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Secondary progressive MS: Sustained immunotherapy may improve disability outcomes
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
High-dose biotin treatment tied to increased risk of relapse in progressive MS
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
FDA approves ofatumumab (Kesimpta) for relapsing forms of MS
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
Risk factors for severe COVID-19 in MS patients
Key clinical point: Age, disability, and obesity were independent risk factors for severe COVID-19 in patients with multiple sclerosis (MS).
Major finding: Higher age (odds ratio [OR] per 10 years, 1.9; 95% confidence interval [CI], 1.4-2.5), Expanded Disability Severity Status scores of ≥6 (OR, 6.3; 95% CI, 2.8-14.4), and obesity (OR, 3.0; 95% CI, 1.03-8.7) were independently associated with severe COVID-19 (severity score ≥3) Modification of disease-modifying therapies had no association with COVID-19 outcomes.
Study details: A multicenter, retrospective, observational cohort study analyzed data for 347 MS patients with confirmed or highly suspected COVID-19.
Disclosures: The study did not receive any specific funding. The authors reported relationships with multiple pharmaceutical companies and institutions.
Citation: Louapre C et al. JAMA Neurol. 2020 Jun 26. doi: 10.1001/jamaneurol.2020.2581.
Key clinical point: Age, disability, and obesity were independent risk factors for severe COVID-19 in patients with multiple sclerosis (MS).
Major finding: Higher age (odds ratio [OR] per 10 years, 1.9; 95% confidence interval [CI], 1.4-2.5), Expanded Disability Severity Status scores of ≥6 (OR, 6.3; 95% CI, 2.8-14.4), and obesity (OR, 3.0; 95% CI, 1.03-8.7) were independently associated with severe COVID-19 (severity score ≥3) Modification of disease-modifying therapies had no association with COVID-19 outcomes.
Study details: A multicenter, retrospective, observational cohort study analyzed data for 347 MS patients with confirmed or highly suspected COVID-19.
Disclosures: The study did not receive any specific funding. The authors reported relationships with multiple pharmaceutical companies and institutions.
Citation: Louapre C et al. JAMA Neurol. 2020 Jun 26. doi: 10.1001/jamaneurol.2020.2581.
Key clinical point: Age, disability, and obesity were independent risk factors for severe COVID-19 in patients with multiple sclerosis (MS).
Major finding: Higher age (odds ratio [OR] per 10 years, 1.9; 95% confidence interval [CI], 1.4-2.5), Expanded Disability Severity Status scores of ≥6 (OR, 6.3; 95% CI, 2.8-14.4), and obesity (OR, 3.0; 95% CI, 1.03-8.7) were independently associated with severe COVID-19 (severity score ≥3) Modification of disease-modifying therapies had no association with COVID-19 outcomes.
Study details: A multicenter, retrospective, observational cohort study analyzed data for 347 MS patients with confirmed or highly suspected COVID-19.
Disclosures: The study did not receive any specific funding. The authors reported relationships with multiple pharmaceutical companies and institutions.
Citation: Louapre C et al. JAMA Neurol. 2020 Jun 26. doi: 10.1001/jamaneurol.2020.2581.
MS: Rituximab effective in controlling disability and relapse rates
Key clinical point: Treatment with rituximab could effectively reduce disability levels and relapse rates in patients with multiple sclerosis (MS).
Major finding: The mean Expanded Disability Status Scale (EDSS) scores decreased by 0.29 (95% confidence interval [CI], 0.16-0.42) after rituximab treatment. Analysis of 3 studies showed a mean reduction in annualized relapse rates (–1.24; 95% CI, –1.04 to –1.44) after rituximab treatment. The overall proportion of adverse effects was 23% (95% CI, 20%-26%).
Study details: A systematic review and meta-analysis of 7 studies including 399 patients with MS treated with rituximab.
Disclosures: No information was available on funding and conflicts of interest.
Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Jun 10. doi:10.1016/j.autrev.2020.102585.
Key clinical point: Treatment with rituximab could effectively reduce disability levels and relapse rates in patients with multiple sclerosis (MS).
Major finding: The mean Expanded Disability Status Scale (EDSS) scores decreased by 0.29 (95% confidence interval [CI], 0.16-0.42) after rituximab treatment. Analysis of 3 studies showed a mean reduction in annualized relapse rates (–1.24; 95% CI, –1.04 to –1.44) after rituximab treatment. The overall proportion of adverse effects was 23% (95% CI, 20%-26%).
