ICYMI Multiple Sclerosis

Key clinical point: Extended treatment with ofatumumab for up to 3.5 years was well tolerated without any new risks in patients with relapsing multiple sclerosis (RMS).

Major finding: Overall, 83.8% and 9.7% of patients experienced at least 1 adverse event (AE) and serious AE, respectively. Systemic injection-related reactions, infections, and malignancies were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum immunoglobulin (Ig) G and IgM levels were stable and above the lower limit of normal and the risk for serious infections was low.

Study details: Findings are from the ongoing phase 3b ALITHIOS umbrella extension trial involving 1,969 patients with RMS who completed ASCLEPIOS I/II, APLIOS, or APOLITOS trial and continued or switched to ofatumumab in ALITHIOS.

Disclosures: This study was funded by Novartis Pharma AG (Basel, Switzerland). The authors declared receiving consultancy fees, personal compensation, travel reimbursement, research support, or serving on advisory boards for various sources including Novartis Pharma AG. Some authors declared being employees of Novartis Pharma AG.

Source: Hauser SL et al. Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Mult Scler. 2022 (Mar 1). Doi: 10.1177/13524585221079731

Key clinical point: Extended treatment with ofatumumab for up to 3.5 years was well tolerated without any new risks in patients with relapsing multiple sclerosis (RMS).

Major finding: Overall, 83.8% and 9.7% of patients experienced at least 1 adverse event (AE) and serious AE, respectively. Systemic injection-related reactions, infections, and malignancies were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum immunoglobulin (Ig) G and IgM levels were stable and above the lower limit of normal and the risk for serious infections was low.

Study details: Findings are from the ongoing phase 3b ALITHIOS umbrella extension trial involving 1,969 patients with RMS who completed ASCLEPIOS I/II, APLIOS, or APOLITOS trial and continued or switched to ofatumumab in ALITHIOS.

Disclosures: This study was funded by Novartis Pharma AG (Basel, Switzerland). The authors declared receiving consultancy fees, personal compensation, travel reimbursement, research support, or serving on advisory boards for various sources including Novartis Pharma AG. Some authors declared being employees of Novartis Pharma AG.

Source: Hauser SL et al. Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Mult Scler. 2022 (Mar 1). Doi: 10.1177/13524585221079731

Key clinical point: Extended treatment with ofatumumab for up to 3.5 years was well tolerated without any new risks in patients with relapsing multiple sclerosis (RMS).

Major finding: Overall, 83.8% and 9.7% of patients experienced at least 1 adverse event (AE) and serious AE, respectively. Systemic injection-related reactions, infections, and malignancies were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum immunoglobulin (Ig) G and IgM levels were stable and above the lower limit of normal and the risk for serious infections was low.

Study details: Findings are from the ongoing phase 3b ALITHIOS umbrella extension trial involving 1,969 patients with RMS who completed ASCLEPIOS I/II, APLIOS, or APOLITOS trial and continued or switched to ofatumumab in ALITHIOS.

Disclosures: This study was funded by Novartis Pharma AG (Basel, Switzerland). The authors declared receiving consultancy fees, personal compensation, travel reimbursement, research support, or serving on advisory boards for various sources including Novartis Pharma AG. Some authors declared being employees of Novartis Pharma AG.

Source: Hauser SL et al. Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Mult Scler. 2022 (Mar 1). Doi: 10.1177/13524585221079731

Key clinical point: Short-term fingolimod discontinuation until the absolute lymphocyte count increases to >1,000 cells/mm³ may improve the SARS-CoV-2 mRNA vaccine-specific humoral response in patients with multiple sclerosis (MS) but not the adaptive cellular response.

Major finding: Overall, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 1 month after the third vaccine dose, with a significantly higher median immunoglobulin (Ig) G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022).

Study details: This was a prospective monocentric 3-month randomized clinical trial involving 20 patients with relapsing-remitting MS on fingolimod therapy who received the third dose of BNT162b2 vaccine after failing to develop a humoral IgG immune response to the previous 2 doses and were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group.

Disclosures: This study was supported by Sheba Multiple Sclerosis Research Grant. The authors declared no conflicts of interest.

Source: Achiron A et al. Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod. J Neurol. 2022 (Mar 2). Doi: 10.1007/s00415-022-11030-0

Key clinical point: Short-term fingolimod discontinuation until the absolute lymphocyte count increases to >1,000 cells/mm³ may improve the SARS-CoV-2 mRNA vaccine-specific humoral response in patients with multiple sclerosis (MS) but not the adaptive cellular response.

Major finding: Overall, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 1 month after the third vaccine dose, with a significantly higher median immunoglobulin (Ig) G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022).

Study details: This was a prospective monocentric 3-month randomized clinical trial involving 20 patients with relapsing-remitting MS on fingolimod therapy who received the third dose of BNT162b2 vaccine after failing to develop a humoral IgG immune response to the previous 2 doses and were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group.

Disclosures: This study was supported by Sheba Multiple Sclerosis Research Grant. The authors declared no conflicts of interest.

Source: Achiron A et al. Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod. J Neurol. 2022 (Mar 2). Doi: 10.1007/s00415-022-11030-0

Key clinical point: Short-term fingolimod discontinuation until the absolute lymphocyte count increases to >1,000 cells/mm³ may improve the SARS-CoV-2 mRNA vaccine-specific humoral response in patients with multiple sclerosis (MS) but not the adaptive cellular response.

Major finding: Overall, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 1 month after the third vaccine dose, with a significantly higher median immunoglobulin (Ig) G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022).

Study details: This was a prospective monocentric 3-month randomized clinical trial involving 20 patients with relapsing-remitting MS on fingolimod therapy who received the third dose of BNT162b2 vaccine after failing to develop a humoral IgG immune response to the previous 2 doses and were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group.

Disclosures: This study was supported by Sheba Multiple Sclerosis Research Grant. The authors declared no conflicts of interest.

Source: Achiron A et al. Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod. J Neurol. 2022 (Mar 2). Doi: 10.1007/s00415-022-11030-0

Key clinical point: Vaccination against influenza was well tolerated in patients with multiple sclerosis (MS) who mainly experienced short-term nonserious adverse events following immunization (AEFI), with the risk for MS relapse not being significantly different than those who were not vaccinated.

Major finding: Overall, 60.2% of patients did not experience any vaccine-related AEFIs, with pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%) being the major nonserious short-term AEFIs. The long-term AEFIs included flu-like symptoms, COVID-19, and MS relapse, with incidences of infection or MS relapse (P = .65) and cumulative survival rate (P = .21) not being significantly different between the vaccinated and unvaccinated groups.

