User login
Change in approach advised for treatment-resistant depression
WASHINGTON – Successfully treating patients who have treatment-resistant depression (TRD) means leaving acute intervention behind and adopting more chronic remediation techniques, Scott T. Aaronson, MD, said at the annual conference of the Anxiety and Depression Association of America.
“We need to change the paradigm; most of the research is looking at a 6- to 12-week outcome measure,” said Dr. Aaronson, director of the clinical research program at Sheppard Pratt Health System, Baltimore. “These are folks who have been depressed for most of their adult lives, and we don’t tend to take a longer-term perspective when looking at this.”
Treatment-resistant depression, Dr. Aaronson said, can be conceptualized as two levels. The first is failure of two agents or treatments, and the second is a failure of four or more agents – including electroconvulsive therapy. In light of those levels, Dr. Aaronson suggests approaching depression as one would cancer, with different stages of failure determining payment for more expensive treatments.
Before planning how best to handle treatment-resistant depression, it is important for psychiatrists to understand its complexity, and address the issues associated with current psychiatric diagnoses, Dr. Aaronson said.
Diagnoses now are based purely on phenomenological analysis rather than biological analysis, he said. “Basically, it’s a room full of people getting together to decide what the diagnostic criteria are,” Dr. Aaronson said. “It’s eminence-based medicine, not evidence-based medicine.”
This approach creates a large gray area in which diagnoses can fall, making it more difficult to distinguish between bipolar and unipolar depression, as well as tough to distinguish psychotic and nonpsychotic illnesses.
If a patient displayed mood instability, for example, but not enough to fit the criteria of bipolar disorder, this scenario would present a dilemma for psychiatrists unable to diagnose the patient as bipolar and unconvinced that it would help to treat the patient as only being depressed, according to an example from Dr. Aaronson.
In such cases, Dr. Aaronson explained, it makes sense to treat patients as though they were displaying full symptoms. “If you see a patient and think ‘this may be bipolar or this may be psychosis,’ you’re better off rounding up than rounding down,” Dr. Aaronson said. “If you’re wrong, you may have more side effects from medication, but an advantage – or disadvantage – of patients with TRD is they’ve already failed six different antidepressants.”
After navigating through the gray zone with a patient, choosing the right medication can be just as onerous. Most antidepressant medications target serotonin, norepinephrine, or, in some capacity, dopamine. Such targets are extremely limiting, because they ignore other neurotransmitters related to mood disorders, Dr. Aaronson said.
The promise of remission is another limiting aspect of treatment. Patients may be better suited if psychiatrists shifted away from the search for a cure and toward helping patients manage their symptoms to give them the best life they can lead, Dr. Aaronson said.
Having a candid discussion about the realistic possibility of remission, as well as encouraging a more healthy lifestyle, can be extremely helpful for patients with treatment-resistant depression.
“Core components of the recovery model are remediation of functioning, collaborative restoration of skills and competencies, and active community reconnection by reestablishing a place in the community – and by exploring opportunities for independence and social inclusion,” Dr. Aaronson said.
Looking ahead, it is important for the research paradigm to shift as well. One example would be to establish treatment registries for evaluating treatment effectiveness through something like genetic testing or neuroimaging, Dr. Aaronson said. Studying nonpharmacologic interventions such as diet and exercise also would be beneficial.
Dr. Aaronson has helped with research for Neuronetics, and serves as a consultant for LivaNova, Neuronetics, Alkermes, and Genomind. He also has spoken for Sunovion, Neurocrine, and Otsuka.
WASHINGTON – Successfully treating patients who have treatment-resistant depression (TRD) means leaving acute intervention behind and adopting more chronic remediation techniques, Scott T. Aaronson, MD, said at the annual conference of the Anxiety and Depression Association of America.
“We need to change the paradigm; most of the research is looking at a 6- to 12-week outcome measure,” said Dr. Aaronson, director of the clinical research program at Sheppard Pratt Health System, Baltimore. “These are folks who have been depressed for most of their adult lives, and we don’t tend to take a longer-term perspective when looking at this.”
Treatment-resistant depression, Dr. Aaronson said, can be conceptualized as two levels. The first is failure of two agents or treatments, and the second is a failure of four or more agents – including electroconvulsive therapy. In light of those levels, Dr. Aaronson suggests approaching depression as one would cancer, with different stages of failure determining payment for more expensive treatments.
Before planning how best to handle treatment-resistant depression, it is important for psychiatrists to understand its complexity, and address the issues associated with current psychiatric diagnoses, Dr. Aaronson said.
Diagnoses now are based purely on phenomenological analysis rather than biological analysis, he said. “Basically, it’s a room full of people getting together to decide what the diagnostic criteria are,” Dr. Aaronson said. “It’s eminence-based medicine, not evidence-based medicine.”
This approach creates a large gray area in which diagnoses can fall, making it more difficult to distinguish between bipolar and unipolar depression, as well as tough to distinguish psychotic and nonpsychotic illnesses.
If a patient displayed mood instability, for example, but not enough to fit the criteria of bipolar disorder, this scenario would present a dilemma for psychiatrists unable to diagnose the patient as bipolar and unconvinced that it would help to treat the patient as only being depressed, according to an example from Dr. Aaronson.
In such cases, Dr. Aaronson explained, it makes sense to treat patients as though they were displaying full symptoms. “If you see a patient and think ‘this may be bipolar or this may be psychosis,’ you’re better off rounding up than rounding down,” Dr. Aaronson said. “If you’re wrong, you may have more side effects from medication, but an advantage – or disadvantage – of patients with TRD is they’ve already failed six different antidepressants.”
After navigating through the gray zone with a patient, choosing the right medication can be just as onerous. Most antidepressant medications target serotonin, norepinephrine, or, in some capacity, dopamine. Such targets are extremely limiting, because they ignore other neurotransmitters related to mood disorders, Dr. Aaronson said.
The promise of remission is another limiting aspect of treatment. Patients may be better suited if psychiatrists shifted away from the search for a cure and toward helping patients manage their symptoms to give them the best life they can lead, Dr. Aaronson said.
Having a candid discussion about the realistic possibility of remission, as well as encouraging a more healthy lifestyle, can be extremely helpful for patients with treatment-resistant depression.
“Core components of the recovery model are remediation of functioning, collaborative restoration of skills and competencies, and active community reconnection by reestablishing a place in the community – and by exploring opportunities for independence and social inclusion,” Dr. Aaronson said.
Looking ahead, it is important for the research paradigm to shift as well. One example would be to establish treatment registries for evaluating treatment effectiveness through something like genetic testing or neuroimaging, Dr. Aaronson said. Studying nonpharmacologic interventions such as diet and exercise also would be beneficial.
Dr. Aaronson has helped with research for Neuronetics, and serves as a consultant for LivaNova, Neuronetics, Alkermes, and Genomind. He also has spoken for Sunovion, Neurocrine, and Otsuka.
WASHINGTON – Successfully treating patients who have treatment-resistant depression (TRD) means leaving acute intervention behind and adopting more chronic remediation techniques, Scott T. Aaronson, MD, said at the annual conference of the Anxiety and Depression Association of America.
“We need to change the paradigm; most of the research is looking at a 6- to 12-week outcome measure,” said Dr. Aaronson, director of the clinical research program at Sheppard Pratt Health System, Baltimore. “These are folks who have been depressed for most of their adult lives, and we don’t tend to take a longer-term perspective when looking at this.”
