Multiple Sclerosis

Key clinical point: In patients with early multiple sclerosis (MS), depressive symptoms are linked to cognitive multitasking.

Major finding: Depressive symptoms in early MS cohort had a stronger association with cognitive multitasking (R² = 0.125) than with traditional monotasking procedures, including a SPEED composite variable (R² = 0.079; P less than .001).

Study details: RADIEMS was a cohort study on 185 patients with MS diagnosed in less than or equal to 5 years.

Disclosures: The study was funded by the U.S. Department of Health and Human Services, National Institutes of Health, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors declared no conflicts of interest.

Source: Glukhovsky L et al. Mult Scler. 2020 Nov 16. doi: 10.1177/1352458520958359.

Key clinical point: In patients with early multiple sclerosis (MS), depressive symptoms are linked to cognitive multitasking.

Major finding: Depressive symptoms in early MS cohort had a stronger association with cognitive multitasking (R² = 0.125) than with traditional monotasking procedures, including a SPEED composite variable (R² = 0.079; P less than .001).

Study details: RADIEMS was a cohort study on 185 patients with MS diagnosed in less than or equal to 5 years.

Disclosures: The study was funded by the U.S. Department of Health and Human Services, National Institutes of Health, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors declared no conflicts of interest.

Source: Glukhovsky L et al. Mult Scler. 2020 Nov 16. doi: 10.1177/1352458520958359.

Key clinical point: In patients with early multiple sclerosis (MS), depressive symptoms are linked to cognitive multitasking.

Major finding: Depressive symptoms in early MS cohort had a stronger association with cognitive multitasking (R² = 0.125) than with traditional monotasking procedures, including a SPEED composite variable (R² = 0.079; P less than .001).

Study details: RADIEMS was a cohort study on 185 patients with MS diagnosed in less than or equal to 5 years.

Disclosures: The study was funded by the U.S. Department of Health and Human Services, National Institutes of Health, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors declared no conflicts of interest.

Source: Glukhovsky L et al. Mult Scler. 2020 Nov 16. doi: 10.1177/1352458520958359.

Key clinical point: This meta-analysis found no significant association between multiple sclerosis and vitiligo.

Major finding: No significant association of multiple sclerosis with prevalent vitiligo was found (pooled odds ratio, 1.33; 95% confidence interval, 0.80-2.22).

Study details: A meta-analysis of 6 case-control studies including 12,930 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Shen MH et al. Sci Rep. 2020 Oct 20. doi: 10.1038/s41598-020-74298-0.

Key clinical point: This meta-analysis found no significant association between multiple sclerosis and vitiligo.

Major finding: No significant association of multiple sclerosis with prevalent vitiligo was found (pooled odds ratio, 1.33; 95% confidence interval, 0.80-2.22).

Study details: A meta-analysis of 6 case-control studies including 12,930 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Shen MH et al. Sci Rep. 2020 Oct 20. doi: 10.1038/s41598-020-74298-0.

Key clinical point: This meta-analysis found no significant association between multiple sclerosis and vitiligo.

Major finding: No significant association of multiple sclerosis with prevalent vitiligo was found (pooled odds ratio, 1.33; 95% confidence interval, 0.80-2.22).

Study details: A meta-analysis of 6 case-control studies including 12,930 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Shen MH et al. Sci Rep. 2020 Oct 20. doi: 10.1038/s41598-020-74298-0.

Bruton tyrosine kinase (BTK) inhibitors effectively treat certain leukemias and lymphomas, due to their ability to inhibit a protein kinase that is critical for B cell receptor signaling.  These agents can inhibit antigen-triggered activation and maturation of B cells and their release of pro-inflammatory cytokines. BTK is also a key signaling protein that controls activation of monocytes, macrophages and neutrophils and its inhibition reduces the activation of these cells.

Judging from the papers presented at the recent MS Virtual 2020—the 8^th Joint ACTRIMS-ECTRIMS Meeting, BTK inhibitors are showing promise in the management of multiple sclerosis (MS), as well, as researchers eye next-generation treatment options.  They may prove to be effective not only in relapsing remitting multiple sclerosis, but also on progressive disease through their effect on brain macrophages and microglial cells. 

Leading the way at MS Virtual 2020 was a presentation by Patrick Vermersch, MD, PhD, who summarized the results to date of masitinib’s role in primary progressive MS (PPMS) and non-active secondar progressive MS (nSPMS). The professor of neurology at Lille University in Lille, France, and his colleagues conducted a phase 3 study to assess masitinib’s efficacy at two dosage levels – 4.5 mg/kg/day (n=199) and a 6.0 mg/kg/day (n=199) -- vs placebo (n=101). The randomized, double-blinded, placebo controlled, two-parallel group trial involved adult participants with EDSS scores between 2.0 and 6.0 with either PPMS or nSPMS. Investigators looked at overall EDSS change from baseline using a variety of repeated measures, with an emphasis on determining whether participants improved, were stable, or worsened. Among the results

• In the lower-dose contingent, the odds of either a reduction in EDSS progression or increased EDSS improvement improved by 39% for patients taking masitinib, vs those receiving placebo

• Also, among those receiving the lower dose, the odds of experiencing disability progression decreased by 37% in the treatment group, compared with placebo
• Results using the higher dose of masitinib were inconclusive

Based on these results, investigators concluded that masitinib 4.5 mg/kg/day is very likely to emerge as a new treatment option for individuals with for PPMS and nSPMS.

Another MS Virtual 2020 presentation focused on fenebrutinib, an investigational, noncovalent investigational BTK inhibitor being studies as a possible treatment for MS. Investigators assessed the potency, selectivity, and kinetics of inhibition of the BTK enzyme via fenebrutinib, compared with two other BTK inhibitors, evobrutinib and tolebrutinib, in a panel of 219 human kinases.

Fenebrutinib was found to be a more potent inhibitor, compared with the other two BTK inhibitors. Additionally, fenebrutinib effectively blocked B cell and basophil activation. Moreover, fenebrutinib inhibited fewer off target kinases >50%, compared with the other two BTK inhibitors. Investigators concluded that fenebrutinib’s high selectivity and potency shows promise as a drug linked with fewer adverse events and a better treatment profile than other investigational BTK inhibitors.

These encouraging findings are leading to the initiation of three phase 3 clinical trials involving fenebrutinib, announced at MS Virtual 2020 by Stephen L. Hauser, MD, professor of neurology, and director of the UCSF Weill Institute for Neurosciences. The trials will evaluate fenebrutinib’s impact on disease progression in relapsing MS and primary progressive MS. The primary endpoint of the studies will be 12-week composite Confirmed Disability Progression, which investigators hope will provide a stronger, more thorough assessment of disability progression, vs EDSS score alone.

