Multiple Sclerosis

Key clinical point: Ocrelizumab may be preferred over fingolimod as an exit strategy after natalizumab discontinuation in patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: At 1 year, fewer relapses were observed in patients receiving ocrelizumab vs fingolimod (0.12±0.39 vs 0.41±0.71; P = .035), realizing a 70.7% lower annualized relapse rate. The cumulative probability of relapse was significantly higher with fingolimod vs ocrelizumab (31.5% vs 10.4%; adjusted hazard ratio, 3.4; P = .04).

Study details: The data come from an observational, retrospective study involving 102 patients with RRMS who received either fingolimod (n=54) or ocrelizumab (n=48) after natalizumab cessation.

Disclosures: No source of funding was disclosed. Some of the authors including the lead author reported receiving consultancy fees and travel grants from various pharmaceutical companies.

Source: Bigaut K et al. J Neurol. 2022 Jan 4. doi: 10.1007/s00415-021-10950-7.

Key clinical point: Ocrelizumab may be preferred over fingolimod as an exit strategy after natalizumab discontinuation in patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: At 1 year, fewer relapses were observed in patients receiving ocrelizumab vs fingolimod (0.12±0.39 vs 0.41±0.71; P = .035), realizing a 70.7% lower annualized relapse rate. The cumulative probability of relapse was significantly higher with fingolimod vs ocrelizumab (31.5% vs 10.4%; adjusted hazard ratio, 3.4; P = .04).

Study details: The data come from an observational, retrospective study involving 102 patients with RRMS who received either fingolimod (n=54) or ocrelizumab (n=48) after natalizumab cessation.

Disclosures: No source of funding was disclosed. Some of the authors including the lead author reported receiving consultancy fees and travel grants from various pharmaceutical companies.

Source: Bigaut K et al. J Neurol. 2022 Jan 4. doi: 10.1007/s00415-021-10950-7.

Key clinical point: Ocrelizumab may be preferred over fingolimod as an exit strategy after natalizumab discontinuation in patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: At 1 year, fewer relapses were observed in patients receiving ocrelizumab vs fingolimod (0.12±0.39 vs 0.41±0.71; P = .035), realizing a 70.7% lower annualized relapse rate. The cumulative probability of relapse was significantly higher with fingolimod vs ocrelizumab (31.5% vs 10.4%; adjusted hazard ratio, 3.4; P = .04).

Study details: The data come from an observational, retrospective study involving 102 patients with RRMS who received either fingolimod (n=54) or ocrelizumab (n=48) after natalizumab cessation.

Disclosures: No source of funding was disclosed. Some of the authors including the lead author reported receiving consultancy fees and travel grants from various pharmaceutical companies.

Source: Bigaut K et al. J Neurol. 2022 Jan 4. doi: 10.1007/s00415-021-10950-7.

Key clinical point: Cognitive dysfunction in patients with multiple sclerosis (MS) is predictive of a higher risk for conversion from relapse-remitting MS to secondary progressive MS and a higher risk for death.

Major finding: Cognitive dysfunction was linked to a greater risk of converting from relapse-remitting course to progressive disease course (adjusted odds ratio, 2.29; P = .043) and shorter survival (adjusted hazard ratio, 3.07; P = .006).

Study details: This was a retrospective analysis of 408 patients with MS.

Disclosures: No external funding was received for this study. The authors reported no conflict of interests.

Source: Cavaco S et al. Mult Scler. 2021 Dec 30. doi: 10.1177/13524585211066598.

Key clinical point: Cognitive dysfunction in patients with multiple sclerosis (MS) is predictive of a higher risk for conversion from relapse-remitting MS to secondary progressive MS and a higher risk for death.

Major finding: Cognitive dysfunction was linked to a greater risk of converting from relapse-remitting course to progressive disease course (adjusted odds ratio, 2.29; P = .043) and shorter survival (adjusted hazard ratio, 3.07; P = .006).

Study details: This was a retrospective analysis of 408 patients with MS.

Disclosures: No external funding was received for this study. The authors reported no conflict of interests.

Source: Cavaco S et al. Mult Scler. 2021 Dec 30. doi: 10.1177/13524585211066598.

Key clinical point: Cognitive dysfunction in patients with multiple sclerosis (MS) is predictive of a higher risk for conversion from relapse-remitting MS to secondary progressive MS and a higher risk for death.

Major finding: Cognitive dysfunction was linked to a greater risk of converting from relapse-remitting course to progressive disease course (adjusted odds ratio, 2.29; P = .043) and shorter survival (adjusted hazard ratio, 3.07; P = .006).