Treatment-resistant depression, Dr. Aaronson said, can be conceptualized as two levels. The first is failure of two agents or treatments, and the second is a failure of four or more agents – including electroconvulsive therapy. In light of those levels, Dr. Aaronson suggests approaching depression as one would cancer, with different stages of failure determining payment for more expensive treatments.
Before planning how best to handle treatment-resistant depression, it is important for psychiatrists to understand its complexity, and address the issues associated with current psychiatric diagnoses, Dr. Aaronson said.
Diagnoses now are based purely on phenomenological analysis rather than biological analysis, he said. “Basically, it’s a room full of people getting together to decide what the diagnostic criteria are,” Dr. Aaronson said. “It’s eminence-based medicine, not evidence-based medicine.”
This approach creates a large gray area in which diagnoses can fall, making it more difficult to distinguish between bipolar and unipolar depression, as well as tough to distinguish psychotic and nonpsychotic illnesses.
If a patient displayed mood instability, for example, but not enough to fit the criteria of bipolar disorder, this scenario would present a dilemma for psychiatrists unable to diagnose the patient as bipolar and unconvinced that it would help to treat the patient as only being depressed, according to an example from Dr. Aaronson.
In such cases, Dr. Aaronson explained, it makes sense to treat patients as though they were displaying full symptoms. “If you see a patient and think ‘this may be bipolar or this may be psychosis,’ you’re better off rounding up than rounding down,” Dr. Aaronson said. “If you’re wrong, you may have more side effects from medication, but an advantage – or disadvantage – of patients with TRD is they’ve already failed six different antidepressants.”
After navigating through the gray zone with a patient, choosing the right medication can be just as onerous. Most antidepressant medications target serotonin, norepinephrine, or, in some capacity, dopamine. Such targets are extremely limiting, because they ignore other neurotransmitters related to mood disorders, Dr. Aaronson said.
The promise of remission is another limiting aspect of treatment. Patients may be better suited if psychiatrists shifted away from the search for a cure and toward helping patients manage their symptoms to give them the best life they can lead, Dr. Aaronson said.
Having a candid discussion about the realistic possibility of remission, as well as encouraging a more healthy lifestyle, can be extremely helpful for patients with treatment-resistant depression.
“Core components of the recovery model are remediation of functioning, collaborative restoration of skills and competencies, and active community reconnection by reestablishing a place in the community – and by exploring opportunities for independence and social inclusion,” Dr. Aaronson said.
Looking ahead, it is important for the research paradigm to shift as well. One example would be to establish treatment registries for evaluating treatment effectiveness through something like genetic testing or neuroimaging, Dr. Aaronson said. Studying nonpharmacologic interventions such as diet and exercise also would be beneficial.
Dr. Aaronson has helped with research for Neuronetics, and serves as a consultant for LivaNova, Neuronetics, Alkermes, and Genomind. He also has spoken for Sunovion, Neurocrine, and Otsuka.
REPORTING FROM ANXIETY AND DEPRESSION CONFERENCE 2018
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.
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.
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.
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.
Targeting obesity could slow brain aging in psychosis
, new research suggests.
The investigators found significant associations between BrainAGE scores and a diagnosis of FEP (P = .005), overweight/obesity category (P = .007), and body mass index (P = .02). Furthermore, the association found between BrainAGE score and BMI was related to an association between BrainAGE score and weight (P = .009), but not to height (P = .13).
“These findings raise the possibility that targeting metabolic health in FEP and intervening already at the level of overweight/obesity could slow brain aging in schizophrenia and related disorders,” reported Marian Kolenic of the National Institute of Mental Health in Klecany, Czech Republic, and his coauthors.
The researchers recruited 120 patients with FEP as defined by the ICD-10 during their first psychiatric hospitalization. People with psychotic mood disorders were excluded.
“We wanted to recruit participants at the early stages of illness, to minimize the effects of illness and medications on brain structure,” the investigators wrote.
One hundred fourteen healthy controls were recruited through advertisements, and exclusion criteria included a lifetime history of any psychiatric disorders and the presence of psychotic disorders in either first- or second-degree relatives.
All participants were asked about their medical history, including their use and/or abuse of substances. Fasting blood samples were collected on the scanning day.
A psychiatrist used the Mini-International Neuropsychiatric Interview and the Positive and Negative Syndrome Scale to determine diagnostic assessments and symptom ratings. Several CV risk factors were measured, including blood pressure, triglycerides, HDL, and LDL. Using the charts, the researchers verified the absence of diabetes by fasting glucose. They also checked participants’ BMI and height.
“This study suggests that overweight/obesity, which is frequent in schizophrenia, may contribute to neurostructural changes already early in the course of illness,” the investigators wrote. “Specifically, the brains of participants with FEP appeared on average 2.64 years older than their chronological age.”
Among participants with both FEP and overweight/obesity, the investigators found the average discrepancy between brain and chronological age to be as high as 3.83 years.
They cited several limitations. Because the study was not prospective, the researchers could not establish causality of the association between metabolic alterations and brain structure. In addition, the existence of insulin resistance could not be ruled out – although none of the participants reported a history of type 2 diabetes.
Still, “,” the investigators wrote.
They reported no conflicts of interest.
[email protected]
SOURCE: Kolenic M et al. J Psychiatric Res. 2018 Apr. 99:151-8.
, new research suggests.
The investigators found significant associations between BrainAGE scores and a diagnosis of FEP (P = .005), overweight/obesity category (P = .007), and body mass index (P = .02). Furthermore, the association found between BrainAGE score and BMI was related to an association between BrainAGE score and weight (P = .009), but not to height (P = .13).
“These findings raise the possibility that targeting metabolic health in FEP and intervening already at the level of overweight/obesity could slow brain aging in schizophrenia and related disorders,” reported Marian Kolenic of the National Institute of Mental Health in Klecany, Czech Republic, and his coauthors.
The researchers recruited 120 patients with FEP as defined by the ICD-10 during their first psychiatric hospitalization. People with psychotic mood disorders were excluded.
“We wanted to recruit participants at the early stages of illness, to minimize the effects of illness and medications on brain structure,” the investigators wrote.
One hundred fourteen healthy controls were recruited through advertisements, and exclusion criteria included a lifetime history of any psychiatric disorders and the presence of psychotic disorders in either first- or second-degree relatives.
All participants were asked about their medical history, including their use and/or abuse of substances. Fasting blood samples were collected on the scanning day.
A psychiatrist used the Mini-International Neuropsychiatric Interview and the Positive and Negative Syndrome Scale to determine diagnostic assessments and symptom ratings. Several CV risk factors were measured, including blood pressure, triglycerides, HDL, and LDL. Using the charts, the researchers verified the absence of diabetes by fasting glucose. They also checked participants’ BMI and height.
“This study suggests that overweight/obesity, which is frequent in schizophrenia, may contribute to neurostructural changes already early in the course of illness,” the investigators wrote. “Specifically, the brains of participants with FEP appeared on average 2.64 years older than their chronological age.”
Among participants with both FEP and overweight/obesity, the investigators found the average discrepancy between brain and chronological age to be as high as 3.83 years.
They cited several limitations. Because the study was not prospective, the researchers could not establish causality of the association between metabolic alterations and brain structure. In addition, the existence of insulin resistance could not be ruled out – although none of the participants reported a history of type 2 diabetes.
