ICYMI Multiple Sclerosis

Key clinical point: A significant reduction in absolute lymphocyte counts (ALC) early after the initiation of dimethyl fumarate (DMF) was strongly associated with the development of severe lymphopenia in patients with relapsing multiple sclerosis (MS).

Major finding: A decline in mean ALC of ≥21.2% within the first 3 months of treatment increased the risk for DMF associated-lymphopenia by 6.5-fold (adjusted hazard risk [aHR] 6.503), whereas a decline of ≥40.2% increased the risk for severe lymphopenia by 12.67-fold (aHR 12.67; both P < .001).

Study details: The findings come from a multicenter, noninterventional, prospective real-world study involving 532 patients with relapsing MS who initiated taking DMF.

Disclosures: No funding was received for conducting this study. The authors, including the lead author, declared serving on the advisory board or receiving research/travel grants and speaker/consultancy fees from various sources.

Source: Sainz de la Maza S et al. Mult Scler Relat Disor. 2022;59:103669 (Feb 4). Doi:  10.1016/j.msard.2022.103669.

Key clinical point: A significant reduction in absolute lymphocyte counts (ALC) early after the initiation of dimethyl fumarate (DMF) was strongly associated with the development of severe lymphopenia in patients with relapsing multiple sclerosis (MS).

Major finding: A decline in mean ALC of ≥21.2% within the first 3 months of treatment increased the risk for DMF associated-lymphopenia by 6.5-fold (adjusted hazard risk [aHR] 6.503), whereas a decline of ≥40.2% increased the risk for severe lymphopenia by 12.67-fold (aHR 12.67; both P < .001).

Study details: The findings come from a multicenter, noninterventional, prospective real-world study involving 532 patients with relapsing MS who initiated taking DMF.

Disclosures: No funding was received for conducting this study. The authors, including the lead author, declared serving on the advisory board or receiving research/travel grants and speaker/consultancy fees from various sources.

Source: Sainz de la Maza S et al. Mult Scler Relat Disor. 2022;59:103669 (Feb 4). Doi:  10.1016/j.msard.2022.103669.

Key clinical point: A significant reduction in absolute lymphocyte counts (ALC) early after the initiation of dimethyl fumarate (DMF) was strongly associated with the development of severe lymphopenia in patients with relapsing multiple sclerosis (MS).

Major finding: A decline in mean ALC of ≥21.2% within the first 3 months of treatment increased the risk for DMF associated-lymphopenia by 6.5-fold (adjusted hazard risk [aHR] 6.503), whereas a decline of ≥40.2% increased the risk for severe lymphopenia by 12.67-fold (aHR 12.67; both P < .001).

Study details: The findings come from a multicenter, noninterventional, prospective real-world study involving 532 patients with relapsing MS who initiated taking DMF.

Disclosures: No funding was received for conducting this study. The authors, including the lead author, declared serving on the advisory board or receiving research/travel grants and speaker/consultancy fees from various sources.

Source: Sainz de la Maza S et al. Mult Scler Relat Disor. 2022;59:103669 (Feb 4). Doi:  10.1016/j.msard.2022.103669.

Key clinical point: The time to confirmed disability progression (CDP) and serum neurofilament light chain levels (sNfL) was not significantly different in patients with primary progressive multiple sclerosis (pwPPMS), who received treatment with rituximab or ocrelizumab.

Major finding: After a mean follow-up of 18.3 months, rituximab vs. ocrelizumab groups showed no significant difference in the proportion of patients with CDP (30.6% vs. 23.9%; P = .356). The mean sNfL level was not significantly different between the groups (P = .192).

Study details: The findings come from a multicentric observational study involving 111 pwPPMS who started treatment with ocrelizumab or rituximab.

Disclosures: This study was supported by the Health Institute Carlos III and FEDER funding. Four authors reported receiving travel grants and consulting/speaker fees from various sources.

Source: Alcalá C et al. J Neurol. 2022 (Feb 2). Doi: 10.1007/s00415-022-10989-0

Key clinical point: The time to confirmed disability progression (CDP) and serum neurofilament light chain levels (sNfL) was not significantly different in patients with primary progressive multiple sclerosis (pwPPMS), who received treatment with rituximab or ocrelizumab.