Study details: A systematic review and meta-analysis of 7 studies including 399 patients with MS treated with rituximab.
Disclosures: No information was available on funding and conflicts of interest.
Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Jun 10. doi:10.1016/j.autrev.2020.102585.
Key clinical point: Treatment with rituximab could effectively reduce disability levels and relapse rates in patients with multiple sclerosis (MS).
Major finding: The mean Expanded Disability Status Scale (EDSS) scores decreased by 0.29 (95% confidence interval [CI], 0.16-0.42) after rituximab treatment. Analysis of 3 studies showed a mean reduction in annualized relapse rates (–1.24; 95% CI, –1.04 to –1.44) after rituximab treatment. The overall proportion of adverse effects was 23% (95% CI, 20%-26%).
Study details: A systematic review and meta-analysis of 7 studies including 399 patients with MS treated with rituximab.
Disclosures: No information was available on funding and conflicts of interest.
Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Jun 10. doi:10.1016/j.autrev.2020.102585.
Study suggests potential prognostic value of enlarged perivascular spaces in MS
Key clinical point: The prevalence of enlarged perivascular spaces (EPVS) on magnetic resonance imaging is higher in patients with multiple sclerosis (MS), with higher EPVS burden vs. controls. This supports a potential role of EPVS in MS etiopathogenesis and its use as marker with prognostic potential.
Major finding: Whole brain EPVSs were more common in patients with MS vs. controls (odds ratio [OR], 4.61; P = .001). Patients with MS had a larger EPVS volume (standardized mean difference [SMD], 0.88; P = .01), area (SMD, 0.79; P = .06), and count (SMD, 0.46; P less than .0001) compared with controls.
Study details: Systematic review and meta-analysis of 9 studies including 457 patients with MS and 352 control participants.
Disclosures: This study was supported by grants of the Swiss National Science Foundation and the Region of Stockholm. The authors declared no conflict of interest.
Citation: Granberg T et al. J Neurol. 2020 Jun 13. doi: 10.1007/s00415-020-09971-5.
Key clinical point: The prevalence of enlarged perivascular spaces (EPVS) on magnetic resonance imaging is higher in patients with multiple sclerosis (MS), with higher EPVS burden vs. controls. This supports a potential role of EPVS in MS etiopathogenesis and its use as marker with prognostic potential.
Major finding: Whole brain EPVSs were more common in patients with MS vs. controls (odds ratio [OR], 4.61; P = .001). Patients with MS had a larger EPVS volume (standardized mean difference [SMD], 0.88; P = .01), area (SMD, 0.79; P = .06), and count (SMD, 0.46; P less than .0001) compared with controls.
Study details: Systematic review and meta-analysis of 9 studies including 457 patients with MS and 352 control participants.
Disclosures: This study was supported by grants of the Swiss National Science Foundation and the Region of Stockholm. The authors declared no conflict of interest.
Citation: Granberg T et al. J Neurol. 2020 Jun 13. doi: 10.1007/s00415-020-09971-5.
Key clinical point: The prevalence of enlarged perivascular spaces (EPVS) on magnetic resonance imaging is higher in patients with multiple sclerosis (MS), with higher EPVS burden vs. controls. This supports a potential role of EPVS in MS etiopathogenesis and its use as marker with prognostic potential.
Major finding: Whole brain EPVSs were more common in patients with MS vs. controls (odds ratio [OR], 4.61; P = .001). Patients with MS had a larger EPVS volume (standardized mean difference [SMD], 0.88; P = .01), area (SMD, 0.79; P = .06), and count (SMD, 0.46; P less than .0001) compared with controls.
Study details: Systematic review and meta-analysis of 9 studies including 457 patients with MS and 352 control participants.
Disclosures: This study was supported by grants of the Swiss National Science Foundation and the Region of Stockholm. The authors declared no conflict of interest.
Citation: Granberg T et al. J Neurol. 2020 Jun 13. doi: 10.1007/s00415-020-09971-5.
Effect of hookworm treatment on relapsing MS
Key clinical point: Treatment with hookworm was safe and possibly associated with an immunobiological effect in relapsing multiple sclerosis.
