Multiple sclerosis “top picks” from AAN 2018

 

Clinical Neurology News editorial advisory board member Jonathan L. Carter, MD, scoured the pages of the American Academy of Neurology’s annual meeting program for his “top picks” in multiple sclerosis at this year’s meeting.

The top personal choices of Dr. Carter, an associate professor of neurology at the Mayo Clinic Arizona in Phoenix who specializes in multiple sclerosis (MS), are abstracts about neurofilament light chains (NFLCs) as biomarkers for disease progression and response; cognitive function outcomes in MS clinical trials; better outcome measures; the relative impact of age versus relapse on treatment response; what makes neuromyelitis optica spectrum disorders different from other autoimmune CNS diseases; and data updates on recently approved or investigational MS therapies.

NFLCs in serum as a biomarker for MS and treatment response. Multiple abstracts explore the use of NFLCs as a marker for disease progression and response to MS therapies, including:

• Hot Topics Plenary Session presentation: “Monitoring Multiple Sclerosis Using Blood Neurofilament Light Protein” by Jens Kuhle, MD.
• P5.036, Serum and CSF Neurofilament Light Chain levels normalise following Bone Marrow Transplant in MS Patients.
• S24.002, Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS).
• S24.003, Serum Neurofilament Light (NfL): Towards a Blood Test for Prognosis and Disease/Treatment Monitoring in Multiple Sclerosis Patients.
• S24.004, Long-term Prognosis of Disease Evolution and Evidence for Sustained Fingolimod Treatment Effect by Blood Neurofilament Light in RRMS Patients.
• S24.007, Including Blood Neurofilament Light Chain in the NEDA Concept in Relapsing Remitting Multiple Sclerosis Trials.
• S8.006, Siponimod Reduces Neurofilament Light Chain Blood Levels in Secondary Progressive Multiple Sclerosis Patients.

Cognitive function as an outcome measure in MS clinical trials. Several abstracts examine cognition as an outcome measure in clinical trials and show slowing of cognitive worsening in patients on MS disease-modifying therapies:

• S44.004, Impact of Siponimod on Cognition in Patients With Secondary Progressive Multiple Sclerosis: Results From Phase 3 EXPAND Study.
• S44.005, Time to Cognitive Worsening in Patients With Relapsing Multiple Sclerosis in Ocrelizumab Phase 3 Trials.
• S44.007, Benchmarks of Cognitive Performance in a Large, Representative Patient Population.

 

Improved disability outcome measures and predictors of disability in MS. Several abstracts assess novel disability outcome measures and neuroimaging techniques to better predict progression of clinical disability:

• P4.380, Overall Response Score: A Novel Disability Endpoint That Allows for the Integrated Assessment of Improvement and Worsening over Time in Patients with MS.
• S47.001, Longitudinal Changes in Quantitative Spinal Cord MRI in Multiple Sclerosis Patients: Results of a 5-year Study.
• P6.354, Effect of Fingolimod 0.5 mg/day versus Placebo on Two Newly Developed Expanded Disability Status Scale (EDSS) Subscales for Patients with Relapsing Remitting MS: EDSS Factor Analysis.

Is treatment response in MS an age-dependent or relapse-driven phenomenon, and is it safe to discontinue MS therapies with advancing age? Several abstracts address this question:

• S47.004, Meta-Analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.
• S8.005, Uncoupling the Impact on Relapses and Disability Progression: Siponimod in Relapsing and Nonrelapsing Patients With Secondary Progressive Multiple Sclerosis in the Phase 3 EXPAND Study.
• S8.008, Discontinuation of Disease Modifying Therapies in Stable MS Patients is Associated with Disability Progression Regardless of Age.

Neuromyelitis optica spectrum disorders and MS mimics. Multiple abstracts explore the differences between neuromyelitis optica spectrum disorder because of aquaporin-4 versus myelin oligodendrocyte glycoprotein antibodies; describe unique features of another recently described autoimmune disorder, autoimmune GFAP astrocytopathy; and explore the differential diagnosis of idiopathic transverse myelitis:

• S13.002, Clinical Characteristics of MOG and AQP associated Neuromyelitis Optica Spectrum Disorder (NMOSD) in Adults, through S13.008, It’s Not All Transverse Myelitis: The Differential Diagnosis of Spinal Cord Myelopathy.
• P6.409, The Mayo Clinic Glial Autoimmunity Study: Glial autoantibody (AQP4/MOG/GFAP) serostatus in recurrent longitudinally extensive transverse myelitis.
• P6.417, Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.
• S6.003, Brain and Spinal Cord Imaging Features in Neuromyelitis Optica Spectrum Disorders.