Major finding: After a mean follow-up of 18.3 months, rituximab vs. ocrelizumab groups showed no significant difference in the proportion of patients with CDP (30.6% vs. 23.9%; P = .356). The mean sNfL level was not significantly different between the groups (P = .192).

Study details: The findings come from a multicentric observational study involving 111 pwPPMS who started treatment with ocrelizumab or rituximab.

Disclosures: This study was supported by the Health Institute Carlos III and FEDER funding. Four authors reported receiving travel grants and consulting/speaker fees from various sources.

Source: Alcalá C et al. J Neurol. 2022 (Feb 2). Doi: 10.1007/s00415-022-10989-0

Key clinical point: The time to confirmed disability progression (CDP) and serum neurofilament light chain levels (sNfL) was not significantly different in patients with primary progressive multiple sclerosis (pwPPMS), who received treatment with rituximab or ocrelizumab.

Major finding: After a mean follow-up of 18.3 months, rituximab vs. ocrelizumab groups showed no significant difference in the proportion of patients with CDP (30.6% vs. 23.9%; P = .356). The mean sNfL level was not significantly different between the groups (P = .192).

Study details: The findings come from a multicentric observational study involving 111 pwPPMS who started treatment with ocrelizumab or rituximab.

Disclosures: This study was supported by the Health Institute Carlos III and FEDER funding. Four authors reported receiving travel grants and consulting/speaker fees from various sources.

Source: Alcalá C et al. J Neurol. 2022 (Feb 2). Doi: 10.1007/s00415-022-10989-0

Key clinical point: Changes in serum neurofilament light chain (sNfL) may not be a dynamic biomarker related to confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS) without acute inflammation.

Major finding: At 48 weeks, changes in sNfL were not associated with the risk for CDP in the natalizumab (odds ratio [OR] per 10% increase in sNfL 1.02; 95% CI 0.86-1.21) and placebo (OR per 10% increase in sNfL 0.90; 95% CI 0.64-1.27) groups.

Study details: The findings come from a post hoc analysis of the ASCEND trial involving 317 patients with SPMS without acute inflammation who were randomly assigned to receive either natalizumab (n = 214) or placebo (n = 103).

Disclosures: This study was supported by Biogen. Dr. Zetterberg and Dr. Fox reported receiving personal fees or research contracts from various sources including Biogen. Dr. Belachew reported being an employee and shareholder of Biogen.

Source: Gafson AR et al. JAMA Netw Open. 2022;5(2):e2147588 (Feb 8). Doi:  10.1001/jamanetworkopen.2021.47588

Key clinical point: Changes in serum neurofilament light chain (sNfL) may not be a dynamic biomarker related to confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS) without acute inflammation.

Major finding: At 48 weeks, changes in sNfL were not associated with the risk for CDP in the natalizumab (odds ratio [OR] per 10% increase in sNfL 1.02; 95% CI 0.86-1.21) and placebo (OR per 10% increase in sNfL 0.90; 95% CI 0.64-1.27) groups.

Study details: The findings come from a post hoc analysis of the ASCEND trial involving 317 patients with SPMS without acute inflammation who were randomly assigned to receive either natalizumab (n = 214) or placebo (n = 103).

Disclosures: This study was supported by Biogen. Dr. Zetterberg and Dr. Fox reported receiving personal fees or research contracts from various sources including Biogen. Dr. Belachew reported being an employee and shareholder of Biogen.

Source: Gafson AR et al. JAMA Netw Open. 2022;5(2):e2147588 (Feb 8). Doi:  10.1001/jamanetworkopen.2021.47588

Key clinical point: Changes in serum neurofilament light chain (sNfL) may not be a dynamic biomarker related to confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS) without acute inflammation.

Major finding: At 48 weeks, changes in sNfL were not associated with the risk for CDP in the natalizumab (odds ratio [OR] per 10% increase in sNfL 1.02; 95% CI 0.86-1.21) and placebo (OR per 10% increase in sNfL 0.90; 95% CI 0.64-1.27) groups.

Study details: The findings come from a post hoc analysis of the ASCEND trial involving 317 patients with SPMS without acute inflammation who were randomly assigned to receive either natalizumab (n = 214) or placebo (n = 103).