Study details: This was a single-center, prospective, vaccination-vigilance trial including 194 patients with MS, of whom 113 patients received any of the recommended flu vaccines and 81 did not.

Disclosures: The study received no external funding. GT Maniscalco declared serving on speaking and advisory boards and receiving speaker fees from various sources. Other authors declared no conflicts of interest.

Source: Maniscalco GT et al. Flu vaccination in multiple sclerosis patients: A monocentric prospective vaccine-vigilance study. Expert Opin Drug Saf. 2022 (Feb 22). Doi: 10.1080/14740338.2022.2044787

Key clinical point: Vaccination against influenza was well tolerated in patients with multiple sclerosis (MS) who mainly experienced short-term nonserious adverse events following immunization (AEFI), with the risk for MS relapse not being significantly different than those who were not vaccinated.

Major finding: Overall, 60.2% of patients did not experience any vaccine-related AEFIs, with pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%) being the major nonserious short-term AEFIs. The long-term AEFIs included flu-like symptoms, COVID-19, and MS relapse, with incidences of infection or MS relapse (P = .65) and cumulative survival rate (P = .21) not being significantly different between the vaccinated and unvaccinated groups.

Study details: This was a single-center, prospective, vaccination-vigilance trial including 194 patients with MS, of whom 113 patients received any of the recommended flu vaccines and 81 did not.

Disclosures: The study received no external funding. GT Maniscalco declared serving on speaking and advisory boards and receiving speaker fees from various sources. Other authors declared no conflicts of interest.

Source: Maniscalco GT et al. Flu vaccination in multiple sclerosis patients: A monocentric prospective vaccine-vigilance study. Expert Opin Drug Saf. 2022 (Feb 22). Doi: 10.1080/14740338.2022.2044787

Key clinical point: Vaccination against influenza was well tolerated in patients with multiple sclerosis (MS) who mainly experienced short-term nonserious adverse events following immunization (AEFI), with the risk for MS relapse not being significantly different than those who were not vaccinated.

Major finding: Overall, 60.2% of patients did not experience any vaccine-related AEFIs, with pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%) being the major nonserious short-term AEFIs. The long-term AEFIs included flu-like symptoms, COVID-19, and MS relapse, with incidences of infection or MS relapse (P = .65) and cumulative survival rate (P = .21) not being significantly different between the vaccinated and unvaccinated groups.

Study details: This was a single-center, prospective, vaccination-vigilance trial including 194 patients with MS, of whom 113 patients received any of the recommended flu vaccines and 81 did not.

Disclosures: The study received no external funding. GT Maniscalco declared serving on speaking and advisory boards and receiving speaker fees from various sources. Other authors declared no conflicts of interest.

Source: Maniscalco GT et al. Flu vaccination in multiple sclerosis patients: A monocentric prospective vaccine-vigilance study. Expert Opin Drug Saf. 2022 (Feb 22). Doi: 10.1080/14740338.2022.2044787

Key clinical point: Over 22 years of follow-up found no association between the use of hormone therapy (HT) and the risk for disability accrual in women with multiple sclerosis (MS) treated with a disease-modifying therapy (DMT) when used for <5 years.

Major finding: Overall, current HT use vs. no use was not associated with a significantly higher risk for disability accrual; however, the risk of reaching 6-month confirmed and sustained Expanded Disability Status Scale 4 increased from 0.6 (95% CI 0.3-1.2) after <1 year of use to 1.4 (95% CI 0.9-2.2) after >5 years of HT use vs. no use.

Study details: The data come from a nationwide, population-based cohort study of 3,325 women with relapsing-remitting MS treated with DMT.

Disclosures: This study received no external funding. TI Kopp revealed his role as an adviser for Novartis and received Biogen's sponsorship for congress participation. M Magyari declared serving as an advisor and receiving honoraria for lecturing and research support for congress participation from various sources. Ø Lidegaard had no conflicts of interest.

Source: Kopp TI et al. Hormone therapy and disease activity in Danish women with multiple sclerosis: A population-based cohort study. Eur J Neurol. 2022 (Feb 23). Doi: 10.1111/ene.15299

Key clinical point: Over 22 years of follow-up found no association between the use of hormone therapy (HT) and the risk for disability accrual in women with multiple sclerosis (MS) treated with a disease-modifying therapy (DMT) when used for <5 years.

Major finding: Overall, current HT use vs. no use was not associated with a significantly higher risk for disability accrual; however, the risk of reaching 6-month confirmed and sustained Expanded Disability Status Scale 4 increased from 0.6 (95% CI 0.3-1.2) after <1 year of use to 1.4 (95% CI 0.9-2.2) after >5 years of HT use vs. no use.

Study details: The data come from a nationwide, population-based cohort study of 3,325 women with relapsing-remitting MS treated with DMT.

Disclosures: This study received no external funding. TI Kopp revealed his role as an adviser for Novartis and received Biogen's sponsorship for congress participation. M Magyari declared serving as an advisor and receiving honoraria for lecturing and research support for congress participation from various sources. Ø Lidegaard had no conflicts of interest.

Source: Kopp TI et al. Hormone therapy and disease activity in Danish women with multiple sclerosis: A population-based cohort study. Eur J Neurol. 2022 (Feb 23). Doi: 10.1111/ene.15299

Key clinical point: Over 22 years of follow-up found no association between the use of hormone therapy (HT) and the risk for disability accrual in women with multiple sclerosis (MS) treated with a disease-modifying therapy (DMT) when used for <5 years.

Major finding: Overall, current HT use vs. no use was not associated with a significantly higher risk for disability accrual; however, the risk of reaching 6-month confirmed and sustained Expanded Disability Status Scale 4 increased from 0.6 (95% CI 0.3-1.2) after <1 year of use to 1.4 (95% CI 0.9-2.2) after >5 years of HT use vs. no use.

Study details: The data come from a nationwide, population-based cohort study of 3,325 women with relapsing-remitting MS treated with DMT.

Disclosures: This study received no external funding. TI Kopp revealed his role as an adviser for Novartis and received Biogen's sponsorship for congress participation. M Magyari declared serving as an advisor and receiving honoraria for lecturing and research support for congress participation from various sources. Ø Lidegaard had no conflicts of interest.

Source: Kopp TI et al. Hormone therapy and disease activity in Danish women with multiple sclerosis: A population-based cohort study. Eur J Neurol. 2022 (Feb 23). Doi: 10.1111/ene.15299

Key clinical point: Masitinib at a dose of 4.5 mg/kg/day may benefit patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive multiple sclerosis (nSPMS).

