Multiple Sclerosis

Patients with multiple sclerosis (MS) should follow local vaccine standards and receive the yearly influenza vaccine, unless there are specific contraindications, such as active treatment with immunosuppressive or immunomodulating agents, according to an American Academy of Neurology practice guideline.

itsmejust/Thinkstock

A summary of the guideline on vaccine-preventable infections and immunization in MS was published online Aug. 28 in Neurology. The new effort updates a 2002 guideline on this topic and incorporates new evidence, vaccines, and disease-modifying therapies (DMTs). The guideline was endorsed by the Consortium of Multiple Sclerosis Centers and by the Multiple Sclerosis Association of America.

To create the guideline, lead author Mauricio F. Farez, MD, of the Raúl Carrea Institute for Neurological Research (FLENI) in Buenos Aires and colleagues on the 17-member guideline panel performed a systematic review of the evidence and reached consensus on recommendations using a modified Delphi voting process. The review included randomized, controlled trials; cohort studies; and case-control studies published between 1990 and March 2018.

“Immunosuppressive or immunomodulating agents used to treat MS may suppress or modulate normal immune function. These drugs may increase susceptibility to infections and may reduce vaccine effectiveness because of a decreased ability to mount an immune response,” the authors said.

Based on its review of the evidence, principles of care, and inferences, the authors made the following eight recommendations:

• Clinicians should discuss with patients the evidence regarding immunization in MS (Level B). In addition, clinicians should examine patients’ opinions, preferences, and questions regarding immunizations (Level B).
• Clinicians should recommend that patients with MS follow all local vaccine standards in the absence of specific contraindications (Level B).
• Clinicians should consider local risks of vaccine-preventable diseases when counseling patients (Level B).
• Clinicians should recommend that patients with MS receive the influenza vaccination if there is no specific contraindication, such as a previous severe reaction (Level B).
• When treatment with an immunosuppressive or immunomodulating agent is considered, clinicians should counsel patients about infection risks associated with the specific medication and the treatment-specific vaccination guidance in the medication’s prescribing instructions (Level B). In addition, physicians should assess patients’ vaccination status before prescribing immunosuppressive or immunomodulating therapy and vaccinate patients according to local regulatory standards and treatment-specific infectious risks at least 4-6 weeks before initiating therapy, as advised by the prescribing information (Level B). Furthermore, clinicians may discuss the advantages of vaccination soon after MS diagnosis, regardless of initial therapeutic plans, to prevent delays should immunosuppressive or immunomodulating therapies be initiated in the future (Level C, based on variation in patient preferences).
• Clinicians must screen for certain infections (such as hepatitis, tuberculosis, and varicella zoster virus) according to a medication’s prescribing information before starting immunosuppressive or immunomodulating treatment (Level A) and should treat patients who have latent infections before MS treatment according to the medication prescribing information (Level B, based on feasibility and cost relative to benefit). Further, in high-risk populations or in countries with a high burden of infectious disease, clinicians must screen for latent infections before starting immunosuppressive or immunomodulating medications, even when such screening is not specifically mentioned in the prescribing information (Level A). Clinicians should consult infectious disease or other specialists about treating patients with latent infection before starting immunosuppressive or immunomodulating medications (Level B).
• Clinicians should recommend against live-attenuated vaccines in people with MS who receive immunosuppressive or immunomodulating therapies or have recently discontinued these therapies (Level B, based on importance of outcomes). When the risk of infection is high, clinicians may recommend live-attenuated vaccines if killed vaccines are unavailable (Level C, based on variation in patient preferences, benefit relative to harm, and importance of outcomes).
• If a patient with MS is experiencing a relapse, clinicians should delay vaccination until the relapse has clinically resolved or is no longer active, often many weeks after relapse onset (Level B).

Personal and population-level benefits

“There is no evidence that vaccination increases the risk of MS exacerbation, although the literature is sparse,” the authors said. “In addition to conferring personal benefits, vaccination of the MS patient population contributes to the well-established phenomenon of herd immunity for the communities in which patients with MS live,” the authors wrote.

Because influenza infection has known risks of exacerbation and morbidity, whereas influenza vaccine has no identified risks of exacerbation, “benefits of influenza vaccination outweigh the risks in most scenarios, although patients with MS receiving some [immunosuppressive or immunomodulating] treatments (fingolimod [Gilenya], glatiramer acetate [Copaxone], and mitoxantrone) may have a reduced response to influenza vaccination,” the authors said. Studies in patients with diseases other than MS suggest that rituximab (Rituxan) also may be associated with reduced influenza vaccine responsiveness.

Immunosuppressive or immunomodulatory medications including alemtuzumab (Lemtrada), dimethyl fumarate (Tecfidera), fingolimod, mitoxantrone, natalizumab (Tysabri), ocrelizumab (Ocrevus), rituximab, and teriflunomide (Aubagio) have been associated with severe occurrences or recurrences of vaccine-preventable infections, and many package inserts approved by the Food and Drug Administration provide guidance regarding immunization with live vaccines and treatment.

Prescribing information for alemtuzumab, fingolimod, ocrelizumab, and teriflunomide recommends against the use of live vaccines during and immediately preceding treatment. Furthermore, the prescribing information recommends waiting 2-6 months after treatment to immunize with live vaccines, depending on the half-life of the specific therapy.

“The guideline panel identified no evidence that vaccines increase the risk of relapse or worsen relapse severity, but studies are limited,” Dr. Farez and colleagues wrote. “Experts remain concerned that vaccines may worsen relapse severity if given to patients who are actively experiencing an MS relapse.” In addition, use of glucocorticoids may raise concerns about the safety of live-virus vaccines. “Immunization is not typically an urgent need and, in most cases, can be temporarily delayed without a marked increase in infection risk,” the guideline says.
 

Few high-quality studies

Data were lacking or insufficient to assess whether most vaccine-preventable diseases increase the risk of MS exacerbations. “It is probable that individuals with active MS exacerbations have higher odds of varicella zoster virus viral DNA present in peripheral blood mononuclear cells than individuals with MS in remission,” the guideline says.

Human papillomavirus, pertussis, and tetanus toxoid vaccinations probably are associated with a lower likelihood of a subsequent MS diagnosis, and smallpox vaccination is possibly associated with a lower likelihood of a subsequent MS diagnosis, the review found.

Studies included in the systematic review did not address whether live-attenuated vaccines are as effective in patients with MS as they are in the general population. With regard to the effectiveness of inactivated vaccines, patients with MS possibly are less likely to have a sufficient response to influenza vaccination, compared with controls.

The systematic review “found few high-quality studies to inform recommendations,” the authors said. “As more [immunosuppressive or immunomodulating] agents are developed to manage chronic diseases such as MS, long-term prospective cohort studies are required to evaluate both the safety and effectiveness of immunizations in MS.”

Dr. Farez has received funding for travel from Teva Argentina, Novartis Argentina, and Merck Serono Argentina and has received research support from Biogen. Coauthors’ disclosures included financial ties to pharmaceutical companies.

[email protected]

SOURCE: Farez M et al. Neurology. 2019 Aug 28. doi: 10.1212/WNL.0000000000008157.

Patients with multiple sclerosis (MS) should follow local vaccine standards and receive the yearly influenza vaccine, unless there are specific contraindications, such as active treatment with immunosuppressive or immunomodulating agents, according to an American Academy of Neurology practice guideline.

itsmejust/Thinkstock

A summary of the guideline on vaccine-preventable infections and immunization in MS was published online Aug. 28 in Neurology. The new effort updates a 2002 guideline on this topic and incorporates new evidence, vaccines, and disease-modifying therapies (DMTs). The guideline was endorsed by the Consortium of Multiple Sclerosis Centers and by the Multiple Sclerosis Association of America.

To create the guideline, lead author Mauricio F. Farez, MD, of the Raúl Carrea Institute for Neurological Research (FLENI) in Buenos Aires and colleagues on the 17-member guideline panel performed a systematic review of the evidence and reached consensus on recommendations using a modified Delphi voting process. The review included randomized, controlled trials; cohort studies; and case-control studies published between 1990 and March 2018.

“Immunosuppressive or immunomodulating agents used to treat MS may suppress or modulate normal immune function. These drugs may increase susceptibility to infections and may reduce vaccine effectiveness because of a decreased ability to mount an immune response,” the authors said.