Disclosures: This study was supported by Biogen. Dr. Zetterberg and Dr. Fox reported receiving personal fees or research contracts from various sources including Biogen. Dr. Belachew reported being an employee and shareholder of Biogen.

Source: Gafson AR et al. JAMA Netw Open. 2022;5(2):e2147588 (Feb 8). Doi:  10.1001/jamanetworkopen.2021.47588

Key clinical point: Both elevated levels of baseline serum neurofilament light chain (sNfL) and increasing levels from a low baseline were associated with multiple sclerosis (MS) relapses, indicating the utility of sNfL in identifying patients who may benefit from early treatment optimization.

Major finding: A 2-fold increase in baseline sNfL was associated with a 1.9-fold increased risk for relapse during follow-up (adjusted hazard ratio [aHR] 1.90; P < .01) and a 2-fold longitudinal increase in sNfL from its first measurement increased the risk for relapse by 1.41-fold (aHR 1.41; P = .04).

Study details: Findings are from an analysis of 58 patients with active MS who were prospectively followed for 1 year as a part of clinical trial.

Disclosures: This study received funding from the MS Society of Canada, Fondazione Italiana Sclerosi Multipla, and Research Manitoba. The authors reported no conflict of interests.

Source: Thebault S et al. Mult Scler Relat Disord. 2022;59:103535 (Jan 18). Doi:  10.1016/j.msard.2022.103535

Key clinical point: Both elevated levels of baseline serum neurofilament light chain (sNfL) and increasing levels from a low baseline were associated with multiple sclerosis (MS) relapses, indicating the utility of sNfL in identifying patients who may benefit from early treatment optimization.

Major finding: A 2-fold increase in baseline sNfL was associated with a 1.9-fold increased risk for relapse during follow-up (adjusted hazard ratio [aHR] 1.90; P < .01) and a 2-fold longitudinal increase in sNfL from its first measurement increased the risk for relapse by 1.41-fold (aHR 1.41; P = .04).

Study details: Findings are from an analysis of 58 patients with active MS who were prospectively followed for 1 year as a part of clinical trial.

Disclosures: This study received funding from the MS Society of Canada, Fondazione Italiana Sclerosi Multipla, and Research Manitoba. The authors reported no conflict of interests.

Source: Thebault S et al. Mult Scler Relat Disord. 2022;59:103535 (Jan 18). Doi:  10.1016/j.msard.2022.103535

Key clinical point: Both elevated levels of baseline serum neurofilament light chain (sNfL) and increasing levels from a low baseline were associated with multiple sclerosis (MS) relapses, indicating the utility of sNfL in identifying patients who may benefit from early treatment optimization.

Major finding: A 2-fold increase in baseline sNfL was associated with a 1.9-fold increased risk for relapse during follow-up (adjusted hazard ratio [aHR] 1.90; P < .01) and a 2-fold longitudinal increase in sNfL from its first measurement increased the risk for relapse by 1.41-fold (aHR 1.41; P = .04).

Study details: Findings are from an analysis of 58 patients with active MS who were prospectively followed for 1 year as a part of clinical trial.

Disclosures: This study received funding from the MS Society of Canada, Fondazione Italiana Sclerosi Multipla, and Research Manitoba. The authors reported no conflict of interests.

Source: Thebault S et al. Mult Scler Relat Disord. 2022;59:103535 (Jan 18). Doi:  10.1016/j.msard.2022.103535

Key clinical point: Patients with multiple sclerosis (MS) who were untreated or received immunomodulatory disease-modifying treatments (IM-DMT) showed excellent seroconversion rates after SARS-CoV-2 vaccination; however, immunosuppressive DMT (IS-DMT) was associated with lower seroconversion rates.

Major finding: For these patients 3 months after vaccine dose seroconversion occurred in 96.7% of untreated, 97.1% of IM-DMT treated, and 61.1% of IS-DMT treated patients vs. 97.4% of healthy control individuals (P < .001), with IS-DMT being the only significant predictor of seroconversion (odds ratio 0.04; P < .001).

Study details: The finding comes from a multicenter, prospective study involving 456 patients with MS who were either untreated (n = 91) or treated with DMT (IM-DMT, n = 139; IS-DMT, n = 226) and 116 healthy control individuals, all of whom were willing to be vaccinated against SARS-CoV-2.

