Anti-SARS-CoV-2 mAbs safe and effective for acute COVID-19 in immunocompromised patients with MS
Key clinical point: Early use of anti-SARS-CoV-2 monoclonal antibodies (mAb) was effective and safe in treating acute COVID-19 in patients with multiple sclerosis (MS) treated with fingolimod or ocrelizumab.
Major finding: Overall, 74% of patients with MS were managed as outpatients (median duration to mAb 4 days), and 48% of patients with MS recovered from COVID-19 infection in <7 days after mAb receipt, with no clinical MS relapses documented during or shortly after COVID-19 infection (median follow-up 18 days). No adverse events or deaths were reported.
Study details: Findings are from an observational study including 23 patients with MS, most of whom had completed the initial COVID-19 vaccine series prior to infection, were either untreated or treated with fingolimod/ocrelizumab, and received anti-SARS-CoV2-mAb (bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab, or undocumented formulation) for treatment of active COVID-19 infection.
Disclosures: This study did not receive any funding. Some authors reported receiving consulting fees and research support from various sources.
Source: Manzano GS et al. Anti-SARS-CoV-2 monoclonal antibodies for the treatment of active COVID-19 in multiple sclerosis: An observational study. Mult Scler. 2022 (Apr 27). Doi: 10.1177/13524585221092309
Key clinical point: Early use of anti-SARS-CoV-2 monoclonal antibodies (mAb) was effective and safe in treating acute COVID-19 in patients with multiple sclerosis (MS) treated with fingolimod or ocrelizumab.
Major finding: Overall, 74% of patients with MS were managed as outpatients (median duration to mAb 4 days), and 48% of patients with MS recovered from COVID-19 infection in <7 days after mAb receipt, with no clinical MS relapses documented during or shortly after COVID-19 infection (median follow-up 18 days). No adverse events or deaths were reported.
Study details: Findings are from an observational study including 23 patients with MS, most of whom had completed the initial COVID-19 vaccine series prior to infection, were either untreated or treated with fingolimod/ocrelizumab, and received anti-SARS-CoV2-mAb (bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab, or undocumented formulation) for treatment of active COVID-19 infection.
Disclosures: This study did not receive any funding. Some authors reported receiving consulting fees and research support from various sources.
Source: Manzano GS et al. Anti-SARS-CoV-2 monoclonal antibodies for the treatment of active COVID-19 in multiple sclerosis: An observational study. Mult Scler. 2022 (Apr 27). Doi: 10.1177/13524585221092309
Key clinical point: Early use of anti-SARS-CoV-2 monoclonal antibodies (mAb) was effective and safe in treating acute COVID-19 in patients with multiple sclerosis (MS) treated with fingolimod or ocrelizumab.
Major finding: Overall, 74% of patients with MS were managed as outpatients (median duration to mAb 4 days), and 48% of patients with MS recovered from COVID-19 infection in <7 days after mAb receipt, with no clinical MS relapses documented during or shortly after COVID-19 infection (median follow-up 18 days). No adverse events or deaths were reported.
Study details: Findings are from an observational study including 23 patients with MS, most of whom had completed the initial COVID-19 vaccine series prior to infection, were either untreated or treated with fingolimod/ocrelizumab, and received anti-SARS-CoV2-mAb (bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab, or undocumented formulation) for treatment of active COVID-19 infection.
Disclosures: This study did not receive any funding. Some authors reported receiving consulting fees and research support from various sources.
Source: Manzano GS et al. Anti-SARS-CoV-2 monoclonal antibodies for the treatment of active COVID-19 in multiple sclerosis: An observational study. Mult Scler. 2022 (Apr 27). Doi: 10.1177/13524585221092309
Progressive MS: sNfL shows promise as an effective biomarker for long-term disability progression
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
Switching to extended-interval natalizumab dosing effective in RRMS
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
Two MS meds tied to higher COVID rates
Patients taking ocrelizumab (Ocrevus) or fingolimod (Gilenya) for treat multiple sclerosis (MS) have higher rates of COVID-19 infection and hospitalization before and after COVID vaccination, compared with those taking other treatments, a nationwide study in England found.
The study draws on a database that includes every patient with MS in England treated with a disease-modifying therapy (DMT) and national data on rates of COVID infection, hospitalization, mortality, and vaccination in those patients.
It’s the latest work to suggest varying levels of vaccine efficacy based on DMT use and is the first known study to offer this level of detail on the subject.