Major finding: The Expanded Disability Status Scale(EDSS)-based disability worsening was slower with 4.5 mg/kg/day masitinib 4.5 mg/kg/day vs. placebo (change in EDSS 0.001 vs. 0.098), with a between-group difference of −0.097 (P = .027). No new safety signals were identified.

Study details: The findings come from the 96-week, phase 3 Study AB07002 trial involving 611 patients with PPMS or nSPMS who were randomly assigned to parallel groups of either 4.5 mg/kg/day masitinib, 6 mg/kg/day uptitrated masitinib, or an equivalent placebo.

Disclosures: This study was funded by AB Science, Paris, France. A Moussy, C Mansfield, and O Hermine reported being employees and shareholders of AB Science, and the other authors reported receiving research support and nonfinancial support or personal fees from various sources, including AB Science.

Source: Vermersch P et al, on behalf of the AB07002 Study Group. Efficacy and safety of masitinib in progressive forms of multiple sclerosis: A randomized, phase 3, clinical trial. Neurol Neuroimmunol Neuroinflamm. 2022;9(3):e1148 (Feb 21). Doi: 10.1212/NXI.0000000000001148

Key clinical point: Masitinib at a dose of 4.5 mg/kg/day may benefit patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive multiple sclerosis (nSPMS).

Major finding: The Expanded Disability Status Scale(EDSS)-based disability worsening was slower with 4.5 mg/kg/day masitinib 4.5 mg/kg/day vs. placebo (change in EDSS 0.001 vs. 0.098), with a between-group difference of −0.097 (P = .027). No new safety signals were identified.

Study details: The findings come from the 96-week, phase 3 Study AB07002 trial involving 611 patients with PPMS or nSPMS who were randomly assigned to parallel groups of either 4.5 mg/kg/day masitinib, 6 mg/kg/day uptitrated masitinib, or an equivalent placebo.

Disclosures: This study was funded by AB Science, Paris, France. A Moussy, C Mansfield, and O Hermine reported being employees and shareholders of AB Science, and the other authors reported receiving research support and nonfinancial support or personal fees from various sources, including AB Science.

Source: Vermersch P et al, on behalf of the AB07002 Study Group. Efficacy and safety of masitinib in progressive forms of multiple sclerosis: A randomized, phase 3, clinical trial. Neurol Neuroimmunol Neuroinflamm. 2022;9(3):e1148 (Feb 21). Doi: 10.1212/NXI.0000000000001148

Key clinical point: Masitinib at a dose of 4.5 mg/kg/day may benefit patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive multiple sclerosis (nSPMS).

Major finding: The Expanded Disability Status Scale(EDSS)-based disability worsening was slower with 4.5 mg/kg/day masitinib 4.5 mg/kg/day vs. placebo (change in EDSS 0.001 vs. 0.098), with a between-group difference of −0.097 (P = .027). No new safety signals were identified.

Study details: The findings come from the 96-week, phase 3 Study AB07002 trial involving 611 patients with PPMS or nSPMS who were randomly assigned to parallel groups of either 4.5 mg/kg/day masitinib, 6 mg/kg/day uptitrated masitinib, or an equivalent placebo.

Disclosures: This study was funded by AB Science, Paris, France. A Moussy, C Mansfield, and O Hermine reported being employees and shareholders of AB Science, and the other authors reported receiving research support and nonfinancial support or personal fees from various sources, including AB Science.

Source: Vermersch P et al, on behalf of the AB07002 Study Group. Efficacy and safety of masitinib in progressive forms of multiple sclerosis: A randomized, phase 3, clinical trial. Neurol Neuroimmunol Neuroinflamm. 2022;9(3):e1148 (Feb 21). Doi: 10.1212/NXI.0000000000001148

Key clinical point: Plasma levels of S100A12 and apolipoprotein A1 (Apo-A1) could serve as effective biomarkers for the early detection and screening of relapsing-remitting multiple sclerosis (RRMS) in patients with early disease and those at high risk.

Major finding: The mean plasma S100A12 level was significantly lower in patients with new untreated RRMS (36.781 pg/mL) and their first-degree family members (15.979 pg/mL) vs. healthy control (HC) participants (42.586 pg/mL; P ≤ .05). Mean plasma Apo-A1 levels were significantly lower in the first-degree family members of patients with RRMS vs. HC participants (111.78 pg/mL vs. 205.88 pg/mL; P ≤ .05).

Study details: The study involved 35 patients with new untreated RRMS, 26 first-degree relatives of patients with RRMS, and 24 participants who formed the HC group.

Disclosure: No source of funding was declared. The authors reported no conflicts of interest.

Source: Samangooei M et al. Evaluation of S100A12 and Apo-A1 plasma level potency in untreated new relapsing–remitting multiple sclerosis patients and their family members. Sci Rep. 2022;12:2160 (Feb 9). Doi: 10.1038/s41598-022-06322-4

Key clinical point: Plasma levels of S100A12 and apolipoprotein A1 (Apo-A1) could serve as effective biomarkers for the early detection and screening of relapsing-remitting multiple sclerosis (RRMS) in patients with early disease and those at high risk.

Major finding: The mean plasma S100A12 level was significantly lower in patients with new untreated RRMS (36.781 pg/mL) and their first-degree family members (15.979 pg/mL) vs. healthy control (HC) participants (42.586 pg/mL; P ≤ .05). Mean plasma Apo-A1 levels were significantly lower in the first-degree family members of patients with RRMS vs. HC participants (111.78 pg/mL vs. 205.88 pg/mL; P ≤ .05).

Study details: The study involved 35 patients with new untreated RRMS, 26 first-degree relatives of patients with RRMS, and 24 participants who formed the HC group.

Disclosure: No source of funding was declared. The authors reported no conflicts of interest.

Source: Samangooei M et al. Evaluation of S100A12 and Apo-A1 plasma level potency in untreated new relapsing–remitting multiple sclerosis patients and their family members. Sci Rep. 2022;12:2160 (Feb 9). Doi: 10.1038/s41598-022-06322-4

Key clinical point: Plasma levels of S100A12 and apolipoprotein A1 (Apo-A1) could serve as effective biomarkers for the early detection and screening of relapsing-remitting multiple sclerosis (RRMS) in patients with early disease and those at high risk.