Disclosures: This study was supported by the Austrian Multiple Sclerosis Society and others. Some of the authors declared serving as an advisor or receiving speaker honoraria, scientific grants, travel funding, and consulting from various sources.

Source: Bsteh G et al. Eur J Neurol. 2022 (Feb 1). Doi: 10.1111/ene.15265

Key clinical point: Patients with multiple sclerosis (MS) who were untreated or received immunomodulatory disease-modifying treatments (IM-DMT) showed excellent seroconversion rates after SARS-CoV-2 vaccination; however, immunosuppressive DMT (IS-DMT) was associated with lower seroconversion rates.

Major finding: For these patients 3 months after vaccine dose seroconversion occurred in 96.7% of untreated, 97.1% of IM-DMT treated, and 61.1% of IS-DMT treated patients vs. 97.4% of healthy control individuals (P < .001), with IS-DMT being the only significant predictor of seroconversion (odds ratio 0.04; P < .001).

Study details: The finding comes from a multicenter, prospective study involving 456 patients with MS who were either untreated (n = 91) or treated with DMT (IM-DMT, n = 139; IS-DMT, n = 226) and 116 healthy control individuals, all of whom were willing to be vaccinated against SARS-CoV-2.

Disclosures: This study was supported by the Austrian Multiple Sclerosis Society and others. Some of the authors declared serving as an advisor or receiving speaker honoraria, scientific grants, travel funding, and consulting from various sources.

Source: Bsteh G et al. Eur J Neurol. 2022 (Feb 1). Doi: 10.1111/ene.15265

Key clinical point: Patients with multiple sclerosis (MS) who were untreated or received immunomodulatory disease-modifying treatments (IM-DMT) showed excellent seroconversion rates after SARS-CoV-2 vaccination; however, immunosuppressive DMT (IS-DMT) was associated with lower seroconversion rates.

Major finding: For these patients 3 months after vaccine dose seroconversion occurred in 96.7% of untreated, 97.1% of IM-DMT treated, and 61.1% of IS-DMT treated patients vs. 97.4% of healthy control individuals (P < .001), with IS-DMT being the only significant predictor of seroconversion (odds ratio 0.04; P < .001).

Study details: The finding comes from a multicenter, prospective study involving 456 patients with MS who were either untreated (n = 91) or treated with DMT (IM-DMT, n = 139; IS-DMT, n = 226) and 116 healthy control individuals, all of whom were willing to be vaccinated against SARS-CoV-2.

Disclosures: This study was supported by the Austrian Multiple Sclerosis Society and others. Some of the authors declared serving as an advisor or receiving speaker honoraria, scientific grants, travel funding, and consulting from various sources.

Source: Bsteh G et al. Eur J Neurol. 2022 (Feb 1). Doi: 10.1111/ene.15265

Key clinical point: Spike receptor-binding domain (RBD) immunoglobulin G (IgG) levels following SARS-CoV-2 vaccination were higher in patients with multiple sclerosis (MS) treated with dimethyl fumarate or natalizumab vs. healthy controls; however, the levels were significantly lower in patients receiving sphingosine-1-phosphate receptor modulators (S1P) or anti-CD20 monoclonal antibody (mAb).

Major finding: Postvaccination spike RBD IgG levels were significantly higher in patients treated with dimethyl fumarate (P = .038) and natalizumab (P < .0001) than in healthy controls, whereas patients receiving S1P (P = .01), rituximab (P = .002), or ocrelizumab (P = .0004) showed significantly reduced levels.

Study details: The findings come from a prospective observational study including healthy controls (n =  13) and patients with MS who were either untreated (n = 9) or received treatment with glatiramer acetate (n = 5), dimethyl fumarate (n = 5), natalizumab (n = 6), S1P (n = 7), or anti-CD20 mAbs, including rituximab (n = 13) or ocrelizumab (n = 22).

Disclosures: The study was supported by the National Institutes of Health and others. Some of the authors declared serving on Data Safety Monitoring Boards for or receiving research grant funding and consulting/speaking honoraria from various sources.