Still, “,” the investigators wrote.
They reported no conflicts of interest.
[email protected]
SOURCE: Kolenic M et al. J Psychiatric Res. 2018 Apr. 99:151-8.
, new research suggests.
The investigators found significant associations between BrainAGE scores and a diagnosis of FEP (P = .005), overweight/obesity category (P = .007), and body mass index (P = .02). Furthermore, the association found between BrainAGE score and BMI was related to an association between BrainAGE score and weight (P = .009), but not to height (P = .13).
“These findings raise the possibility that targeting metabolic health in FEP and intervening already at the level of overweight/obesity could slow brain aging in schizophrenia and related disorders,” reported Marian Kolenic of the National Institute of Mental Health in Klecany, Czech Republic, and his coauthors.
The researchers recruited 120 patients with FEP as defined by the ICD-10 during their first psychiatric hospitalization. People with psychotic mood disorders were excluded.
“We wanted to recruit participants at the early stages of illness, to minimize the effects of illness and medications on brain structure,” the investigators wrote.
One hundred fourteen healthy controls were recruited through advertisements, and exclusion criteria included a lifetime history of any psychiatric disorders and the presence of psychotic disorders in either first- or second-degree relatives.
All participants were asked about their medical history, including their use and/or abuse of substances. Fasting blood samples were collected on the scanning day.
A psychiatrist used the Mini-International Neuropsychiatric Interview and the Positive and Negative Syndrome Scale to determine diagnostic assessments and symptom ratings. Several CV risk factors were measured, including blood pressure, triglycerides, HDL, and LDL. Using the charts, the researchers verified the absence of diabetes by fasting glucose. They also checked participants’ BMI and height.
“This study suggests that overweight/obesity, which is frequent in schizophrenia, may contribute to neurostructural changes already early in the course of illness,” the investigators wrote. “Specifically, the brains of participants with FEP appeared on average 2.64 years older than their chronological age.”
Among participants with both FEP and overweight/obesity, the investigators found the average discrepancy between brain and chronological age to be as high as 3.83 years.
They cited several limitations. Because the study was not prospective, the researchers could not establish causality of the association between metabolic alterations and brain structure. In addition, the existence of insulin resistance could not be ruled out – although none of the participants reported a history of type 2 diabetes.
Still, “,” the investigators wrote.
They reported no conflicts of interest.
[email protected]
SOURCE: Kolenic M et al. J Psychiatric Res. 2018 Apr. 99:151-8.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
Key clinical point: Being overweight or obese could be a risk factor for the kind of brain aging seen in some patients with first-episode psychosis.
Major finding: The investigators found significant associations between BrainAGE scores and a diagnosis of FEP (P = .005), overweight/obesity category (P = .007) and BMI (P = .02).
Study details: A analysis of 120 patients with first-episode psychosis and 114 healthy controls.
Disclosures: .The authors reported no conflicts of interest.
Source: Kolenic M et al. J Psychiatric Res. 2018 Apr. 99:151-8.
Ibrutinib plus carfilzomib active in relapsed multiple myeloma
In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.
Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.
The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.
Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.
In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.
To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.
A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.
Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.
Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.
Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.
Enrollment in phase 2b of the study is ongoing.
Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.
Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.
The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.
Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.
In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.
To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.
A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.
Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.
Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.
Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.
Enrollment in phase 2b of the study is ongoing.
Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.
Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.
The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.
Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.
In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.
To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.
A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.
Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.
Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.
Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.
Enrollment in phase 2b of the study is ongoing.
Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
FROM LEUKEMIA & LYMPHOMA
Key clinical point:
Major finding: The overall response rate was 67%, including a 21% very good partial response and 2% stringent complete response.
Study details: A phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy.
Disclosures: Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
Source: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
High 5-year mortality in patients admitted with heart failure regardless of ejection fraction
Background: Heart failure with preserved EF is a common cause of inpatient admission and previously was thought to carry a better prognosis than heart failure with reduced EF. Recent analysis using data from Get With the Guidelines–Heart Failure (GWTG-HF) registry has shown similarly poor survival rates at 30 days and 1 year when compared with heart failure with reduced EF.
Study design: Multicenter retrospective cohort study.
Setting: 276 hospitals in the GWTG-HF registry during 2005-2009, with 5 years of follow-up through 2014.
Synopsis: A total 39,982 patients who were admitted for heart failure during 2005-2009 were included in the study with stratification into three groups based on ejection fraction; 18,398 (46%) with heart failure with reduced EF; 2,385 (8.2%) with heart failure with borderline EF; and 18,299 (46%) with heart failure with preserved EF. The 5-year mortality rate for the entire cohort was 75.4% with similar mortality rates for patient with preserved EF (75.3%), compared with those with reduced EF (75.7%).
Bottom line: Among patients hospitalized with heart failure, irrespective of their ejection fraction, the 5-year survival rates were equally dismal. Hospitalists may wish to use this information in goals of care discussions.
Citation: Shah KS et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol. 2017 Oct 31. doi: 10.1016/j.jacc.2017.08.074.
Dr. Gomez-Sanchez is a hospitalist at the University of Virginia Medical Center.
Background: Heart failure with preserved EF is a common cause of inpatient admission and previously was thought to carry a better prognosis than heart failure with reduced EF. Recent analysis using data from Get With the Guidelines–Heart Failure (GWTG-HF) registry has shown similarly poor survival rates at 30 days and 1 year when compared with heart failure with reduced EF.
Study design: Multicenter retrospective cohort study.
Setting: 276 hospitals in the GWTG-HF registry during 2005-2009, with 5 years of follow-up through 2014.
Synopsis: A total 39,982 patients who were admitted for heart failure during 2005-2009 were included in the study with stratification into three groups based on ejection fraction; 18,398 (46%) with heart failure with reduced EF; 2,385 (8.2%) with heart failure with borderline EF; and 18,299 (46%) with heart failure with preserved EF. The 5-year mortality rate for the entire cohort was 75.4% with similar mortality rates for patient with preserved EF (75.3%), compared with those with reduced EF (75.7%).
Bottom line: Among patients hospitalized with heart failure, irrespective of their ejection fraction, the 5-year survival rates were equally dismal. Hospitalists may wish to use this information in goals of care discussions.
Citation: Shah KS et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol. 2017 Oct 31. doi: 10.1016/j.jacc.2017.08.074.
Dr. Gomez-Sanchez is a hospitalist at the University of Virginia Medical Center.
Background: Heart failure with preserved EF is a common cause of inpatient admission and previously was thought to carry a better prognosis than heart failure with reduced EF. Recent analysis using data from Get With the Guidelines–Heart Failure (GWTG-HF) registry has shown similarly poor survival rates at 30 days and 1 year when compared with heart failure with reduced EF.
Study design: Multicenter retrospective cohort study.
Setting: 276 hospitals in the GWTG-HF registry during 2005-2009, with 5 years of follow-up through 2014.
Synopsis: A total 39,982 patients who were admitted for heart failure during 2005-2009 were included in the study with stratification into three groups based on ejection fraction; 18,398 (46%) with heart failure with reduced EF; 2,385 (8.2%) with heart failure with borderline EF; and 18,299 (46%) with heart failure with preserved EF. The 5-year mortality rate for the entire cohort was 75.4% with similar mortality rates for patient with preserved EF (75.3%), compared with those with reduced EF (75.7%).