“What is obvious is that current vaccination protocols for these DMTs are not really working properly,” lead investigator Afagh Garjani, MD, clinical research fellow at the University of Nottingham (England), said in an interview.
Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Dr. Garjani noted, offering further evidence that vaccines are effective in most patients with MS.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Low mortality rate
The prospective, longitudinal study included National Health Service data on 44,170 people with MS. The data on hospitalization came from 29,353 patients with MS who had received at least two doses of a COVID-19 vaccine.
Patients taking dimethyl fumarate, the most commonly prescribed DMT in England, had similar rates of COVID infection in January 2021 – before they were fully vaccinated – and in December 2022, after they had received at least two vaccine doses.
However, among patients taking fingolimod and ocrelizumab there were significant increases in infection rates in that same time period. The incidence rate ratio in the fingolimod group was 0.50 (95% confidence interval, 0.37-0.66) in January 2021 and rose to 0.91 (95% CI, 0.80-1.03) in December 2022. In the ocrelizumab group, the IRR rose from 1.01 (95% CI, 0.79-1.26) to 1.57 (95% CI, 1.44-1.72) during that time frame.
Hospitalization rates were also higher in fully vaccinated patients with MS taking fingolimod and ocrelizumab. People taking dimethyl fumarate had a hospitalization rate of 32 (per 10,000 people), compared with a rate of 140 in patients on ocrelizumab and 94 in patients on fingolimod.
Mortality rates were low in all groups, but were slightly higher in the ocrelizumab group.
“However, the number of people who died due to COVID overall was small,” Dr. Garjani noted.
Following receipt of a third COVID-19 vaccine, the only hospitalizations were in patients taking ocrelizumab (4 out of 65 infections) and fingolimod (11 out of 78 infections), with no deaths.
Potential mechanism
Researchers suspect the reason for varying COVID-19 infection rates and vaccine efficacy among DMTs is related to their mode of action.
“With MS, the immune system attacks the central nervous system and the aim of these treatments is to modulate or suppress the immune system,” Dr. Garjani said. “Some of these medications are immune suppressants and therefore, in addition to preventing MS, might also put people at increased risk of infection from COVID or other diseases.”
Ocrelizumab and fingolimod have different modes of action, but both act as immunosuppressants.
Study data on beta-interferon offered an interesting twist. Patients taking that medication had far lower infection rates, compared with other DMTs and to the general population, and no COVID-related hospitalizations.
Interferons are known to have some antiviral effects, Dr. Garjani said. In fact, interferon is one of several existing drugs that scientists have considered as possible candidates to fight COVID infection.
Studies on COVID infection rates and vaccine efficacy have yielded conflicting results. Some suggest no differences based on DMT use, whereas others have shown immunological evidence pointing to lower or higher infections rates among the different therapies.
Based on some of those findings, up to 80% of specialists who treat MS in the United States said the pandemic may have changed their use of DMTs, one study found, which later studies suggested may not have been necessary.
While the findings shouldn’t necessarily prompt clinicians to consider changing their treatment approach, Dr. Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.
A balancing act
Commenting on the findings, Tyler Smith, MD, clinical assistant professor of neurology at New York University, said that, although the data suggest these MS therapies may affect COVID vaccine efficacy to varying degrees, there’s more to the story.
“This data builds upon a growing body of evidence that these treatments may attenuate vaccine responses to different degrees, and this should be balanced with their efficacy in controlling multiple sclerosis relapses, Dr. Smith said, adding that “real-life studies examining the effect of vaccines show benefit in limiting hospitalization and death.”
“Developing evidence continues to demonstrate the benefits of vaccination,” he said, “and I encourage all patients to follow the latest federal health guidelines regarding COVID-19 vaccinations.”
Dr. Garjani has received personal compensation for serving as a speaker with MS Academy and Biogen. Dr. Smith’s 2020-2021 fellowship was supported in part by Biogen and the National Multiple Sclerosis Society Clinical Care Physician Fellowship 2020-2021. Dr. Smith also received honoraria from the American Academy of Neurology in 2020.
A version of this article first appeared on Medscape.com.
Patients taking ocrelizumab (Ocrevus) or fingolimod (Gilenya) for treat multiple sclerosis (MS) have higher rates of COVID-19 infection and hospitalization before and after COVID vaccination, compared with those taking other treatments, a nationwide study in England found.
The study draws on a database that includes every patient with MS in England treated with a disease-modifying therapy (DMT) and national data on rates of COVID infection, hospitalization, mortality, and vaccination in those patients.