 

Updated safety and efficacy data for recently approved or investigational MS therapies. Multiple abstracts report updated safety and efficacy data from MS clinical trials of ozanimod, ocrelizumab (Ocrevus), and hematopoietic stem cell transplantation:

• Clinical Trials Plenary Session presentation: “A Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis” by Robert J. Fox, MD.
• Contemporary Clinical Issues Plenary Session presentation: “Biosimilars and Nonbiologic Complex Drugs” by Jeffrey Allan Cohen, MD.
• S6.002, Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase 3 Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis.
• P3.410, Clinical and Magnetic Resonance Imaging Results From RADIANCE Part B, a Multicenter, Randomized, Double-Blind, Phase 3 Trial of Ozanimod Versus Intramuscular Interferon beta-1a in Relapsing Multiple Sclerosis (RMS).
• P3.396, Ozanimod Demonstrates Efficacy and Safety in a Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Phase 3 Trial of Relapsing Multiple Sclerosis (SUNBEAM).
• S36.001, Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis.
• S36.004, Nonmyeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial.
• S36.005, Efficacy of Ozanimod Versus Interferon beta-1a by Prior Treatment and Baseline Disability in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).
• S36.006, Safety of Ozanimod Versus Interferon beta-1a in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).

New thoughts on MS pathogenesis.

• Frontiers in Neuroscience Plenary Session presentation: “Pediatric MS: A Unique Window into Environmental and Genetic Risk Factors for MS” by Emmanuelle Waubant, MD.

Dr. Carter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Pharmaceuticals. He has received research support from Roche/Genentech and MedDay Pharmaceuticals.
 

 

Clinical Neurology News editorial advisory board member Jonathan L. Carter, MD, scoured the pages of the American Academy of Neurology’s annual meeting program for his “top picks” in multiple sclerosis at this year’s meeting.

The top personal choices of Dr. Carter, an associate professor of neurology at the Mayo Clinic Arizona in Phoenix who specializes in multiple sclerosis (MS), are abstracts about neurofilament light chains (NFLCs) as biomarkers for disease progression and response; cognitive function outcomes in MS clinical trials; better outcome measures; the relative impact of age versus relapse on treatment response; what makes neuromyelitis optica spectrum disorders different from other autoimmune CNS diseases; and data updates on recently approved or investigational MS therapies.

NFLCs in serum as a biomarker for MS and treatment response. Multiple abstracts explore the use of NFLCs as a marker for disease progression and response to MS therapies, including:

• Hot Topics Plenary Session presentation: “Monitoring Multiple Sclerosis Using Blood Neurofilament Light Protein” by Jens Kuhle, MD.
• P5.036, Serum and CSF Neurofilament Light Chain levels normalise following Bone Marrow Transplant in MS Patients.
• S24.002, Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS).
• S24.003, Serum Neurofilament Light (NfL): Towards a Blood Test for Prognosis and Disease/Treatment Monitoring in Multiple Sclerosis Patients.
• S24.004, Long-term Prognosis of Disease Evolution and Evidence for Sustained Fingolimod Treatment Effect by Blood Neurofilament Light in RRMS Patients.
• S24.007, Including Blood Neurofilament Light Chain in the NEDA Concept in Relapsing Remitting Multiple Sclerosis Trials.
• S8.006, Siponimod Reduces Neurofilament Light Chain Blood Levels in Secondary Progressive Multiple Sclerosis Patients.

Cognitive function as an outcome measure in MS clinical trials. Several abstracts examine cognition as an outcome measure in clinical trials and show slowing of cognitive worsening in patients on MS disease-modifying therapies:

• S44.004, Impact of Siponimod on Cognition in Patients With Secondary Progressive Multiple Sclerosis: Results From Phase 3 EXPAND Study.
• S44.005, Time to Cognitive Worsening in Patients With Relapsing Multiple Sclerosis in Ocrelizumab Phase 3 Trials.
• S44.007, Benchmarks of Cognitive Performance in a Large, Representative Patient Population.

 

Improved disability outcome measures and predictors of disability in MS. Several abstracts assess novel disability outcome measures and neuroimaging techniques to better predict progression of clinical disability:

• P4.380, Overall Response Score: A Novel Disability Endpoint That Allows for the Integrated Assessment of Improvement and Worsening over Time in Patients with MS.
• S47.001, Longitudinal Changes in Quantitative Spinal Cord MRI in Multiple Sclerosis Patients: Results of a 5-year Study.
• P6.354, Effect of Fingolimod 0.5 mg/day versus Placebo on Two Newly Developed Expanded Disability Status Scale (EDSS) Subscales for Patients with Relapsing Remitting MS: EDSS Factor Analysis.