Bottom line: Among patients hospitalized with heart failure, irrespective of their ejection fraction, the 5-year survival rates were equally dismal. Hospitalists may wish to use this information in goals of care discussions.
Citation: Shah KS et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol. 2017 Oct 31. doi: 10.1016/j.jacc.2017.08.074.
Dr. Gomez-Sanchez is a hospitalist at the University of Virginia Medical Center.
FDA approves burosumab to treat X-linked hypophosphatemia
The Food and Drug Administration has approved burosumab to treat X-linked hypophosphatemia, a rare, heritable form of rickets, in adults and children at least 1 year of age. Burosumab received expedited review by the FDA as a breakthrough therapy, and it also has been designated an orphan drug.
X-linked hypophosphatemia (XLH) “differs from other forms of rickets in that vitamin D therapy is not effective. This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease,” said Julie Beitz, MD, in an FDA press release announcing the approval of the fully human monoclonal antibody. Dr. Beitz is director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.
Four clinical trials formed the basis for the FDA’s approval of burosumab. A pivotal randomized, placebo-controlled, double-blind study of adults with XLH that randomized 134 patients 1:1 to subcutaneous burosumab or placebo found that normal phosphorus levels were achieved in 94% of adults receiving burosumab, compared with 8% of those who received placebo.
For children, biweekly burosumab resulted in normal phosphorus levels for 94%-100% of participants. Significant skeletal radiographic improvement also was seen for adults and children taking burosumab.
In both adults and children, burosumab had a good safety profile, with no significant changes in serum or urine levels of calcium or in serum levels of intact parathyroid hormone.
X-linked hypophosphatemia is variable in severity; many patients with XLH will have bone pain, bowed legs, and a waddling gait; enthesopathy with associated joint pain; and dental problems and pain. Many also have short stature and, unlike rickets caused by dietary deficiency and some malabsorption problems, XLH is not improved by conventional vitamin D therapy.
The rare disorder, affecting about 3,000 children and 12,000 adults in the United States, is caused by a mutation in the PHEX gene, with resultant overactivity of fibroblast growth factor 23 (FGF23). Burosumab binds FGF23, increasing renal tubular reabsorption of phosphorus and 1,25-dihydroxycholecalciferol, also called calcitriol.
Previously, XLH had been treated by frequent oral supplementation with phosphate and calcitriol. Burosumab will be marketed by Ultragenyx Pharmaceutical as Crysvita. It is given as a once-monthly or biweekly subcutaneous injection.
The Food and Drug Administration has approved burosumab to treat X-linked hypophosphatemia, a rare, heritable form of rickets, in adults and children at least 1 year of age. Burosumab received expedited review by the FDA as a breakthrough therapy, and it also has been designated an orphan drug.
X-linked hypophosphatemia (XLH) “differs from other forms of rickets in that vitamin D therapy is not effective. This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease,” said Julie Beitz, MD, in an FDA press release announcing the approval of the fully human monoclonal antibody. Dr. Beitz is director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.
Four clinical trials formed the basis for the FDA’s approval of burosumab. A pivotal randomized, placebo-controlled, double-blind study of adults with XLH that randomized 134 patients 1:1 to subcutaneous burosumab or placebo found that normal phosphorus levels were achieved in 94% of adults receiving burosumab, compared with 8% of those who received placebo.
For children, biweekly burosumab resulted in normal phosphorus levels for 94%-100% of participants. Significant skeletal radiographic improvement also was seen for adults and children taking burosumab.
In both adults and children, burosumab had a good safety profile, with no significant changes in serum or urine levels of calcium or in serum levels of intact parathyroid hormone.
X-linked hypophosphatemia is variable in severity; many patients with XLH will have bone pain, bowed legs, and a waddling gait; enthesopathy with associated joint pain; and dental problems and pain. Many also have short stature and, unlike rickets caused by dietary deficiency and some malabsorption problems, XLH is not improved by conventional vitamin D therapy.
The rare disorder, affecting about 3,000 children and 12,000 adults in the United States, is caused by a mutation in the PHEX gene, with resultant overactivity of fibroblast growth factor 23 (FGF23). Burosumab binds FGF23, increasing renal tubular reabsorption of phosphorus and 1,25-dihydroxycholecalciferol, also called calcitriol.
Previously, XLH had been treated by frequent oral supplementation with phosphate and calcitriol. Burosumab will be marketed by Ultragenyx Pharmaceutical as Crysvita. It is given as a once-monthly or biweekly subcutaneous injection.
The Food and Drug Administration has approved burosumab to treat X-linked hypophosphatemia, a rare, heritable form of rickets, in adults and children at least 1 year of age. Burosumab received expedited review by the FDA as a breakthrough therapy, and it also has been designated an orphan drug.
X-linked hypophosphatemia (XLH) “differs from other forms of rickets in that vitamin D therapy is not effective. This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease,” said Julie Beitz, MD, in an FDA press release announcing the approval of the fully human monoclonal antibody. Dr. Beitz is director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.
Four clinical trials formed the basis for the FDA’s approval of burosumab. A pivotal randomized, placebo-controlled, double-blind study of adults with XLH that randomized 134 patients 1:1 to subcutaneous burosumab or placebo found that normal phosphorus levels were achieved in 94% of adults receiving burosumab, compared with 8% of those who received placebo.
For children, biweekly burosumab resulted in normal phosphorus levels for 94%-100% of participants. Significant skeletal radiographic improvement also was seen for adults and children taking burosumab.
In both adults and children, burosumab had a good safety profile, with no significant changes in serum or urine levels of calcium or in serum levels of intact parathyroid hormone.
X-linked hypophosphatemia is variable in severity; many patients with XLH will have bone pain, bowed legs, and a waddling gait; enthesopathy with associated joint pain; and dental problems and pain. Many also have short stature and, unlike rickets caused by dietary deficiency and some malabsorption problems, XLH is not improved by conventional vitamin D therapy.
The rare disorder, affecting about 3,000 children and 12,000 adults in the United States, is caused by a mutation in the PHEX gene, with resultant overactivity of fibroblast growth factor 23 (FGF23). Burosumab binds FGF23, increasing renal tubular reabsorption of phosphorus and 1,25-dihydroxycholecalciferol, also called calcitriol.
Previously, XLH had been treated by frequent oral supplementation with phosphate and calcitriol. Burosumab will be marketed by Ultragenyx Pharmaceutical as Crysvita. It is given as a once-monthly or biweekly subcutaneous injection.
Adding CBT to substance use treatment may increase success
WASHINGTON – Using schema therapy as an adjunct for substance use disorder might help fill the gaps in traditional cognitive-behavioral therapy, according to a presentation at the annual conference of the Anxiety and Depression Association of America.
Schema therapy, developed for treatment-resistant diagnoses, allows clinicians to challenge cognitive distortions and negative coping styles that develop during childhood or adolescence. As an extension of the cognitive-behavioral therapy (CBT) model of Aaron T. Beck, MD, – which are present in more than 50% of SUD patients, said presenter Katharine D. Wojcik, of the University of British Columbia, Vancouver.
“The combination of a dual diagnosis makes the traditional 12-step addiction therapy less effective,” said Ms. Wojcik, a doctoral candidate at the university. “Additionally, traditional treatment approaches have been found to be ineffective against comorbid mental health and substance use disorders.”