Based on its review of the evidence, principles of care, and inferences, the authors made the following eight recommendations:

• Clinicians should discuss with patients the evidence regarding immunization in MS (Level B). In addition, clinicians should examine patients’ opinions, preferences, and questions regarding immunizations (Level B).
• Clinicians should recommend that patients with MS follow all local vaccine standards in the absence of specific contraindications (Level B).
• Clinicians should consider local risks of vaccine-preventable diseases when counseling patients (Level B).
• Clinicians should recommend that patients with MS receive the influenza vaccination if there is no specific contraindication, such as a previous severe reaction (Level B).
• When treatment with an immunosuppressive or immunomodulating agent is considered, clinicians should counsel patients about infection risks associated with the specific medication and the treatment-specific vaccination guidance in the medication’s prescribing instructions (Level B). In addition, physicians should assess patients’ vaccination status before prescribing immunosuppressive or immunomodulating therapy and vaccinate patients according to local regulatory standards and treatment-specific infectious risks at least 4-6 weeks before initiating therapy, as advised by the prescribing information (Level B). Furthermore, clinicians may discuss the advantages of vaccination soon after MS diagnosis, regardless of initial therapeutic plans, to prevent delays should immunosuppressive or immunomodulating therapies be initiated in the future (Level C, based on variation in patient preferences).
• Clinicians must screen for certain infections (such as hepatitis, tuberculosis, and varicella zoster virus) according to a medication’s prescribing information before starting immunosuppressive or immunomodulating treatment (Level A) and should treat patients who have latent infections before MS treatment according to the medication prescribing information (Level B, based on feasibility and cost relative to benefit). Further, in high-risk populations or in countries with a high burden of infectious disease, clinicians must screen for latent infections before starting immunosuppressive or immunomodulating medications, even when such screening is not specifically mentioned in the prescribing information (Level A). Clinicians should consult infectious disease or other specialists about treating patients with latent infection before starting immunosuppressive or immunomodulating medications (Level B).
• Clinicians should recommend against live-attenuated vaccines in people with MS who receive immunosuppressive or immunomodulating therapies or have recently discontinued these therapies (Level B, based on importance of outcomes). When the risk of infection is high, clinicians may recommend live-attenuated vaccines if killed vaccines are unavailable (Level C, based on variation in patient preferences, benefit relative to harm, and importance of outcomes).
• If a patient with MS is experiencing a relapse, clinicians should delay vaccination until the relapse has clinically resolved or is no longer active, often many weeks after relapse onset (Level B).

Personal and population-level benefits

“There is no evidence that vaccination increases the risk of MS exacerbation, although the literature is sparse,” the authors said. “In addition to conferring personal benefits, vaccination of the MS patient population contributes to the well-established phenomenon of herd immunity for the communities in which patients with MS live,” the authors wrote.

Because influenza infection has known risks of exacerbation and morbidity, whereas influenza vaccine has no identified risks of exacerbation, “benefits of influenza vaccination outweigh the risks in most scenarios, although patients with MS receiving some [immunosuppressive or immunomodulating] treatments (fingolimod [Gilenya], glatiramer acetate [Copaxone], and mitoxantrone) may have a reduced response to influenza vaccination,” the authors said. Studies in patients with diseases other than MS suggest that rituximab (Rituxan) also may be associated with reduced influenza vaccine responsiveness.

Immunosuppressive or immunomodulatory medications including alemtuzumab (Lemtrada), dimethyl fumarate (Tecfidera), fingolimod, mitoxantrone, natalizumab (Tysabri), ocrelizumab (Ocrevus), rituximab, and teriflunomide (Aubagio) have been associated with severe occurrences or recurrences of vaccine-preventable infections, and many package inserts approved by the Food and Drug Administration provide guidance regarding immunization with live vaccines and treatment.

Prescribing information for alemtuzumab, fingolimod, ocrelizumab, and teriflunomide recommends against the use of live vaccines during and immediately preceding treatment. Furthermore, the prescribing information recommends waiting 2-6 months after treatment to immunize with live vaccines, depending on the half-life of the specific therapy.

“The guideline panel identified no evidence that vaccines increase the risk of relapse or worsen relapse severity, but studies are limited,” Dr. Farez and colleagues wrote. “Experts remain concerned that vaccines may worsen relapse severity if given to patients who are actively experiencing an MS relapse.” In addition, use of glucocorticoids may raise concerns about the safety of live-virus vaccines. “Immunization is not typically an urgent need and, in most cases, can be temporarily delayed without a marked increase in infection risk,” the guideline says.
 

Few high-quality studies

Data were lacking or insufficient to assess whether most vaccine-preventable diseases increase the risk of MS exacerbations. “It is probable that individuals with active MS exacerbations have higher odds of varicella zoster virus viral DNA present in peripheral blood mononuclear cells than individuals with MS in remission,” the guideline says.

Human papillomavirus, pertussis, and tetanus toxoid vaccinations probably are associated with a lower likelihood of a subsequent MS diagnosis, and smallpox vaccination is possibly associated with a lower likelihood of a subsequent MS diagnosis, the review found.

Studies included in the systematic review did not address whether live-attenuated vaccines are as effective in patients with MS as they are in the general population. With regard to the effectiveness of inactivated vaccines, patients with MS possibly are less likely to have a sufficient response to influenza vaccination, compared with controls.

The systematic review “found few high-quality studies to inform recommendations,” the authors said. “As more [immunosuppressive or immunomodulating] agents are developed to manage chronic diseases such as MS, long-term prospective cohort studies are required to evaluate both the safety and effectiveness of immunizations in MS.”

Dr. Farez has received funding for travel from Teva Argentina, Novartis Argentina, and Merck Serono Argentina and has received research support from Biogen. Coauthors’ disclosures included financial ties to pharmaceutical companies.

[email protected]

SOURCE: Farez M et al. Neurology. 2019 Aug 28. doi: 10.1212/WNL.0000000000008157.

Patients with multiple sclerosis (MS) should follow local vaccine standards and receive the yearly influenza vaccine, unless there are specific contraindications, such as active treatment with immunosuppressive or immunomodulating agents, according to an American Academy of Neurology practice guideline.

itsmejust/Thinkstock

A summary of the guideline on vaccine-preventable infections and immunization in MS was published online Aug. 28 in Neurology. The new effort updates a 2002 guideline on this topic and incorporates new evidence, vaccines, and disease-modifying therapies (DMTs). The guideline was endorsed by the Consortium of Multiple Sclerosis Centers and by the Multiple Sclerosis Association of America.

To create the guideline, lead author Mauricio F. Farez, MD, of the Raúl Carrea Institute for Neurological Research (FLENI) in Buenos Aires and colleagues on the 17-member guideline panel performed a systematic review of the evidence and reached consensus on recommendations using a modified Delphi voting process. The review included randomized, controlled trials; cohort studies; and case-control studies published between 1990 and March 2018.

“Immunosuppressive or immunomodulating agents used to treat MS may suppress or modulate normal immune function. These drugs may increase susceptibility to infections and may reduce vaccine effectiveness because of a decreased ability to mount an immune response,” the authors said.

Based on its review of the evidence, principles of care, and inferences, the authors made the following eight recommendations:

• Clinicians should discuss with patients the evidence regarding immunization in MS (Level B). In addition, clinicians should examine patients’ opinions, preferences, and questions regarding immunizations (Level B).
• Clinicians should recommend that patients with MS follow all local vaccine standards in the absence of specific contraindications (Level B).
• Clinicians should consider local risks of vaccine-preventable diseases when counseling patients (Level B).
• Clinicians should recommend that patients with MS receive the influenza vaccination if there is no specific contraindication, such as a previous severe reaction (Level B).
• When treatment with an immunosuppressive or immunomodulating agent is considered, clinicians should counsel patients about infection risks associated with the specific medication and the treatment-specific vaccination guidance in the medication’s prescribing instructions (Level B). In addition, physicians should assess patients’ vaccination status before prescribing immunosuppressive or immunomodulating therapy and vaccinate patients according to local regulatory standards and treatment-specific infectious risks at least 4-6 weeks before initiating therapy, as advised by the prescribing information (Level B). Furthermore, clinicians may discuss the advantages of vaccination soon after MS diagnosis, regardless of initial therapeutic plans, to prevent delays should immunosuppressive or immunomodulating therapies be initiated in the future (Level C, based on variation in patient preferences).
• Clinicians must screen for certain infections (such as hepatitis, tuberculosis, and varicella zoster virus) according to a medication’s prescribing information before starting immunosuppressive or immunomodulating treatment (Level A) and should treat patients who have latent infections before MS treatment according to the medication prescribing information (Level B, based on feasibility and cost relative to benefit). Further, in high-risk populations or in countries with a high burden of infectious disease, clinicians must screen for latent infections before starting immunosuppressive or immunomodulating medications, even when such screening is not specifically mentioned in the prescribing information (Level A). Clinicians should consult infectious disease or other specialists about treating patients with latent infection before starting immunosuppressive or immunomodulating medications (Level B).
• Clinicians should recommend against live-attenuated vaccines in people with MS who receive immunosuppressive or immunomodulating therapies or have recently discontinued these therapies (Level B, based on importance of outcomes). When the risk of infection is high, clinicians may recommend live-attenuated vaccines if killed vaccines are unavailable (Level C, based on variation in patient preferences, benefit relative to harm, and importance of outcomes).
• If a patient with MS is experiencing a relapse, clinicians should delay vaccination until the relapse has clinically resolved or is no longer active, often many weeks after relapse onset (Level B).