Study details: This was a retrospective analysis of 408 patients with MS.

Disclosures: No external funding was received for this study. The authors reported no conflict of interests.

Source: Cavaco S et al. Mult Scler. 2021 Dec 30. doi: 10.1177/13524585211066598.

Key clinical point: Spending more time outdoors in the summer and higher exposure to summer ultraviolet radiation (UVR) markedly reduces the risk of developing pediatric multiple sclerosis (MS).

Major finding: Compared with spending <30 minutes outdoors daily during the most recent summer, greater time spent outdoors was associated with a significantly decreased risk of developing MS (30-60 minutes: adjusted odds ratio [aOR], 0.48; P = .05; 1-2 hours: aOR, 0.19; P < .001). Additionally, the ambient UVR dose also showed a protective effect (aOR, 0.76; P = .01).

Study details: This was a multicenter case-control study involving children with MS (n=332) compared with age- and gender-matched controls (n=534).

Disclosures: This study was funded by the NIH and the National MS Society. Some of the authors declared receiving grants from National MS Society and NIH and/or financial support and consulting/personal fees from various other sources.

Source: Sebastian P et al. Neurology. 2021 Dec 8. doi: 10.1212/WNL.0000000000013045.

Key clinical point: Spending more time outdoors in the summer and higher exposure to summer ultraviolet radiation (UVR) markedly reduces the risk of developing pediatric multiple sclerosis (MS).

Major finding: Compared with spending <30 minutes outdoors daily during the most recent summer, greater time spent outdoors was associated with a significantly decreased risk of developing MS (30-60 minutes: adjusted odds ratio [aOR], 0.48; P = .05; 1-2 hours: aOR, 0.19; P < .001). Additionally, the ambient UVR dose also showed a protective effect (aOR, 0.76; P = .01).

Study details: This was a multicenter case-control study involving children with MS (n=332) compared with age- and gender-matched controls (n=534).

Disclosures: This study was funded by the NIH and the National MS Society. Some of the authors declared receiving grants from National MS Society and NIH and/or financial support and consulting/personal fees from various other sources.

Source: Sebastian P et al. Neurology. 2021 Dec 8. doi: 10.1212/WNL.0000000000013045.

Key clinical point: Spending more time outdoors in the summer and higher exposure to summer ultraviolet radiation (UVR) markedly reduces the risk of developing pediatric multiple sclerosis (MS).

Major finding: Compared with spending <30 minutes outdoors daily during the most recent summer, greater time spent outdoors was associated with a significantly decreased risk of developing MS (30-60 minutes: adjusted odds ratio [aOR], 0.48; P = .05; 1-2 hours: aOR, 0.19; P < .001). Additionally, the ambient UVR dose also showed a protective effect (aOR, 0.76; P = .01).

Study details: This was a multicenter case-control study involving children with MS (n=332) compared with age- and gender-matched controls (n=534).

Disclosures: This study was funded by the NIH and the National MS Society. Some of the authors declared receiving grants from National MS Society and NIH and/or financial support and consulting/personal fees from various other sources.

Source: Sebastian P et al. Neurology. 2021 Dec 8. doi: 10.1212/WNL.0000000000013045.

Key clinical point: Patients with multiple sclerosis (MS) are at an increased risk for cancer than the general population.

Major finding: Compared with the general population, patients with MS were at a significantly higher risk for cancer (hazard ratio [HR], 1.36; 95% CI, 1.29-1.43), particularly prostate cancer (HR, 2.08; 95% CI, 1.68-2.58), colorectal and anal cancer (HR, 1.35; 95% CI, 1.16-1.58), and trachea bronchus and lung cancer (HR, 2.36; 95% CI, 1.96-2.84).

Study details: This population-based matched-cohort study included 95,474 patients with MS matched with 95,474 individuals from the general population.

Disclosures: This study was sponsored by Merck Healthcare KGaA. Four authors including the lead author reported being employees of the Bordeaux PharmacoEpi, and the remaining authors reported being full-time employees of Merck Healthcare KGaA, Darmstadt, Germany. The lead author reported receiving speaker fees from Biogen.

Source: Bosco-Lévy P et al. Eur J Neurol. 2021 Dec 22. doi: 10.1111/ene.15226.

Key clinical point: Patients with multiple sclerosis (MS) are at an increased risk for cancer than the general population.

Major finding: Compared with the general population, patients with MS were at a significantly higher risk for cancer (hazard ratio [HR], 1.36; 95% CI, 1.29-1.43), particularly prostate cancer (HR, 2.08; 95% CI, 1.68-2.58), colorectal and anal cancer (HR, 1.35; 95% CI, 1.16-1.58), and trachea bronchus and lung cancer (HR, 2.36; 95% CI, 1.96-2.84).