Is treatment response in MS an age-dependent or relapse-driven phenomenon, and is it safe to discontinue MS therapies with advancing age? Several abstracts address this question:

• S47.004, Meta-Analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.
• S8.005, Uncoupling the Impact on Relapses and Disability Progression: Siponimod in Relapsing and Nonrelapsing Patients With Secondary Progressive Multiple Sclerosis in the Phase 3 EXPAND Study.
• S8.008, Discontinuation of Disease Modifying Therapies in Stable MS Patients is Associated with Disability Progression Regardless of Age.

Neuromyelitis optica spectrum disorders and MS mimics. Multiple abstracts explore the differences between neuromyelitis optica spectrum disorder because of aquaporin-4 versus myelin oligodendrocyte glycoprotein antibodies; describe unique features of another recently described autoimmune disorder, autoimmune GFAP astrocytopathy; and explore the differential diagnosis of idiopathic transverse myelitis:

• S13.002, Clinical Characteristics of MOG and AQP associated Neuromyelitis Optica Spectrum Disorder (NMOSD) in Adults, through S13.008, It’s Not All Transverse Myelitis: The Differential Diagnosis of Spinal Cord Myelopathy.
• P6.409, The Mayo Clinic Glial Autoimmunity Study: Glial autoantibody (AQP4/MOG/GFAP) serostatus in recurrent longitudinally extensive transverse myelitis.
• P6.417, Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.
• S6.003, Brain and Spinal Cord Imaging Features in Neuromyelitis Optica Spectrum Disorders.

 

Updated safety and efficacy data for recently approved or investigational MS therapies. Multiple abstracts report updated safety and efficacy data from MS clinical trials of ozanimod, ocrelizumab (Ocrevus), and hematopoietic stem cell transplantation:

• Clinical Trials Plenary Session presentation: “A Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis” by Robert J. Fox, MD.
• Contemporary Clinical Issues Plenary Session presentation: “Biosimilars and Nonbiologic Complex Drugs” by Jeffrey Allan Cohen, MD.
• S6.002, Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase 3 Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis.
• P3.410, Clinical and Magnetic Resonance Imaging Results From RADIANCE Part B, a Multicenter, Randomized, Double-Blind, Phase 3 Trial of Ozanimod Versus Intramuscular Interferon beta-1a in Relapsing Multiple Sclerosis (RMS).
• P3.396, Ozanimod Demonstrates Efficacy and Safety in a Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Phase 3 Trial of Relapsing Multiple Sclerosis (SUNBEAM).
• S36.001, Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis.
• S36.004, Nonmyeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial.
• S36.005, Efficacy of Ozanimod Versus Interferon beta-1a by Prior Treatment and Baseline Disability in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).
• S36.006, Safety of Ozanimod Versus Interferon beta-1a in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).

New thoughts on MS pathogenesis.

• Frontiers in Neuroscience Plenary Session presentation: “Pediatric MS: A Unique Window into Environmental and Genetic Risk Factors for MS” by Emmanuelle Waubant, MD.

Dr. Carter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Pharmaceuticals. He has received research support from Roche/Genentech and MedDay Pharmaceuticals.
 

 

Clinical Neurology News editorial advisory board member Jonathan L. Carter, MD, scoured the pages of the American Academy of Neurology’s annual meeting program for his “top picks” in multiple sclerosis at this year’s meeting.

The top personal choices of Dr. Carter, an associate professor of neurology at the Mayo Clinic Arizona in Phoenix who specializes in multiple sclerosis (MS), are abstracts about neurofilament light chains (NFLCs) as biomarkers for disease progression and response; cognitive function outcomes in MS clinical trials; better outcome measures; the relative impact of age versus relapse on treatment response; what makes neuromyelitis optica spectrum disorders different from other autoimmune CNS diseases; and data updates on recently approved or investigational MS therapies.

NFLCs in serum as a biomarker for MS and treatment response. Multiple abstracts explore the use of NFLCs as a marker for disease progression and response to MS therapies, including:

• Hot Topics Plenary Session presentation: “Monitoring Multiple Sclerosis Using Blood Neurofilament Light Protein” by Jens Kuhle, MD.
• P5.036, Serum and CSF Neurofilament Light Chain levels normalise following Bone Marrow Transplant in MS Patients.
• S24.002, Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS).
• S24.003, Serum Neurofilament Light (NfL): Towards a Blood Test for Prognosis and Disease/Treatment Monitoring in Multiple Sclerosis Patients.
• S24.004, Long-term Prognosis of Disease Evolution and Evidence for Sustained Fingolimod Treatment Effect by Blood Neurofilament Light in RRMS Patients.
• S24.007, Including Blood Neurofilament Light Chain in the NEDA Concept in Relapsing Remitting Multiple Sclerosis Trials.
• S8.006, Siponimod Reduces Neurofilament Light Chain Blood Levels in Secondary Progressive Multiple Sclerosis Patients.