Personal and population-level benefits

“There is no evidence that vaccination increases the risk of MS exacerbation, although the literature is sparse,” the authors said. “In addition to conferring personal benefits, vaccination of the MS patient population contributes to the well-established phenomenon of herd immunity for the communities in which patients with MS live,” the authors wrote.

Because influenza infection has known risks of exacerbation and morbidity, whereas influenza vaccine has no identified risks of exacerbation, “benefits of influenza vaccination outweigh the risks in most scenarios, although patients with MS receiving some [immunosuppressive or immunomodulating] treatments (fingolimod [Gilenya], glatiramer acetate [Copaxone], and mitoxantrone) may have a reduced response to influenza vaccination,” the authors said. Studies in patients with diseases other than MS suggest that rituximab (Rituxan) also may be associated with reduced influenza vaccine responsiveness.

Immunosuppressive or immunomodulatory medications including alemtuzumab (Lemtrada), dimethyl fumarate (Tecfidera), fingolimod, mitoxantrone, natalizumab (Tysabri), ocrelizumab (Ocrevus), rituximab, and teriflunomide (Aubagio) have been associated with severe occurrences or recurrences of vaccine-preventable infections, and many package inserts approved by the Food and Drug Administration provide guidance regarding immunization with live vaccines and treatment.

Prescribing information for alemtuzumab, fingolimod, ocrelizumab, and teriflunomide recommends against the use of live vaccines during and immediately preceding treatment. Furthermore, the prescribing information recommends waiting 2-6 months after treatment to immunize with live vaccines, depending on the half-life of the specific therapy.

“The guideline panel identified no evidence that vaccines increase the risk of relapse or worsen relapse severity, but studies are limited,” Dr. Farez and colleagues wrote. “Experts remain concerned that vaccines may worsen relapse severity if given to patients who are actively experiencing an MS relapse.” In addition, use of glucocorticoids may raise concerns about the safety of live-virus vaccines. “Immunization is not typically an urgent need and, in most cases, can be temporarily delayed without a marked increase in infection risk,” the guideline says.
 

Few high-quality studies

Data were lacking or insufficient to assess whether most vaccine-preventable diseases increase the risk of MS exacerbations. “It is probable that individuals with active MS exacerbations have higher odds of varicella zoster virus viral DNA present in peripheral blood mononuclear cells than individuals with MS in remission,” the guideline says.

Human papillomavirus, pertussis, and tetanus toxoid vaccinations probably are associated with a lower likelihood of a subsequent MS diagnosis, and smallpox vaccination is possibly associated with a lower likelihood of a subsequent MS diagnosis, the review found.

Studies included in the systematic review did not address whether live-attenuated vaccines are as effective in patients with MS as they are in the general population. With regard to the effectiveness of inactivated vaccines, patients with MS possibly are less likely to have a sufficient response to influenza vaccination, compared with controls.

The systematic review “found few high-quality studies to inform recommendations,” the authors said. “As more [immunosuppressive or immunomodulating] agents are developed to manage chronic diseases such as MS, long-term prospective cohort studies are required to evaluate both the safety and effectiveness of immunizations in MS.”

Dr. Farez has received funding for travel from Teva Argentina, Novartis Argentina, and Merck Serono Argentina and has received research support from Biogen. Coauthors’ disclosures included financial ties to pharmaceutical companies.

[email protected]

SOURCE: Farez M et al. Neurology. 2019 Aug 28. doi: 10.1212/WNL.0000000000008157.

Key clinical point: Clinical and imaging outcomes improve among patients with MS who switch from interferon beta-1a to alemtuzumab.

Major finding: The rate of freedom from relapse ranged from 83% to 90%, and disability scores were stable for 51% of patients.

Study details: An examination of data for 117 patients with MS who participated in extensions of the CARE-MS II trial.

Disclosures: Sanofi and Bayer HealthCare Pharmaceuticals supported this study. Dr. Ionete received research support from Biogen, Roche, and Sanofi. She reported receiving compensation for advisory board participation from Sanofi.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Clinical and imaging outcomes improve among patients with MS who switch from interferon beta-1a to alemtuzumab.

Major finding: The rate of freedom from relapse ranged from 83% to 90%, and disability scores were stable for 51% of patients.

Study details: An examination of data for 117 patients with MS who participated in extensions of the CARE-MS II trial.

Disclosures: Sanofi and Bayer HealthCare Pharmaceuticals supported this study. Dr. Ionete received research support from Biogen, Roche, and Sanofi. She reported receiving compensation for advisory board participation from Sanofi.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Clinical and imaging outcomes improve among patients with MS who switch from interferon beta-1a to alemtuzumab.

Major finding: The rate of freedom from relapse ranged from 83% to 90%, and disability scores were stable for 51% of patients.

Study details: An examination of data for 117 patients with MS who participated in extensions of the CARE-MS II trial.

Disclosures: Sanofi and Bayer HealthCare Pharmaceuticals supported this study. Dr. Ionete received research support from Biogen, Roche, and Sanofi. She reported receiving compensation for advisory board participation from Sanofi.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Patients with multiple sclerosis who consider marijuana use are more likely to smoke and drink alcohol.

Major finding: Among multiple sclerosis patients who responded to a survey, 25.4% had used marijuana for their multiple sclerosis, 20.0% had discussed it with their doctors, and 16.1% were currently using some form of marijuana.

Study details: Questionnaire responses about health behaviors from 5,481 active participants in the North American Research Committee on Multiple Sclerosis.

Disclosures: The North American Research Committee on Multiple Sclerosis is funded in part by the Consortium of Multiple Sclerosis Centers and the Foundation of the CMSC. The present study had no funding support. Dr. Cofield reported receiving a consulting fee from the U.S. Department of Defense.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Patients with multiple sclerosis who consider marijuana use are more likely to smoke and drink alcohol.

Major finding: Among multiple sclerosis patients who responded to a survey, 25.4% had used marijuana for their multiple sclerosis, 20.0% had discussed it with their doctors, and 16.1% were currently using some form of marijuana.

Study details: Questionnaire responses about health behaviors from 5,481 active participants in the North American Research Committee on Multiple Sclerosis.

Disclosures: The North American Research Committee on Multiple Sclerosis is funded in part by the Consortium of Multiple Sclerosis Centers and the Foundation of the CMSC. The present study had no funding support. Dr. Cofield reported receiving a consulting fee from the U.S. Department of Defense.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Patients with multiple sclerosis who consider marijuana use are more likely to smoke and drink alcohol.

Major finding: Among multiple sclerosis patients who responded to a survey, 25.4% had used marijuana for their multiple sclerosis, 20.0% had discussed it with their doctors, and 16.1% were currently using some form of marijuana.

Study details: Questionnaire responses about health behaviors from 5,481 active participants in the North American Research Committee on Multiple Sclerosis.

Disclosures: The North American Research Committee on Multiple Sclerosis is funded in part by the Consortium of Multiple Sclerosis Centers and the Foundation of the CMSC. The present study had no funding support. Dr. Cofield reported receiving a consulting fee from the U.S. Department of Defense.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Patients with pediatric-onset multiple sclerosis (MS) are more likely than those with adult-onset MS to have cognitive impairment in adulthood.

Major finding: At age 35 years, the mean Symbol Digit Modalities Test score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

Study details: A Swedish population-based, longitudinal cohort study of 5,704 patients with MS, 300 of whom had pediatric-onset MS (5%).

Disclosures: The study was supported by the Swedish Research Council, the Swedish Brain Foundation, and by postdoctoral awards from the Canadian Institutes of Health Research and European Committee for Treatment and Research in Multiple Sclerosis, both to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

Citation: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.

Key clinical point: Patients with pediatric-onset multiple sclerosis (MS) are more likely than those with adult-onset MS to have cognitive impairment in adulthood.

Major finding: At age 35 years, the mean Symbol Digit Modalities Test score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

Study details: A Swedish population-based, longitudinal cohort study of 5,704 patients with MS, 300 of whom had pediatric-onset MS (5%).

Disclosures: The study was supported by the Swedish Research Council, the Swedish Brain Foundation, and by postdoctoral awards from the Canadian Institutes of Health Research and European Committee for Treatment and Research in Multiple Sclerosis, both to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

Citation: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.

Key clinical point: Patients with pediatric-onset multiple sclerosis (MS) are more likely than those with adult-onset MS to have cognitive impairment in adulthood.

Major finding: At age 35 years, the mean Symbol Digit Modalities Test score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

Study details: A Swedish population-based, longitudinal cohort study of 5,704 patients with MS, 300 of whom had pediatric-onset MS (5%).

Disclosures: The study was supported by the Swedish Research Council, the Swedish Brain Foundation, and by postdoctoral awards from the Canadian Institutes of Health Research and European Committee for Treatment and Research in Multiple Sclerosis, both to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

Citation: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.

