Mark Gudesblatt, MD

In another recent prospective study, Cabeza and colleagues noted that ocrelizumab-treated PWMS who received a third SARS-CoV-2 vaccine dose had a boosted T-cell response, but there was no additive effect on the maximal T-cell response. The study included PWMS taking DMT (ocrelizumab, n = 24; fingolimod, n = 12; or no DMT, n = 10) and healthy controls (n = 12), all of whom received three SARS-CoV-2 vaccine doses (BioNTech-Pfizer or Moderna). The SARS-CoV-2–specific T-cell response in patients treated with ocrelizumab was comparable to that in PWMS who were not treated with DMT and to that in healthy controls 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).

The relationship and interplay of both T-cell and B-cell responses to viral infection is important to understand and appreciate. However, for PWMS who have had, do have, or will experience breakthrough infection, early use of anti-SARS-CoV-2 monoclonal antibodies (mAb) was effective and safe in treating acute COVID-19 in PWMS treated with fingolimod or ocrelizumab. Manzano and colleagues reported on an observational study including 23 PWMS, most of whom had completed the initial COVID-19 vaccine series before infection and were either untreated or treated with fingolimod+ ocrelizumab and then received anti–SARS-CoV2 mAbs (bamlanivimab + etesevimab, casirivimab + imdevimab, sotrovimab, or an undocumented formulation) for treatment of active COVID-19. In this study, 74% of PWMS were able to be managed as outpatients (median duration to mAb receipt, 4 days), and 48% of PWMS recovered from COVID-19 within 7 days after mAb receipt, with no clinical MS relapses documented during or shortly after COVID-19 (median follow-up, 18 days). No adverse events or deaths were reported in this series.

Pivotal trials and package insert information affect DMT choice and dosing, the timing of ongoing treatment, and the awareness of efficacy and potential adverse reactions. Foley and colleagues  demonstrated that 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 MS (RRMS). In the phase 3b NOVA trial (N = 499), patients with RRMS receiving stable intravenous natalizumab QW4 dosing were randomly assigned to continue QW4 (n = 248) or switch to QW6 (n = 251) natalizumab dosing. The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) with natalizumab QW6 vs 0.05 (95% CI 0.01-0.22) with natalizumab QW4, with only two of the PWMS developing 25 or more lesions; this contributed to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Both DMT choice and vaccine-related antibody production matter. Various DMT have different and problematic impact on antibody production and response, and unrecognized immune deficiency or poor antibody response are problematic as variant COVID-19 strains continue to evolve. Protection against both MS disease activity and infections from variants remain a complex issue. Establishing and maintaining protection are important. Identifying PWMS who are at high risk for poor or sustained antibody response is important in addition to the ongoing effective treatment of MS. The landscape of available DMT choice, treatment paradigms, and COVID-19 variants and COVID-19 family protection continues to evolve.

In another recent prospective study, Cabeza and colleagues noted that ocrelizumab-treated PWMS who received a third SARS-CoV-2 vaccine dose had a boosted T-cell response, but there was no additive effect on the maximal T-cell response. The study included PWMS taking DMT (ocrelizumab, n = 24; fingolimod, n = 12; or no DMT, n = 10) and healthy controls (n = 12), all of whom received three SARS-CoV-2 vaccine doses (BioNTech-Pfizer or Moderna). The SARS-CoV-2–specific T-cell response in patients treated with ocrelizumab was comparable to that in PWMS who were not treated with DMT and to that in healthy controls 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).

The relationship and interplay of both T-cell and B-cell responses to viral infection is important to understand and appreciate. However, for PWMS who have had, do have, or will experience breakthrough infection, early use of anti-SARS-CoV-2 monoclonal antibodies (mAb) was effective and safe in treating acute COVID-19 in PWMS treated with fingolimod or ocrelizumab. Manzano and colleagues reported on an observational study including 23 PWMS, most of whom had completed the initial COVID-19 vaccine series before infection and were either untreated or treated with fingolimod+ ocrelizumab and then received anti–SARS-CoV2 mAbs (bamlanivimab + etesevimab, casirivimab + imdevimab, sotrovimab, or an undocumented formulation) for treatment of active COVID-19. In this study, 74% of PWMS were able to be managed as outpatients (median duration to mAb receipt, 4 days), and 48% of PWMS recovered from COVID-19 within 7 days after mAb receipt, with no clinical MS relapses documented during or shortly after COVID-19 (median follow-up, 18 days). No adverse events or deaths were reported in this series.