To investigate the effects of schema therapy, Ms. Wojcik collected data on more than 100 residents of a treatment program for patients with addictions and mental illness. The patients took the Young Schema Questionnaire 3 so the investigators could assess the presence and extent of early maladaptive schemas. The patients, mostly white females, participated in the schema therapy protocol for 30 days.
Medication management, a 12-step program, individual sessions, and a CBT intervention – including prolonged exposure, behavior activation, and schema therapy – were incorporated to target their multiple diagnoses, Ms. Wojcik said.
In the initial assessments, the investigators found that self-sacrifice, unrelenting standards, and insufficient self-control were the most common schema among the subject group, with notably elevated levels of disconnection, rejection, overvigilance, and inhibition.
After the assessments, patients and clinicians sat down to discuss the schema clinicians found present. If patients bought into the report, they began self-monitoring through daily activities such as journaling.
Ms. Wojcik and her colleagues said those self-monitoring practices will help change patients’ schema. But such practices were not the only tool in the program aimed at sparking these changes, patients worked with clinicians on cognitive strategies as well. Addressing core beliefs, schema bias, schema activation formulation, and schema rules and assumptions were a few of the strategies implemented by clinicians.
“We also work on schema challenging, which means [when] in session with a client, as a clinician you are able to say: ‘I wonder if this schema is coming up for you right now,’ or ‘Are you noticing any schemas as we’re talking about this?’ ” Ms. Wojcik said. “Since there is such a high comorbidity, a lot of times it does come down to these experiences that they’ve had that tie into trauma history.”
After the end of their stay, patients were given a reassessment and then shown the results to see how they had progressed. The reassessment did show some subtle changes, but the short length of the program hindered any patients from seeing complete deescalation of their schema, Ms. Wojcik said.
She discussed the case of a 30-year-old woman with diagnoses of SUD, PTSD, and bipolar disorder – and an extensive treatment history. Therapists found that the combination of traditional and CBT helped significantly with the patient’s elevated abandonment schema.
“We were able to have her close her eyes and walk through not only what it was like when that schema developed, but also have her talk about what were the things that went unmet in that situation that caused this to happen,” Ms. Wojcik said. “She successfully completed her treatment with us, noticed a lot of her schema had decreased in elevation, and expressed pride that she had done this.”
Ms. Wojcik and her colleagues reported no relevant financial disclosures.
SOURCE: Wojcik KD et al. ADAA 2018, Abstract 173C.
WASHINGTON – Using schema therapy as an adjunct for substance use disorder might help fill the gaps in traditional cognitive-behavioral therapy, according to a presentation at the annual conference of the Anxiety and Depression Association of America.
Schema therapy, developed for treatment-resistant diagnoses, allows clinicians to challenge cognitive distortions and negative coping styles that develop during childhood or adolescence. As an extension of the cognitive-behavioral therapy (CBT) model of Aaron T. Beck, MD, – which are present in more than 50% of SUD patients, said presenter Katharine D. Wojcik, of the University of British Columbia, Vancouver.
“The combination of a dual diagnosis makes the traditional 12-step addiction therapy less effective,” said Ms. Wojcik, a doctoral candidate at the university. “Additionally, traditional treatment approaches have been found to be ineffective against comorbid mental health and substance use disorders.”
To investigate the effects of schema therapy, Ms. Wojcik collected data on more than 100 residents of a treatment program for patients with addictions and mental illness. The patients took the Young Schema Questionnaire 3 so the investigators could assess the presence and extent of early maladaptive schemas. The patients, mostly white females, participated in the schema therapy protocol for 30 days.
Medication management, a 12-step program, individual sessions, and a CBT intervention – including prolonged exposure, behavior activation, and schema therapy – were incorporated to target their multiple diagnoses, Ms. Wojcik said.
In the initial assessments, the investigators found that self-sacrifice, unrelenting standards, and insufficient self-control were the most common schema among the subject group, with notably elevated levels of disconnection, rejection, overvigilance, and inhibition.
After the assessments, patients and clinicians sat down to discuss the schema clinicians found present. If patients bought into the report, they began self-monitoring through daily activities such as journaling.
Ms. Wojcik and her colleagues said those self-monitoring practices will help change patients’ schema. But such practices were not the only tool in the program aimed at sparking these changes, patients worked with clinicians on cognitive strategies as well. Addressing core beliefs, schema bias, schema activation formulation, and schema rules and assumptions were a few of the strategies implemented by clinicians.
“We also work on schema challenging, which means [when] in session with a client, as a clinician you are able to say: ‘I wonder if this schema is coming up for you right now,’ or ‘Are you noticing any schemas as we’re talking about this?’ ” Ms. Wojcik said. “Since there is such a high comorbidity, a lot of times it does come down to these experiences that they’ve had that tie into trauma history.”
After the end of their stay, patients were given a reassessment and then shown the results to see how they had progressed. The reassessment did show some subtle changes, but the short length of the program hindered any patients from seeing complete deescalation of their schema, Ms. Wojcik said.
She discussed the case of a 30-year-old woman with diagnoses of SUD, PTSD, and bipolar disorder – and an extensive treatment history. Therapists found that the combination of traditional and CBT helped significantly with the patient’s elevated abandonment schema.
“We were able to have her close her eyes and walk through not only what it was like when that schema developed, but also have her talk about what were the things that went unmet in that situation that caused this to happen,” Ms. Wojcik said. “She successfully completed her treatment with us, noticed a lot of her schema had decreased in elevation, and expressed pride that she had done this.”
Ms. Wojcik and her colleagues reported no relevant financial disclosures.
SOURCE: Wojcik KD et al. ADAA 2018, Abstract 173C.
WASHINGTON – Using schema therapy as an adjunct for substance use disorder might help fill the gaps in traditional cognitive-behavioral therapy, according to a presentation at the annual conference of the Anxiety and Depression Association of America.
Schema therapy, developed for treatment-resistant diagnoses, allows clinicians to challenge cognitive distortions and negative coping styles that develop during childhood or adolescence. As an extension of the cognitive-behavioral therapy (CBT) model of Aaron T. Beck, MD, – which are present in more than 50% of SUD patients, said presenter Katharine D. Wojcik, of the University of British Columbia, Vancouver.
“The combination of a dual diagnosis makes the traditional 12-step addiction therapy less effective,” said Ms. Wojcik, a doctoral candidate at the university. “Additionally, traditional treatment approaches have been found to be ineffective against comorbid mental health and substance use disorders.”
To investigate the effects of schema therapy, Ms. Wojcik collected data on more than 100 residents of a treatment program for patients with addictions and mental illness. The patients took the Young Schema Questionnaire 3 so the investigators could assess the presence and extent of early maladaptive schemas. The patients, mostly white females, participated in the schema therapy protocol for 30 days.
Medication management, a 12-step program, individual sessions, and a CBT intervention – including prolonged exposure, behavior activation, and schema therapy – were incorporated to target their multiple diagnoses, Ms. Wojcik said.
In the initial assessments, the investigators found that self-sacrifice, unrelenting standards, and insufficient self-control were the most common schema among the subject group, with notably elevated levels of disconnection, rejection, overvigilance, and inhibition.
After the assessments, patients and clinicians sat down to discuss the schema clinicians found present. If patients bought into the report, they began self-monitoring through daily activities such as journaling.
Ms. Wojcik and her colleagues said those self-monitoring practices will help change patients’ schema. But such practices were not the only tool in the program aimed at sparking these changes, patients worked with clinicians on cognitive strategies as well. Addressing core beliefs, schema bias, schema activation formulation, and schema rules and assumptions were a few of the strategies implemented by clinicians.