Source: Sabatino JJ Jr et al. JCI Insight. 2022 (Jan 14). Doi: 10.1172/jci.insight.156978

Key clinical point: Spike receptor-binding domain (RBD) immunoglobulin G (IgG) levels following SARS-CoV-2 vaccination were higher in patients with multiple sclerosis (MS) treated with dimethyl fumarate or natalizumab vs. healthy controls; however, the levels were significantly lower in patients receiving sphingosine-1-phosphate receptor modulators (S1P) or anti-CD20 monoclonal antibody (mAb).

Major finding: Postvaccination spike RBD IgG levels were significantly higher in patients treated with dimethyl fumarate (P = .038) and natalizumab (P < .0001) than in healthy controls, whereas patients receiving S1P (P = .01), rituximab (P = .002), or ocrelizumab (P = .0004) showed significantly reduced levels.

Study details: The findings come from a prospective observational study including healthy controls (n =  13) and patients with MS who were either untreated (n = 9) or received treatment with glatiramer acetate (n = 5), dimethyl fumarate (n = 5), natalizumab (n = 6), S1P (n = 7), or anti-CD20 mAbs, including rituximab (n = 13) or ocrelizumab (n = 22).

Disclosures: The study was supported by the National Institutes of Health and others. Some of the authors declared serving on Data Safety Monitoring Boards for or receiving research grant funding and consulting/speaking honoraria from various sources.

Source: Sabatino JJ Jr et al. JCI Insight. 2022 (Jan 14). Doi: 10.1172/jci.insight.156978

Key clinical point: Spike receptor-binding domain (RBD) immunoglobulin G (IgG) levels following SARS-CoV-2 vaccination were higher in patients with multiple sclerosis (MS) treated with dimethyl fumarate or natalizumab vs. healthy controls; however, the levels were significantly lower in patients receiving sphingosine-1-phosphate receptor modulators (S1P) or anti-CD20 monoclonal antibody (mAb).

Major finding: Postvaccination spike RBD IgG levels were significantly higher in patients treated with dimethyl fumarate (P = .038) and natalizumab (P < .0001) than in healthy controls, whereas patients receiving S1P (P = .01), rituximab (P = .002), or ocrelizumab (P = .0004) showed significantly reduced levels.

Study details: The findings come from a prospective observational study including healthy controls (n =  13) and patients with MS who were either untreated (n = 9) or received treatment with glatiramer acetate (n = 5), dimethyl fumarate (n = 5), natalizumab (n = 6), S1P (n = 7), or anti-CD20 mAbs, including rituximab (n = 13) or ocrelizumab (n = 22).

Disclosures: The study was supported by the National Institutes of Health and others. Some of the authors declared serving on Data Safety Monitoring Boards for or receiving research grant funding and consulting/speaking honoraria from various sources.

Source: Sabatino JJ Jr et al. JCI Insight. 2022 (Jan 14). Doi: 10.1172/jci.insight.156978

Key clinical point: Disease-modifying treatments (DMT) do not influence the risk for neoplasms in patients with multiple sclerosis (MS), indicating either a low carcinogenic potential of DMTs or neoplasia latencies exceeding the typical trial observation periods.

Major finding: The pooled analysis of trials conducted between 1991 and 2020 showed no increased risk for neoplasm between active-DMT treated vs. placebo arms (incidence rate ratio 1.0797; P = .5711).

Study details: This was a meta-analysis of 42 randomized controlled trials of DMTs published between 1991 and 2020, involving 16,360 active-DMT treated and 10,638 placebo-treated patients with MS.

Disclosures: This study received no external funding. D Papadopoulos, DD Mitsikostas, and R Nicholas reported receiving speaker/consultancy fees and travel grants from various sources.

Source: Papadopoulos D et al. J Neurol. 2022 (Jan 23). Doi: 10.1007/s00415-021-10932-9

Key clinical point: Disease-modifying treatments (DMT) do not influence the risk for neoplasms in patients with multiple sclerosis (MS), indicating either a low carcinogenic potential of DMTs or neoplasia latencies exceeding the typical trial observation periods.

Major finding: The pooled analysis of trials conducted between 1991 and 2020 showed no increased risk for neoplasm between active-DMT treated vs. placebo arms (incidence rate ratio 1.0797; P = .5711).

Study details: This was a meta-analysis of 42 randomized controlled trials of DMTs published between 1991 and 2020, involving 16,360 active-DMT treated and 10,638 placebo-treated patients with MS.