Other BTK inhibitors worth watching include:

• Evobrutinib: An open-label phase 2 study has shown that the drug is linked with reduced annualized relapse rate through 108 weeks
• BIIB091: Safety and tolerability has been demonstrated in phase 1, clearing the way for further investigation
• Tolebrutinib: Under assessment for its ability to inhibit microglia-driven inflammation in murine models

Bruton tyrosine kinase (BTK) inhibitors effectively treat certain leukemias and lymphomas, due to their ability to inhibit a protein kinase that is critical for B cell receptor signaling.  These agents can inhibit antigen-triggered activation and maturation of B cells and their release of pro-inflammatory cytokines. BTK is also a key signaling protein that controls activation of monocytes, macrophages and neutrophils and its inhibition reduces the activation of these cells.

Judging from the papers presented at the recent MS Virtual 2020—the 8^th Joint ACTRIMS-ECTRIMS Meeting, BTK inhibitors are showing promise in the management of multiple sclerosis (MS), as well, as researchers eye next-generation treatment options.  They may prove to be effective not only in relapsing remitting multiple sclerosis, but also on progressive disease through their effect on brain macrophages and microglial cells. 

Leading the way at MS Virtual 2020 was a presentation by Patrick Vermersch, MD, PhD, who summarized the results to date of masitinib’s role in primary progressive MS (PPMS) and non-active secondar progressive MS (nSPMS). The professor of neurology at Lille University in Lille, France, and his colleagues conducted a phase 3 study to assess masitinib’s efficacy at two dosage levels – 4.5 mg/kg/day (n=199) and a 6.0 mg/kg/day (n=199) -- vs placebo (n=101). The randomized, double-blinded, placebo controlled, two-parallel group trial involved adult participants with EDSS scores between 2.0 and 6.0 with either PPMS or nSPMS. Investigators looked at overall EDSS change from baseline using a variety of repeated measures, with an emphasis on determining whether participants improved, were stable, or worsened. Among the results

• In the lower-dose contingent, the odds of either a reduction in EDSS progression or increased EDSS improvement improved by 39% for patients taking masitinib, vs those receiving placebo

• Also, among those receiving the lower dose, the odds of experiencing disability progression decreased by 37% in the treatment group, compared with placebo
• Results using the higher dose of masitinib were inconclusive

Based on these results, investigators concluded that masitinib 4.5 mg/kg/day is very likely to emerge as a new treatment option for individuals with for PPMS and nSPMS.

Another MS Virtual 2020 presentation focused on fenebrutinib, an investigational, noncovalent investigational BTK inhibitor being studies as a possible treatment for MS. Investigators assessed the potency, selectivity, and kinetics of inhibition of the BTK enzyme via fenebrutinib, compared with two other BTK inhibitors, evobrutinib and tolebrutinib, in a panel of 219 human kinases.

Fenebrutinib was found to be a more potent inhibitor, compared with the other two BTK inhibitors. Additionally, fenebrutinib effectively blocked B cell and basophil activation. Moreover, fenebrutinib inhibited fewer off target kinases >50%, compared with the other two BTK inhibitors. Investigators concluded that fenebrutinib’s high selectivity and potency shows promise as a drug linked with fewer adverse events and a better treatment profile than other investigational BTK inhibitors.

These encouraging findings are leading to the initiation of three phase 3 clinical trials involving fenebrutinib, announced at MS Virtual 2020 by Stephen L. Hauser, MD, professor of neurology, and director of the UCSF Weill Institute for Neurosciences. The trials will evaluate fenebrutinib’s impact on disease progression in relapsing MS and primary progressive MS. The primary endpoint of the studies will be 12-week composite Confirmed Disability Progression, which investigators hope will provide a stronger, more thorough assessment of disability progression, vs EDSS score alone.

Other BTK inhibitors worth watching include:

• Evobrutinib: An open-label phase 2 study has shown that the drug is linked with reduced annualized relapse rate through 108 weeks
• BIIB091: Safety and tolerability has been demonstrated in phase 1, clearing the way for further investigation
• Tolebrutinib: Under assessment for its ability to inhibit microglia-driven inflammation in murine models

Bruton tyrosine kinase (BTK) inhibitors effectively treat certain leukemias and lymphomas, due to their ability to inhibit a protein kinase that is critical for B cell receptor signaling.  These agents can inhibit antigen-triggered activation and maturation of B cells and their release of pro-inflammatory cytokines. BTK is also a key signaling protein that controls activation of monocytes, macrophages and neutrophils and its inhibition reduces the activation of these cells.

Judging from the papers presented at the recent MS Virtual 2020—the 8^th Joint ACTRIMS-ECTRIMS Meeting, BTK inhibitors are showing promise in the management of multiple sclerosis (MS), as well, as researchers eye next-generation treatment options.  They may prove to be effective not only in relapsing remitting multiple sclerosis, but also on progressive disease through their effect on brain macrophages and microglial cells. 

Leading the way at MS Virtual 2020 was a presentation by Patrick Vermersch, MD, PhD, who summarized the results to date of masitinib’s role in primary progressive MS (PPMS) and non-active secondar progressive MS (nSPMS). The professor of neurology at Lille University in Lille, France, and his colleagues conducted a phase 3 study to assess masitinib’s efficacy at two dosage levels – 4.5 mg/kg/day (n=199) and a 6.0 mg/kg/day (n=199) -- vs placebo (n=101). The randomized, double-blinded, placebo controlled, two-parallel group trial involved adult participants with EDSS scores between 2.0 and 6.0 with either PPMS or nSPMS. Investigators looked at overall EDSS change from baseline using a variety of repeated measures, with an emphasis on determining whether participants improved, were stable, or worsened. Among the results

• In the lower-dose contingent, the odds of either a reduction in EDSS progression or increased EDSS improvement improved by 39% for patients taking masitinib, vs those receiving placebo

• Also, among those receiving the lower dose, the odds of experiencing disability progression decreased by 37% in the treatment group, compared with placebo
• Results using the higher dose of masitinib were inconclusive

Based on these results, investigators concluded that masitinib 4.5 mg/kg/day is very likely to emerge as a new treatment option for individuals with for PPMS and nSPMS.

Another MS Virtual 2020 presentation focused on fenebrutinib, an investigational, noncovalent investigational BTK inhibitor being studies as a possible treatment for MS. Investigators assessed the potency, selectivity, and kinetics of inhibition of the BTK enzyme via fenebrutinib, compared with two other BTK inhibitors, evobrutinib and tolebrutinib, in a panel of 219 human kinases.

Fenebrutinib was found to be a more potent inhibitor, compared with the other two BTK inhibitors. Additionally, fenebrutinib effectively blocked B cell and basophil activation. Moreover, fenebrutinib inhibited fewer off target kinases >50%, compared with the other two BTK inhibitors. Investigators concluded that fenebrutinib’s high selectivity and potency shows promise as a drug linked with fewer adverse events and a better treatment profile than other investigational BTK inhibitors.