“We also work on schema challenging, which means [when] in session with a client, as a clinician you are able to say: ‘I wonder if this schema is coming up for you right now,’ or ‘Are you noticing any schemas as we’re talking about this?’ ” Ms. Wojcik said. “Since there is such a high comorbidity, a lot of times it does come down to these experiences that they’ve had that tie into trauma history.”
After the end of their stay, patients were given a reassessment and then shown the results to see how they had progressed. The reassessment did show some subtle changes, but the short length of the program hindered any patients from seeing complete deescalation of their schema, Ms. Wojcik said.
She discussed the case of a 30-year-old woman with diagnoses of SUD, PTSD, and bipolar disorder – and an extensive treatment history. Therapists found that the combination of traditional and CBT helped significantly with the patient’s elevated abandonment schema.
“We were able to have her close her eyes and walk through not only what it was like when that schema developed, but also have her talk about what were the things that went unmet in that situation that caused this to happen,” Ms. Wojcik said. “She successfully completed her treatment with us, noticed a lot of her schema had decreased in elevation, and expressed pride that she had done this.”
Ms. Wojcik and her colleagues reported no relevant financial disclosures.
SOURCE: Wojcik KD et al. ADAA 2018, Abstract 173C.
REPORTING FROM THE ANXIETY AND DEPRESSION CONFERENCE 2018
5- and 10-day decitabine go head-to-head in poor-risk AML
NEWPORT BEACH, CALIF. – Response and survival rates are similar with 5- and 10-day dosing of decitabine in poor-risk older adults with previously untreated acute myeloid leukemia, according to findings from a randomized phase 2 trial.
The overall response rates in 25 patients randomized to receive 5 days of decitabine and 40 patients randomized to receive 10 days of decitabine were 44% and 38%, respectively. Complete response rates were 28% and 30%, respectively, and the median number of cycles to best response was two in both arms, Nicholas J. Short, MD, reported in a poster at the Acute Leukemia Forum of Hemedicus.
Patients were followed for a median of 38 months. Median remission duration was 9.4 months in 11 responders who received 5 days of decitabine, and 6.4 months in 15 responders in the 10-day treatment arm. The 1-year continued remission rates were 25% and 30%, respectively (P = .85). Median overall survival was 4.9 and 7.1 months, respectively, and 1-year overall survival rates were 27% and 25%, respectively, he said, adding that none of the differences in the groups were statistically significant.
Further, no differences in survival were seen when patients in the two treatment arms were stratified by cytogenetics, de novo versus secondary or treatment-related disease, or TP53 mutations; however, these subgroups were small, he noted.
Study subjects were adults aged 60 years or older (median, 77 and 78 years) with newly diagnosed and untreated acute myeloid leukemia (AML), and adults under age 60 years who were not suitable candidates for intensive chemotherapy. They were enrolled between February 2013 and July 2017. About 30% of patients had performance status scores of 2-3, and 45% of patients had secondary AML.
“About 40% of patients in the 5-day arm had poor-risk cytogenetics, and about half in the 10-day arm had poor-risk cytogenetics,” Dr. Short said in an interview, adding that 6 of 21 tested patients in the 5-day arm and 16 of 38 tested patients in the 10-day arm had a TP53 mutation.
Patients received intravenous decitabine at a dose of 20 mg/m2 for the assigned duration of either 5 or 10 consecutive days for the first three cycles of induction, and those who responded to treatment received additional consolidation cycles every 4-8 weeks for up to 24 total cycles. Patients in the 10-day arm were switched to 5-day dosing after achieving complete response or complete response with incomplete blood count recovery.
The groups were well balanced with respect to baseline characteristics and the imbalance in patient numbers in the arms was mainly because of adaptive randomization; the 10-day patients had better responses during the early part of the study, Dr. Short explained.
None of the patients underwent allogeneic stem cell transplantation, he added.
Older patients with acute AML often have poor tolerance for intensive chemotherapy, but decitabine has been shown to improve survival when compared with supportive care or low-dose cytarabine in these patients. However, while some single-arm studies have suggested that 5- and 10-day dosing may result in similar outcomes, and another suggested that 10-day dosing may be superior in TP53-mutated AML, no studies have directly compared 5- and 10-day dosing, he said.
“In this relatively poor-risk cohort of older adults with newly diagnosed AML, decitabine for 5 and 10 days resulted in similar response rates, survival, and early mortality,” he concluded.
This study was funded by a University of Texas MD Anderson Cancer Center support grant. Dr. Short reported having no financial disclosures.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
SOURCE: Short NJ et al. ALF 2018, Poster Session.
NEWPORT BEACH, CALIF. – Response and survival rates are similar with 5- and 10-day dosing of decitabine in poor-risk older adults with previously untreated acute myeloid leukemia, according to findings from a randomized phase 2 trial.
The overall response rates in 25 patients randomized to receive 5 days of decitabine and 40 patients randomized to receive 10 days of decitabine were 44% and 38%, respectively. Complete response rates were 28% and 30%, respectively, and the median number of cycles to best response was two in both arms, Nicholas J. Short, MD, reported in a poster at the Acute Leukemia Forum of Hemedicus.
Patients were followed for a median of 38 months. Median remission duration was 9.4 months in 11 responders who received 5 days of decitabine, and 6.4 months in 15 responders in the 10-day treatment arm. The 1-year continued remission rates were 25% and 30%, respectively (P = .85). Median overall survival was 4.9 and 7.1 months, respectively, and 1-year overall survival rates were 27% and 25%, respectively, he said, adding that none of the differences in the groups were statistically significant.
Further, no differences in survival were seen when patients in the two treatment arms were stratified by cytogenetics, de novo versus secondary or treatment-related disease, or TP53 mutations; however, these subgroups were small, he noted.
Study subjects were adults aged 60 years or older (median, 77 and 78 years) with newly diagnosed and untreated acute myeloid leukemia (AML), and adults under age 60 years who were not suitable candidates for intensive chemotherapy. They were enrolled between February 2013 and July 2017. About 30% of patients had performance status scores of 2-3, and 45% of patients had secondary AML.
“About 40% of patients in the 5-day arm had poor-risk cytogenetics, and about half in the 10-day arm had poor-risk cytogenetics,” Dr. Short said in an interview, adding that 6 of 21 tested patients in the 5-day arm and 16 of 38 tested patients in the 10-day arm had a TP53 mutation.
Patients received intravenous decitabine at a dose of 20 mg/m2 for the assigned duration of either 5 or 10 consecutive days for the first three cycles of induction, and those who responded to treatment received additional consolidation cycles every 4-8 weeks for up to 24 total cycles. Patients in the 10-day arm were switched to 5-day dosing after achieving complete response or complete response with incomplete blood count recovery.
The groups were well balanced with respect to baseline characteristics and the imbalance in patient numbers in the arms was mainly because of adaptive randomization; the 10-day patients had better responses during the early part of the study, Dr. Short explained.
None of the patients underwent allogeneic stem cell transplantation, he added.
Older patients with acute AML often have poor tolerance for intensive chemotherapy, but decitabine has been shown to improve survival when compared with supportive care or low-dose cytarabine in these patients. However, while some single-arm studies have suggested that 5- and 10-day dosing may result in similar outcomes, and another suggested that 10-day dosing may be superior in TP53-mutated AML, no studies have directly compared 5- and 10-day dosing, he said.