Disclosures: This study received no external funding. D Papadopoulos, DD Mitsikostas, and R Nicholas reported receiving speaker/consultancy fees and travel grants from various sources.

Source: Papadopoulos D et al. J Neurol. 2022 (Jan 23). Doi: 10.1007/s00415-021-10932-9

Key clinical point: Disease-modifying treatments (DMT) do not influence the risk for neoplasms in patients with multiple sclerosis (MS), indicating either a low carcinogenic potential of DMTs or neoplasia latencies exceeding the typical trial observation periods.

Major finding: The pooled analysis of trials conducted between 1991 and 2020 showed no increased risk for neoplasm between active-DMT treated vs. placebo arms (incidence rate ratio 1.0797; P = .5711).

Study details: This was a meta-analysis of 42 randomized controlled trials of DMTs published between 1991 and 2020, involving 16,360 active-DMT treated and 10,638 placebo-treated patients with MS.

Disclosures: This study received no external funding. D Papadopoulos, DD Mitsikostas, and R Nicholas reported receiving speaker/consultancy fees and travel grants from various sources.

Source: Papadopoulos D et al. J Neurol. 2022 (Jan 23). Doi: 10.1007/s00415-021-10932-9

Key clinical point: At 1 year postpartum, clinically meaningful disability from pregnancy-related multiple sclerosis (MS) relapses after natalizumab cessation was retained by over 10% of patients with neither restarting natalizumab shortly after delivery nor solely breastfeeding the infant, providing protection against relapse.

Major finding: Overall, 10.58% of pregnancies accrued significant relapse-related disability at 1 year postpartum. Exclusive breastfeeding (adjusted hazard ratio [aHR] 1.34; 95% CI 0.86-2.10) or restarting natalizumab within 4 weeks postpartum (aHR 1.06; 95% CI 0.48-2.36) was not linked to a lower risk for early postpartum relapses 6 months after delivery.

Study details: The findings come from a prospective cohort study that evaluated 274 successful pregnancies in 255 women with MS from the German MS and Pregnancy Registry. The patients stopped natalizumab before pregnancy or in the first trimester.

Disclosures: The registry was partly supported by the German Federal Joint Committee's Innovation Fund and various pharmaceutical companies. Some authors reported receiving speaker fees, honoraria, research support, and travel grants from or serving on advisory boards for various sources.

Source: Hellwig K et al. JAMA Netw Open. 2022;5(1):e2144750 (Jan 24). Doi:  10.1001/jamanetworkopen.2021.44750

Key clinical point: At 1 year postpartum, clinically meaningful disability from pregnancy-related multiple sclerosis (MS) relapses after natalizumab cessation was retained by over 10% of patients with neither restarting natalizumab shortly after delivery nor solely breastfeeding the infant, providing protection against relapse.

Major finding: Overall, 10.58% of pregnancies accrued significant relapse-related disability at 1 year postpartum. Exclusive breastfeeding (adjusted hazard ratio [aHR] 1.34; 95% CI 0.86-2.10) or restarting natalizumab within 4 weeks postpartum (aHR 1.06; 95% CI 0.48-2.36) was not linked to a lower risk for early postpartum relapses 6 months after delivery.

Study details: The findings come from a prospective cohort study that evaluated 274 successful pregnancies in 255 women with MS from the German MS and Pregnancy Registry. The patients stopped natalizumab before pregnancy or in the first trimester.

Disclosures: The registry was partly supported by the German Federal Joint Committee's Innovation Fund and various pharmaceutical companies. Some authors reported receiving speaker fees, honoraria, research support, and travel grants from or serving on advisory boards for various sources.

Source: Hellwig K et al. JAMA Netw Open. 2022;5(1):e2144750 (Jan 24). Doi:  10.1001/jamanetworkopen.2021.44750

Key clinical point: At 1 year postpartum, clinically meaningful disability from pregnancy-related multiple sclerosis (MS) relapses after natalizumab cessation was retained by over 10% of patients with neither restarting natalizumab shortly after delivery nor solely breastfeeding the infant, providing protection against relapse.