From 2006 to 2016, the prices of self-administered disease-modifying therapies for multiple sclerosis increased markedly, according to an analysis published in JAMA Neurology. The increased prices raise concern “because they demonstrate that the approval of new therapies did not ameliorate and could have even contributed to high inflation rates observed for incumbent drugs,” wrote the authors.

Four self-administered disease-modifying therapies (DMTs) for multiple sclerosis (MS) were available before 2009, and seven new branded DMTs were introduced after that year. Previous research indicated that the prices of DMTs for MS increased at higher rates than the prices of drugs for other disorders. How these price increases affected pharmaceutical spending during the past decade is uncertain, however.

A review of Medicare claims data

Alvaro San-Juan-Rodriguez, PharmD, a fellow in pharmacoeconomics, outcomes, and pharmacoanalytics research at the University of Pittsburgh, and colleagues examined claims data from 2006 to 2016 from a 5% random sample of Medicare beneficiaries. Information for a mean of 2.8 million Medicare beneficiaries per year was available. The researchers extracted all prescription claims for self-administered DMTs for MS (that is, glatiramer acetate, interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and peginterferon beta-1a).

Dr. San-Juan-Rodriguez and associates chose three main outcomes. The first was the annual cost of treatment with each medication, which was based on Medicare Part D prescription claims gross costs and Food and Drug Administration–approved recommended dosing. The second was the market share of each medication, which the researchers defined as the proportion of pharmaceutical spending accounted for by each drug. The third was pharmaceutical spending per 1,000 Medicare beneficiaries for all drugs. The investigators also examined the relative contributions of Medicare Part D Plans’ payments, patients’ out-of-pocket costs, and other payments toward pharmaceutical spending.

Prices defied market expectations

The annual costs of treatment with self-administered DMTs for MS increased more than 300%. The mean annual cost was $18,660 in 2006 and $75,847 in 2016, and the mean annual rate of price increase was 12.8%. “Prices of most self-administered DMTs for MS increased in parallel, defying standard market expectations,” the investigators wrote.

Branded formulations of glatiramer acetate maintained the largest market share throughout the study period, ranging between 32.2% and 48.4%. However, the market share of platform therapies – glatiramer acetate, interferon beta-1a, and interferon beta-1b – decreased significantly from 2006 to 2016. Market shares for brand-name glatiramers declined from 36.7% to 32.2%, for intramuscular interferon beta-1a (30 mcg) from 32.3% to 14.2%, for interferon beta-1b from 18.7% to 4.5%, and for interferon beta-1a (8.8, 22, or 44 mcg) from 12.2% to 8.3%. The market shares of newer therapies, however, increased to 7.9% for fingolimod, 9.0% for teriflunomide, and 19.2% for dimethyl fumarate.

Pharmaceutical spending per 1,000 beneficiaries increased by a factor of 10.2 throughout the study period (from $7,794 to $79,411). Patients’ out-of-pocket spending per 1,000 beneficiaries increased by a factor of 7.2 (from $372 to $2,673). Furthermore, the relative contribution of federal payments toward pharmaceutical spending increased from 68.5% to 73.8%.

“Large increases in drug prices have not been specific to MS drugs,” said Dr. San-Juan-Rodriguez in an interview. “We previously described similar trends in other specialty medications used to treat severe disease states, such as tumor necrosis factor inhibitors [TNFi] for the treatment of rheumatoid arthritis. Yet these increases took place at a slower pace. For instance, list prices of TNFi increased at an average annual rate of 9.9% in the same time period, 2006-2016.

“It is important to acknowledge that rising list prices of drugs may partially reflect competition for rebates,” he added. “Yet the specific reasons behind the faster growth of prices of MS drugs, compared with the prices of drugs used in other disease states, remain uncertain.”

Neurologists should bear in mind that, although generic drugs are substantially cheaper than branded drugs, generic specialty medications do not always reduce costs for Medicare Part D beneficiaries. “On the contrary, due to incentive misalignments created by the Medicare Part D benefit design, beneficiaries using generic drugs such as Glatopa ... may pay more than those using the branded drug,” Dr. San-Juan-Rodriguez said.

What are neurologists’ responsibilities?

Although the original annual price of interferon beta-1b ($10,920) was stunning, physicians now recall it with nostalgia, wrote Daniel M. Hartung, PharmD, associate professor of biostatistics and epidemiology, and Dennis Bourdette, MD, professor of neurology, both at Oregon Health and Science University, Portland, in an accompanying editorial. “The prices for DMTs for MS have risen dramatically over the last 15 years, far outpacing inflation, and now have a mean price of more than $86,000 per year.”

Neurologists should be concerned about these rising prices, Dr. Hartung and Dr. Bourdette wrote. They should feel responsibility toward the health care system that pays for these medications, and toward patients who pay out of their own pockets. “Neurologists should be seeking to minimize the financial adverse effects of these therapies as much as they try to minimize physical adverse effects.”

One way for neurologists to address increasing prices is to urge state and federal lawmakers to pass legislation to curb them, they wrote. Neurologists also should reexamine their relationships with pharmaceutical and biotechnology companies. “Remaining silent should not be an option. ... Neurologists should not allow the unfettered increases in price for these drugs to hurt the health care system or patients.”

The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded the research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

[email protected]

SOURCEs: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

From 2006 to 2016, the prices of self-administered disease-modifying therapies for multiple sclerosis increased markedly, according to an analysis published in JAMA Neurology. The increased prices raise concern “because they demonstrate that the approval of new therapies did not ameliorate and could have even contributed to high inflation rates observed for incumbent drugs,” wrote the authors.

Four self-administered disease-modifying therapies (DMTs) for multiple sclerosis (MS) were available before 2009, and seven new branded DMTs were introduced after that year. Previous research indicated that the prices of DMTs for MS increased at higher rates than the prices of drugs for other disorders. How these price increases affected pharmaceutical spending during the past decade is uncertain, however.

A review of Medicare claims data

Alvaro San-Juan-Rodriguez, PharmD, a fellow in pharmacoeconomics, outcomes, and pharmacoanalytics research at the University of Pittsburgh, and colleagues examined claims data from 2006 to 2016 from a 5% random sample of Medicare beneficiaries. Information for a mean of 2.8 million Medicare beneficiaries per year was available. The researchers extracted all prescription claims for self-administered DMTs for MS (that is, glatiramer acetate, interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and peginterferon beta-1a).

Dr. San-Juan-Rodriguez and associates chose three main outcomes. The first was the annual cost of treatment with each medication, which was based on Medicare Part D prescription claims gross costs and Food and Drug Administration–approved recommended dosing. The second was the market share of each medication, which the researchers defined as the proportion of pharmaceutical spending accounted for by each drug. The third was pharmaceutical spending per 1,000 Medicare beneficiaries for all drugs. The investigators also examined the relative contributions of Medicare Part D Plans’ payments, patients’ out-of-pocket costs, and other payments toward pharmaceutical spending.

Prices defied market expectations

The annual costs of treatment with self-administered DMTs for MS increased more than 300%. The mean annual cost was $18,660 in 2006 and $75,847 in 2016, and the mean annual rate of price increase was 12.8%. “Prices of most self-administered DMTs for MS increased in parallel, defying standard market expectations,” the investigators wrote.

Branded formulations of glatiramer acetate maintained the largest market share throughout the study period, ranging between 32.2% and 48.4%. However, the market share of platform therapies – glatiramer acetate, interferon beta-1a, and interferon beta-1b – decreased significantly from 2006 to 2016. Market shares for brand-name glatiramers declined from 36.7% to 32.2%, for intramuscular interferon beta-1a (30 mcg) from 32.3% to 14.2%, for interferon beta-1b from 18.7% to 4.5%, and for interferon beta-1a (8.8, 22, or 44 mcg) from 12.2% to 8.3%. The market shares of newer therapies, however, increased to 7.9% for fingolimod, 9.0% for teriflunomide, and 19.2% for dimethyl fumarate.

Pharmaceutical spending per 1,000 beneficiaries increased by a factor of 10.2 throughout the study period (from $7,794 to $79,411). Patients’ out-of-pocket spending per 1,000 beneficiaries increased by a factor of 7.2 (from $372 to $2,673). Furthermore, the relative contribution of federal payments toward pharmaceutical spending increased from 68.5% to 73.8%.

“Large increases in drug prices have not been specific to MS drugs,” said Dr. San-Juan-Rodriguez in an interview. “We previously described similar trends in other specialty medications used to treat severe disease states, such as tumor necrosis factor inhibitors [TNFi] for the treatment of rheumatoid arthritis. Yet these increases took place at a slower pace. For instance, list prices of TNFi increased at an average annual rate of 9.9% in the same time period, 2006-2016.

“It is important to acknowledge that rising list prices of drugs may partially reflect competition for rebates,” he added. “Yet the specific reasons behind the faster growth of prices of MS drugs, compared with the prices of drugs used in other disease states, remain uncertain.”