It’s the latest work to suggest varying levels of vaccine efficacy based on DMT use and is the first known study to offer this level of detail on the subject.
“What is obvious is that current vaccination protocols for these DMTs are not really working properly,” lead investigator Afagh Garjani, MD, clinical research fellow at the University of Nottingham (England), said in an interview.
Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Dr. Garjani noted, offering further evidence that vaccines are effective in most patients with MS.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Low mortality rate
The prospective, longitudinal study included National Health Service data on 44,170 people with MS. The data on hospitalization came from 29,353 patients with MS who had received at least two doses of a COVID-19 vaccine.
Patients taking dimethyl fumarate, the most commonly prescribed DMT in England, had similar rates of COVID infection in January 2021 – before they were fully vaccinated – and in December 2022, after they had received at least two vaccine doses.
However, among patients taking fingolimod and ocrelizumab there were significant increases in infection rates in that same time period. The incidence rate ratio in the fingolimod group was 0.50 (95% confidence interval, 0.37-0.66) in January 2021 and rose to 0.91 (95% CI, 0.80-1.03) in December 2022. In the ocrelizumab group, the IRR rose from 1.01 (95% CI, 0.79-1.26) to 1.57 (95% CI, 1.44-1.72) during that time frame.
Hospitalization rates were also higher in fully vaccinated patients with MS taking fingolimod and ocrelizumab. People taking dimethyl fumarate had a hospitalization rate of 32 (per 10,000 people), compared with a rate of 140 in patients on ocrelizumab and 94 in patients on fingolimod.
Mortality rates were low in all groups, but were slightly higher in the ocrelizumab group.
“However, the number of people who died due to COVID overall was small,” Dr. Garjani noted.
Following receipt of a third COVID-19 vaccine, the only hospitalizations were in patients taking ocrelizumab (4 out of 65 infections) and fingolimod (11 out of 78 infections), with no deaths.
Potential mechanism
Researchers suspect the reason for varying COVID-19 infection rates and vaccine efficacy among DMTs is related to their mode of action.
“With MS, the immune system attacks the central nervous system and the aim of these treatments is to modulate or suppress the immune system,” Dr. Garjani said. “Some of these medications are immune suppressants and therefore, in addition to preventing MS, might also put people at increased risk of infection from COVID or other diseases.”
Ocrelizumab and fingolimod have different modes of action, but both act as immunosuppressants.
Study data on beta-interferon offered an interesting twist. Patients taking that medication had far lower infection rates, compared with other DMTs and to the general population, and no COVID-related hospitalizations.
Interferons are known to have some antiviral effects, Dr. Garjani said. In fact, interferon is one of several existing drugs that scientists have considered as possible candidates to fight COVID infection.
Studies on COVID infection rates and vaccine efficacy have yielded conflicting results. Some suggest no differences based on DMT use, whereas others have shown immunological evidence pointing to lower or higher infections rates among the different therapies.
Based on some of those findings, up to 80% of specialists who treat MS in the United States said the pandemic may have changed their use of DMTs, one study found, which later studies suggested may not have been necessary.
While the findings shouldn’t necessarily prompt clinicians to consider changing their treatment approach, Dr. Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.
A balancing act
Commenting on the findings, Tyler Smith, MD, clinical assistant professor of neurology at New York University, said that, although the data suggest these MS therapies may affect COVID vaccine efficacy to varying degrees, there’s more to the story.
“This data builds upon a growing body of evidence that these treatments may attenuate vaccine responses to different degrees, and this should be balanced with their efficacy in controlling multiple sclerosis relapses, Dr. Smith said, adding that “real-life studies examining the effect of vaccines show benefit in limiting hospitalization and death.”
“Developing evidence continues to demonstrate the benefits of vaccination,” he said, “and I encourage all patients to follow the latest federal health guidelines regarding COVID-19 vaccinations.”
Dr. Garjani has received personal compensation for serving as a speaker with MS Academy and Biogen. Dr. Smith’s 2020-2021 fellowship was supported in part by Biogen and the National Multiple Sclerosis Society Clinical Care Physician Fellowship 2020-2021. Dr. Smith also received honoraria from the American Academy of Neurology in 2020.
A version of this article first appeared on Medscape.com.
Patients taking ocrelizumab (Ocrevus) or fingolimod (Gilenya) for treat multiple sclerosis (MS) have higher rates of COVID-19 infection and hospitalization before and after COVID vaccination, compared with those taking other treatments, a nationwide study in England found.