These encouraging findings are leading to the initiation of three phase 3 clinical trials involving fenebrutinib, announced at MS Virtual 2020 by Stephen L. Hauser, MD, professor of neurology, and director of the UCSF Weill Institute for Neurosciences. The trials will evaluate fenebrutinib’s impact on disease progression in relapsing MS and primary progressive MS. The primary endpoint of the studies will be 12-week composite Confirmed Disability Progression, which investigators hope will provide a stronger, more thorough assessment of disability progression, vs EDSS score alone.

Other BTK inhibitors worth watching include:

• Evobrutinib: An open-label phase 2 study has shown that the drug is linked with reduced annualized relapse rate through 108 weeks
• BIIB091: Safety and tolerability has been demonstrated in phase 1, clearing the way for further investigation
• Tolebrutinib: Under assessment for its ability to inhibit microglia-driven inflammation in murine models

New clinical practice guidelines on Lyme disease place a strong emphasis on antibody testing to assess for rheumatologic and neurologic syndromes. “Diagnostically, we recommend testing via antibodies, and an index of antibodies in cerebrospinal fluid [CSF] versus serum. Importantly, we recommend against using polymerase chain reaction [PCR] in CSF,” Jeffrey A. Rumbaugh, MD, PhD, a coauthor of the guidelines and a member of the American Academy of Neurology, said in an interview.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

The Infectious Diseases Society of America, AAN, and the American College of Rheumatology convened a multidisciplinary panel to develop the 43 recommendations, seeking input from 12 additional medical specialties, and patients. The panel conducted a systematic review of available evidence on preventing, diagnosing, and treating Lyme disease, using the Grading of Recommendations Assessment, Development and Evaluation model to evaluate clinical evidence and strength of recommendations. The guidelines were simultaneous published in Clinical Infectious Diseases, Neurology, Arthritis & Rheumatology, and Arthritis Care & Research.

This is the first time these organizations have collaborated on joint Lyme disease guidelines, which focus mainly on neurologic, cardiac, and rheumatologic manifestations.

“We are very excited to provide these updated guidelines to assist clinicians working in numerous medical specialties around the country, and even the world, as they care for patients suffering from Lyme disease,” Dr. Rumbaugh said.
 

When to use and not to use PCR

Guideline authors called for specific testing regimens depending on presentation of symptoms. Generally, they advised that individuals with a skin rash suggestive of early disease seek a clinical diagnosis instead of laboratory testing.

Recommendations on Lyme arthritis support previous IDSA guidelines published in 2006, Linda K. Bockenstedt, MD, professor of medicine at Yale University, New Haven, Conn., and a coauthor of the guidelines, said in an interview.

To evaluate for potential Lyme arthritis, clinicians should choose serum antibody testing over PCR or culture of blood or synovial fluid/tissue. However, if a doctor is assessing a seropositive patient for Lyme arthritis diagnosis but needs more information for treatment decisions, the authors recommended PCR applied to synovial fluid or tissue over Borrelia culture.

“Synovial fluid can be analyzed by PCR, but sensitivity is generally lower than serology,” Dr. Bockenstedt explained. Additionally, culture of joint fluid or synovial tissue for Lyme spirochetes has 0% sensitivity in multiple studies. “For these reasons, we recommend serum antibody testing over PCR of joint fluid or other methods for an initial diagnosis.”

Serum antibody testing over PCR or culture is also recommended for identifying Lyme neuroborreliosis in the peripheral nervous system (PNS) or CNS.

Despite the recent popularity of Lyme PCR testing in hospitals and labs, “with Lyme at least, antibodies are better in the CSF,” Dr. Rumbaugh said. Studies have shown that “most patients with even early neurologic Lyme disease are seropositive by conventional antibody testing at time of initial clinical presentation, and that intrathecal antibody production, as demonstrated by an elevated CSF:serum index, is highly specific for CNS involvement.”

If done correctly, antibody testing is both sensitive and specific for neurologic Lyme disease. “On the other hand, sensitivity of Lyme PCR performed on CSF has been only in the 5%-17% range in studies. Incidentally, Lyme PCR on blood is also not sensitive and therefore not recommended,” Dr. Rumbaugh said.

Guideline authors recommended testing in patients with the following conditions: acute neurologic disorders such as meningitis, painful radiculoneuritis, mononeuropathy multiplex; evidence of spinal cord or brain inflammation; and acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting.

They did not recommend testing in patients with typical amyotrophic lateral sclerosis; relapsing remitting multiple sclerosis; Parkinson’s disease, dementia, or cognitive decline; new-onset seizures; other neurologic syndromes or those lacking clinical or epidemiologic history that would support a diagnosis of Lyme disease; and patients with chronic cardiomyopathy of unknown cause.

The authors also called for judicious use of electrocardiogram to screen for Lyme carditis, recommending it only in patients signs or symptoms of this condition. However, patients at risk for or showing signs of severe cardiac complications of Lyme disease should be hospitalized and monitored via ECG.

Timelines for antibiotics

Most patients with Lyme disease should receive oral antibiotics, although duration times vary depending on the disease state. “We recommend that prophylactic antibiotic therapy be given to adults and children only within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk,” according to the guideline authors.

Specific antibiotic treatment regimens by condition are as follows: 10-14 days for early-stage disease, 14 days for Lyme carditis, 14-21 days for neurologic Lyme disease, and 28 days for late Lyme arthritis.

“Despite arthritis occurring late in the course of infection, treatment with a 28-day course of oral antibiotic is effective, although the rates of complete resolution of joint swelling can vary,” Dr. Bockenstedt said. Clinicians may consider a second 28-day course of oral antibiotics or a 2- to 4-week course of ceftriaxone in patients with persistent swelling, after an initial course of oral antibiotics.

Citing knowledge gaps, the authors made no recommendation on secondary antibiotic treatment for unresolved Lyme arthritis. Rheumatologists can play an important role in the care of this small subset of patients, Dr. Bockenstedt noted. “Studies of patients with ‘postantibiotic Lyme arthritis’ show that they can be treated successfully with intra-articular steroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, biologic response modifiers, and even synovectomy with successful outcomes.” Some of these therapies also work in cases where first courses of oral and intravenous antibiotics are unsuccessful.

“Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included one course of IV therapy,” the authors clarified.

For patients with Lyme disease–associated meningitis, cranial neuropathy, radiculoneuropathy, or other PNS manifestations, the authors recommended intravenous ceftriaxone, cefotaxime, penicillin G, or oral doxycycline over other antimicrobials.

“For most neurologic presentations, oral doxycycline is just as effective as appropriate IV antibiotics,” Dr. Rumbaugh said. “The exception is the relatively rare situation where the patient is felt to have parenchymal involvement of brain or spinal cord, in which case the guidelines recommend IV antibiotics over oral antibiotics.” In the studies, there was no statistically significant difference between oral or intravenous regimens in response rate or risk of adverse effects.