Neurologists should bear in mind that, although generic drugs are substantially cheaper than branded drugs, generic specialty medications do not always reduce costs for Medicare Part D beneficiaries. “On the contrary, due to incentive misalignments created by the Medicare Part D benefit design, beneficiaries using generic drugs such as Glatopa ... may pay more than those using the branded drug,” Dr. San-Juan-Rodriguez said.

What are neurologists’ responsibilities?

Although the original annual price of interferon beta-1b ($10,920) was stunning, physicians now recall it with nostalgia, wrote Daniel M. Hartung, PharmD, associate professor of biostatistics and epidemiology, and Dennis Bourdette, MD, professor of neurology, both at Oregon Health and Science University, Portland, in an accompanying editorial. “The prices for DMTs for MS have risen dramatically over the last 15 years, far outpacing inflation, and now have a mean price of more than $86,000 per year.”

Neurologists should be concerned about these rising prices, Dr. Hartung and Dr. Bourdette wrote. They should feel responsibility toward the health care system that pays for these medications, and toward patients who pay out of their own pockets. “Neurologists should be seeking to minimize the financial adverse effects of these therapies as much as they try to minimize physical adverse effects.”

One way for neurologists to address increasing prices is to urge state and federal lawmakers to pass legislation to curb them, they wrote. Neurologists also should reexamine their relationships with pharmaceutical and biotechnology companies. “Remaining silent should not be an option. ... Neurologists should not allow the unfettered increases in price for these drugs to hurt the health care system or patients.”

The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded the research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

[email protected]

SOURCEs: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

From 2006 to 2016, the prices of self-administered disease-modifying therapies for multiple sclerosis increased markedly, according to an analysis published in JAMA Neurology. The increased prices raise concern “because they demonstrate that the approval of new therapies did not ameliorate and could have even contributed to high inflation rates observed for incumbent drugs,” wrote the authors.

Four self-administered disease-modifying therapies (DMTs) for multiple sclerosis (MS) were available before 2009, and seven new branded DMTs were introduced after that year. Previous research indicated that the prices of DMTs for MS increased at higher rates than the prices of drugs for other disorders. How these price increases affected pharmaceutical spending during the past decade is uncertain, however.

A review of Medicare claims data

Alvaro San-Juan-Rodriguez, PharmD, a fellow in pharmacoeconomics, outcomes, and pharmacoanalytics research at the University of Pittsburgh, and colleagues examined claims data from 2006 to 2016 from a 5% random sample of Medicare beneficiaries. Information for a mean of 2.8 million Medicare beneficiaries per year was available. The researchers extracted all prescription claims for self-administered DMTs for MS (that is, glatiramer acetate, interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and peginterferon beta-1a).

Dr. San-Juan-Rodriguez and associates chose three main outcomes. The first was the annual cost of treatment with each medication, which was based on Medicare Part D prescription claims gross costs and Food and Drug Administration–approved recommended dosing. The second was the market share of each medication, which the researchers defined as the proportion of pharmaceutical spending accounted for by each drug. The third was pharmaceutical spending per 1,000 Medicare beneficiaries for all drugs. The investigators also examined the relative contributions of Medicare Part D Plans’ payments, patients’ out-of-pocket costs, and other payments toward pharmaceutical spending.

Prices defied market expectations

The annual costs of treatment with self-administered DMTs for MS increased more than 300%. The mean annual cost was $18,660 in 2006 and $75,847 in 2016, and the mean annual rate of price increase was 12.8%. “Prices of most self-administered DMTs for MS increased in parallel, defying standard market expectations,” the investigators wrote.

Branded formulations of glatiramer acetate maintained the largest market share throughout the study period, ranging between 32.2% and 48.4%. However, the market share of platform therapies – glatiramer acetate, interferon beta-1a, and interferon beta-1b – decreased significantly from 2006 to 2016. Market shares for brand-name glatiramers declined from 36.7% to 32.2%, for intramuscular interferon beta-1a (30 mcg) from 32.3% to 14.2%, for interferon beta-1b from 18.7% to 4.5%, and for interferon beta-1a (8.8, 22, or 44 mcg) from 12.2% to 8.3%. The market shares of newer therapies, however, increased to 7.9% for fingolimod, 9.0% for teriflunomide, and 19.2% for dimethyl fumarate.

Pharmaceutical spending per 1,000 beneficiaries increased by a factor of 10.2 throughout the study period (from $7,794 to $79,411). Patients’ out-of-pocket spending per 1,000 beneficiaries increased by a factor of 7.2 (from $372 to $2,673). Furthermore, the relative contribution of federal payments toward pharmaceutical spending increased from 68.5% to 73.8%.

“Large increases in drug prices have not been specific to MS drugs,” said Dr. San-Juan-Rodriguez in an interview. “We previously described similar trends in other specialty medications used to treat severe disease states, such as tumor necrosis factor inhibitors [TNFi] for the treatment of rheumatoid arthritis. Yet these increases took place at a slower pace. For instance, list prices of TNFi increased at an average annual rate of 9.9% in the same time period, 2006-2016.

“It is important to acknowledge that rising list prices of drugs may partially reflect competition for rebates,” he added. “Yet the specific reasons behind the faster growth of prices of MS drugs, compared with the prices of drugs used in other disease states, remain uncertain.”

Neurologists should bear in mind that, although generic drugs are substantially cheaper than branded drugs, generic specialty medications do not always reduce costs for Medicare Part D beneficiaries. “On the contrary, due to incentive misalignments created by the Medicare Part D benefit design, beneficiaries using generic drugs such as Glatopa ... may pay more than those using the branded drug,” Dr. San-Juan-Rodriguez said.

What are neurologists’ responsibilities?

Although the original annual price of interferon beta-1b ($10,920) was stunning, physicians now recall it with nostalgia, wrote Daniel M. Hartung, PharmD, associate professor of biostatistics and epidemiology, and Dennis Bourdette, MD, professor of neurology, both at Oregon Health and Science University, Portland, in an accompanying editorial. “The prices for DMTs for MS have risen dramatically over the last 15 years, far outpacing inflation, and now have a mean price of more than $86,000 per year.”

Neurologists should be concerned about these rising prices, Dr. Hartung and Dr. Bourdette wrote. They should feel responsibility toward the health care system that pays for these medications, and toward patients who pay out of their own pockets. “Neurologists should be seeking to minimize the financial adverse effects of these therapies as much as they try to minimize physical adverse effects.”

One way for neurologists to address increasing prices is to urge state and federal lawmakers to pass legislation to curb them, they wrote. Neurologists also should reexamine their relationships with pharmaceutical and biotechnology companies. “Remaining silent should not be an option. ... Neurologists should not allow the unfettered increases in price for these drugs to hurt the health care system or patients.”

The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded the research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

[email protected]

SOURCEs: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

In patients with multiple sclerosis (MS), serum neurofilament light chain (sNfL) levels are associated with brain atrophy, according to an investigation published online August 12 in JAMA Neurology. Furthermore, changes in sNfL levels are associated with disability worsening, and sNfL levels may be influenced by treatment. These data support the potential of sNfL as an objective surrogate of ongoing MS disease activity, according to the researchers.

Neuronal and axonal loss increase levels of NfL in cerebrospinal fluid (CSF) in patients with MS. Previous research indicated that sNfL levels are correlated with CSF levels of NfL and are associated with clinical and imaging measures of disease activity. For the purpose of repeated sampling, collecting blood from patients would be more practical than performing lumbar punctures, said the investigators. No long-term studies of sNfL concentrations and their associations with MS disease outcomes had been performed, however.

Ester Cantó, PhD, of the University of California, San Francisco (UCSF), and colleagues examined data from the prospective Expression, Proteomics, Imaging, Clinical (EPIC) study to assess sNfL as a biomarker of MS disease activity and progression. The ongoing EPIC study is being conducted at UCSF. Dr. Cantó and colleagues analyzed data collected from July 1, 2004, through August 31, 2017, for 607 patients with MS. Participants underwent clinical examinations and serum sample collections annually for 5 years, then at various time points for as long as 12 years. The median follow-up duration was 10 years. The researchers measured sNfL levels with a sensitive single-molecule array platform and compared them with clinical and MRI variables using univariable and multivariable analyses. Dr. Cantó and colleagues chose disability progression, defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score, and brain fraction atrophy as their primary outcomes.

The population’s mean age was 42.5 years. About 70% of participants were women, and all were of non-Hispanic European descent. At baseline, sNfL levels were significantly associated with EDSS score, MS subtype, and treatment status.

Dr. Cantó and colleagues found a significant interaction between EDSS worsening and change in levels of sNfL over time. Baseline sNfL levels were associated with approximately 11.6% of the variance in participants’ brain fraction atrophy at year 10. When the investigators controlled for sex, age, and disease duration, they found that baseline sNfL levels were associated with 18% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNfL. High-efficacy treatments were associated with greater decreases in sNfL levels, compared with platform therapies.