Major finding: During 3-9 months postinfection, no significant difference was detected between hookworm and placebo groups in total number of new T2 lesions, newly enhancing T1-weighted lesions, or T2 enlarging lesions. Hookworm group was somewhat less likely to have any magnetic resonance imaging activity (odds ratio, 0.33), higher percentage of CD4+CD25highCD127negT cells in peripheral blood (4.4% vs. 3.9%; P = .01), and lower relapse rate per patient (14.3% vs. 30.6%). No patients withdrew because of adverse effects. The only differing adverse event was more application-site skin discomfort in the hookworm group (82.86% vs. 27.78%).
Study details: In this phase 2 trial, 71 patients with relapsing MS without disease-modifying treatment were randomly assigned (1:1) to receive 25 Necator americanus larvae transcutaneously or placebo.
Disclosures: This study was supported by the MS Society of the Great Britain and Northern Ireland, the Forman Hardy Charitable Trust via the University of Nottingham, and an unrestricted grant from Bayer-Schering. Some of the investigators reported receiving grants and personal fees from multiple pharmaceutical companies.
Citation: Tanasescu R et al. JAMA Neurol. 2020 Jun 15. doi: 10.1001/jamaneurol.2020.1118.
Key clinical point: Treatment with hookworm was safe and possibly associated with an immunobiological effect in relapsing multiple sclerosis.
Major finding: During 3-9 months postinfection, no significant difference was detected between hookworm and placebo groups in total number of new T2 lesions, newly enhancing T1-weighted lesions, or T2 enlarging lesions. Hookworm group was somewhat less likely to have any magnetic resonance imaging activity (odds ratio, 0.33), higher percentage of CD4+CD25highCD127negT cells in peripheral blood (4.4% vs. 3.9%; P = .01), and lower relapse rate per patient (14.3% vs. 30.6%). No patients withdrew because of adverse effects. The only differing adverse event was more application-site skin discomfort in the hookworm group (82.86% vs. 27.78%).
Study details: In this phase 2 trial, 71 patients with relapsing MS without disease-modifying treatment were randomly assigned (1:1) to receive 25 Necator americanus larvae transcutaneously or placebo.
Disclosures: This study was supported by the MS Society of the Great Britain and Northern Ireland, the Forman Hardy Charitable Trust via the University of Nottingham, and an unrestricted grant from Bayer-Schering. Some of the investigators reported receiving grants and personal fees from multiple pharmaceutical companies.
Citation: Tanasescu R et al. JAMA Neurol. 2020 Jun 15. doi: 10.1001/jamaneurol.2020.1118.
Key clinical point: Treatment with hookworm was safe and possibly associated with an immunobiological effect in relapsing multiple sclerosis.
Major finding: During 3-9 months postinfection, no significant difference was detected between hookworm and placebo groups in total number of new T2 lesions, newly enhancing T1-weighted lesions, or T2 enlarging lesions. Hookworm group was somewhat less likely to have any magnetic resonance imaging activity (odds ratio, 0.33), higher percentage of CD4+CD25highCD127negT cells in peripheral blood (4.4% vs. 3.9%; P = .01), and lower relapse rate per patient (14.3% vs. 30.6%). No patients withdrew because of adverse effects. The only differing adverse event was more application-site skin discomfort in the hookworm group (82.86% vs. 27.78%).
Study details: In this phase 2 trial, 71 patients with relapsing MS without disease-modifying treatment were randomly assigned (1:1) to receive 25 Necator americanus larvae transcutaneously or placebo.
Disclosures: This study was supported by the MS Society of the Great Britain and Northern Ireland, the Forman Hardy Charitable Trust via the University of Nottingham, and an unrestricted grant from Bayer-Schering. Some of the investigators reported receiving grants and personal fees from multiple pharmaceutical companies.
Citation: Tanasescu R et al. JAMA Neurol. 2020 Jun 15. doi: 10.1001/jamaneurol.2020.1118.
MSBase study validates therapy for relapse in secondary progressive MS
An observational cohort study of a prospective international database of patients with multiple sclerosis has reported that medical therapy can reduce disability progression in patients with active secondary progressive MS (SPMS) who are prone to inflammatory relapses.
The international researchers, led by Nathanial Lizak, MMBS, of the University of Melbourne, conducted the cohort study of 1,621 patients with SPMS from the MSBase international registry, which prospectively collected the information from 1995 to 2018. Their findings were published in JAMA Neurology.
“ wrote Dr. Lizak and colleagues of the MSBase Study Group.