Study details: This population-based matched-cohort study included 95,474 patients with MS matched with 95,474 individuals from the general population.

Disclosures: This study was sponsored by Merck Healthcare KGaA. Four authors including the lead author reported being employees of the Bordeaux PharmacoEpi, and the remaining authors reported being full-time employees of Merck Healthcare KGaA, Darmstadt, Germany. The lead author reported receiving speaker fees from Biogen.

Source: Bosco-Lévy P et al. Eur J Neurol. 2021 Dec 22. doi: 10.1111/ene.15226.

Key clinical point: Patients with multiple sclerosis (MS) are at an increased risk for cancer than the general population.

Major finding: Compared with the general population, patients with MS were at a significantly higher risk for cancer (hazard ratio [HR], 1.36; 95% CI, 1.29-1.43), particularly prostate cancer (HR, 2.08; 95% CI, 1.68-2.58), colorectal and anal cancer (HR, 1.35; 95% CI, 1.16-1.58), and trachea bronchus and lung cancer (HR, 2.36; 95% CI, 1.96-2.84).

Study details: This population-based matched-cohort study included 95,474 patients with MS matched with 95,474 individuals from the general population.

Disclosures: This study was sponsored by Merck Healthcare KGaA. Four authors including the lead author reported being employees of the Bordeaux PharmacoEpi, and the remaining authors reported being full-time employees of Merck Healthcare KGaA, Darmstadt, Germany. The lead author reported receiving speaker fees from Biogen.

Source: Bosco-Lévy P et al. Eur J Neurol. 2021 Dec 22. doi: 10.1111/ene.15226.

Key clinical point: Cognitive impairments may be evaluated up to 30 days before and up to 550 days after a relapse, beyond which they revert to prerelapse levels in patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: From 30 days prerelapse to 550 days postrelapse, there was a significant drop in the Symbol Digit Modalities Test (SDMT) score, with the largest decline occurring at 0-30 days postrelapse (β-coefficient, −4.00; 95% CI, −4.61 to −3.39) compared with the period of remission.

Study details: This nationwide cohort study recorded 31,529 SDMTs from among 3,877 patients with incident RRMS, each having a minimum of 2 SDMT scores recorded.

Disclosures: This study was funded by a postdoctoral fellowship award to KA McKay from the Swedish Research Council for Health, Working Life, and Welfare (Forte). The authors reported no conflict of interests.

Source: McKay KA et al. Ann Neurol. 2022 Jan 4. doi: 10.1002/ana.26301.

Key clinical point: Cognitive impairments may be evaluated up to 30 days before and up to 550 days after a relapse, beyond which they revert to prerelapse levels in patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: From 30 days prerelapse to 550 days postrelapse, there was a significant drop in the Symbol Digit Modalities Test (SDMT) score, with the largest decline occurring at 0-30 days postrelapse (β-coefficient, −4.00; 95% CI, −4.61 to −3.39) compared with the period of remission.

Study details: This nationwide cohort study recorded 31,529 SDMTs from among 3,877 patients with incident RRMS, each having a minimum of 2 SDMT scores recorded.

Disclosures: This study was funded by a postdoctoral fellowship award to KA McKay from the Swedish Research Council for Health, Working Life, and Welfare (Forte). The authors reported no conflict of interests.

Source: McKay KA et al. Ann Neurol. 2022 Jan 4. doi: 10.1002/ana.26301.

Key clinical point: Cognitive impairments may be evaluated up to 30 days before and up to 550 days after a relapse, beyond which they revert to prerelapse levels in patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: From 30 days prerelapse to 550 days postrelapse, there was a significant drop in the Symbol Digit Modalities Test (SDMT) score, with the largest decline occurring at 0-30 days postrelapse (β-coefficient, −4.00; 95% CI, −4.61 to −3.39) compared with the period of remission.

Study details: This nationwide cohort study recorded 31,529 SDMTs from among 3,877 patients with incident RRMS, each having a minimum of 2 SDMT scores recorded.

Disclosures: This study was funded by a postdoctoral fellowship award to KA McKay from the Swedish Research Council for Health, Working Life, and Welfare (Forte). The authors reported no conflict of interests.

Source: McKay KA et al. Ann Neurol. 2022 Jan 4. doi: 10.1002/ana.26301.