Patients with nonspecific symptoms such as fatigue, pain, or cognitive impairment following treatment should not receive additional antibiotic therapy if there’s no evidence of treatment failure or infection. These two markers “would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy,” the guideline authors wrote in comments accompanying the recommendation.

Clinicians caring for patients with symptomatic bradycardia caused by Lyme carditis should consider temporary pacing measures instead of a permanent pacemaker. For patients hospitalized with Lyme carditis, “we suggest initially using IV ceftriaxone over oral antibiotics until there is evidence of clinical improvement, then switching to oral antibiotics to complete treatment,” they advised. Outpatients with this condition should receive oral antibiotics instead of intravenous antibiotics.

Advice on antibodies testing ‘particularly cogent’

For individuals without expertise in these areas, the recommendations are clear and useful, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy), said in an interview.

“As a rheumatologist, I would have appreciated literature references for some of the recommendations but, nevertheless, find these useful. I applaud the care with which the evidence was gathered and the general formatting, which tried to review multiple possible scenarios surrounding Lyme arthritis,” said Dr. Furst, offering a third-party perspective.

The advice on using antibodies tests to make a diagnosis of Lyme arthritis “is particularly cogent and more useful than trying to culture these fastidious organisms,” he added.

The IDSA, AAN, and ACR provided support for the guideline. Dr. Bockenstedt reported receiving research funding from the National Institutes of Health and the Gordon and the Llura Gund Foundation and remuneration from L2 Diagnostics for investigator-initiated NIH-sponsored research. Dr. Rumbaugh had no conflicts of interest to disclose. Dr. Furst reported no conflicts of interest in commenting on these guidelines.

SOURCE: Rumbaugh JA et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1215.

New clinical practice guidelines on Lyme disease place a strong emphasis on antibody testing to assess for rheumatologic and neurologic syndromes. “Diagnostically, we recommend testing via antibodies, and an index of antibodies in cerebrospinal fluid [CSF] versus serum. Importantly, we recommend against using polymerase chain reaction [PCR] in CSF,” Jeffrey A. Rumbaugh, MD, PhD, a coauthor of the guidelines and a member of the American Academy of Neurology, said in an interview.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

The Infectious Diseases Society of America, AAN, and the American College of Rheumatology convened a multidisciplinary panel to develop the 43 recommendations, seeking input from 12 additional medical specialties, and patients. The panel conducted a systematic review of available evidence on preventing, diagnosing, and treating Lyme disease, using the Grading of Recommendations Assessment, Development and Evaluation model to evaluate clinical evidence and strength of recommendations. The guidelines were simultaneous published in Clinical Infectious Diseases, Neurology, Arthritis & Rheumatology, and Arthritis Care & Research.

This is the first time these organizations have collaborated on joint Lyme disease guidelines, which focus mainly on neurologic, cardiac, and rheumatologic manifestations.

“We are very excited to provide these updated guidelines to assist clinicians working in numerous medical specialties around the country, and even the world, as they care for patients suffering from Lyme disease,” Dr. Rumbaugh said.
 

When to use and not to use PCR

Guideline authors called for specific testing regimens depending on presentation of symptoms. Generally, they advised that individuals with a skin rash suggestive of early disease seek a clinical diagnosis instead of laboratory testing.

Recommendations on Lyme arthritis support previous IDSA guidelines published in 2006, Linda K. Bockenstedt, MD, professor of medicine at Yale University, New Haven, Conn., and a coauthor of the guidelines, said in an interview.

To evaluate for potential Lyme arthritis, clinicians should choose serum antibody testing over PCR or culture of blood or synovial fluid/tissue. However, if a doctor is assessing a seropositive patient for Lyme arthritis diagnosis but needs more information for treatment decisions, the authors recommended PCR applied to synovial fluid or tissue over Borrelia culture.

“Synovial fluid can be analyzed by PCR, but sensitivity is generally lower than serology,” Dr. Bockenstedt explained. Additionally, culture of joint fluid or synovial tissue for Lyme spirochetes has 0% sensitivity in multiple studies. “For these reasons, we recommend serum antibody testing over PCR of joint fluid or other methods for an initial diagnosis.”

Serum antibody testing over PCR or culture is also recommended for identifying Lyme neuroborreliosis in the peripheral nervous system (PNS) or CNS.

Despite the recent popularity of Lyme PCR testing in hospitals and labs, “with Lyme at least, antibodies are better in the CSF,” Dr. Rumbaugh said. Studies have shown that “most patients with even early neurologic Lyme disease are seropositive by conventional antibody testing at time of initial clinical presentation, and that intrathecal antibody production, as demonstrated by an elevated CSF:serum index, is highly specific for CNS involvement.”

If done correctly, antibody testing is both sensitive and specific for neurologic Lyme disease. “On the other hand, sensitivity of Lyme PCR performed on CSF has been only in the 5%-17% range in studies. Incidentally, Lyme PCR on blood is also not sensitive and therefore not recommended,” Dr. Rumbaugh said.

Guideline authors recommended testing in patients with the following conditions: acute neurologic disorders such as meningitis, painful radiculoneuritis, mononeuropathy multiplex; evidence of spinal cord or brain inflammation; and acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting.

They did not recommend testing in patients with typical amyotrophic lateral sclerosis; relapsing remitting multiple sclerosis; Parkinson’s disease, dementia, or cognitive decline; new-onset seizures; other neurologic syndromes or those lacking clinical or epidemiologic history that would support a diagnosis of Lyme disease; and patients with chronic cardiomyopathy of unknown cause.

The authors also called for judicious use of electrocardiogram to screen for Lyme carditis, recommending it only in patients signs or symptoms of this condition. However, patients at risk for or showing signs of severe cardiac complications of Lyme disease should be hospitalized and monitored via ECG.

Timelines for antibiotics

Most patients with Lyme disease should receive oral antibiotics, although duration times vary depending on the disease state. “We recommend that prophylactic antibiotic therapy be given to adults and children only within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk,” according to the guideline authors.

Specific antibiotic treatment regimens by condition are as follows: 10-14 days for early-stage disease, 14 days for Lyme carditis, 14-21 days for neurologic Lyme disease, and 28 days for late Lyme arthritis.

“Despite arthritis occurring late in the course of infection, treatment with a 28-day course of oral antibiotic is effective, although the rates of complete resolution of joint swelling can vary,” Dr. Bockenstedt said. Clinicians may consider a second 28-day course of oral antibiotics or a 2- to 4-week course of ceftriaxone in patients with persistent swelling, after an initial course of oral antibiotics.