The study draws on a database that includes every patient with MS in England treated with a disease-modifying therapy (DMT) and national data on rates of COVID infection, hospitalization, mortality, and vaccination in those patients.
It’s the latest work to suggest varying levels of vaccine efficacy based on DMT use and is the first known study to offer this level of detail on the subject.
“What is obvious is that current vaccination protocols for these DMTs are not really working properly,” lead investigator Afagh Garjani, MD, clinical research fellow at the University of Nottingham (England), said in an interview.
Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Dr. Garjani noted, offering further evidence that vaccines are effective in most patients with MS.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Low mortality rate
The prospective, longitudinal study included National Health Service data on 44,170 people with MS. The data on hospitalization came from 29,353 patients with MS who had received at least two doses of a COVID-19 vaccine.
Patients taking dimethyl fumarate, the most commonly prescribed DMT in England, had similar rates of COVID infection in January 2021 – before they were fully vaccinated – and in December 2022, after they had received at least two vaccine doses.
However, among patients taking fingolimod and ocrelizumab there were significant increases in infection rates in that same time period. The incidence rate ratio in the fingolimod group was 0.50 (95% confidence interval, 0.37-0.66) in January 2021 and rose to 0.91 (95% CI, 0.80-1.03) in December 2022. In the ocrelizumab group, the IRR rose from 1.01 (95% CI, 0.79-1.26) to 1.57 (95% CI, 1.44-1.72) during that time frame.
Hospitalization rates were also higher in fully vaccinated patients with MS taking fingolimod and ocrelizumab. People taking dimethyl fumarate had a hospitalization rate of 32 (per 10,000 people), compared with a rate of 140 in patients on ocrelizumab and 94 in patients on fingolimod.
Mortality rates were low in all groups, but were slightly higher in the ocrelizumab group.
“However, the number of people who died due to COVID overall was small,” Dr. Garjani noted.
Following receipt of a third COVID-19 vaccine, the only hospitalizations were in patients taking ocrelizumab (4 out of 65 infections) and fingolimod (11 out of 78 infections), with no deaths.
Potential mechanism
Researchers suspect the reason for varying COVID-19 infection rates and vaccine efficacy among DMTs is related to their mode of action.
“With MS, the immune system attacks the central nervous system and the aim of these treatments is to modulate or suppress the immune system,” Dr. Garjani said. “Some of these medications are immune suppressants and therefore, in addition to preventing MS, might also put people at increased risk of infection from COVID or other diseases.”
Ocrelizumab and fingolimod have different modes of action, but both act as immunosuppressants.
Study data on beta-interferon offered an interesting twist. Patients taking that medication had far lower infection rates, compared with other DMTs and to the general population, and no COVID-related hospitalizations.
Interferons are known to have some antiviral effects, Dr. Garjani said. In fact, interferon is one of several existing drugs that scientists have considered as possible candidates to fight COVID infection.
Studies on COVID infection rates and vaccine efficacy have yielded conflicting results. Some suggest no differences based on DMT use, whereas others have shown immunological evidence pointing to lower or higher infections rates among the different therapies.
Based on some of those findings, up to 80% of specialists who treat MS in the United States said the pandemic may have changed their use of DMTs, one study found, which later studies suggested may not have been necessary.
While the findings shouldn’t necessarily prompt clinicians to consider changing their treatment approach, Dr. Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.
A balancing act
Commenting on the findings, Tyler Smith, MD, clinical assistant professor of neurology at New York University, said that, although the data suggest these MS therapies may affect COVID vaccine efficacy to varying degrees, there’s more to the story.
“This data builds upon a growing body of evidence that these treatments may attenuate vaccine responses to different degrees, and this should be balanced with their efficacy in controlling multiple sclerosis relapses, Dr. Smith said, adding that “real-life studies examining the effect of vaccines show benefit in limiting hospitalization and death.”
“Developing evidence continues to demonstrate the benefits of vaccination,” he said, “and I encourage all patients to follow the latest federal health guidelines regarding COVID-19 vaccinations.”
Dr. Garjani has received personal compensation for serving as a speaker with MS Academy and Biogen. Dr. Smith’s 2020-2021 fellowship was supported in part by Biogen and the National Multiple Sclerosis Society Clinical Care Physician Fellowship 2020-2021. Dr. Smith also received honoraria from the American Academy of Neurology in 2020.
A version of this article first appeared on Medscape.com.
FROM AAN 2022