Pivotal trials and package insert information affect DMT choice and dosing, the timing of ongoing treatment, and the awareness of efficacy and potential adverse reactions. Foley and colleagues  demonstrated that 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 MS (RRMS). In the phase 3b NOVA trial (N = 499), patients with RRMS receiving stable intravenous natalizumab QW4 dosing were randomly assigned to continue QW4 (n = 248) or switch to QW6 (n = 251) natalizumab dosing. The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) with natalizumab QW6 vs 0.05 (95% CI 0.01-0.22) with natalizumab QW4, with only two of the PWMS developing 25 or more lesions; this contributed to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Both DMT choice and vaccine-related antibody production matter. Various DMT have different and problematic impact on antibody production and response, and unrecognized immune deficiency or poor antibody response are problematic as variant COVID-19 strains continue to evolve. Protection against both MS disease activity and infections from variants remain a complex issue. Establishing and maintaining protection are important. Identifying PWMS who are at high risk for poor or sustained antibody response is important in addition to the ongoing effective treatment of MS. The landscape of available DMT choice, treatment paradigms, and COVID-19 variants and COVID-19 family protection continues to evolve.

In another recent prospective study, Cabeza and colleagues noted that ocrelizumab-treated PWMS who received a third SARS-CoV-2 vaccine dose had a boosted T-cell response, but there was no additive effect on the maximal T-cell response. The study included PWMS taking DMT (ocrelizumab, n = 24; fingolimod, n = 12; or no DMT, n = 10) and healthy controls (n = 12), all of whom received three SARS-CoV-2 vaccine doses (BioNTech-Pfizer or Moderna). The SARS-CoV-2–specific T-cell response in patients treated with ocrelizumab was comparable to that in PWMS who were not treated with DMT and to that in healthy controls 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).

The relationship and interplay of both T-cell and B-cell responses to viral infection is important to understand and appreciate. However, for PWMS who have had, do have, or will experience breakthrough infection, early use of anti-SARS-CoV-2 monoclonal antibodies (mAb) was effective and safe in treating acute COVID-19 in PWMS treated with fingolimod or ocrelizumab. Manzano and colleagues reported on an observational study including 23 PWMS, most of whom had completed the initial COVID-19 vaccine series before infection and were either untreated or treated with fingolimod+ ocrelizumab and then received anti–SARS-CoV2 mAbs (bamlanivimab + etesevimab, casirivimab + imdevimab, sotrovimab, or an undocumented formulation) for treatment of active COVID-19. In this study, 74% of PWMS were able to be managed as outpatients (median duration to mAb receipt, 4 days), and 48% of PWMS recovered from COVID-19 within 7 days after mAb receipt, with no clinical MS relapses documented during or shortly after COVID-19 (median follow-up, 18 days). No adverse events or deaths were reported in this series.

Pivotal trials and package insert information affect DMT choice and dosing, the timing of ongoing treatment, and the awareness of efficacy and potential adverse reactions. Foley and colleagues  demonstrated that 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 MS (RRMS). In the phase 3b NOVA trial (N = 499), patients with RRMS receiving stable intravenous natalizumab QW4 dosing were randomly assigned to continue QW4 (n = 248) or switch to QW6 (n = 251) natalizumab dosing. The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) with natalizumab QW6 vs 0.05 (95% CI 0.01-0.22) with natalizumab QW4, with only two of the PWMS developing 25 or more lesions; this contributed to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Both DMT choice and vaccine-related antibody production matter. Various DMT have different and problematic impact on antibody production and response, and unrecognized immune deficiency or poor antibody response are problematic as variant COVID-19 strains continue to evolve. Protection against both MS disease activity and infections from variants remain a complex issue. Establishing and maintaining protection are important. Identifying PWMS who are at high risk for poor or sustained antibody response is important in addition to the ongoing effective treatment of MS. The landscape of available DMT choice, treatment paradigms, and COVID-19 variants and COVID-19 family protection continues to evolve.