More frequent sample acquisition could provide greater detail about changes in sNfL levels, wrote Dr. Cantó and colleagues. They acknowledged that their study had insufficient power for the researchers to assess the outcomes of individual MS therapies. Other limitations included the lack of data on NfL stability and the lack of a group of healthy controls.

“For an individual patient, the biomarker prognostic power of sNfL level for clinical and MRI outcomes was limited,” said the investigators. “Further prospective studies are necessary to assess the assay’s utility for decision making in individual patients.”

The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.
 

[email protected]

SOURCE: Cantó E et al. JAMA Neurol. 2019 Aug. 12. doi: 10.1001/jamaneurol.2019.2137.

In patients with multiple sclerosis (MS), serum neurofilament light chain (sNfL) levels are associated with brain atrophy, according to an investigation published online August 12 in JAMA Neurology. Furthermore, changes in sNfL levels are associated with disability worsening, and sNfL levels may be influenced by treatment. These data support the potential of sNfL as an objective surrogate of ongoing MS disease activity, according to the researchers.

Neuronal and axonal loss increase levels of NfL in cerebrospinal fluid (CSF) in patients with MS. Previous research indicated that sNfL levels are correlated with CSF levels of NfL and are associated with clinical and imaging measures of disease activity. For the purpose of repeated sampling, collecting blood from patients would be more practical than performing lumbar punctures, said the investigators. No long-term studies of sNfL concentrations and their associations with MS disease outcomes had been performed, however.

Ester Cantó, PhD, of the University of California, San Francisco (UCSF), and colleagues examined data from the prospective Expression, Proteomics, Imaging, Clinical (EPIC) study to assess sNfL as a biomarker of MS disease activity and progression. The ongoing EPIC study is being conducted at UCSF. Dr. Cantó and colleagues analyzed data collected from July 1, 2004, through August 31, 2017, for 607 patients with MS. Participants underwent clinical examinations and serum sample collections annually for 5 years, then at various time points for as long as 12 years. The median follow-up duration was 10 years. The researchers measured sNfL levels with a sensitive single-molecule array platform and compared them with clinical and MRI variables using univariable and multivariable analyses. Dr. Cantó and colleagues chose disability progression, defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score, and brain fraction atrophy as their primary outcomes.

The population’s mean age was 42.5 years. About 70% of participants were women, and all were of non-Hispanic European descent. At baseline, sNfL levels were significantly associated with EDSS score, MS subtype, and treatment status.

Dr. Cantó and colleagues found a significant interaction between EDSS worsening and change in levels of sNfL over time. Baseline sNfL levels were associated with approximately 11.6% of the variance in participants’ brain fraction atrophy at year 10. When the investigators controlled for sex, age, and disease duration, they found that baseline sNfL levels were associated with 18% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNfL. High-efficacy treatments were associated with greater decreases in sNfL levels, compared with platform therapies.

More frequent sample acquisition could provide greater detail about changes in sNfL levels, wrote Dr. Cantó and colleagues. They acknowledged that their study had insufficient power for the researchers to assess the outcomes of individual MS therapies. Other limitations included the lack of data on NfL stability and the lack of a group of healthy controls.

“For an individual patient, the biomarker prognostic power of sNfL level for clinical and MRI outcomes was limited,” said the investigators. “Further prospective studies are necessary to assess the assay’s utility for decision making in individual patients.”

The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.
 

[email protected]

SOURCE: Cantó E et al. JAMA Neurol. 2019 Aug. 12. doi: 10.1001/jamaneurol.2019.2137.

In patients with multiple sclerosis (MS), serum neurofilament light chain (sNfL) levels are associated with brain atrophy, according to an investigation published online August 12 in JAMA Neurology. Furthermore, changes in sNfL levels are associated with disability worsening, and sNfL levels may be influenced by treatment. These data support the potential of sNfL as an objective surrogate of ongoing MS disease activity, according to the researchers.

Neuronal and axonal loss increase levels of NfL in cerebrospinal fluid (CSF) in patients with MS. Previous research indicated that sNfL levels are correlated with CSF levels of NfL and are associated with clinical and imaging measures of disease activity. For the purpose of repeated sampling, collecting blood from patients would be more practical than performing lumbar punctures, said the investigators. No long-term studies of sNfL concentrations and their associations with MS disease outcomes had been performed, however.

Ester Cantó, PhD, of the University of California, San Francisco (UCSF), and colleagues examined data from the prospective Expression, Proteomics, Imaging, Clinical (EPIC) study to assess sNfL as a biomarker of MS disease activity and progression. The ongoing EPIC study is being conducted at UCSF. Dr. Cantó and colleagues analyzed data collected from July 1, 2004, through August 31, 2017, for 607 patients with MS. Participants underwent clinical examinations and serum sample collections annually for 5 years, then at various time points for as long as 12 years. The median follow-up duration was 10 years. The researchers measured sNfL levels with a sensitive single-molecule array platform and compared them with clinical and MRI variables using univariable and multivariable analyses. Dr. Cantó and colleagues chose disability progression, defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score, and brain fraction atrophy as their primary outcomes.

The population’s mean age was 42.5 years. About 70% of participants were women, and all were of non-Hispanic European descent. At baseline, sNfL levels were significantly associated with EDSS score, MS subtype, and treatment status.

Dr. Cantó and colleagues found a significant interaction between EDSS worsening and change in levels of sNfL over time. Baseline sNfL levels were associated with approximately 11.6% of the variance in participants’ brain fraction atrophy at year 10. When the investigators controlled for sex, age, and disease duration, they found that baseline sNfL levels were associated with 18% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNfL. High-efficacy treatments were associated with greater decreases in sNfL levels, compared with platform therapies.

More frequent sample acquisition could provide greater detail about changes in sNfL levels, wrote Dr. Cantó and colleagues. They acknowledged that their study had insufficient power for the researchers to assess the outcomes of individual MS therapies. Other limitations included the lack of data on NfL stability and the lack of a group of healthy controls.

“For an individual patient, the biomarker prognostic power of sNfL level for clinical and MRI outcomes was limited,” said the investigators. “Further prospective studies are necessary to assess the assay’s utility for decision making in individual patients.”

The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.
 

[email protected]

SOURCE: Cantó E et al. JAMA Neurol. 2019 Aug. 12. doi: 10.1001/jamaneurol.2019.2137.

Key clinical point: Data do not support an association between vaccination and increased risk of MS.

Major finding: The odds of MS were lower in participants who received vaccination, compared with participants without autoimmune disease (odds ratio, 0.870).

Study details: A systematic retrospective analysis of claims data for 12,262 patients with MS and 210,773 controls.

Disclosures: A grant from the German Federal Ministry of Education and Research Competence Network MS supported the study. The authors had no relevant conflicts.

Citation: Hapfelmeier A et al. Neurology. 2019 Jul 30. doi: 10.1212/WNL.0000000000008012.

Key clinical point: Data do not support an association between vaccination and increased risk of MS.

Major finding: The odds of MS were lower in participants who received vaccination, compared with participants without autoimmune disease (odds ratio, 0.870).

Study details: A systematic retrospective analysis of claims data for 12,262 patients with MS and 210,773 controls.

Disclosures: A grant from the German Federal Ministry of Education and Research Competence Network MS supported the study. The authors had no relevant conflicts.

Citation: Hapfelmeier A et al. Neurology. 2019 Jul 30. doi: 10.1212/WNL.0000000000008012.

Key clinical point: Data do not support an association between vaccination and increased risk of MS.

Major finding: The odds of MS were lower in participants who received vaccination, compared with participants without autoimmune disease (odds ratio, 0.870).

Study details: A systematic retrospective analysis of claims data for 12,262 patients with MS and 210,773 controls.

Disclosures: A grant from the German Federal Ministry of Education and Research Competence Network MS supported the study. The authors had no relevant conflicts.

Citation: Hapfelmeier A et al. Neurology. 2019 Jul 30. doi: 10.1212/WNL.0000000000008012.

Key clinical point: Evaluating black holes as part of routine clinical practice could be a quick method for screening people with MS for referral to a comprehensive cognitive assessment.

Major finding: Mean Symbol Digit Modalities Test score was 49.0 in patients without a black hole and 42.9 in patients with at least one black hole.

Study details: A prospective study of 226 patients with MS.

Disclosures: The investigators had no disclosures and conducted their study without financial support.

Citation: Özakbas S et al. CMSC 2019, Abstract IMG02.

Key clinical point: Evaluating black holes as part of routine clinical practice could be a quick method for screening people with MS for referral to a comprehensive cognitive assessment.

Major finding: Mean Symbol Digit Modalities Test score was 49.0 in patients without a black hole and 42.9 in patients with at least one black hole.

Study details: A prospective study of 226 patients with MS.

Disclosures: The investigators had no disclosures and conducted their study without financial support.

Citation: Özakbas S et al. CMSC 2019, Abstract IMG02.

Key clinical point: Evaluating black holes as part of routine clinical practice could be a quick method for screening people with MS for referral to a comprehensive cognitive assessment.