Major finding: The mean plasma S100A12 level was significantly lower in patients with new untreated RRMS (36.781 pg/mL) and their first-degree family members (15.979 pg/mL) vs. healthy control (HC) participants (42.586 pg/mL; P ≤ .05). Mean plasma Apo-A1 levels were significantly lower in the first-degree family members of patients with RRMS vs. HC participants (111.78 pg/mL vs. 205.88 pg/mL; P ≤ .05).

Study details: The study involved 35 patients with new untreated RRMS, 26 first-degree relatives of patients with RRMS, and 24 participants who formed the HC group.

Disclosure: No source of funding was declared. The authors reported no conflicts of interest.

Source: Samangooei M et al. Evaluation of S100A12 and Apo-A1 plasma level potency in untreated new relapsing–remitting multiple sclerosis patients and their family members. Sci Rep. 2022;12:2160 (Feb 9). Doi: 10.1038/s41598-022-06322-4

Key clinical point: Bacillus Calmette-Guérin (BCG) vaccination had no effect on the incidence of relapsing-remitting multiple sclerosis (RRMS), but was positively associated with the incidence of MS diagnosed later in life.

Major finding: BCG vaccination was not associated with the incidence of RRMS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but was positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36).

Study details: Findings are from an analysis of 400,563 individuals from the Quebec Birth Cohort for Immunity and Health (QBCIH) who were followed up from 1983 to 2014.

Disclosures: The establishment of QBCIH was supported by the Canada Foundation for Innovation; Québec Ministry of Education, Leisure, and Sports; Canadian Institutes of Health Research; Fonds de recherche du Québec-Santé, and the Multiple Sclerosis Society of Canada. The authors declared no conflicts of interest.

Source: Corsenac P et al. Bacillus Calmette–Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada. Eur J Neurol. 2022 (Feb 15). Doi: 10.1111/ene.15290

Key clinical point: Bacillus Calmette-Guérin (BCG) vaccination had no effect on the incidence of relapsing-remitting multiple sclerosis (RRMS), but was positively associated with the incidence of MS diagnosed later in life.

Major finding: BCG vaccination was not associated with the incidence of RRMS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but was positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36).

Study details: Findings are from an analysis of 400,563 individuals from the Quebec Birth Cohort for Immunity and Health (QBCIH) who were followed up from 1983 to 2014.

Disclosures: The establishment of QBCIH was supported by the Canada Foundation for Innovation; Québec Ministry of Education, Leisure, and Sports; Canadian Institutes of Health Research; Fonds de recherche du Québec-Santé, and the Multiple Sclerosis Society of Canada. The authors declared no conflicts of interest.

Source: Corsenac P et al. Bacillus Calmette–Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada. Eur J Neurol. 2022 (Feb 15). Doi: 10.1111/ene.15290

Key clinical point: Bacillus Calmette-Guérin (BCG) vaccination had no effect on the incidence of relapsing-remitting multiple sclerosis (RRMS), but was positively associated with the incidence of MS diagnosed later in life.

Major finding: BCG vaccination was not associated with the incidence of RRMS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but was positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36).

Study details: Findings are from an analysis of 400,563 individuals from the Quebec Birth Cohort for Immunity and Health (QBCIH) who were followed up from 1983 to 2014.

Disclosures: The establishment of QBCIH was supported by the Canada Foundation for Innovation; Québec Ministry of Education, Leisure, and Sports; Canadian Institutes of Health Research; Fonds de recherche du Québec-Santé, and the Multiple Sclerosis Society of Canada. The authors declared no conflicts of interest.

Source: Corsenac P et al. Bacillus Calmette–Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada. Eur J Neurol. 2022 (Feb 15). Doi: 10.1111/ene.15290

Key clinical point: Serum neurofilament light chain (sNfL) could serve as an effective biomarker for identifying subclinical disease activity and monitoring drug response in multiple sclerosis (MS).

Major finding: An sNfL Z score of >1.5 indicated an increased risk for future disease activity in all patients with MS (odds ratio [OR] 3.15; P < .0001) and in patients considered stable without evidence of disease activity (OR 2.66; P = .034). The sNfL values could depict a treatment effectiveness hierarchy, with an estimated additive effect on sNfL Z score of −0.14 (P = .0018) for high efficacy monoclonal antibody therapy vs. oral therapy.

Study details: Findings are from an analysis of 1,313 patients with relapsing or secondary progressive MS from a Swiss MS cohort and 5,390 individuals without evidence of central nervous system disease.

Disclosures: The study was funded by Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, and Roche. Some authors declared receiving grants, travel compensation, speaker honoraria, and advisory board/lecture and consultancy fees from various sources including the funding sources.

Source: Benkert P et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 2022;21(3):246-257 (Mar 1). Doi: 10.1016/S1474-4422(22)00009-6

Key clinical point: Serum neurofilament light chain (sNfL) could serve as an effective biomarker for identifying subclinical disease activity and monitoring drug response in multiple sclerosis (MS).

Major finding: An sNfL Z score of >1.5 indicated an increased risk for future disease activity in all patients with MS (odds ratio [OR] 3.15; P < .0001) and in patients considered stable without evidence of disease activity (OR 2.66; P = .034). The sNfL values could depict a treatment effectiveness hierarchy, with an estimated additive effect on sNfL Z score of −0.14 (P = .0018) for high efficacy monoclonal antibody therapy vs. oral therapy.

Study details: Findings are from an analysis of 1,313 patients with relapsing or secondary progressive MS from a Swiss MS cohort and 5,390 individuals without evidence of central nervous system disease.

Disclosures: The study was funded by Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, and Roche. Some authors declared receiving grants, travel compensation, speaker honoraria, and advisory board/lecture and consultancy fees from various sources including the funding sources.

Source: Benkert P et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 2022;21(3):246-257 (Mar 1). Doi: 10.1016/S1474-4422(22)00009-6

Key clinical point: Serum neurofilament light chain (sNfL) could serve as an effective biomarker for identifying subclinical disease activity and monitoring drug response in multiple sclerosis (MS).

Major finding: An sNfL Z score of >1.5 indicated an increased risk for future disease activity in all patients with MS (odds ratio [OR] 3.15; P < .0001) and in patients considered stable without evidence of disease activity (OR 2.66; P = .034). The sNfL values could depict a treatment effectiveness hierarchy, with an estimated additive effect on sNfL Z score of −0.14 (P = .0018) for high efficacy monoclonal antibody therapy vs. oral therapy.

Study details: Findings are from an analysis of 1,313 patients with relapsing or secondary progressive MS from a Swiss MS cohort and 5,390 individuals without evidence of central nervous system disease.

