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Dr. Gudesblatt scans the journals, so you don’t have to!

Mark Gudesblatt, MD
Treatment of multiple sclerosis (MS) has never seemed so easy, with so many available and effective disease-modifying therapy (DMT) treatment choices that vary in frequency, route of administration, and mechanism of action (MOA). However, patient-centric and appropriate choices require a breadth of knowledge and ability to determine the relevance and application of this information. COVID-19 continues to be an issue because of the effect of DMT choice on vaccination response as well as the effect of viral infection. Despite the popularity of B-cell–depleting therapies, multiple studies highlight the impact of this DMT MOA on vaccine response. Gyang and colleagues note that people with MS demonstrated reduced neutralizing antibody (nAb) response to SARS-CoV-2 mRNA vaccine efficacy across varied SARS-CoV-2 vaccine types (BNT162b2 [Pfizer/BioNTech], mRNA-1273 [Moderna], or Ad26.COV2 [Johnson & Johnson]) in a prospective longitudinal study. In 51 people with MS treated with B-cell–depleting therapies vs other or no therapy, a greater than nine-fold decrease was seen in the quantitative nAb response (P < .001), where 61.5% of patients showed no detectable levels of nAb. B-cell–depleting therapy (P < .0001) was associated with significantly reduced neutralization titer 50% values. Being aware of the effect of vaccination on DMT choice requires simultaneous recognition of this effect, whether in terms of relapse or by progression of the disease.

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.

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Dr. Gudesblatt scans the journals, so you don’t have to!
Dr. Gudesblatt scans the journals, so you don’t have to!

Mark Gudesblatt, MD
Treatment of multiple sclerosis (MS) has never seemed so easy, with so many available and effective disease-modifying therapy (DMT) treatment choices that vary in frequency, route of administration, and mechanism of action (MOA). However, patient-centric and appropriate choices require a breadth of knowledge and ability to determine the relevance and application of this information. COVID-19 continues to be an issue because of the effect of DMT choice on vaccination response as well as the effect of viral infection. Despite the popularity of B-cell–depleting therapies, multiple studies highlight the impact of this DMT MOA on vaccine response. Gyang and colleagues note that people with MS demonstrated reduced neutralizing antibody (nAb) response to SARS-CoV-2 mRNA vaccine efficacy across varied SARS-CoV-2 vaccine types (BNT162b2 [Pfizer/BioNTech], mRNA-1273 [Moderna], or Ad26.COV2 [Johnson & Johnson]) in a prospective longitudinal study. In 51 people with MS treated with B-cell–depleting therapies vs other or no therapy, a greater than nine-fold decrease was seen in the quantitative nAb response (P < .001), where 61.5% of patients showed no detectable levels of nAb. B-cell–depleting therapy (P < .0001) was associated with significantly reduced neutralization titer 50% values. Being aware of the effect of vaccination on DMT choice requires simultaneous recognition of this effect, whether in terms of relapse or by progression of the disease.

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.

Mark Gudesblatt, MD
Treatment of multiple sclerosis (MS) has never seemed so easy, with so many available and effective disease-modifying therapy (DMT) treatment choices that vary in frequency, route of administration, and mechanism of action (MOA). However, patient-centric and appropriate choices require a breadth of knowledge and ability to determine the relevance and application of this information. COVID-19 continues to be an issue because of the effect of DMT choice on vaccination response as well as the effect of viral infection. Despite the popularity of B-cell–depleting therapies, multiple studies highlight the impact of this DMT MOA on vaccine response. Gyang and colleagues note that people with MS demonstrated reduced neutralizing antibody (nAb) response to SARS-CoV-2 mRNA vaccine efficacy across varied SARS-CoV-2 vaccine types (BNT162b2 [Pfizer/BioNTech], mRNA-1273 [Moderna], or Ad26.COV2 [Johnson & Johnson]) in a prospective longitudinal study. In 51 people with MS treated with B-cell–depleting therapies vs other or no therapy, a greater than nine-fold decrease was seen in the quantitative nAb response (P < .001), where 61.5% of patients showed no detectable levels of nAb. B-cell–depleting therapy (P < .0001) was associated with significantly reduced neutralization titer 50% values. Being aware of the effect of vaccination on DMT choice requires simultaneous recognition of this effect, whether in terms of relapse or by progression of the disease.

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.

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