“In this relatively poor-risk cohort of older adults with newly diagnosed AML, decitabine for 5 and 10 days resulted in similar response rates, survival, and early mortality,” he concluded.
This study was funded by a University of Texas MD Anderson Cancer Center support grant. Dr. Short reported having no financial disclosures.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
SOURCE: Short NJ et al. ALF 2018, Poster Session.
NEWPORT BEACH, CALIF. – Response and survival rates are similar with 5- and 10-day dosing of decitabine in poor-risk older adults with previously untreated acute myeloid leukemia, according to findings from a randomized phase 2 trial.
The overall response rates in 25 patients randomized to receive 5 days of decitabine and 40 patients randomized to receive 10 days of decitabine were 44% and 38%, respectively. Complete response rates were 28% and 30%, respectively, and the median number of cycles to best response was two in both arms, Nicholas J. Short, MD, reported in a poster at the Acute Leukemia Forum of Hemedicus.
Patients were followed for a median of 38 months. Median remission duration was 9.4 months in 11 responders who received 5 days of decitabine, and 6.4 months in 15 responders in the 10-day treatment arm. The 1-year continued remission rates were 25% and 30%, respectively (P = .85). Median overall survival was 4.9 and 7.1 months, respectively, and 1-year overall survival rates were 27% and 25%, respectively, he said, adding that none of the differences in the groups were statistically significant.
Further, no differences in survival were seen when patients in the two treatment arms were stratified by cytogenetics, de novo versus secondary or treatment-related disease, or TP53 mutations; however, these subgroups were small, he noted.
Study subjects were adults aged 60 years or older (median, 77 and 78 years) with newly diagnosed and untreated acute myeloid leukemia (AML), and adults under age 60 years who were not suitable candidates for intensive chemotherapy. They were enrolled between February 2013 and July 2017. About 30% of patients had performance status scores of 2-3, and 45% of patients had secondary AML.
“About 40% of patients in the 5-day arm had poor-risk cytogenetics, and about half in the 10-day arm had poor-risk cytogenetics,” Dr. Short said in an interview, adding that 6 of 21 tested patients in the 5-day arm and 16 of 38 tested patients in the 10-day arm had a TP53 mutation.
Patients received intravenous decitabine at a dose of 20 mg/m2 for the assigned duration of either 5 or 10 consecutive days for the first three cycles of induction, and those who responded to treatment received additional consolidation cycles every 4-8 weeks for up to 24 total cycles. Patients in the 10-day arm were switched to 5-day dosing after achieving complete response or complete response with incomplete blood count recovery.
The groups were well balanced with respect to baseline characteristics and the imbalance in patient numbers in the arms was mainly because of adaptive randomization; the 10-day patients had better responses during the early part of the study, Dr. Short explained.
None of the patients underwent allogeneic stem cell transplantation, he added.
Older patients with acute AML often have poor tolerance for intensive chemotherapy, but decitabine has been shown to improve survival when compared with supportive care or low-dose cytarabine in these patients. However, while some single-arm studies have suggested that 5- and 10-day dosing may result in similar outcomes, and another suggested that 10-day dosing may be superior in TP53-mutated AML, no studies have directly compared 5- and 10-day dosing, he said.
“In this relatively poor-risk cohort of older adults with newly diagnosed AML, decitabine for 5 and 10 days resulted in similar response rates, survival, and early mortality,” he concluded.
This study was funded by a University of Texas MD Anderson Cancer Center support grant. Dr. Short reported having no financial disclosures.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
SOURCE: Short NJ et al. ALF 2018, Poster Session.
REPORTING FROM ALF 2018
Key clinical point:
Major finding: Overall response rates were 44% with 5-day dosing and 38% with 10-day dosing.
Study details: A randomized phase 2 study of 65 patients.
Disclosures: This study was funded by an University of Texas MD Anderson Cancer Center support grant. Dr. Short reported having no financial disclosures.
Source: Short NJ et al. ALF 2018, Poster Session.
Meta-analysis: Thin struts equal better outcomes for drug-eluting stents
WASHINGTON – Consistent with experimental and recent clinical studies, a meta-analysis of 69 randomized controlled trials found that increasing strut thickness correlated with increasing risk of stent thrombosis as well as risk of myocardial infarction.
The report was presented at CRT 2018, sponsored by the Cardiovascular Research Institute at Medstar Washington (D.C.) Hospital Center.
In the meta-analysis, which compared four categories of strut thickness, the relationship between strut thickness and rates of stent thrombosis was almost linear, according to Micaela Iantorno, MD, a clinical fellow in interventional cardiology at the hospital center.
Thirty-six of the studies compared devices with thin struts to those with thick struts, 15 studies compared devices with ultrathin struts to devices with thin struts, and 11 compared devices with thin struts to devices with struts in the intermediate category. The remaining seven studies compared other strut thicknesses, such as ultrathin to intermediate.
When compared to devices with the thickest struts, there was a stepwise reduction in risk of strut thrombosis for each grade reduction in thickness. Expressed as an odds ratio, devices with intermediate struts were associated with 33% risk reduction, devices with thin struts were associated with a 42% risk reduction, and devices with ultrathin struts were associated with a 57% risk reduction. Each was statistically significant based on the 95% confidence interval, although P values were not reported.
When devices with ultrathin struts were compared to those with thin struts or to those with intermediate thickness struts, the differences in stent thrombosis were not statistically significant, but there were trends favoring the devices with thinner struts. However, the lower risk of stent thrombosis for devices with thin struts relative to those with intermediate thickness was modest and did not approach significance.
For risk of MI, the same type of gradient was observed. Relative to devices with thick struts, devices with ultrathin struts were associated with a 27% reduction, devices with thin struts were associated with a 21% reduction, and devices with struts of intermediate thickness were associated with a 15% reduction. Only the difference for the intermediate-thickness devices fell short of statistical significance.
There were 22 different stent devices represented in this analysis. Bare metal stents and stents with bioresorbable scaffolds were excluded, but devices from all three generations of drug-eluting stents, including devices with bioabsorbable polymers, were included.
Other outcomes, including mortality, cardiovascular mortality, and major adverse cardiovascular events, were evaluated, but a gradient relationship between strut thickness and these outcomes was less apparent. For example, when devices with thick struts were compared to devices with thinner struts, only the ultrathin devices achieved a significant, 15%, reduction in cardiovascular mortality. The 10% reduction in all-cause mortality fell short of statistical significance.
Emphasizing that other factors, such as stent geometry, polymer type, and type of eluting drug, were not considered in this analysis, Dr. Iantorno acknowledged that there are important limitations of this study, but the data are consistent with the hypothesis that “reducing strut thickness might be the key to improving the efficacy and safety profile of coronary stents.”
Sachin Kumar, MD, an interventional cardiologist at the University of Texas Health Science Center at Houston, cautioned that strut thickness “is just one side of the story.” Moderator of the session in which these data were presented, Dr. Kumar said that other factors Dr. Iantorno listed as potentially important, including polymer type and eluting drug, should not be discounted. However, he conceded that in the context of other recent evidence that strut thickness may be important to outcomes, particularly risk of stent thrombosis, this variable has become a focus of design improvements.
SOURCE: Iantorno M. Abstract CRT-100.87.