Disclosures: The study was funded by Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, and Roche. Some authors declared receiving grants, travel compensation, speaker honoraria, and advisory board/lecture and consultancy fees from various sources including the funding sources.

Source: Benkert P et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 2022;21(3):246-257 (Mar 1). Doi: 10.1016/S1474-4422(22)00009-6

WEST PALM BEACH, FL – Including serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) at multiple sclerosis (MS) onset may lead to better prediction of long-term outcomes and relapse risk, new research suggests.

The research shows that once standard clinical models can be incorporated into practice, the early measurement of these biomarkers will provide useful information in predicting who may be at risk of poorer outcomes, researcher Gauruv Bose, MD, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, told this news organization.

The findings were presented at annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Better together?

Although higher baseline sNfL levels in MS have previously been linked to greater brain atrophy and other long-term outcomes, and sGFAP changes are also associated with inflammation and damage through the disease course, less is known about longer-term effects of the two biomarker measures combined, Dr. Bose said.

“The value of using both sNfL and sGFAP in predictive models is of interest, since one correlates with neuroaxonal damage, while the other has correlated with astrocytic glial damage/cell turnover – potentially, though differently, reflecting inflammatory damage and neurodegeneration,” he added.

To investigate the relationship, the researchers evaluated patients with MS enrolled at the Brigham Multiple Sclerosis Center. All underwent neurologic examinations every 6 months, and MRI scans and blood samples were collected every year. Some had more than 20 years of follow-up.

The first study involved 144 patients (mean age, 37.4 years) from whom two samples of sNfL and sGFAP were collected within 3 years of MS onset.

The median baseline sNfL level was 10.7 pg/mL, and 50 patients (34.7%) already showed increases in sNfL at the 1-year follow-up. Their median sGFAP level at onset was 96 pg/mL, and 59 patients (41%) showed increases in sGFAP at the 1-year follow-up.

Results showed that higher baseline sNfL levels were significantly associated with increased risk for MS relapse at 10 years (hazard ratio, 1.34; P = .04), as well as with the development of new MRI lesions (HR, 1.35; P = .022).

Of the study group, 25 (17.4%) developed secondary progressive MS (SPMS) by the 10-year follow-up. For those prognostic assessments, the investigators compared utilization of a model using well-established clinical predictors of SPMS with and without the inclusion of sNfL and sGFAP.

The clinical model included key factors such as age, sex, body mass index, Extended Disability Status Scale (EDSS), timed 25-foot walk, and other measures.

The researchers found the clinical model alone predicted 10-year outcomes with an area under the receiver operating characteristic curve (AUC) of 0.75. However, with the addition of baseline sNfL and sGFAP measures, the AUC was improved to 0.79 (P = .0008).

Furthermore, the inclusion of additional follow-up sNfL and sGFAP measurements taken after baseline further improved the model’s AUC (0.82; P = .046).

The addition of the sNfL and sGFAP measures to the clinical models also improved the prediction of disability in MS at 10 years on EDSS (P = .068), as well as prediction of 10-year brain T2 lesion volume (P = .009) and brain parenchymal fraction (P = .04).
 

Relapse predictor?

In the second study, Dr. Bose and colleagues evaluated the role of the two serum measures in predicting relapse after disease-modifying therapy (DMT) discontinuation. That study included 42 patients who discontinued DMT treatment after having been disease-activity free for 2 years while on the drugs. They were compared with 36 patients who had similar characteristics and had continued DMT treatment.

All patients (mean age, 44.5 years) had a mean of 7.4 years since prior disease activity.

Increases in sNfL following DMT discontinuation, but not before, were associated with a significantly greater risk for clinical disease worsening at a mean follow-up of 7.5 years (HR, 9.4; P = .007). Change in sGFAP was associated with new MRI lesions (HR, 8.3; P = .039), compared with no changes.

“The crux of this study” was that patients with increased biomarker levels after stopping DMTs “were at a significantly higher risk for disease activity in the future compared to those whose biomarker levels remained stable,” Dr. Bose noted.

“We think this finding, if replicated in another cohort, has the potential to be included in guidelines regarding stopping DMT in patients with MS,” he added.
 

Clinically useful?

Jeffrey Cohen, MD, current president of ACTRIMS, said the first study supports mounting evidence on how sNfL and sGFAP at onset can predict future disease and have the potential to improve current predictive models.

“Combining clinical, MRI, and serum biomarkers into a single model works better than any of the three factors individually,” said Dr. Cohen, who is director of the Mellen Center for MS Treatment and Research and professor of neurology at the Cleveland Clinic.

“For the clinician, this information may help with treatment selection,” he added.

Dr. Cohen noted that the suggestion that the biomarkers could also be helpful in predicting relapse after discontinuation is of importance.

“Increasingly, we are considering this issue in the clinical setting,” he said. However, he also noted some caveats.

“Interpretation of the results of the study is not straightforward, illustrating the complexity of the issue,” Dr. Cohen said. “One issue is that the patients in the study were relatively young, with an average age of 45, which is not a group in which we typically would consider stopping therapy.”

Dr. Bose has received a postdoctoral fellowship grant from the Multiple Sclerosis Society of Canada. Dr. Cohen reports having received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an editor of the Multiple Sclerosis Journal.

A version of this article first appeared on Medscape.com.

WEST PALM BEACH, FL – Including serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) at multiple sclerosis (MS) onset may lead to better prediction of long-term outcomes and relapse risk, new research suggests.

The research shows that once standard clinical models can be incorporated into practice, the early measurement of these biomarkers will provide useful information in predicting who may be at risk of poorer outcomes, researcher Gauruv Bose, MD, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, told this news organization.

The findings were presented at annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Better together?

Although higher baseline sNfL levels in MS have previously been linked to greater brain atrophy and other long-term outcomes, and sGFAP changes are also associated with inflammation and damage through the disease course, less is known about longer-term effects of the two biomarker measures combined, Dr. Bose said.

“The value of using both sNfL and sGFAP in predictive models is of interest, since one correlates with neuroaxonal damage, while the other has correlated with astrocytic glial damage/cell turnover – potentially, though differently, reflecting inflammatory damage and neurodegeneration,” he added.

To investigate the relationship, the researchers evaluated patients with MS enrolled at the Brigham Multiple Sclerosis Center. All underwent neurologic examinations every 6 months, and MRI scans and blood samples were collected every year. Some had more than 20 years of follow-up.