Citing knowledge gaps, the authors made no recommendation on secondary antibiotic treatment for unresolved Lyme arthritis. Rheumatologists can play an important role in the care of this small subset of patients, Dr. Bockenstedt noted. “Studies of patients with ‘postantibiotic Lyme arthritis’ show that they can be treated successfully with intra-articular steroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, biologic response modifiers, and even synovectomy with successful outcomes.” Some of these therapies also work in cases where first courses of oral and intravenous antibiotics are unsuccessful.

“Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included one course of IV therapy,” the authors clarified.

For patients with Lyme disease–associated meningitis, cranial neuropathy, radiculoneuropathy, or other PNS manifestations, the authors recommended intravenous ceftriaxone, cefotaxime, penicillin G, or oral doxycycline over other antimicrobials.

“For most neurologic presentations, oral doxycycline is just as effective as appropriate IV antibiotics,” Dr. Rumbaugh said. “The exception is the relatively rare situation where the patient is felt to have parenchymal involvement of brain or spinal cord, in which case the guidelines recommend IV antibiotics over oral antibiotics.” In the studies, there was no statistically significant difference between oral or intravenous regimens in response rate or risk of adverse effects.

Patients with nonspecific symptoms such as fatigue, pain, or cognitive impairment following treatment should not receive additional antibiotic therapy if there’s no evidence of treatment failure or infection. These two markers “would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy,” the guideline authors wrote in comments accompanying the recommendation.

Clinicians caring for patients with symptomatic bradycardia caused by Lyme carditis should consider temporary pacing measures instead of a permanent pacemaker. For patients hospitalized with Lyme carditis, “we suggest initially using IV ceftriaxone over oral antibiotics until there is evidence of clinical improvement, then switching to oral antibiotics to complete treatment,” they advised. Outpatients with this condition should receive oral antibiotics instead of intravenous antibiotics.

Advice on antibodies testing ‘particularly cogent’

For individuals without expertise in these areas, the recommendations are clear and useful, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy), said in an interview.

“As a rheumatologist, I would have appreciated literature references for some of the recommendations but, nevertheless, find these useful. I applaud the care with which the evidence was gathered and the general formatting, which tried to review multiple possible scenarios surrounding Lyme arthritis,” said Dr. Furst, offering a third-party perspective.

The advice on using antibodies tests to make a diagnosis of Lyme arthritis “is particularly cogent and more useful than trying to culture these fastidious organisms,” he added.

The IDSA, AAN, and ACR provided support for the guideline. Dr. Bockenstedt reported receiving research funding from the National Institutes of Health and the Gordon and the Llura Gund Foundation and remuneration from L2 Diagnostics for investigator-initiated NIH-sponsored research. Dr. Rumbaugh had no conflicts of interest to disclose. Dr. Furst reported no conflicts of interest in commenting on these guidelines.

SOURCE: Rumbaugh JA et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1215.

New clinical practice guidelines on Lyme disease place a strong emphasis on antibody testing to assess for rheumatologic and neurologic syndromes. “Diagnostically, we recommend testing via antibodies, and an index of antibodies in cerebrospinal fluid [CSF] versus serum. Importantly, we recommend against using polymerase chain reaction [PCR] in CSF,” Jeffrey A. Rumbaugh, MD, PhD, a coauthor of the guidelines and a member of the American Academy of Neurology, said in an interview.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

The Infectious Diseases Society of America, AAN, and the American College of Rheumatology convened a multidisciplinary panel to develop the 43 recommendations, seeking input from 12 additional medical specialties, and patients. The panel conducted a systematic review of available evidence on preventing, diagnosing, and treating Lyme disease, using the Grading of Recommendations Assessment, Development and Evaluation model to evaluate clinical evidence and strength of recommendations. The guidelines were simultaneous published in Clinical Infectious Diseases, Neurology, Arthritis & Rheumatology, and Arthritis Care & Research.

This is the first time these organizations have collaborated on joint Lyme disease guidelines, which focus mainly on neurologic, cardiac, and rheumatologic manifestations.

“We are very excited to provide these updated guidelines to assist clinicians working in numerous medical specialties around the country, and even the world, as they care for patients suffering from Lyme disease,” Dr. Rumbaugh said.
 

When to use and not to use PCR

Guideline authors called for specific testing regimens depending on presentation of symptoms. Generally, they advised that individuals with a skin rash suggestive of early disease seek a clinical diagnosis instead of laboratory testing.

Recommendations on Lyme arthritis support previous IDSA guidelines published in 2006, Linda K. Bockenstedt, MD, professor of medicine at Yale University, New Haven, Conn., and a coauthor of the guidelines, said in an interview.

To evaluate for potential Lyme arthritis, clinicians should choose serum antibody testing over PCR or culture of blood or synovial fluid/tissue. However, if a doctor is assessing a seropositive patient for Lyme arthritis diagnosis but needs more information for treatment decisions, the authors recommended PCR applied to synovial fluid or tissue over Borrelia culture.

“Synovial fluid can be analyzed by PCR, but sensitivity is generally lower than serology,” Dr. Bockenstedt explained. Additionally, culture of joint fluid or synovial tissue for Lyme spirochetes has 0% sensitivity in multiple studies. “For these reasons, we recommend serum antibody testing over PCR of joint fluid or other methods for an initial diagnosis.”

Serum antibody testing over PCR or culture is also recommended for identifying Lyme neuroborreliosis in the peripheral nervous system (PNS) or CNS.

Despite the recent popularity of Lyme PCR testing in hospitals and labs, “with Lyme at least, antibodies are better in the CSF,” Dr. Rumbaugh said. Studies have shown that “most patients with even early neurologic Lyme disease are seropositive by conventional antibody testing at time of initial clinical presentation, and that intrathecal antibody production, as demonstrated by an elevated CSF:serum index, is highly specific for CNS involvement.”

If done correctly, antibody testing is both sensitive and specific for neurologic Lyme disease. “On the other hand, sensitivity of Lyme PCR performed on CSF has been only in the 5%-17% range in studies. Incidentally, Lyme PCR on blood is also not sensitive and therefore not recommended,” Dr. Rumbaugh said.

Guideline authors recommended testing in patients with the following conditions: acute neurologic disorders such as meningitis, painful radiculoneuritis, mononeuropathy multiplex; evidence of spinal cord or brain inflammation; and acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting.

They did not recommend testing in patients with typical amyotrophic lateral sclerosis; relapsing remitting multiple sclerosis; Parkinson’s disease, dementia, or cognitive decline; new-onset seizures; other neurologic syndromes or those lacking clinical or epidemiologic history that would support a diagnosis of Lyme disease; and patients with chronic cardiomyopathy of unknown cause.

The authors also called for judicious use of electrocardiogram to screen for Lyme carditis, recommending it only in patients signs or symptoms of this condition. However, patients at risk for or showing signs of severe cardiac complications of Lyme disease should be hospitalized and monitored via ECG.