Major finding: Overall, 10.58% of pregnancies accrued significant relapse-related disability at 1 year postpartum. Exclusive breastfeeding (adjusted hazard ratio [aHR] 1.34; 95% CI 0.86-2.10) or restarting natalizumab within 4 weeks postpartum (aHR 1.06; 95% CI 0.48-2.36) was not linked to a lower risk for early postpartum relapses 6 months after delivery.

Study details: The findings come from a prospective cohort study that evaluated 274 successful pregnancies in 255 women with MS from the German MS and Pregnancy Registry. The patients stopped natalizumab before pregnancy or in the first trimester.

Disclosures: The registry was partly supported by the German Federal Joint Committee's Innovation Fund and various pharmaceutical companies. Some authors reported receiving speaker fees, honoraria, research support, and travel grants from or serving on advisory boards for various sources.

Source: Hellwig K et al. JAMA Netw Open. 2022;5(1):e2144750 (Jan 24). Doi:  10.1001/jamanetworkopen.2021.44750

Key clinical point: The third dose of COVID-19 mRNA vaccine increased the levels of anti-SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies in patients with multiple sclerosis (MS) treated with anti-CD20 therapy or fingolimod who had a weak humoral response after 2 doses of mRNA COVID-19 vaccine.

Major finding: After revaccination, the mean levels of anti-SARS-CoV-2 spike RBD IgG titers increased significantly in both anti-CD20 (75.7 arbitrary units [AU]; P < .001) and fingolimod (29.6 AU; P = .006) treated groups. No serious adverse events were recorded.

Study details: The findings come from an observational cohort study involving 130 patients with MS treated with anti-CD20 therapy (n = 101) or fingolimod (n = 29) who had a weak humoral response after 2 doses of mRNA COVID-19 vaccines and were offered a third dose.

Disclosures: The Coalition for Epidemic Preparedness Innovations and Oslo university hospital provided funding for conducting the study. Dr. König and Dr. Holmøy reported receiving speaker honoraria from various sources.

Source: König M et al. JAMA Neurol. 2022 (Jan 24). Doi: 10.1001/jamaneurol.2021.5109

Key clinical point: The third dose of COVID-19 mRNA vaccine increased the levels of anti-SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies in patients with multiple sclerosis (MS) treated with anti-CD20 therapy or fingolimod who had a weak humoral response after 2 doses of mRNA COVID-19 vaccine.

Major finding: After revaccination, the mean levels of anti-SARS-CoV-2 spike RBD IgG titers increased significantly in both anti-CD20 (75.7 arbitrary units [AU]; P < .001) and fingolimod (29.6 AU; P = .006) treated groups. No serious adverse events were recorded.

Study details: The findings come from an observational cohort study involving 130 patients with MS treated with anti-CD20 therapy (n = 101) or fingolimod (n = 29) who had a weak humoral response after 2 doses of mRNA COVID-19 vaccines and were offered a third dose.

Disclosures: The Coalition for Epidemic Preparedness Innovations and Oslo university hospital provided funding for conducting the study. Dr. König and Dr. Holmøy reported receiving speaker honoraria from various sources.

Source: König M et al. JAMA Neurol. 2022 (Jan 24). Doi: 10.1001/jamaneurol.2021.5109

Key clinical point: The third dose of COVID-19 mRNA vaccine increased the levels of anti-SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies in patients with multiple sclerosis (MS) treated with anti-CD20 therapy or fingolimod who had a weak humoral response after 2 doses of mRNA COVID-19 vaccine.

Major finding: After revaccination, the mean levels of anti-SARS-CoV-2 spike RBD IgG titers increased significantly in both anti-CD20 (75.7 arbitrary units [AU]; P < .001) and fingolimod (29.6 AU; P = .006) treated groups. No serious adverse events were recorded.

Study details: The findings come from an observational cohort study involving 130 patients with MS treated with anti-CD20 therapy (n = 101) or fingolimod (n = 29) who had a weak humoral response after 2 doses of mRNA COVID-19 vaccines and were offered a third dose.

Disclosures: The Coalition for Epidemic Preparedness Innovations and Oslo university hospital provided funding for conducting the study. Dr. König and Dr. Holmøy reported receiving speaker honoraria from various sources.

Source: König M et al. JAMA Neurol. 2022 (Jan 24). Doi: 10.1001/jamaneurol.2021.5109

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.