The first study involved 144 patients (mean age, 37.4 years) from whom two samples of sNfL and sGFAP were collected within 3 years of MS onset.

The median baseline sNfL level was 10.7 pg/mL, and 50 patients (34.7%) already showed increases in sNfL at the 1-year follow-up. Their median sGFAP level at onset was 96 pg/mL, and 59 patients (41%) showed increases in sGFAP at the 1-year follow-up.

Results showed that higher baseline sNfL levels were significantly associated with increased risk for MS relapse at 10 years (hazard ratio, 1.34; P = .04), as well as with the development of new MRI lesions (HR, 1.35; P = .022).

Of the study group, 25 (17.4%) developed secondary progressive MS (SPMS) by the 10-year follow-up. For those prognostic assessments, the investigators compared utilization of a model using well-established clinical predictors of SPMS with and without the inclusion of sNfL and sGFAP.

The clinical model included key factors such as age, sex, body mass index, Extended Disability Status Scale (EDSS), timed 25-foot walk, and other measures.

The researchers found the clinical model alone predicted 10-year outcomes with an area under the receiver operating characteristic curve (AUC) of 0.75. However, with the addition of baseline sNfL and sGFAP measures, the AUC was improved to 0.79 (P = .0008).

Furthermore, the inclusion of additional follow-up sNfL and sGFAP measurements taken after baseline further improved the model’s AUC (0.82; P = .046).

The addition of the sNfL and sGFAP measures to the clinical models also improved the prediction of disability in MS at 10 years on EDSS (P = .068), as well as prediction of 10-year brain T2 lesion volume (P = .009) and brain parenchymal fraction (P = .04).
 

Relapse predictor?

In the second study, Dr. Bose and colleagues evaluated the role of the two serum measures in predicting relapse after disease-modifying therapy (DMT) discontinuation. That study included 42 patients who discontinued DMT treatment after having been disease-activity free for 2 years while on the drugs. They were compared with 36 patients who had similar characteristics and had continued DMT treatment.

All patients (mean age, 44.5 years) had a mean of 7.4 years since prior disease activity.

Increases in sNfL following DMT discontinuation, but not before, were associated with a significantly greater risk for clinical disease worsening at a mean follow-up of 7.5 years (HR, 9.4; P = .007). Change in sGFAP was associated with new MRI lesions (HR, 8.3; P = .039), compared with no changes.

“The crux of this study” was that patients with increased biomarker levels after stopping DMTs “were at a significantly higher risk for disease activity in the future compared to those whose biomarker levels remained stable,” Dr. Bose noted.

“We think this finding, if replicated in another cohort, has the potential to be included in guidelines regarding stopping DMT in patients with MS,” he added.
 

Clinically useful?

Jeffrey Cohen, MD, current president of ACTRIMS, said the first study supports mounting evidence on how sNfL and sGFAP at onset can predict future disease and have the potential to improve current predictive models.

“Combining clinical, MRI, and serum biomarkers into a single model works better than any of the three factors individually,” said Dr. Cohen, who is director of the Mellen Center for MS Treatment and Research and professor of neurology at the Cleveland Clinic.

“For the clinician, this information may help with treatment selection,” he added.

Dr. Cohen noted that the suggestion that the biomarkers could also be helpful in predicting relapse after discontinuation is of importance.

“Increasingly, we are considering this issue in the clinical setting,” he said. However, he also noted some caveats.

“Interpretation of the results of the study is not straightforward, illustrating the complexity of the issue,” Dr. Cohen said. “One issue is that the patients in the study were relatively young, with an average age of 45, which is not a group in which we typically would consider stopping therapy.”

Dr. Bose has received a postdoctoral fellowship grant from the Multiple Sclerosis Society of Canada. Dr. Cohen reports having received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an editor of the Multiple Sclerosis Journal.

A version of this article first appeared on Medscape.com.

WEST PALM BEACH, FL – Including serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) at multiple sclerosis (MS) onset may lead to better prediction of long-term outcomes and relapse risk, new research suggests.

The research shows that once standard clinical models can be incorporated into practice, the early measurement of these biomarkers will provide useful information in predicting who may be at risk of poorer outcomes, researcher Gauruv Bose, MD, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, told this news organization.

The findings were presented at annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Better together?

Although higher baseline sNfL levels in MS have previously been linked to greater brain atrophy and other long-term outcomes, and sGFAP changes are also associated with inflammation and damage through the disease course, less is known about longer-term effects of the two biomarker measures combined, Dr. Bose said.

“The value of using both sNfL and sGFAP in predictive models is of interest, since one correlates with neuroaxonal damage, while the other has correlated with astrocytic glial damage/cell turnover – potentially, though differently, reflecting inflammatory damage and neurodegeneration,” he added.

To investigate the relationship, the researchers evaluated patients with MS enrolled at the Brigham Multiple Sclerosis Center. All underwent neurologic examinations every 6 months, and MRI scans and blood samples were collected every year. Some had more than 20 years of follow-up.

The first study involved 144 patients (mean age, 37.4 years) from whom two samples of sNfL and sGFAP were collected within 3 years of MS onset.

The median baseline sNfL level was 10.7 pg/mL, and 50 patients (34.7%) already showed increases in sNfL at the 1-year follow-up. Their median sGFAP level at onset was 96 pg/mL, and 59 patients (41%) showed increases in sGFAP at the 1-year follow-up.

Results showed that higher baseline sNfL levels were significantly associated with increased risk for MS relapse at 10 years (hazard ratio, 1.34; P = .04), as well as with the development of new MRI lesions (HR, 1.35; P = .022).

Of the study group, 25 (17.4%) developed secondary progressive MS (SPMS) by the 10-year follow-up. For those prognostic assessments, the investigators compared utilization of a model using well-established clinical predictors of SPMS with and without the inclusion of sNfL and sGFAP.

The clinical model included key factors such as age, sex, body mass index, Extended Disability Status Scale (EDSS), timed 25-foot walk, and other measures.

The researchers found the clinical model alone predicted 10-year outcomes with an area under the receiver operating characteristic curve (AUC) of 0.75. However, with the addition of baseline sNfL and sGFAP measures, the AUC was improved to 0.79 (P = .0008).

Furthermore, the inclusion of additional follow-up sNfL and sGFAP measurements taken after baseline further improved the model’s AUC (0.82; P = .046).

The addition of the sNfL and sGFAP measures to the clinical models also improved the prediction of disability in MS at 10 years on EDSS (P = .068), as well as prediction of 10-year brain T2 lesion volume (P = .009) and brain parenchymal fraction (P = .04).
 

