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

Mark Gudesblatt, MD
The past several months' reviews have focused on issues related to the effect of COVID-19 infection, vaccine responses, and disease-modifying therapies on care of people with multiple sclerosis (MS). Although SARS-CoV-2 infection and its complications presently appear to be less important, we must keep our collective eyes on COVID-19 trends and how they might influence future treatment and disease management. Vaccination's effect on disease remains an issue of concern. A recent prospective study of vaccination vigilance (N = 194) noted that influenza vaccines were well tolerated in people with MS. Although some experienced short-term and nonserious adverse events following immunization (AEFI), the risk for MS relapse was not significantly different from that of people with MS who were not vaccinated (Maniscalco et al). Overall, 60.2% of people with MS did not experience any vaccine-related AEFI. The 39.8% who experienced nonserious short-term symptoms reported pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%). Long-term AEFI included flu-like symptoms, COVID-19, and MS relapse. The incidence of both infection and MS relapse (P = .65), and the cumulative survival rate (P = .21), were not significantly different between the vaccinated and unvaccinated people with MS groups. Another study exploring links between vaccination and the occurrence of MS included 400,563 individuals from the Québec Birth Cohort on Immunity and Health who were followed from 1983 to 2014 (Corsenac et al). This study concluded that bacillus Calmette-Guérin (BCG) vaccination was not associated with the incidence of relapsing-remitting MS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but BCG vaccinations were positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36). This vaccine relationship is less of an issue in the United States, where BCG vaccination for tuberculosis is uncommon.

 

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.

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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
The past several months' reviews have focused on issues related to the effect of COVID-19 infection, vaccine responses, and disease-modifying therapies on care of people with multiple sclerosis (MS). Although SARS-CoV-2 infection and its complications presently appear to be less important, we must keep our collective eyes on COVID-19 trends and how they might influence future treatment and disease management. Vaccination's effect on disease remains an issue of concern. A recent prospective study of vaccination vigilance (N = 194) noted that influenza vaccines were well tolerated in people with MS. Although some experienced short-term and nonserious adverse events following immunization (AEFI), the risk for MS relapse was not significantly different from that of people with MS who were not vaccinated (Maniscalco et al). Overall, 60.2% of people with MS did not experience any vaccine-related AEFI. The 39.8% who experienced nonserious short-term symptoms reported pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%). Long-term AEFI included flu-like symptoms, COVID-19, and MS relapse. The incidence of both infection and MS relapse (P = .65), and the cumulative survival rate (P = .21), were not significantly different between the vaccinated and unvaccinated people with MS groups. Another study exploring links between vaccination and the occurrence of MS included 400,563 individuals from the Québec Birth Cohort on Immunity and Health who were followed from 1983 to 2014 (Corsenac et al). This study concluded that bacillus Calmette-Guérin (BCG) vaccination was not associated with the incidence of relapsing-remitting MS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but BCG vaccinations were positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36). This vaccine relationship is less of an issue in the United States, where BCG vaccination for tuberculosis is uncommon.

 

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.

Mark Gudesblatt, MD
The past several months' reviews have focused on issues related to the effect of COVID-19 infection, vaccine responses, and disease-modifying therapies on care of people with multiple sclerosis (MS). Although SARS-CoV-2 infection and its complications presently appear to be less important, we must keep our collective eyes on COVID-19 trends and how they might influence future treatment and disease management. Vaccination's effect on disease remains an issue of concern. A recent prospective study of vaccination vigilance (N = 194) noted that influenza vaccines were well tolerated in people with MS. Although some experienced short-term and nonserious adverse events following immunization (AEFI), the risk for MS relapse was not significantly different from that of people with MS who were not vaccinated (Maniscalco et al). Overall, 60.2% of people with MS did not experience any vaccine-related AEFI. The 39.8% who experienced nonserious short-term symptoms reported pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%). Long-term AEFI included flu-like symptoms, COVID-19, and MS relapse. The incidence of both infection and MS relapse (P = .65), and the cumulative survival rate (P = .21), were not significantly different between the vaccinated and unvaccinated people with MS groups. Another study exploring links between vaccination and the occurrence of MS included 400,563 individuals from the Québec Birth Cohort on Immunity and Health who were followed from 1983 to 2014 (Corsenac et al). This study concluded that bacillus Calmette-Guérin (BCG) vaccination was not associated with the incidence of relapsing-remitting MS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but BCG vaccinations were positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36). This vaccine relationship is less of an issue in the United States, where BCG vaccination for tuberculosis is uncommon.

 

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.

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