Therapy’s impact on disease progression
To ensure that they had timely data on the early disease course of all study patients, they researchers only included patients whose diagnosis and first documented Expanded Disability Status Scale (EDSS) score were no more than 24 months apart. At SPMS conversion, 1,494 patients had an EDSS score of less than 7 (on a scale of 0-10); during the follow-up period, 267 of them (17.9%) crossed over the threshold of 7.
Dr. Lizak and colleagues noted that early treatment during relapsing remitting MS didn’t impact outcomes after SPMS conversion.
For evaluating the MS Severity Score (MSSS), the study split the cohort into three groups depending on the efficacy of therapy: low-efficacy treatments, mostly consisting of interferon-beta and glatiramer acetate; medium-efficacy treatments, mostly fingolimod and dimethyl fumarate; and high-efficacy treatments, predominately natalizumab and mitoxantrone.
The MSSS progression slope in the cohort had an average reduction of 0.02 points per year. “For patients who experienced superimposed relapses during SPMS, a reduced MSSS progression slope during SPMS was observed among those who received disease-modifying therapies for a greater proportion of time during SPMS,” Dr. Lizak and colleagues wrote.
MSSS progression slope reduction was more pronounced in the medium- and high-efficacy groups, with a reduction of beta 0.22 (P = .06) and 0.034 (P = .002), respectively.
“Based on our models, the level of disability in patients with active SPMS who are continuously treated with high-efficacy immunotherapies would progress more slowly in comparison with the general population with MS by a mean (standard deviation) of 1.56 (4.60) deciles over 10 years,” Dr. Lizak and colleagues wrote.
While the researchers cited a number of studies that didn’t support immunotherapy for SPMS, they also did cite the EXPAND trial to support treatment with siponimod in SPMS patients (Lancet. 2018;391:1263-73). The ASCEND trial of natalizumab enrolled a largely relapse-free cohort and found no link between treatment and disability progression in SPMS (Lancet Neurol. 2018;17:405-15), and a previous report by the MSBase Study Group found no benefit of therapy when adjusted for SPMS relapse rates (Neurology. 2017;89:1050-9).
“Together with the present study, the existing data converge on the suggestion that relapses during SPMS provide a therapeutic target and a marker of future response to immunotherapy during SPMS,” Dr. Lizak and colleagues wrote.
Challenging dogma
Commenting on the research, Mark Freedman, HBSc, MSc, MD, said that the MSBase study makes an important contribution to the literature on management of SPMS. “Up until this point we’ve been basing our assumptions on secondary progressive MS on natural history studies, which are actually quite old, dating back 20-30 years.” Dr. Freedman is senior scientist in the Neuroscience Program at the Ottawa Hospital Research Institute and professor of medicine in neurology at the University of Ottawa.
He said “the most damaging” of those studies was by the late Christian Confavreaux, MD, and colleagues in Lyon, France (N Engl J Med. 2000;343:1430-8), that reported relapses didn’t alter the progression of disability. “In other words, once you’re in EDSS of 4, it’s a runaway train; it doesn’t matter what you do,” Dr. Freedman said.
“That was kind of dogma for years,” he said. “The reason this publication is important is because it’s suggesting that’s not the case.” In other words, the MSBase cohort study is validating what neurologists have been doing in the real world for years: treating patients with SPMS who have relapses.
Dr Lizak reported receiving travel compensation from Merck outside the scope of the study. His coauthors reported numerous financial relationships.
SOURCE: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453
An observational cohort study of a prospective international database of patients with multiple sclerosis has reported that medical therapy can reduce disability progression in patients with active secondary progressive MS (SPMS) who are prone to inflammatory relapses.
The international researchers, led by Nathanial Lizak, MMBS, of the University of Melbourne, conducted the cohort study of 1,621 patients with SPMS from the MSBase international registry, which prospectively collected the information from 1995 to 2018. Their findings were published in JAMA Neurology.
“ wrote Dr. Lizak and colleagues of the MSBase Study Group.
Therapy’s impact on disease progression
To ensure that they had timely data on the early disease course of all study patients, they researchers only included patients whose diagnosis and first documented Expanded Disability Status Scale (EDSS) score were no more than 24 months apart. At SPMS conversion, 1,494 patients had an EDSS score of less than 7 (on a scale of 0-10); during the follow-up period, 267 of them (17.9%) crossed over the threshold of 7.
Dr. Lizak and colleagues noted that early treatment during relapsing remitting MS didn’t impact outcomes after SPMS conversion.