Key clinical point: Treatment with interferon (IFN)-beta 1A improved the SARS-CoV-2-mRNA vaccine-specific humoral response in patients with multiple sclerosis (MS), which was significantly reduced in patients treated with cladribine, fingolimod, or ocrelizumab.

Major finding: Antispike immunoglobulin (Ig)G levels were significantly higher in IFN-treated patients with MS vs healthy controls (median, 1,916 vs 1,089; P = .029); however, antispike IgG levels were significantly lower in patients treated with cladribine (P = .002), fingolimod (P < .0001), or ocrelizumab (P < .0001).

Study details: This was a prospective monocentric study involving 149 patients with MS treated with disease-modifying therapies who were age- and gender-matched to 26 healthy controls, all of whom had no history of SARS-CoV-2 infection and received 2 doses of BNT162b2-mRNA COVID-19 vaccine.

Disclosures: This study was supported by Fondazione Italiana Sclerosi Multipla and others. The authors declared no conflict of interests.

Source: Maniscalco GT et al. Mult Scler Relat Disord. 2021 Dec 18. doi: 10.1016/j.msard.2021.103455.

Key clinical point: Treatment with interferon (IFN)-beta 1A improved the SARS-CoV-2-mRNA vaccine-specific humoral response in patients with multiple sclerosis (MS), which was significantly reduced in patients treated with cladribine, fingolimod, or ocrelizumab.

Major finding: Antispike immunoglobulin (Ig)G levels were significantly higher in IFN-treated patients with MS vs healthy controls (median, 1,916 vs 1,089; P = .029); however, antispike IgG levels were significantly lower in patients treated with cladribine (P = .002), fingolimod (P < .0001), or ocrelizumab (P < .0001).

Study details: This was a prospective monocentric study involving 149 patients with MS treated with disease-modifying therapies who were age- and gender-matched to 26 healthy controls, all of whom had no history of SARS-CoV-2 infection and received 2 doses of BNT162b2-mRNA COVID-19 vaccine.

Disclosures: This study was supported by Fondazione Italiana Sclerosi Multipla and others. The authors declared no conflict of interests.

Source: Maniscalco GT et al. Mult Scler Relat Disord. 2021 Dec 18. doi: 10.1016/j.msard.2021.103455.

Key clinical point: Treatment with interferon (IFN)-beta 1A improved the SARS-CoV-2-mRNA vaccine-specific humoral response in patients with multiple sclerosis (MS), which was significantly reduced in patients treated with cladribine, fingolimod, or ocrelizumab.

Major finding: Antispike immunoglobulin (Ig)G levels were significantly higher in IFN-treated patients with MS vs healthy controls (median, 1,916 vs 1,089; P = .029); however, antispike IgG levels were significantly lower in patients treated with cladribine (P = .002), fingolimod (P < .0001), or ocrelizumab (P < .0001).

Study details: This was a prospective monocentric study involving 149 patients with MS treated with disease-modifying therapies who were age- and gender-matched to 26 healthy controls, all of whom had no history of SARS-CoV-2 infection and received 2 doses of BNT162b2-mRNA COVID-19 vaccine.

Disclosures: This study was supported by Fondazione Italiana Sclerosi Multipla and others. The authors declared no conflict of interests.

Source: Maniscalco GT et al. Mult Scler Relat Disord. 2021 Dec 18. doi: 10.1016/j.msard.2021.103455.

Key clinical point: Discontinuation of natalizumab seemed safe in patients with multiple sclerosis (MS), who converted to secondary MS during treatment, with a high annual relapse rate (ARR) before natalizumab treatment being a risk factor for early relapse posttreatment discontinuation.

Major finding: After natalizumab discontinuation, conversion to secondary MS during treatment was protective for disease reactivation (odds ratio [OR], 0.08; P = .03), whereas ARR before treatment was the only risk factor for early relapse (OR, 1.46; P = .014).

Study details: This was a retrospective analysis of 235 patients with MS who were treated with natalizumab, of whom 105 discontinued the treatment.

Disclosures: No information on funding was provided. E Fava reported no conflict of interests, and the other authors reported receiving fees for acting as an advisor/speaker/consultant or receiving grants for travel/research from various sources.

Source: Auer M et al. Sci Rep. 2021 Dec 2. doi: 10.1038/s41598-021-02665-6.

Key clinical point: Discontinuation of natalizumab seemed safe in patients with multiple sclerosis (MS), who converted to secondary MS during treatment, with a high annual relapse rate (ARR) before natalizumab treatment being a risk factor for early relapse posttreatment discontinuation.