WASHINGTON – Consistent with experimental and recent clinical studies, a meta-analysis of 69 randomized controlled trials found that increasing strut thickness correlated with increasing risk of stent thrombosis as well as risk of myocardial infarction.
The report was presented at CRT 2018, sponsored by the Cardiovascular Research Institute at Medstar Washington (D.C.) Hospital Center.
In the meta-analysis, which compared four categories of strut thickness, the relationship between strut thickness and rates of stent thrombosis was almost linear, according to Micaela Iantorno, MD, a clinical fellow in interventional cardiology at the hospital center.
Thirty-six of the studies compared devices with thin struts to those with thick struts, 15 studies compared devices with ultrathin struts to devices with thin struts, and 11 compared devices with thin struts to devices with struts in the intermediate category. The remaining seven studies compared other strut thicknesses, such as ultrathin to intermediate.
When compared to devices with the thickest struts, there was a stepwise reduction in risk of strut thrombosis for each grade reduction in thickness. Expressed as an odds ratio, devices with intermediate struts were associated with 33% risk reduction, devices with thin struts were associated with a 42% risk reduction, and devices with ultrathin struts were associated with a 57% risk reduction. Each was statistically significant based on the 95% confidence interval, although P values were not reported.
When devices with ultrathin struts were compared to those with thin struts or to those with intermediate thickness struts, the differences in stent thrombosis were not statistically significant, but there were trends favoring the devices with thinner struts. However, the lower risk of stent thrombosis for devices with thin struts relative to those with intermediate thickness was modest and did not approach significance.
For risk of MI, the same type of gradient was observed. Relative to devices with thick struts, devices with ultrathin struts were associated with a 27% reduction, devices with thin struts were associated with a 21% reduction, and devices with struts of intermediate thickness were associated with a 15% reduction. Only the difference for the intermediate-thickness devices fell short of statistical significance.
There were 22 different stent devices represented in this analysis. Bare metal stents and stents with bioresorbable scaffolds were excluded, but devices from all three generations of drug-eluting stents, including devices with bioabsorbable polymers, were included.
Other outcomes, including mortality, cardiovascular mortality, and major adverse cardiovascular events, were evaluated, but a gradient relationship between strut thickness and these outcomes was less apparent. For example, when devices with thick struts were compared to devices with thinner struts, only the ultrathin devices achieved a significant, 15%, reduction in cardiovascular mortality. The 10% reduction in all-cause mortality fell short of statistical significance.
Emphasizing that other factors, such as stent geometry, polymer type, and type of eluting drug, were not considered in this analysis, Dr. Iantorno acknowledged that there are important limitations of this study, but the data are consistent with the hypothesis that “reducing strut thickness might be the key to improving the efficacy and safety profile of coronary stents.”
Sachin Kumar, MD, an interventional cardiologist at the University of Texas Health Science Center at Houston, cautioned that strut thickness “is just one side of the story.” Moderator of the session in which these data were presented, Dr. Kumar said that other factors Dr. Iantorno listed as potentially important, including polymer type and eluting drug, should not be discounted. However, he conceded that in the context of other recent evidence that strut thickness may be important to outcomes, particularly risk of stent thrombosis, this variable has become a focus of design improvements.
SOURCE: Iantorno M. Abstract CRT-100.87.
WASHINGTON – Consistent with experimental and recent clinical studies, a meta-analysis of 69 randomized controlled trials found that increasing strut thickness correlated with increasing risk of stent thrombosis as well as risk of myocardial infarction.
The report was presented at CRT 2018, sponsored by the Cardiovascular Research Institute at Medstar Washington (D.C.) Hospital Center.
In the meta-analysis, which compared four categories of strut thickness, the relationship between strut thickness and rates of stent thrombosis was almost linear, according to Micaela Iantorno, MD, a clinical fellow in interventional cardiology at the hospital center.
Thirty-six of the studies compared devices with thin struts to those with thick struts, 15 studies compared devices with ultrathin struts to devices with thin struts, and 11 compared devices with thin struts to devices with struts in the intermediate category. The remaining seven studies compared other strut thicknesses, such as ultrathin to intermediate.
When compared to devices with the thickest struts, there was a stepwise reduction in risk of strut thrombosis for each grade reduction in thickness. Expressed as an odds ratio, devices with intermediate struts were associated with 33% risk reduction, devices with thin struts were associated with a 42% risk reduction, and devices with ultrathin struts were associated with a 57% risk reduction. Each was statistically significant based on the 95% confidence interval, although P values were not reported.
When devices with ultrathin struts were compared to those with thin struts or to those with intermediate thickness struts, the differences in stent thrombosis were not statistically significant, but there were trends favoring the devices with thinner struts. However, the lower risk of stent thrombosis for devices with thin struts relative to those with intermediate thickness was modest and did not approach significance.
For risk of MI, the same type of gradient was observed. Relative to devices with thick struts, devices with ultrathin struts were associated with a 27% reduction, devices with thin struts were associated with a 21% reduction, and devices with struts of intermediate thickness were associated with a 15% reduction. Only the difference for the intermediate-thickness devices fell short of statistical significance.
There were 22 different stent devices represented in this analysis. Bare metal stents and stents with bioresorbable scaffolds were excluded, but devices from all three generations of drug-eluting stents, including devices with bioabsorbable polymers, were included.
Other outcomes, including mortality, cardiovascular mortality, and major adverse cardiovascular events, were evaluated, but a gradient relationship between strut thickness and these outcomes was less apparent. For example, when devices with thick struts were compared to devices with thinner struts, only the ultrathin devices achieved a significant, 15%, reduction in cardiovascular mortality. The 10% reduction in all-cause mortality fell short of statistical significance.
Emphasizing that other factors, such as stent geometry, polymer type, and type of eluting drug, were not considered in this analysis, Dr. Iantorno acknowledged that there are important limitations of this study, but the data are consistent with the hypothesis that “reducing strut thickness might be the key to improving the efficacy and safety profile of coronary stents.”
Sachin Kumar, MD, an interventional cardiologist at the University of Texas Health Science Center at Houston, cautioned that strut thickness “is just one side of the story.” Moderator of the session in which these data were presented, Dr. Kumar said that other factors Dr. Iantorno listed as potentially important, including polymer type and eluting drug, should not be discounted. However, he conceded that in the context of other recent evidence that strut thickness may be important to outcomes, particularly risk of stent thrombosis, this variable has become a focus of design improvements.
SOURCE: Iantorno M. Abstract CRT-100.87.
REPORTING FROM CRT 2018
Key clinical point: The thickness of struts in drug-eluting stents is inversely related to the risk of stent thrombosis.
Major finding: The risk of stent thrombosis is 57% lower for DES devices with ultrathin (less than 81 mcg) rather than thick (at least 121 mcg) struts.
Data source: Meta-analysis of randomized trials.
Disclosures: Dr. Iantorno reports no financial relationships relevant to this study.
Source: Iantorno M. Abstract CRT-100.87.
MDedge Psychcast: Interview with Dr. Henry Nasrallah
Welcome to the MDedge Psychcast, the new podcast from Clinical Psychiatry News and Current Psychiatry.
In this first episode,
Welcome to the MDedge Psychcast, the new podcast from Clinical Psychiatry News and Current Psychiatry.
In this first episode,
Welcome to the MDedge Psychcast, the new podcast from Clinical Psychiatry News and Current Psychiatry.
In this first episode,