For evaluating the MS Severity Score (MSSS), the study split the cohort into three groups depending on the efficacy of therapy: low-efficacy treatments, mostly consisting of interferon-beta and glatiramer acetate; medium-efficacy treatments, mostly fingolimod and dimethyl fumarate; and high-efficacy treatments, predominately natalizumab and mitoxantrone.
The MSSS progression slope in the cohort had an average reduction of 0.02 points per year. “For patients who experienced superimposed relapses during SPMS, a reduced MSSS progression slope during SPMS was observed among those who received disease-modifying therapies for a greater proportion of time during SPMS,” Dr. Lizak and colleagues wrote.
MSSS progression slope reduction was more pronounced in the medium- and high-efficacy groups, with a reduction of beta 0.22 (P = .06) and 0.034 (P = .002), respectively.
“Based on our models, the level of disability in patients with active SPMS who are continuously treated with high-efficacy immunotherapies would progress more slowly in comparison with the general population with MS by a mean (standard deviation) of 1.56 (4.60) deciles over 10 years,” Dr. Lizak and colleagues wrote.
While the researchers cited a number of studies that didn’t support immunotherapy for SPMS, they also did cite the EXPAND trial to support treatment with siponimod in SPMS patients (Lancet. 2018;391:1263-73). The ASCEND trial of natalizumab enrolled a largely relapse-free cohort and found no link between treatment and disability progression in SPMS (Lancet Neurol. 2018;17:405-15), and a previous report by the MSBase Study Group found no benefit of therapy when adjusted for SPMS relapse rates (Neurology. 2017;89:1050-9).
“Together with the present study, the existing data converge on the suggestion that relapses during SPMS provide a therapeutic target and a marker of future response to immunotherapy during SPMS,” Dr. Lizak and colleagues wrote.
Challenging dogma
Commenting on the research, Mark Freedman, HBSc, MSc, MD, said that the MSBase study makes an important contribution to the literature on management of SPMS. “Up until this point we’ve been basing our assumptions on secondary progressive MS on natural history studies, which are actually quite old, dating back 20-30 years.” Dr. Freedman is senior scientist in the Neuroscience Program at the Ottawa Hospital Research Institute and professor of medicine in neurology at the University of Ottawa.
He said “the most damaging” of those studies was by the late Christian Confavreaux, MD, and colleagues in Lyon, France (N Engl J Med. 2000;343:1430-8), that reported relapses didn’t alter the progression of disability. “In other words, once you’re in EDSS of 4, it’s a runaway train; it doesn’t matter what you do,” Dr. Freedman said.
“That was kind of dogma for years,” he said. “The reason this publication is important is because it’s suggesting that’s not the case.” In other words, the MSBase cohort study is validating what neurologists have been doing in the real world for years: treating patients with SPMS who have relapses.
Dr Lizak reported receiving travel compensation from Merck outside the scope of the study. His coauthors reported numerous financial relationships.
SOURCE: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453
An observational cohort study of a prospective international database of patients with multiple sclerosis has reported that medical therapy can reduce disability progression in patients with active secondary progressive MS (SPMS) who are prone to inflammatory relapses.
The international researchers, led by Nathanial Lizak, MMBS, of the University of Melbourne, conducted the cohort study of 1,621 patients with SPMS from the MSBase international registry, which prospectively collected the information from 1995 to 2018. Their findings were published in JAMA Neurology.
“ wrote Dr. Lizak and colleagues of the MSBase Study Group.
Therapy’s impact on disease progression
To ensure that they had timely data on the early disease course of all study patients, they researchers only included patients whose diagnosis and first documented Expanded Disability Status Scale (EDSS) score were no more than 24 months apart. At SPMS conversion, 1,494 patients had an EDSS score of less than 7 (on a scale of 0-10); during the follow-up period, 267 of them (17.9%) crossed over the threshold of 7.
Dr. Lizak and colleagues noted that early treatment during relapsing remitting MS didn’t impact outcomes after SPMS conversion.
For evaluating the MS Severity Score (MSSS), the study split the cohort into three groups depending on the efficacy of therapy: low-efficacy treatments, mostly consisting of interferon-beta and glatiramer acetate; medium-efficacy treatments, mostly fingolimod and dimethyl fumarate; and high-efficacy treatments, predominately natalizumab and mitoxantrone.
