Multiple Sclerosis

WEST PALM BEACH, FLA. – Spinal cord atrophy, as detected on calibrated brain MRI scans, significantly correlates with silent progression of multiple sclerosis (MS) to progressive MS, new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.

“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.

“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.

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

Relatively new concept

Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.

However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.

“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).

To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.

They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.

To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.

Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
 

‘Strongest predictor’

The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).

Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).

“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.

Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.

Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).

“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
 

Standard of care?

While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.

Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.

“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
 

Treatment implications

Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.

“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.

Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.

“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.

Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.

He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.

“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.

Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.

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

WEST PALM BEACH, FLA. – Spinal cord atrophy, as detected on calibrated brain MRI scans, significantly correlates with silent progression of multiple sclerosis (MS) to progressive MS, new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.

“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.

“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.

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

Relatively new concept

Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.

However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.

“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).

To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.

They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.

To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.

Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
 

‘Strongest predictor’

The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).

Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).

“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.

Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.

Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).

“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
 

Standard of care?

While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.

Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.

“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
 

Treatment implications

Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.

“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.

Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.

“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.

Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.

He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.

“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.

Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.

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

WEST PALM BEACH, FLA. – Spinal cord atrophy, as detected on calibrated brain MRI scans, significantly correlates with silent progression of multiple sclerosis (MS) to progressive MS, new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.

“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.

“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.

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

Relatively new concept

Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.

However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.

“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).

To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.

They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.

To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.

Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
 

‘Strongest predictor’

The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).

Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).

“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.

Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.

Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).

“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
 

Standard of care?

While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.

Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.

“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
 

Treatment implications

Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.

“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.

Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.

“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.

Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.

He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.

“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.

Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.

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

Key clinical point: Patients with multiple sclerosis (pwMS) who participated in a web-based mindfulness-based intervention (MBI) showed significant improvements in depressive symptoms and health-related quality of life (HRQoL).

Major finding: The MBI group showed a significant improvement in depressive symptoms compared with the waitlist (Cohen’s d 0.39; 95% CI, 0.034-0.742), with patients with recurrent depressive symptoms benefitting the most (P = .034). MBI had a positive effect on HRQoL regardless of previous depressive history (P = .009).

Study details: The findings come from a randomized controlled trial involving 132 pwMS with or without a history of recurrent depression, and who received either an internet-delivered MBI (n = 69) or were assigned to a waitlist (n = 63).

Disclosures: This study was supported by the National Health and Medical Research Council and Multiple Sclerosis Research, Australia. The authors declared no conflict of interests.

Source: Sesel AL et al. Mult Scler. 2022 (Feb 7). Doi:  10.1177/13524585211068002.

Key clinical point: Patients with multiple sclerosis (pwMS) who participated in a web-based mindfulness-based intervention (MBI) showed significant improvements in depressive symptoms and health-related quality of life (HRQoL).

Major finding: The MBI group showed a significant improvement in depressive symptoms compared with the waitlist (Cohen’s d 0.39; 95% CI, 0.034-0.742), with patients with recurrent depressive symptoms benefitting the most (P = .034). MBI had a positive effect on HRQoL regardless of previous depressive history (P = .009).

Study details: The findings come from a randomized controlled trial involving 132 pwMS with or without a history of recurrent depression, and who received either an internet-delivered MBI (n = 69) or were assigned to a waitlist (n = 63).

Disclosures: This study was supported by the National Health and Medical Research Council and Multiple Sclerosis Research, Australia. The authors declared no conflict of interests.

Source: Sesel AL et al. Mult Scler. 2022 (Feb 7). Doi:  10.1177/13524585211068002.

Key clinical point: Patients with multiple sclerosis (pwMS) who participated in a web-based mindfulness-based intervention (MBI) showed significant improvements in depressive symptoms and health-related quality of life (HRQoL).

Major finding: The MBI group showed a significant improvement in depressive symptoms compared with the waitlist (Cohen’s d 0.39; 95% CI, 0.034-0.742), with patients with recurrent depressive symptoms benefitting the most (P = .034). MBI had a positive effect on HRQoL regardless of previous depressive history (P = .009).

Study details: The findings come from a randomized controlled trial involving 132 pwMS with or without a history of recurrent depression, and who received either an internet-delivered MBI (n = 69) or were assigned to a waitlist (n = 63).

Disclosures: This study was supported by the National Health and Medical Research Council and Multiple Sclerosis Research, Australia. The authors declared no conflict of interests.

Source: Sesel AL et al. Mult Scler. 2022 (Feb 7). Doi:  10.1177/13524585211068002.

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