Major finding: Mean Symbol Digit Modalities Test score was 49.0 in patients without a black hole and 42.9 in patients with at least one black hole.

Study details: A prospective study of 226 patients with MS.

Disclosures: The investigators had no disclosures and conducted their study without financial support.

Citation: Özakbas S et al. CMSC 2019, Abstract IMG02.

Key clinical point: Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years.

Major finding: In a cohort of patients continuously treated with fingolimod for at least 2 years, neutrophils declined over 6 months by about 9%, from an average of 3,698.56 cells per microliter to 3,336.13 cells per microliter.

Study details: Analysis of interim, 6-month data from the ongoing, open-label, phase 4 FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The interim results include data from 216 treatment-experienced patients and 166 treatment-naive patients.

Disclosures: Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

Citation: Mao-Draayer Y et al. CMSC 2019, Abstract DXM03.

Key clinical point: Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years.

Major finding: In a cohort of patients continuously treated with fingolimod for at least 2 years, neutrophils declined over 6 months by about 9%, from an average of 3,698.56 cells per microliter to 3,336.13 cells per microliter.

Study details: Analysis of interim, 6-month data from the ongoing, open-label, phase 4 FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The interim results include data from 216 treatment-experienced patients and 166 treatment-naive patients.

Disclosures: Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

Citation: Mao-Draayer Y et al. CMSC 2019, Abstract DXM03.

Key clinical point: Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years.

Major finding: In a cohort of patients continuously treated with fingolimod for at least 2 years, neutrophils declined over 6 months by about 9%, from an average of 3,698.56 cells per microliter to 3,336.13 cells per microliter.

Study details: Analysis of interim, 6-month data from the ongoing, open-label, phase 4 FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The interim results include data from 216 treatment-experienced patients and 166 treatment-naive patients.

Disclosures: Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

Citation: Mao-Draayer Y et al. CMSC 2019, Abstract DXM03.

Andrew R. Pachner, MD is the Murray B. Bornstein professor of neurology at Geisel School of Medicine at Dartmouth and director of the Multiple Sclerosis Center at Dartmouth-Hitchcock Medical Center. We spoke to Dr. Pachner about his research into the molecular processes of multiple sclerosis (MS) and the potential impact on patient management.

What do we know about the molecular processes behind relapsing-remitting and progressive MS?

DR. PACHNER:  The progress--in terms of molecules--has not been rapid in the field of MS. The only molecular biomarker we use in practice is oligoclonal bands or other measures of immunoglobulin production in the nervous system, and that biomarker was described in 1942. So, it has been a long time since we have seen a relevant molecule that we can use clinically.

But there has been a lot of progress in the general field of neuroinflammation. MS is one of a large number of diseases that results in neuroinflammation and demyelination.

One thing we have learned over time is that there are many different subtypes of MS. They probably have some shared molecular processes, but they also are likely to have divergent molecular processes.

Over the past 5 to 10 years, researchers have been interested in trying to dissect some of the molecular aspects of MS to identify biomarkers that can, in turn, differentiate subtypes of MS. This will help to identify different ways of treating MS that are optimal for individual patients. It is clear that each patient is quite different and unlikely to be standardized in the way they respond to treatment.

The degree to which relapsing-remitting and progressive MS are differentiated on the molecular level is dependent on how much influence there is of the immune system in the periphery. When MS first starts in a patient, the brain has either no or a very primitive immune system, and then over time it changes, and it becomes much more immune-oriented and populated by immune cells and molecules. So, there’s a trend over time of the central nervous system becoming increasingly populated by immune cells and able to make immune molecules.

What has your recent research on murine models representing these disease patterns shown?

DR. PACHNER:  Even though in humans there is a continuum from relapsing remitting to progressive, it is not like they are completely separate. Frequently in the middle of relapsing-remitting disease there is some progression over time.

In mouse models, we like things to be very clear and separate. We try to make things as simple as possible because of the complexity of the nervous and immune systems.

The simple model for the relapsing-remitting disease is experimental autoimmune encephalomyelitis (EAE), the most commonly studied model of neuroinflammation.

For the progressive form of MS, we use the Theiler’s virus model, which is a type of virus called the picornavirus that is injected into the brain of mice resulting in a slowly progressive, chronic viral infection that looks very much like progressive MS.

In EAE, the disease is induced by presenting an antigen to the peripheral immune system, allowing cells from the peripheral immune system to enter into the central nervous system. It is a manifestation of inflammation and the immune response is in the periphery. In the Theiler’s model, it is a localized process within the central nervous system because the virus is injected directly into the brain.

We found that in EAE the pattern is very much dominated by what happens in the periphery and the injury is very transient. There are cells that enter the nervous system that cause inflammation and damage, but there are also processes that downregulate those cells and processes and eventually the animal improves--similar to an MS attack.

By contrast, in the Theiler’s model there is progressive injury that is dominated by two molecular processes in the central nervous system that we do not see in relapsing-remitting MS or in EAE, and that is the activation of Type 1 interferons and also a very pronounced immunoglobulin production along with all the molecules that help support plasma cells making immunoglobulin.

These are two different animal models that provide us insight into how the central nervous system can be injured in the course of neuroinflammation and they look to be very different in how they manifest themselves, both in the periphery and in the central nervous system.

How may these new findings impact the future management and treatment of MS?

DR. PACHNER:  When I see a patient with MS, I tell them that we absolutely need to focus on your own disease and how it responds, rather than taking too much guidance from MS as a whole. Because each patient with MS is different.

One of the things that we have tried to do is to identify molecular markers that might help us in management and treatment. As an example, we have learned that some patients who present with their first episode of MS do very poorly. These patients have many more attacks and/or have very aggressive progression in terms of their disability so that they potentially could be in a wheelchair within a few years. Other patients have what we call a benign variant MS. These patients may have an initial episode that is not that different than the other patient, but this type of patient may not have anything else for the rest of their life.

We would like to have some differentiation of those two types of patients. In the first example you can try to be very aggressive and minimize the neuroinflammation with powerful immune-suppressing drugs that have a high risk of causing side effects, such as cancer or opportunistic infections, but on the other hand may have a high benefit in preventing future inflammatory events and progressive injury. But that would not be the correct treatment choice for the second patient example.

It would be nice to tailor treatment to a predictive biomarker. That is something we have been working very hard on. Based on some of the animal models, we have identified a molecular signature of inflammatory MS that is very predictive of future events and we are hoping that that will help us differentiate patients. In other words, not just treat every MS patient the same, but identify whether they need a very powerful immunosuppressant drug, or a mildly immunosuppressant drug, or no treatment at all.

If you have a patient who has one attack and never has any other problem with their MS, then they do not need to be on any treatment. Unfortunately, we do not have predictive value at this point for any molecule or any other attribute of the patient at this point in time. We are trying to remedy that.

That is one very practical aspect of our work in trying to understand the biology of the disease better--identifying molecules that are associated with future damage and inflammation and using those in a predictive manner in patients to guide treatment.

Another important aspect is the attempt to understand the biology of neuroinflammation and how it causes both demyelination and progressive injury to neurons.

References:

Pachner AR, DiSano K, Royce DB, Gilli F. Clinical utility of a molecular signature in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm.2019;6(1):e520.

Andrew R. Pachner, MD is the Murray B. Bornstein professor of neurology at Geisel School of Medicine at Dartmouth and director of the Multiple Sclerosis Center at Dartmouth-Hitchcock Medical Center. We spoke to Dr. Pachner about his research into the molecular processes of multiple sclerosis (MS) and the potential impact on patient management.

What do we know about the molecular processes behind relapsing-remitting and progressive MS?

DR. PACHNER:  The progress--in terms of molecules--has not been rapid in the field of MS. The only molecular biomarker we use in practice is oligoclonal bands or other measures of immunoglobulin production in the nervous system, and that biomarker was described in 1942. So, it has been a long time since we have seen a relevant molecule that we can use clinically.

But there has been a lot of progress in the general field of neuroinflammation. MS is one of a large number of diseases that results in neuroinflammation and demyelination.

One thing we have learned over time is that there are many different subtypes of MS. They probably have some shared molecular processes, but they also are likely to have divergent molecular processes.

Over the past 5 to 10 years, researchers have been interested in trying to dissect some of the molecular aspects of MS to identify biomarkers that can, in turn, differentiate subtypes of MS. This will help to identify different ways of treating MS that are optimal for individual patients. It is clear that each patient is quite different and unlikely to be standardized in the way they respond to treatment.

The degree to which relapsing-remitting and progressive MS are differentiated on the molecular level is dependent on how much influence there is of the immune system in the periphery. When MS first starts in a patient, the brain has either no or a very primitive immune system, and then over time it changes, and it becomes much more immune-oriented and populated by immune cells and molecules. So, there’s a trend over time of the central nervous system becoming increasingly populated by immune cells and able to make immune molecules.

What has your recent research on murine models representing these disease patterns shown?