The MSSS progression slope in the cohort had an average reduction of 0.02 points per year. “For patients who experienced superimposed relapses during SPMS, a reduced MSSS progression slope during SPMS was observed among those who received disease-modifying therapies for a greater proportion of time during SPMS,” Dr. Lizak and colleagues wrote.
MSSS progression slope reduction was more pronounced in the medium- and high-efficacy groups, with a reduction of beta 0.22 (P = .06) and 0.034 (P = .002), respectively.
“Based on our models, the level of disability in patients with active SPMS who are continuously treated with high-efficacy immunotherapies would progress more slowly in comparison with the general population with MS by a mean (standard deviation) of 1.56 (4.60) deciles over 10 years,” Dr. Lizak and colleagues wrote.
While the researchers cited a number of studies that didn’t support immunotherapy for SPMS, they also did cite the EXPAND trial to support treatment with siponimod in SPMS patients (Lancet. 2018;391:1263-73). The ASCEND trial of natalizumab enrolled a largely relapse-free cohort and found no link between treatment and disability progression in SPMS (Lancet Neurol. 2018;17:405-15), and a previous report by the MSBase Study Group found no benefit of therapy when adjusted for SPMS relapse rates (Neurology. 2017;89:1050-9).
“Together with the present study, the existing data converge on the suggestion that relapses during SPMS provide a therapeutic target and a marker of future response to immunotherapy during SPMS,” Dr. Lizak and colleagues wrote.
Challenging dogma
Commenting on the research, Mark Freedman, HBSc, MSc, MD, said that the MSBase study makes an important contribution to the literature on management of SPMS. “Up until this point we’ve been basing our assumptions on secondary progressive MS on natural history studies, which are actually quite old, dating back 20-30 years.” Dr. Freedman is senior scientist in the Neuroscience Program at the Ottawa Hospital Research Institute and professor of medicine in neurology at the University of Ottawa.
He said “the most damaging” of those studies was by the late Christian Confavreaux, MD, and colleagues in Lyon, France (N Engl J Med. 2000;343:1430-8), that reported relapses didn’t alter the progression of disability. “In other words, once you’re in EDSS of 4, it’s a runaway train; it doesn’t matter what you do,” Dr. Freedman said.
“That was kind of dogma for years,” he said. “The reason this publication is important is because it’s suggesting that’s not the case.” In other words, the MSBase cohort study is validating what neurologists have been doing in the real world for years: treating patients with SPMS who have relapses.
Dr Lizak reported receiving travel compensation from Merck outside the scope of the study. His coauthors reported numerous financial relationships.
SOURCE: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453
FROM JAMA NEUROLOGY
Higher incidence of depression in patients with MS
Key clinical point: Patients with multiple sclerosis (MS) in the United States (US) and the United Kingdom (UK) have a 2- to 3-fold higher incidence of depression than those without MS.
Major finding: A significantly higher incidence of depression was observed among patients with MS vs. non-MS control individuals in the US (incidence rate ratio [IRR], 3.20; 95% confidence interval [CI], 3.05-3.35) and the UK (IRR, 1.90; 95% CI, 1.74-2.06).
Study details: This cohort study included individuals with a first recorded diagnosis of MS and matched non-MS individuals identified from the US Department of Defense military healthcare system and the UK’s Clinical Practice Research Datalink GOLD.
Disclosures: The study was funded by Celgene Corporation, a wholly owned subsidiary of Bristol-Myers Squibb. Sally Lee, Neil Minton, Steve Niemcryk, and Anders Lindholm are employees of Bristol-Myers Squibb. Amber M Evans is an employee of Health ResearchTx LLC, which has a business relationship with Celgene Corporation.
Citation: Persson R et al. Eur J Neurol. 2020 May 12. doi: 10.1111/ene.14314.
Key clinical point: Patients with multiple sclerosis (MS) in the United States (US) and the United Kingdom (UK) have a 2- to 3-fold higher incidence of depression than those without MS.
Major finding: A significantly higher incidence of depression was observed among patients with MS vs. non-MS control individuals in the US (incidence rate ratio [IRR], 3.20; 95% confidence interval [CI], 3.05-3.35) and the UK (IRR, 1.90; 95% CI, 1.74-2.06).
Study details: This cohort study included individuals with a first recorded diagnosis of MS and matched non-MS individuals identified from the US Department of Defense military healthcare system and the UK’s Clinical Practice Research Datalink GOLD.