Relapse predictor?

In the second study, Dr. Bose and colleagues evaluated the role of the two serum measures in predicting relapse after disease-modifying therapy (DMT) discontinuation. That study included 42 patients who discontinued DMT treatment after having been disease-activity free for 2 years while on the drugs. They were compared with 36 patients who had similar characteristics and had continued DMT treatment.

All patients (mean age, 44.5 years) had a mean of 7.4 years since prior disease activity.

Increases in sNfL following DMT discontinuation, but not before, were associated with a significantly greater risk for clinical disease worsening at a mean follow-up of 7.5 years (HR, 9.4; P = .007). Change in sGFAP was associated with new MRI lesions (HR, 8.3; P = .039), compared with no changes.

“The crux of this study” was that patients with increased biomarker levels after stopping DMTs “were at a significantly higher risk for disease activity in the future compared to those whose biomarker levels remained stable,” Dr. Bose noted.

“We think this finding, if replicated in another cohort, has the potential to be included in guidelines regarding stopping DMT in patients with MS,” he added.
 

Clinically useful?

Jeffrey Cohen, MD, current president of ACTRIMS, said the first study supports mounting evidence on how sNfL and sGFAP at onset can predict future disease and have the potential to improve current predictive models.

“Combining clinical, MRI, and serum biomarkers into a single model works better than any of the three factors individually,” said Dr. Cohen, who is director of the Mellen Center for MS Treatment and Research and professor of neurology at the Cleveland Clinic.

“For the clinician, this information may help with treatment selection,” he added.

Dr. Cohen noted that the suggestion that the biomarkers could also be helpful in predicting relapse after discontinuation is of importance.

“Increasingly, we are considering this issue in the clinical setting,” he said. However, he also noted some caveats.

“Interpretation of the results of the study is not straightforward, illustrating the complexity of the issue,” Dr. Cohen said. “One issue is that the patients in the study were relatively young, with an average age of 45, which is not a group in which we typically would consider stopping therapy.”

Dr. Bose has received a postdoctoral fellowship grant from the Multiple Sclerosis Society of Canada. Dr. Cohen reports having received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an editor of the Multiple Sclerosis Journal.

A version of this article first appeared on Medscape.com.

Among patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) receiving ocrelizumab or rituximab, B cell depletion appears to last well past the 6-month dosing regimen typically used with these drugs. The results, drawn from a retrospective analysis, provide support for clinical trials to rest longer re-infusion intervals.

The study appeared online Jan. 21 in the journal Multiple Sclerosis and Related Disorders, presented by lead author Mahmoud AbdelRazek, MD, at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Both drugs were approved based on clinical trials that investigated 6-month doses, but previous studies have suggested depletion can last longer, including a range of 9-26 months in the case of rituximab.

The initial rationale for monitoring B cell depletion was to prevent a relapse by re-infusing a patient if B cells levels rise, but the researchers noted a pattern of sustained depletion, especially in patients who had a delayed infusion for some reason – they often still had low B cell counts at the time of the next drug infusion. “That became not an unusual finding,” said Dr. AbdelRazek in an interview. He is an instructor of neurology at Harvard Medical School.

Patients also found the delay appealing, in part because they often felt unwell in the days following an infusion, and delays could mean fewer infections and other adverse effects. “Most of my patients I’ve discussed this with would be very appreciative of that delay,” said Dr. AbdelRazek. “There’s obviously an economic benefit as well,” said Dr. AbdelRazek.
 

The final answer?

The retrospective nature of the study is a key weakness, and the rationale to delay infusions based on continuing B cell depletion assumes that B cell depletion is in fact the mechanism of action for countering MS. “That is a critical question,” said Mark Gudesblatt, MD, who was asked to comment on the study. But if that is indeed the way the drugs work, then it would make sense to identify patients who repopulate B cells more slowly and tailor drug regimens. “It’s not one size fits all and blindly just re-dosing. The upsides are good: You come in less frequently for dosing, the cost to payers is less. But the bad is, maybe there are other markers. This is the putative mechanism, but what we believe may not be the final answer. There may be more to the story,” said Dr. Gutesblatt, who is Medical Director at South Shore Neurologic Associates, Patchogue, New York.

Dr. AbdelRazek also noted the study’s limitation. “I think a clinical trial is going to be warranted to really have this translated into clinical practice,” he said. His group is planning to conduct just such a trial, pending confirmation of a funding source.
 

B cell depletion beyond 6 months

The researchers analyzed data from 178 patients with MS and 10 patients with NMOSD who received ocrelizumab (n = 111) or rituximab (n = 53), or both (n = 24) at two Harvard Medical School teaching hospitals between 2010 and 2020. The data included 800 infusions and 1,054 CD19 measurements.

The researchers defined B cell depletion as an absolute count of 20 cells/uL or less, a B cell percentage of 2% or less, or if B cells were 5% or less of total lymphocytes.

Among the patient population, B cell depletion that met all 3 criteria occurred as long as 13.8 months after an initial ocrelizumab infusion cycle, and 22.8 months after second or more cycles of ocrelizumab. Following rituximab, the researchers noted B cell depletions. Following 500 mg of rituximab, B cell depletion defined by the first, second, or third criteria occurred as far out as 22.3, 26.2, and 28.5 months. For 1,000 mg doses of rituximab, B cell depletion occurred as long as 18.3, 18.3, and 29.1 months after a dose.

Examining 90 B cell measurements conducted at least 8 months after an ocrelizumab infusion, 50% were depleted by the first definition and 54% by the second definition. At 13 months, the figures were 58% and 62% among 26 B-cell measurements. Eight months or more after rituximab, 113 B-cell measurements showed rates of 43% and 52% B-cell depletion by the first two criteria.

Dr. AbdelRazek and Dr. Gudesblatt have no relevant financial disclosures.

Among patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) receiving ocrelizumab or rituximab, B cell depletion appears to last well past the 6-month dosing regimen typically used with these drugs. The results, drawn from a retrospective analysis, provide support for clinical trials to rest longer re-infusion intervals.

The study appeared online Jan. 21 in the journal Multiple Sclerosis and Related Disorders, presented by lead author Mahmoud AbdelRazek, MD, at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Both drugs were approved based on clinical trials that investigated 6-month doses, but previous studies have suggested depletion can last longer, including a range of 9-26 months in the case of rituximab.