DR. PACHNER:  Even though in humans there is a continuum from relapsing remitting to progressive, it is not like they are completely separate. Frequently in the middle of relapsing-remitting disease there is some progression over time.

In mouse models, we like things to be very clear and separate. We try to make things as simple as possible because of the complexity of the nervous and immune systems.

The simple model for the relapsing-remitting disease is experimental autoimmune encephalomyelitis (EAE), the most commonly studied model of neuroinflammation.

For the progressive form of MS, we use the Theiler’s virus model, which is a type of virus called the picornavirus that is injected into the brain of mice resulting in a slowly progressive, chronic viral infection that looks very much like progressive MS.

In EAE, the disease is induced by presenting an antigen to the peripheral immune system, allowing cells from the peripheral immune system to enter into the central nervous system. It is a manifestation of inflammation and the immune response is in the periphery. In the Theiler’s model, it is a localized process within the central nervous system because the virus is injected directly into the brain.

We found that in EAE the pattern is very much dominated by what happens in the periphery and the injury is very transient. There are cells that enter the nervous system that cause inflammation and damage, but there are also processes that downregulate those cells and processes and eventually the animal improves--similar to an MS attack.

By contrast, in the Theiler’s model there is progressive injury that is dominated by two molecular processes in the central nervous system that we do not see in relapsing-remitting MS or in EAE, and that is the activation of Type 1 interferons and also a very pronounced immunoglobulin production along with all the molecules that help support plasma cells making immunoglobulin.

These are two different animal models that provide us insight into how the central nervous system can be injured in the course of neuroinflammation and they look to be very different in how they manifest themselves, both in the periphery and in the central nervous system.

How may these new findings impact the future management and treatment of MS?

DR. PACHNER:  When I see a patient with MS, I tell them that we absolutely need to focus on your own disease and how it responds, rather than taking too much guidance from MS as a whole. Because each patient with MS is different.

One of the things that we have tried to do is to identify molecular markers that might help us in management and treatment. As an example, we have learned that some patients who present with their first episode of MS do very poorly. These patients have many more attacks and/or have very aggressive progression in terms of their disability so that they potentially could be in a wheelchair within a few years. Other patients have what we call a benign variant MS. These patients may have an initial episode that is not that different than the other patient, but this type of patient may not have anything else for the rest of their life.

We would like to have some differentiation of those two types of patients. In the first example you can try to be very aggressive and minimize the neuroinflammation with powerful immune-suppressing drugs that have a high risk of causing side effects, such as cancer or opportunistic infections, but on the other hand may have a high benefit in preventing future inflammatory events and progressive injury. But that would not be the correct treatment choice for the second patient example.

It would be nice to tailor treatment to a predictive biomarker. That is something we have been working very hard on. Based on some of the animal models, we have identified a molecular signature of inflammatory MS that is very predictive of future events and we are hoping that that will help us differentiate patients. In other words, not just treat every MS patient the same, but identify whether they need a very powerful immunosuppressant drug, or a mildly immunosuppressant drug, or no treatment at all.

If you have a patient who has one attack and never has any other problem with their MS, then they do not need to be on any treatment. Unfortunately, we do not have predictive value at this point for any molecule or any other attribute of the patient at this point in time. We are trying to remedy that.

That is one very practical aspect of our work in trying to understand the biology of the disease better--identifying molecules that are associated with future damage and inflammation and using those in a predictive manner in patients to guide treatment.

Another important aspect is the attempt to understand the biology of neuroinflammation and how it causes both demyelination and progressive injury to neurons.

References:

Pachner AR, DiSano K, Royce DB, Gilli F. Clinical utility of a molecular signature in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm.2019;6(1):e520.

Andrew R. Pachner, MD is the Murray B. Bornstein professor of neurology at Geisel School of Medicine at Dartmouth and director of the Multiple Sclerosis Center at Dartmouth-Hitchcock Medical Center. We spoke to Dr. Pachner about his research into the molecular processes of multiple sclerosis (MS) and the potential impact on patient management.

What do we know about the molecular processes behind relapsing-remitting and progressive MS?

DR. PACHNER:  The progress--in terms of molecules--has not been rapid in the field of MS. The only molecular biomarker we use in practice is oligoclonal bands or other measures of immunoglobulin production in the nervous system, and that biomarker was described in 1942. So, it has been a long time since we have seen a relevant molecule that we can use clinically.

But there has been a lot of progress in the general field of neuroinflammation. MS is one of a large number of diseases that results in neuroinflammation and demyelination.

One thing we have learned over time is that there are many different subtypes of MS. They probably have some shared molecular processes, but they also are likely to have divergent molecular processes.

Over the past 5 to 10 years, researchers have been interested in trying to dissect some of the molecular aspects of MS to identify biomarkers that can, in turn, differentiate subtypes of MS. This will help to identify different ways of treating MS that are optimal for individual patients. It is clear that each patient is quite different and unlikely to be standardized in the way they respond to treatment.

The degree to which relapsing-remitting and progressive MS are differentiated on the molecular level is dependent on how much influence there is of the immune system in the periphery. When MS first starts in a patient, the brain has either no or a very primitive immune system, and then over time it changes, and it becomes much more immune-oriented and populated by immune cells and molecules. So, there’s a trend over time of the central nervous system becoming increasingly populated by immune cells and able to make immune molecules.

What has your recent research on murine models representing these disease patterns shown?

DR. PACHNER:  Even though in humans there is a continuum from relapsing remitting to progressive, it is not like they are completely separate. Frequently in the middle of relapsing-remitting disease there is some progression over time.

In mouse models, we like things to be very clear and separate. We try to make things as simple as possible because of the complexity of the nervous and immune systems.

The simple model for the relapsing-remitting disease is experimental autoimmune encephalomyelitis (EAE), the most commonly studied model of neuroinflammation.

For the progressive form of MS, we use the Theiler’s virus model, which is a type of virus called the picornavirus that is injected into the brain of mice resulting in a slowly progressive, chronic viral infection that looks very much like progressive MS.

In EAE, the disease is induced by presenting an antigen to the peripheral immune system, allowing cells from the peripheral immune system to enter into the central nervous system. It is a manifestation of inflammation and the immune response is in the periphery. In the Theiler’s model, it is a localized process within the central nervous system because the virus is injected directly into the brain.

We found that in EAE the pattern is very much dominated by what happens in the periphery and the injury is very transient. There are cells that enter the nervous system that cause inflammation and damage, but there are also processes that downregulate those cells and processes and eventually the animal improves--similar to an MS attack.

By contrast, in the Theiler’s model there is progressive injury that is dominated by two molecular processes in the central nervous system that we do not see in relapsing-remitting MS or in EAE, and that is the activation of Type 1 interferons and also a very pronounced immunoglobulin production along with all the molecules that help support plasma cells making immunoglobulin.

These are two different animal models that provide us insight into how the central nervous system can be injured in the course of neuroinflammation and they look to be very different in how they manifest themselves, both in the periphery and in the central nervous system.

How may these new findings impact the future management and treatment of MS?

DR. PACHNER:  When I see a patient with MS, I tell them that we absolutely need to focus on your own disease and how it responds, rather than taking too much guidance from MS as a whole. Because each patient with MS is different.

One of the things that we have tried to do is to identify molecular markers that might help us in management and treatment. As an example, we have learned that some patients who present with their first episode of MS do very poorly. These patients have many more attacks and/or have very aggressive progression in terms of their disability so that they potentially could be in a wheelchair within a few years. Other patients have what we call a benign variant MS. These patients may have an initial episode that is not that different than the other patient, but this type of patient may not have anything else for the rest of their life.

We would like to have some differentiation of those two types of patients. In the first example you can try to be very aggressive and minimize the neuroinflammation with powerful immune-suppressing drugs that have a high risk of causing side effects, such as cancer or opportunistic infections, but on the other hand may have a high benefit in preventing future inflammatory events and progressive injury. But that would not be the correct treatment choice for the second patient example.

It would be nice to tailor treatment to a predictive biomarker. That is something we have been working very hard on. Based on some of the animal models, we have identified a molecular signature of inflammatory MS that is very predictive of future events and we are hoping that that will help us differentiate patients. In other words, not just treat every MS patient the same, but identify whether they need a very powerful immunosuppressant drug, or a mildly immunosuppressant drug, or no treatment at all.

If you have a patient who has one attack and never has any other problem with their MS, then they do not need to be on any treatment. Unfortunately, we do not have predictive value at this point for any molecule or any other attribute of the patient at this point in time. We are trying to remedy that.

That is one very practical aspect of our work in trying to understand the biology of the disease better--identifying molecules that are associated with future damage and inflammation and using those in a predictive manner in patients to guide treatment.

Another important aspect is the attempt to understand the biology of neuroinflammation and how it causes both demyelination and progressive injury to neurons.

References:

Pachner AR, DiSano K, Royce DB, Gilli F. Clinical utility of a molecular signature in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm.2019;6(1):e520.