Timelines for antibiotics

Most patients with Lyme disease should receive oral antibiotics, although duration times vary depending on the disease state. “We recommend that prophylactic antibiotic therapy be given to adults and children only within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk,” according to the guideline authors.

Specific antibiotic treatment regimens by condition are as follows: 10-14 days for early-stage disease, 14 days for Lyme carditis, 14-21 days for neurologic Lyme disease, and 28 days for late Lyme arthritis.

“Despite arthritis occurring late in the course of infection, treatment with a 28-day course of oral antibiotic is effective, although the rates of complete resolution of joint swelling can vary,” Dr. Bockenstedt said. Clinicians may consider a second 28-day course of oral antibiotics or a 2- to 4-week course of ceftriaxone in patients with persistent swelling, after an initial course of oral antibiotics.

Citing knowledge gaps, the authors made no recommendation on secondary antibiotic treatment for unresolved Lyme arthritis. Rheumatologists can play an important role in the care of this small subset of patients, Dr. Bockenstedt noted. “Studies of patients with ‘postantibiotic Lyme arthritis’ show that they can be treated successfully with intra-articular steroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, biologic response modifiers, and even synovectomy with successful outcomes.” Some of these therapies also work in cases where first courses of oral and intravenous antibiotics are unsuccessful.

“Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included one course of IV therapy,” the authors clarified.

For patients with Lyme disease–associated meningitis, cranial neuropathy, radiculoneuropathy, or other PNS manifestations, the authors recommended intravenous ceftriaxone, cefotaxime, penicillin G, or oral doxycycline over other antimicrobials.

“For most neurologic presentations, oral doxycycline is just as effective as appropriate IV antibiotics,” Dr. Rumbaugh said. “The exception is the relatively rare situation where the patient is felt to have parenchymal involvement of brain or spinal cord, in which case the guidelines recommend IV antibiotics over oral antibiotics.” In the studies, there was no statistically significant difference between oral or intravenous regimens in response rate or risk of adverse effects.

Patients with nonspecific symptoms such as fatigue, pain, or cognitive impairment following treatment should not receive additional antibiotic therapy if there’s no evidence of treatment failure or infection. These two markers “would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy,” the guideline authors wrote in comments accompanying the recommendation.

Clinicians caring for patients with symptomatic bradycardia caused by Lyme carditis should consider temporary pacing measures instead of a permanent pacemaker. For patients hospitalized with Lyme carditis, “we suggest initially using IV ceftriaxone over oral antibiotics until there is evidence of clinical improvement, then switching to oral antibiotics to complete treatment,” they advised. Outpatients with this condition should receive oral antibiotics instead of intravenous antibiotics.

Advice on antibodies testing ‘particularly cogent’

For individuals without expertise in these areas, the recommendations are clear and useful, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy), said in an interview.

“As a rheumatologist, I would have appreciated literature references for some of the recommendations but, nevertheless, find these useful. I applaud the care with which the evidence was gathered and the general formatting, which tried to review multiple possible scenarios surrounding Lyme arthritis,” said Dr. Furst, offering a third-party perspective.

The advice on using antibodies tests to make a diagnosis of Lyme arthritis “is particularly cogent and more useful than trying to culture these fastidious organisms,” he added.

The IDSA, AAN, and ACR provided support for the guideline. Dr. Bockenstedt reported receiving research funding from the National Institutes of Health and the Gordon and the Llura Gund Foundation and remuneration from L2 Diagnostics for investigator-initiated NIH-sponsored research. Dr. Rumbaugh had no conflicts of interest to disclose. Dr. Furst reported no conflicts of interest in commenting on these guidelines.

SOURCE: Rumbaugh JA et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1215.

Key clinical point: This study found significant increases in blood pressure (BP) during alemtuzumab infusions in patients with multiple sclerosis (MS).

Major finding: For cycle 1, systolic BP (SBP) increased by 19.2 ± 9.4 mmHg during first infusion, with comparable percentage over the next 5 infusions (16%, 22%, 17%, 11%, and 13%), respectively. Diastolic BP (DBP) increased by 6.2 ± 3.8 mmHg with similar percentage increase as well (8.4%, 11.5%, 5.5%, 7%, and 3%). Second cycle (12 months later) showed similar increases in SBP and DBP as the first cycle. Third cycle (at variable follow-up times) showed similar trends with increased SBP and DBP. Overall, 54.8% of patients had increasing BP reading by 20% or more from baseline, while 29% had increased by at least 20 mmHg from baseline.

Study details: The data come from a retrospective study of SBP and DBP in MS patients treated with alemtuzumab at the London MS Clinic (n = 31; 64.5% females; mean age, 35.2 years).

Disclosures: No study sponsor was identified. Eslam Shosha and Christine Tomkinson reported no disclosures. Sarah Morrow and Courtney Casserly reported relationships with multiple pharmaceutical companies.

Source: Shosha E et al. Eur J Neurol. 2020 Nov 11. doi: 10.1111/ene.14633.

Key clinical point: This study found significant increases in blood pressure (BP) during alemtuzumab infusions in patients with multiple sclerosis (MS).

Major finding: For cycle 1, systolic BP (SBP) increased by 19.2 ± 9.4 mmHg during first infusion, with comparable percentage over the next 5 infusions (16%, 22%, 17%, 11%, and 13%), respectively. Diastolic BP (DBP) increased by 6.2 ± 3.8 mmHg with similar percentage increase as well (8.4%, 11.5%, 5.5%, 7%, and 3%). Second cycle (12 months later) showed similar increases in SBP and DBP as the first cycle. Third cycle (at variable follow-up times) showed similar trends with increased SBP and DBP. Overall, 54.8% of patients had increasing BP reading by 20% or more from baseline, while 29% had increased by at least 20 mmHg from baseline.

Study details: The data come from a retrospective study of SBP and DBP in MS patients treated with alemtuzumab at the London MS Clinic (n = 31; 64.5% females; mean age, 35.2 years).

Disclosures: No study sponsor was identified. Eslam Shosha and Christine Tomkinson reported no disclosures. Sarah Morrow and Courtney Casserly reported relationships with multiple pharmaceutical companies.

Source: Shosha E et al. Eur J Neurol. 2020 Nov 11. doi: 10.1111/ene.14633.

Key clinical point: This study found significant increases in blood pressure (BP) during alemtuzumab infusions in patients with multiple sclerosis (MS).

Major finding: For cycle 1, systolic BP (SBP) increased by 19.2 ± 9.4 mmHg during first infusion, with comparable percentage over the next 5 infusions (16%, 22%, 17%, 11%, and 13%), respectively. Diastolic BP (DBP) increased by 6.2 ± 3.8 mmHg with similar percentage increase as well (8.4%, 11.5%, 5.5%, 7%, and 3%). Second cycle (12 months later) showed similar increases in SBP and DBP as the first cycle. Third cycle (at variable follow-up times) showed similar trends with increased SBP and DBP. Overall, 54.8% of patients had increasing BP reading by 20% or more from baseline, while 29% had increased by at least 20 mmHg from baseline.