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.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

In another study (Maniscalco GT et al) exploring vaccine efficacy in 149 PwMS, treatment with interferon (IFN)-beta 1A resulted in improved anti-spike IgG specific humoral response levels than was seen in healthy controls response (median, 1,916 vs 1,089; P = .029) whereas reduced anti-spike IgG levels were significantly lower in patients treated with Cladribine (P = .002), Fingolimod (P < .0001), or Ocrelizumab (P < .0001). Clinical decisions regarding DMT treatment choice and DMT change focused solely on relapse rate and MRI are now insufficient without considering and incorporating vaccine response into the decision-making process. Further information across all DMT’s is needed to allow improved decision making regarding DMT choice.  Confounding this problem is the frequency of unrecognized cognitive impairment (CI) in PwMS and the impact CI has on the shared decision-making process beyond EDSS. 

In another study (Cavaco S et al) regarding CI in 408 PwMS, the presence of cognitive dysfunction was not only predictive of a higher risk for conversion from relapsing-remitting disease to progressive disease (adjusted odds ratio, 2.29; P = .043) and shorter survival (e.g. higher risk for death), (adjusted hazard ratio, 3.07; P = .006). The impact of such CI and progressive CI on vaccine hesitancy is unknown. Monitoring disease impact and change in cognitive function in PwMS remains another great unmet need in routine care of PwMS and evaluating the impact of CI on vaccine hesitancy and the shared decision-making process also requires further exploration and incorporation into routine care. Care of PwMS and the choice of DMT should hinge not only considerations about efficacy and safety but now must also incorporate patient vaccine hesitancy and response to vaccination.

In another study (Maniscalco GT et al) exploring vaccine efficacy in 149 PwMS, treatment with interferon (IFN)-beta 1A resulted in improved anti-spike IgG specific humoral response levels than was seen in healthy controls response (median, 1,916 vs 1,089; P = .029) whereas reduced anti-spike IgG levels were significantly lower in patients treated with Cladribine (P = .002), Fingolimod (P < .0001), or Ocrelizumab (P < .0001). Clinical decisions regarding DMT treatment choice and DMT change focused solely on relapse rate and MRI are now insufficient without considering and incorporating vaccine response into the decision-making process. Further information across all DMT’s is needed to allow improved decision making regarding DMT choice.  Confounding this problem is the frequency of unrecognized cognitive impairment (CI) in PwMS and the impact CI has on the shared decision-making process beyond EDSS. 

In another study (Cavaco S et al) regarding CI in 408 PwMS, the presence of cognitive dysfunction was not only predictive of a higher risk for conversion from relapsing-remitting disease to progressive disease (adjusted odds ratio, 2.29; P = .043) and shorter survival (e.g. higher risk for death), (adjusted hazard ratio, 3.07; P = .006). The impact of such CI and progressive CI on vaccine hesitancy is unknown. Monitoring disease impact and change in cognitive function in PwMS remains another great unmet need in routine care of PwMS and evaluating the impact of CI on vaccine hesitancy and the shared decision-making process also requires further exploration and incorporation into routine care. Care of PwMS and the choice of DMT should hinge not only considerations about efficacy and safety but now must also incorporate patient vaccine hesitancy and response to vaccination.

In another study (Maniscalco GT et al) exploring vaccine efficacy in 149 PwMS, treatment with interferon (IFN)-beta 1A resulted in improved anti-spike IgG specific humoral response levels than was seen in healthy controls response (median, 1,916 vs 1,089; P = .029) whereas reduced anti-spike IgG levels were significantly lower in patients treated with Cladribine (P = .002), Fingolimod (P < .0001), or Ocrelizumab (P < .0001). Clinical decisions regarding DMT treatment choice and DMT change focused solely on relapse rate and MRI are now insufficient without considering and incorporating vaccine response into the decision-making process. Further information across all DMT’s is needed to allow improved decision making regarding DMT choice.  Confounding this problem is the frequency of unrecognized cognitive impairment (CI) in PwMS and the impact CI has on the shared decision-making process beyond EDSS. 

In another study (Cavaco S et al) regarding CI in 408 PwMS, the presence of cognitive dysfunction was not only predictive of a higher risk for conversion from relapsing-remitting disease to progressive disease (adjusted odds ratio, 2.29; P = .043) and shorter survival (e.g. higher risk for death), (adjusted hazard ratio, 3.07; P = .006). The impact of such CI and progressive CI on vaccine hesitancy is unknown. Monitoring disease impact and change in cognitive function in PwMS remains another great unmet need in routine care of PwMS and evaluating the impact of CI on vaccine hesitancy and the shared decision-making process also requires further exploration and incorporation into routine care. Care of PwMS and the choice of DMT should hinge not only considerations about efficacy and safety but now must also incorporate patient vaccine hesitancy and response to vaccination.