The initial rationale for monitoring B cell depletion was to prevent a relapse by re-infusing a patient if B cells levels rise, but the researchers noted a pattern of sustained depletion, especially in patients who had a delayed infusion for some reason – they often still had low B cell counts at the time of the next drug infusion. “That became not an unusual finding,” said Dr. AbdelRazek in an interview. He is an instructor of neurology at Harvard Medical School.

Patients also found the delay appealing, in part because they often felt unwell in the days following an infusion, and delays could mean fewer infections and other adverse effects. “Most of my patients I’ve discussed this with would be very appreciative of that delay,” said Dr. AbdelRazek. “There’s obviously an economic benefit as well,” said Dr. AbdelRazek.
 

The final answer?

The retrospective nature of the study is a key weakness, and the rationale to delay infusions based on continuing B cell depletion assumes that B cell depletion is in fact the mechanism of action for countering MS. “That is a critical question,” said Mark Gudesblatt, MD, who was asked to comment on the study. But if that is indeed the way the drugs work, then it would make sense to identify patients who repopulate B cells more slowly and tailor drug regimens. “It’s not one size fits all and blindly just re-dosing. The upsides are good: You come in less frequently for dosing, the cost to payers is less. But the bad is, maybe there are other markers. This is the putative mechanism, but what we believe may not be the final answer. There may be more to the story,” said Dr. Gutesblatt, who is Medical Director at South Shore Neurologic Associates, Patchogue, New York.

Dr. AbdelRazek also noted the study’s limitation. “I think a clinical trial is going to be warranted to really have this translated into clinical practice,” he said. His group is planning to conduct just such a trial, pending confirmation of a funding source.
 

B cell depletion beyond 6 months

The researchers analyzed data from 178 patients with MS and 10 patients with NMOSD who received ocrelizumab (n = 111) or rituximab (n = 53), or both (n = 24) at two Harvard Medical School teaching hospitals between 2010 and 2020. The data included 800 infusions and 1,054 CD19 measurements.

The researchers defined B cell depletion as an absolute count of 20 cells/uL or less, a B cell percentage of 2% or less, or if B cells were 5% or less of total lymphocytes.

Among the patient population, B cell depletion that met all 3 criteria occurred as long as 13.8 months after an initial ocrelizumab infusion cycle, and 22.8 months after second or more cycles of ocrelizumab. Following rituximab, the researchers noted B cell depletions. Following 500 mg of rituximab, B cell depletion defined by the first, second, or third criteria occurred as far out as 22.3, 26.2, and 28.5 months. For 1,000 mg doses of rituximab, B cell depletion occurred as long as 18.3, 18.3, and 29.1 months after a dose.

Examining 90 B cell measurements conducted at least 8 months after an ocrelizumab infusion, 50% were depleted by the first definition and 54% by the second definition. At 13 months, the figures were 58% and 62% among 26 B-cell measurements. Eight months or more after rituximab, 113 B-cell measurements showed rates of 43% and 52% B-cell depletion by the first two criteria.

Dr. AbdelRazek and Dr. Gudesblatt have no relevant financial disclosures.

Among patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) receiving ocrelizumab or rituximab, B cell depletion appears to last well past the 6-month dosing regimen typically used with these drugs. The results, drawn from a retrospective analysis, provide support for clinical trials to rest longer re-infusion intervals.

The study appeared online Jan. 21 in the journal Multiple Sclerosis and Related Disorders, presented by lead author Mahmoud AbdelRazek, MD, at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Both drugs were approved based on clinical trials that investigated 6-month doses, but previous studies have suggested depletion can last longer, including a range of 9-26 months in the case of rituximab.

The initial rationale for monitoring B cell depletion was to prevent a relapse by re-infusing a patient if B cells levels rise, but the researchers noted a pattern of sustained depletion, especially in patients who had a delayed infusion for some reason – they often still had low B cell counts at the time of the next drug infusion. “That became not an unusual finding,” said Dr. AbdelRazek in an interview. He is an instructor of neurology at Harvard Medical School.

Patients also found the delay appealing, in part because they often felt unwell in the days following an infusion, and delays could mean fewer infections and other adverse effects. “Most of my patients I’ve discussed this with would be very appreciative of that delay,” said Dr. AbdelRazek. “There’s obviously an economic benefit as well,” said Dr. AbdelRazek.
 

The final answer?

The retrospective nature of the study is a key weakness, and the rationale to delay infusions based on continuing B cell depletion assumes that B cell depletion is in fact the mechanism of action for countering MS. “That is a critical question,” said Mark Gudesblatt, MD, who was asked to comment on the study. But if that is indeed the way the drugs work, then it would make sense to identify patients who repopulate B cells more slowly and tailor drug regimens. “It’s not one size fits all and blindly just re-dosing. The upsides are good: You come in less frequently for dosing, the cost to payers is less. But the bad is, maybe there are other markers. This is the putative mechanism, but what we believe may not be the final answer. There may be more to the story,” said Dr. Gutesblatt, who is Medical Director at South Shore Neurologic Associates, Patchogue, New York.

Dr. AbdelRazek also noted the study’s limitation. “I think a clinical trial is going to be warranted to really have this translated into clinical practice,” he said. His group is planning to conduct just such a trial, pending confirmation of a funding source.
 

B cell depletion beyond 6 months

The researchers analyzed data from 178 patients with MS and 10 patients with NMOSD who received ocrelizumab (n = 111) or rituximab (n = 53), or both (n = 24) at two Harvard Medical School teaching hospitals between 2010 and 2020. The data included 800 infusions and 1,054 CD19 measurements.

The researchers defined B cell depletion as an absolute count of 20 cells/uL or less, a B cell percentage of 2% or less, or if B cells were 5% or less of total lymphocytes.

Among the patient population, B cell depletion that met all 3 criteria occurred as long as 13.8 months after an initial ocrelizumab infusion cycle, and 22.8 months after second or more cycles of ocrelizumab. Following rituximab, the researchers noted B cell depletions. Following 500 mg of rituximab, B cell depletion defined by the first, second, or third criteria occurred as far out as 22.3, 26.2, and 28.5 months. For 1,000 mg doses of rituximab, B cell depletion occurred as long as 18.3, 18.3, and 29.1 months after a dose.

Examining 90 B cell measurements conducted at least 8 months after an ocrelizumab infusion, 50% were depleted by the first definition and 54% by the second definition. At 13 months, the figures were 58% and 62% among 26 B-cell measurements. Eight months or more after rituximab, 113 B-cell measurements showed rates of 43% and 52% B-cell depletion by the first two criteria.

Dr. AbdelRazek and Dr. Gudesblatt have no relevant financial disclosures.