Major finding: After natalizumab discontinuation, conversion to secondary MS during treatment was protective for disease reactivation (odds ratio [OR], 0.08; P = .03), whereas ARR before treatment was the only risk factor for early relapse (OR, 1.46; P = .014).

Study details: This was a retrospective analysis of 235 patients with MS who were treated with natalizumab, of whom 105 discontinued the treatment.

Disclosures: No information on funding was provided. E Fava reported no conflict of interests, and the other authors reported receiving fees for acting as an advisor/speaker/consultant or receiving grants for travel/research from various sources.

Source: Auer M et al. Sci Rep. 2021 Dec 2. doi: 10.1038/s41598-021-02665-6.

Key clinical point: Discontinuation of natalizumab seemed safe in patients with multiple sclerosis (MS), who converted to secondary MS during treatment, with a high annual relapse rate (ARR) before natalizumab treatment being a risk factor for early relapse posttreatment discontinuation.

Major finding: After natalizumab discontinuation, conversion to secondary MS during treatment was protective for disease reactivation (odds ratio [OR], 0.08; P = .03), whereas ARR before treatment was the only risk factor for early relapse (OR, 1.46; P = .014).

Study details: This was a retrospective analysis of 235 patients with MS who were treated with natalizumab, of whom 105 discontinued the treatment.

Disclosures: No information on funding was provided. E Fava reported no conflict of interests, and the other authors reported receiving fees for acting as an advisor/speaker/consultant or receiving grants for travel/research from various sources.

Source: Auer M et al. Sci Rep. 2021 Dec 2. doi: 10.1038/s41598-021-02665-6.

Key clinical point: COVID-19 vaccines are safe and elicit a protective humoral response in most patients with multiple sclerosis (MS) who were treated with disease-modifying treatments (DMTs) or remained untreated, except for some patients treated with fingolimod or ocrelizumab.

Major finding: Overall, 86.8% of patients developed a positive humoral response against SARS-CoV-2, with only some patients treated with fingolimod (22.2%) or ocrelizumab (66%) failing to produce a significant humoral response (P < .01). Moreover, immunoglobulin G levels against SARS-CoV2 were significantly lower in patients treated with fingolimod or ocrelizumab than those treated with other DMTs or those who remained untreated (P < .01). None of the patients experienced any adverse events requiring hospitalization.

Study details: This was a prospective cohort study involving 140 patients with MS who were treated with different DMTs and had received vaccination for COVID-19 (mostly BNT162b2).

Disclosures: No source of funding was declared.

Source: Capone F et al. Neurotherapeutics. 2021 Dec 3. doi: 10.1007/s13311-021-01165-9.

Key clinical point: COVID-19 vaccines are safe and elicit a protective humoral response in most patients with multiple sclerosis (MS) who were treated with disease-modifying treatments (DMTs) or remained untreated, except for some patients treated with fingolimod or ocrelizumab.

Major finding: Overall, 86.8% of patients developed a positive humoral response against SARS-CoV-2, with only some patients treated with fingolimod (22.2%) or ocrelizumab (66%) failing to produce a significant humoral response (P < .01). Moreover, immunoglobulin G levels against SARS-CoV2 were significantly lower in patients treated with fingolimod or ocrelizumab than those treated with other DMTs or those who remained untreated (P < .01). None of the patients experienced any adverse events requiring hospitalization.

Study details: This was a prospective cohort study involving 140 patients with MS who were treated with different DMTs and had received vaccination for COVID-19 (mostly BNT162b2).

Disclosures: No source of funding was declared.

Source: Capone F et al. Neurotherapeutics. 2021 Dec 3. doi: 10.1007/s13311-021-01165-9.

Key clinical point: COVID-19 vaccines are safe and elicit a protective humoral response in most patients with multiple sclerosis (MS) who were treated with disease-modifying treatments (DMTs) or remained untreated, except for some patients treated with fingolimod or ocrelizumab.

Major finding: Overall, 86.8% of patients developed a positive humoral response against SARS-CoV-2, with only some patients treated with fingolimod (22.2%) or ocrelizumab (66%) failing to produce a significant humoral response (P < .01). Moreover, immunoglobulin G levels against SARS-CoV2 were significantly lower in patients treated with fingolimod or ocrelizumab than those treated with other DMTs or those who remained untreated (P < .01). None of the patients experienced any adverse events requiring hospitalization.

Study details: This was a prospective cohort study involving 140 patients with MS who were treated with different DMTs and had received vaccination for COVID-19 (mostly BNT162b2).

Disclosures: No source of funding was declared.

Source: Capone F et al. Neurotherapeutics. 2021 Dec 3. doi: 10.1007/s13311-021-01165-9.

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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