Study details: The data come from a retrospective study of SBP and DBP in MS patients treated with alemtuzumab at the London MS Clinic (n = 31; 64.5% females; mean age, 35.2 years).

Disclosures: No study sponsor was identified. Eslam Shosha and Christine Tomkinson reported no disclosures. Sarah Morrow and Courtney Casserly reported relationships with multiple pharmaceutical companies.

Source: Shosha E et al. Eur J Neurol. 2020 Nov 11. doi: 10.1111/ene.14633.

Key clinical point: The proportion of patients with active relapsing-remitting multiple sclerosis (MS) reaching “no evidence of disease activity” (NEDA) was greater with natalizumab (NTZ) vs. fingolimod (FTY) after a year of treatment.

Major finding: At 12 months, 47.8% of NTZ-treated patients reached NEDA vs. 30.4% of FTY-treated patients. The risk of relapse was lower with NTZ vs. FTY after 6 months of treatment (annualized relapse rate, 0.02 vs. 0.09; P = .05). MRI outcomes revealed a higher NTZ effectiveness regarding the number of new T2 (0.44 vs. 1.14; P = .03) and gadolinium-enhancing (0.03 vs. 0.48; P = .03) lesions.

Study details: BEST-MS was a multicentric, prospective study with a 12-month follow-up period that compared the efficacy of NTZ and FTY in active relapsing-remitting MS. A total of 223 patients were included (109 patients were treated with NTZ and 114 with FTY).

Disclosures: The study has received funding from FP7 Health Innovation-1 in 2012. Pierre Labauge received grants from Biogen and Novartis. Kevin Bigaut received grant travel by Biogen Idec and Sanofi-Genzyme. No other disclosures were reported.

Source: Cohen M et al. Mult Scler. 2020 Oct 30. doi: 10.1177/1352458520969145.

Key clinical point: The proportion of patients with active relapsing-remitting multiple sclerosis (MS) reaching “no evidence of disease activity” (NEDA) was greater with natalizumab (NTZ) vs. fingolimod (FTY) after a year of treatment.

Major finding: At 12 months, 47.8% of NTZ-treated patients reached NEDA vs. 30.4% of FTY-treated patients. The risk of relapse was lower with NTZ vs. FTY after 6 months of treatment (annualized relapse rate, 0.02 vs. 0.09; P = .05). MRI outcomes revealed a higher NTZ effectiveness regarding the number of new T2 (0.44 vs. 1.14; P = .03) and gadolinium-enhancing (0.03 vs. 0.48; P = .03) lesions.

Study details: BEST-MS was a multicentric, prospective study with a 12-month follow-up period that compared the efficacy of NTZ and FTY in active relapsing-remitting MS. A total of 223 patients were included (109 patients were treated with NTZ and 114 with FTY).

Disclosures: The study has received funding from FP7 Health Innovation-1 in 2012. Pierre Labauge received grants from Biogen and Novartis. Kevin Bigaut received grant travel by Biogen Idec and Sanofi-Genzyme. No other disclosures were reported.

Source: Cohen M et al. Mult Scler. 2020 Oct 30. doi: 10.1177/1352458520969145.

Key clinical point: The proportion of patients with active relapsing-remitting multiple sclerosis (MS) reaching “no evidence of disease activity” (NEDA) was greater with natalizumab (NTZ) vs. fingolimod (FTY) after a year of treatment.

Major finding: At 12 months, 47.8% of NTZ-treated patients reached NEDA vs. 30.4% of FTY-treated patients. The risk of relapse was lower with NTZ vs. FTY after 6 months of treatment (annualized relapse rate, 0.02 vs. 0.09; P = .05). MRI outcomes revealed a higher NTZ effectiveness regarding the number of new T2 (0.44 vs. 1.14; P = .03) and gadolinium-enhancing (0.03 vs. 0.48; P = .03) lesions.

Study details: BEST-MS was a multicentric, prospective study with a 12-month follow-up period that compared the efficacy of NTZ and FTY in active relapsing-remitting MS. A total of 223 patients were included (109 patients were treated with NTZ and 114 with FTY).

Disclosures: The study has received funding from FP7 Health Innovation-1 in 2012. Pierre Labauge received grants from Biogen and Novartis. Kevin Bigaut received grant travel by Biogen Idec and Sanofi-Genzyme. No other disclosures were reported.

Source: Cohen M et al. Mult Scler. 2020 Oct 30. doi: 10.1177/1352458520969145.

Key clinical point: Earlier and continuous ocrelizumab treatment provided sustained benefits on measures of disease progression in patients with primary progressive multiple sclerosis (PPMS).

Major finding: Over a period of 6.5 study years, the proportion of patients with progression on disability measures at 24 weeks was lower in those who started ocrelizumab early vs. those who started with placebo: Expanded Disability Status Scale Score (51.7% vs. 64.8%; P = .0018), 9-Hole Peg Test (30.6% vs. 43.1%; P = .0035), Timed 25-Foot Walk (63.2% vs. 70.7%; P = .058), and composite progression (73.2% vs. 83.3%; P = .0023). No new safety signals emerged compared with the double-blind phase of ORATORIO.

Study details: The findings are based on a long-term follow-up from the phase 3 ORATORIO extension study. 732 patients with PPMS were randomly assigned (2:1) to receive ocrelizumab or placebo every 24 weeks for at least 120 weeks. Overall, 544 participants completed the double-blind period and 527 people entered the open-label extension phase, during which they continued ocrelizumab or switched from placebo to ocrelizumab.

Disclosures: The study was funded by F Hoffmann-La Roche. The presenting author received personal fees for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Actelion, Alkermes, Brainstorm Cell Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, NervGen Pharma, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, and Sanofi Genzyme; and royalties for out licensed monoclonal antibodies through UTHealth from Millipore Corporation.

Source: Wolinsky JS et al. Lancet Neurol. 2020 Oct 29. doi: 10.1016/S1474-4422(20)30342-2.

Key clinical point: Earlier and continuous ocrelizumab treatment provided sustained benefits on measures of disease progression in patients with primary progressive multiple sclerosis (PPMS).

Major finding: Over a period of 6.5 study years, the proportion of patients with progression on disability measures at 24 weeks was lower in those who started ocrelizumab early vs. those who started with placebo: Expanded Disability Status Scale Score (51.7% vs. 64.8%; P = .0018), 9-Hole Peg Test (30.6% vs. 43.1%; P = .0035), Timed 25-Foot Walk (63.2% vs. 70.7%; P = .058), and composite progression (73.2% vs. 83.3%; P = .0023). No new safety signals emerged compared with the double-blind phase of ORATORIO.