Cognitive function as an outcome measure in MS clinical trials. Several abstracts examine cognition as an outcome measure in clinical trials and show slowing of cognitive worsening in patients on MS disease-modifying therapies:

• S44.004, Impact of Siponimod on Cognition in Patients With Secondary Progressive Multiple Sclerosis: Results From Phase 3 EXPAND Study.
• S44.005, Time to Cognitive Worsening in Patients With Relapsing Multiple Sclerosis in Ocrelizumab Phase 3 Trials.
• S44.007, Benchmarks of Cognitive Performance in a Large, Representative Patient Population.

 

Improved disability outcome measures and predictors of disability in MS. Several abstracts assess novel disability outcome measures and neuroimaging techniques to better predict progression of clinical disability:

• P4.380, Overall Response Score: A Novel Disability Endpoint That Allows for the Integrated Assessment of Improvement and Worsening over Time in Patients with MS.
• S47.001, Longitudinal Changes in Quantitative Spinal Cord MRI in Multiple Sclerosis Patients: Results of a 5-year Study.
• P6.354, Effect of Fingolimod 0.5 mg/day versus Placebo on Two Newly Developed Expanded Disability Status Scale (EDSS) Subscales for Patients with Relapsing Remitting MS: EDSS Factor Analysis.

Is treatment response in MS an age-dependent or relapse-driven phenomenon, and is it safe to discontinue MS therapies with advancing age? Several abstracts address this question:

• S47.004, Meta-Analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.
• S8.005, Uncoupling the Impact on Relapses and Disability Progression: Siponimod in Relapsing and Nonrelapsing Patients With Secondary Progressive Multiple Sclerosis in the Phase 3 EXPAND Study.
• S8.008, Discontinuation of Disease Modifying Therapies in Stable MS Patients is Associated with Disability Progression Regardless of Age.

Neuromyelitis optica spectrum disorders and MS mimics. Multiple abstracts explore the differences between neuromyelitis optica spectrum disorder because of aquaporin-4 versus myelin oligodendrocyte glycoprotein antibodies; describe unique features of another recently described autoimmune disorder, autoimmune GFAP astrocytopathy; and explore the differential diagnosis of idiopathic transverse myelitis:

• S13.002, Clinical Characteristics of MOG and AQP associated Neuromyelitis Optica Spectrum Disorder (NMOSD) in Adults, through S13.008, It’s Not All Transverse Myelitis: The Differential Diagnosis of Spinal Cord Myelopathy.
• P6.409, The Mayo Clinic Glial Autoimmunity Study: Glial autoantibody (AQP4/MOG/GFAP) serostatus in recurrent longitudinally extensive transverse myelitis.
• P6.417, Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.
• S6.003, Brain and Spinal Cord Imaging Features in Neuromyelitis Optica Spectrum Disorders.

 

Updated safety and efficacy data for recently approved or investigational MS therapies. Multiple abstracts report updated safety and efficacy data from MS clinical trials of ozanimod, ocrelizumab (Ocrevus), and hematopoietic stem cell transplantation:

• Clinical Trials Plenary Session presentation: “A Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis” by Robert J. Fox, MD.
• Contemporary Clinical Issues Plenary Session presentation: “Biosimilars and Nonbiologic Complex Drugs” by Jeffrey Allan Cohen, MD.
• S6.002, Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase 3 Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis.
• P3.410, Clinical and Magnetic Resonance Imaging Results From RADIANCE Part B, a Multicenter, Randomized, Double-Blind, Phase 3 Trial of Ozanimod Versus Intramuscular Interferon beta-1a in Relapsing Multiple Sclerosis (RMS).
• P3.396, Ozanimod Demonstrates Efficacy and Safety in a Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Phase 3 Trial of Relapsing Multiple Sclerosis (SUNBEAM).
• S36.001, Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis.
• S36.004, Nonmyeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial.
• S36.005, Efficacy of Ozanimod Versus Interferon beta-1a by Prior Treatment and Baseline Disability in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).
• S36.006, Safety of Ozanimod Versus Interferon beta-1a in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).

New thoughts on MS pathogenesis.

• Frontiers in Neuroscience Plenary Session presentation: “Pediatric MS: A Unique Window into Environmental and Genetic Risk Factors for MS” by Emmanuelle Waubant, MD.

Dr. Carter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Pharmaceuticals. He has received research support from Roche/Genentech and MedDay Pharmaceuticals.