Disclosures: The study was funded by Celgene Corporation, a wholly owned subsidiary of Bristol-Myers Squibb. Sally Lee, Neil Minton, Steve Niemcryk, and Anders Lindholm are employees of Bristol-Myers Squibb. Amber M Evans is an employee of Health ResearchTx LLC, which has a business relationship with Celgene Corporation.
Citation: Persson R et al. Eur J Neurol. 2020 May 12. doi: 10.1111/ene.14314.
Key clinical point: Patients with multiple sclerosis (MS) in the United States (US) and the United Kingdom (UK) have a 2- to 3-fold higher incidence of depression than those without MS.
Major finding: A significantly higher incidence of depression was observed among patients with MS vs. non-MS control individuals in the US (incidence rate ratio [IRR], 3.20; 95% confidence interval [CI], 3.05-3.35) and the UK (IRR, 1.90; 95% CI, 1.74-2.06).
Study details: This cohort study included individuals with a first recorded diagnosis of MS and matched non-MS individuals identified from the US Department of Defense military healthcare system and the UK’s Clinical Practice Research Datalink GOLD.
Disclosures: The study was funded by Celgene Corporation, a wholly owned subsidiary of Bristol-Myers Squibb. Sally Lee, Neil Minton, Steve Niemcryk, and Anders Lindholm are employees of Bristol-Myers Squibb. Amber M Evans is an employee of Health ResearchTx LLC, which has a business relationship with Celgene Corporation.
Citation: Persson R et al. Eur J Neurol. 2020 May 12. doi: 10.1111/ene.14314.
MS: Gadolinium enhancement decreases with advancing age
Key clinical point: Inflammatory activity declines with age in patients with multiple sclerosis (MS), as evidenced by decreased gadolinium enhancement with advancing age.
Major finding: The odds for gadolinium enhancement decreased with advancing age up to 60 years (31-40 years: odds ratio [OR], 0.55; 41-50 years: OR, 0.42; and 51-60 years: OR, 0.24; P less than .0001 for all).
Study details: A cohort study of 1,543 patients with clinically isolated syndrome and MS assessed the association of risk factors, including age, with gadolinium enhancement on cranial magnetic resonance imaging scans.
Disclosures: The study did not receive any funding. Marcus W Koch and Wei-Qiao Liu reported relationships with multiple pharmaceutical companies. Jop Mostert, Jamie Greenfield, and Prof Luanne Metz have declared no conflicts of interest.
Citation: Koch MW et al. J Neurol. 2020 May 09. doi: 10.1007/s00415-020-09895-0.
Key clinical point: Inflammatory activity declines with age in patients with multiple sclerosis (MS), as evidenced by decreased gadolinium enhancement with advancing age.
Major finding: The odds for gadolinium enhancement decreased with advancing age up to 60 years (31-40 years: odds ratio [OR], 0.55; 41-50 years: OR, 0.42; and 51-60 years: OR, 0.24; P less than .0001 for all).
Study details: A cohort study of 1,543 patients with clinically isolated syndrome and MS assessed the association of risk factors, including age, with gadolinium enhancement on cranial magnetic resonance imaging scans.
Disclosures: The study did not receive any funding. Marcus W Koch and Wei-Qiao Liu reported relationships with multiple pharmaceutical companies. Jop Mostert, Jamie Greenfield, and Prof Luanne Metz have declared no conflicts of interest.
Citation: Koch MW et al. J Neurol. 2020 May 09. doi: 10.1007/s00415-020-09895-0.
Key clinical point: Inflammatory activity declines with age in patients with multiple sclerosis (MS), as evidenced by decreased gadolinium enhancement with advancing age.
Major finding: The odds for gadolinium enhancement decreased with advancing age up to 60 years (31-40 years: odds ratio [OR], 0.55; 41-50 years: OR, 0.42; and 51-60 years: OR, 0.24; P less than .0001 for all).
Study details: A cohort study of 1,543 patients with clinically isolated syndrome and MS assessed the association of risk factors, including age, with gadolinium enhancement on cranial magnetic resonance imaging scans.
Disclosures: The study did not receive any funding. Marcus W Koch and Wei-Qiao Liu reported relationships with multiple pharmaceutical companies. Jop Mostert, Jamie Greenfield, and Prof Luanne Metz have declared no conflicts of interest.
Citation: Koch MW et al. J Neurol. 2020 May 09. doi: 10.1007/s00415-020-09895-0.