Study details: The findings are based on a long-term follow-up from the phase 3 ORATORIO extension study. 732 patients with PPMS were randomly assigned (2:1) to receive ocrelizumab or placebo every 24 weeks for at least 120 weeks. Overall, 544 participants completed the double-blind period and 527 people entered the open-label extension phase, during which they continued ocrelizumab or switched from placebo to ocrelizumab.

Disclosures: The study was funded by F Hoffmann-La Roche. The presenting author received personal fees for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Actelion, Alkermes, Brainstorm Cell Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, NervGen Pharma, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, and Sanofi Genzyme; and royalties for out licensed monoclonal antibodies through UTHealth from Millipore Corporation.

Source: Wolinsky JS et al. Lancet Neurol. 2020 Oct 29. doi: 10.1016/S1474-4422(20)30342-2.

Key clinical point: Earlier and continuous ocrelizumab treatment provided sustained benefits on measures of disease progression in patients with primary progressive multiple sclerosis (PPMS).

Major finding: Over a period of 6.5 study years, the proportion of patients with progression on disability measures at 24 weeks was lower in those who started ocrelizumab early vs. those who started with placebo: Expanded Disability Status Scale Score (51.7% vs. 64.8%; P = .0018), 9-Hole Peg Test (30.6% vs. 43.1%; P = .0035), Timed 25-Foot Walk (63.2% vs. 70.7%; P = .058), and composite progression (73.2% vs. 83.3%; P = .0023). No new safety signals emerged compared with the double-blind phase of ORATORIO.

Study details: The findings are based on a long-term follow-up from the phase 3 ORATORIO extension study. 732 patients with PPMS were randomly assigned (2:1) to receive ocrelizumab or placebo every 24 weeks for at least 120 weeks. Overall, 544 participants completed the double-blind period and 527 people entered the open-label extension phase, during which they continued ocrelizumab or switched from placebo to ocrelizumab.

Disclosures: The study was funded by F Hoffmann-La Roche. The presenting author received personal fees for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Actelion, Alkermes, Brainstorm Cell Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, NervGen Pharma, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, and Sanofi Genzyme; and royalties for out licensed monoclonal antibodies through UTHealth from Millipore Corporation.

Source: Wolinsky JS et al. Lancet Neurol. 2020 Oct 29. doi: 10.1016/S1474-4422(20)30342-2.

Key clinical point: Toxoplasma gondii (T. gondii) is negatively associated with multiple sclerosis (MS), suggesting a possible protective role of the parasite in MS.

Major finding: Anti-T. gondii antibodies were detected in 38 MS patients (29.5%) and 130 healthy controls (45.4%). After adjustment, T. gondii seropositivity was significantly associated with a reduced risk of MS (adjusted odds ratio, 0.56; P = .02).

Study details: The data come from an Italian population‑based case-control study of 129 patients with MS and 287 age- and sex-matched controls.

Disclosures: This research was funded by the Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” University of Catania, Italy. The authors declared no conflicts of interest.

Source: Nicoletti A et al. Sci Rep. 2020 Nov 2. doi: 10.1038/s41598-020-75830-y.

Key clinical point: Toxoplasma gondii (T. gondii) is negatively associated with multiple sclerosis (MS), suggesting a possible protective role of the parasite in MS.

Major finding: Anti-T. gondii antibodies were detected in 38 MS patients (29.5%) and 130 healthy controls (45.4%). After adjustment, T. gondii seropositivity was significantly associated with a reduced risk of MS (adjusted odds ratio, 0.56; P = .02).

Study details: The data come from an Italian population‑based case-control study of 129 patients with MS and 287 age- and sex-matched controls.

Disclosures: This research was funded by the Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” University of Catania, Italy. The authors declared no conflicts of interest.

Source: Nicoletti A et al. Sci Rep. 2020 Nov 2. doi: 10.1038/s41598-020-75830-y.

Key clinical point: Toxoplasma gondii (T. gondii) is negatively associated with multiple sclerosis (MS), suggesting a possible protective role of the parasite in MS.

Major finding: Anti-T. gondii antibodies were detected in 38 MS patients (29.5%) and 130 healthy controls (45.4%). After adjustment, T. gondii seropositivity was significantly associated with a reduced risk of MS (adjusted odds ratio, 0.56; P = .02).

Study details: The data come from an Italian population‑based case-control study of 129 patients with MS and 287 age- and sex-matched controls.

Disclosures: This research was funded by the Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” University of Catania, Italy. The authors declared no conflicts of interest.

Source: Nicoletti A et al. Sci Rep. 2020 Nov 2. doi: 10.1038/s41598-020-75830-y.

Best of 2020: The MS Report  is a supplement to Neurology Reviews. 

In this supplement, Neurology Reviews collects the top MS research from 2020. Coverage includes MS highlights from the ACTRIMS, AAN, CMSC, and ECTRIMS annual meetings.

Read Now

Best of 2020: The MS Report  is a supplement to Neurology Reviews. 

In this supplement, Neurology Reviews collects the top MS research from 2020. Coverage includes MS highlights from the ACTRIMS, AAN, CMSC, and ECTRIMS annual meetings.

Read Now

Best of 2020: The MS Report  is a supplement to Neurology Reviews. 

In this supplement, Neurology Reviews collects the top MS research from 2020. Coverage includes MS highlights from the ACTRIMS, AAN, CMSC, and ECTRIMS annual meetings.

Read Now

Key clinical point: Nearly one third of patients with multiple sclerosis (MS) experience migraine.

Major finding: The pooled prevalence rate of migraine was 31% (P less than .001), which significantly varied across the continents (P less than .001).

Study details: A systematic review and meta-analysis of 11 articles and 12 conference abstracts including a total of 11,372 MS cases.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Citation: Mirmosayyeb O et al. J Clin Neuroscience. 2020 Aug 4. doi: 10.1016/j.jocn.2020.06.021.

Key clinical point: Nearly one third of patients with multiple sclerosis (MS) experience migraine.

Major finding: The pooled prevalence rate of migraine was 31% (P less than .001), which significantly varied across the continents (P less than .001).

Study details: A systematic review and meta-analysis of 11 articles and 12 conference abstracts including a total of 11,372 MS cases.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Citation: Mirmosayyeb O et al. J Clin Neuroscience. 2020 Aug 4. doi: 10.1016/j.jocn.2020.06.021.

Key clinical point: Nearly one third of patients with multiple sclerosis (MS) experience migraine.

Major finding: The pooled prevalence rate of migraine was 31% (P less than .001), which significantly varied across the continents (P less than .001).

Study details: A systematic review and meta-analysis of 11 articles and 12 conference abstracts including a total of 11,372 MS cases.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Citation: Mirmosayyeb O et al. J Clin Neuroscience. 2020 Aug 4. doi: 10.1016/j.jocn.2020.06.021.