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Neutrophils may decline in patients on fingolimod
SEATTLE –
A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”
The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.
Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.
In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.
“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
The FLUENT study
Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.
Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.
Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.
The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.
FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
Immune cell subsets
In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.
CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”
Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.
“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
A measure of CNS injury
In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.
Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.
The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.
Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
Adverse events
No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.
Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).
Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.
SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.
SEATTLE –
A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”
The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.
Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.
In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.
“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
The FLUENT study
Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.
Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.
Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.
The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.
FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
Immune cell subsets
In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.
CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”
Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.
“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
A measure of CNS injury
In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.
Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.
The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.
Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
Adverse events
No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.
Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).
Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.
SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.
SEATTLE –
A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”
The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.
Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.
In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.
“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
The FLUENT study
Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.
Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.
Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.
The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.
FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
Immune cell subsets
In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.
CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”
Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.
“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
A measure of CNS injury
In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.
Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.
The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.
Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
Adverse events
No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.
Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).
Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.
SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.
REPORTING FROM CMSC 2019
Being a leader in medicine doesn’t have to mean changing careers
About once a week, along with all the other junk mail, I get a glossy brochure for some university’s online courses to “become a leader in medicine.”
They extol the virtues of their programs: How they equip me to “change the health care system,” “harness market forces to improve medical care,” “empower the next generation of physicians,” and other statements that were almost certainly not written by a doctor.
I’m sure some people are interested in this sort of thing. Maybe they’re ready for a career change from the exam room to the boardroom. But me? I have, pretty much, zero desire to do that. I don’t want to be a corporate leader in medicine. I didn’t come here to sit at a table and watch PowerPoint slides. I didn’t work to get into, and through, medical school, residency, and fellowship to debate earnings ratios and procedure costs with accountants.
I’m here for the patients. I’m sure there are some who became attending physicians, realized this wasn’t for them, and went off to do something else. That’s fine. I have nothing against it.
But, after 20 years in practice, I’m happy where I am. Like most others, I wish I made more money, or that my overhead was less, but I’m overall content with my little world. I have a great staff, a relaxed office, and the majority of my patients are good people.
I have no interest in trading that to be a leader in medicine. In the game of trying to make the world a better place, I’ve found my calling. I can do good for others far more effectively at my second-floor office than in a corporate tower.
And if doing my best for patients day in and day out doesn’t make me a leader in medicine, I don’t know what does.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
About once a week, along with all the other junk mail, I get a glossy brochure for some university’s online courses to “become a leader in medicine.”
They extol the virtues of their programs: How they equip me to “change the health care system,” “harness market forces to improve medical care,” “empower the next generation of physicians,” and other statements that were almost certainly not written by a doctor.
I’m sure some people are interested in this sort of thing. Maybe they’re ready for a career change from the exam room to the boardroom. But me? I have, pretty much, zero desire to do that. I don’t want to be a corporate leader in medicine. I didn’t come here to sit at a table and watch PowerPoint slides. I didn’t work to get into, and through, medical school, residency, and fellowship to debate earnings ratios and procedure costs with accountants.
I’m here for the patients. I’m sure there are some who became attending physicians, realized this wasn’t for them, and went off to do something else. That’s fine. I have nothing against it.
But, after 20 years in practice, I’m happy where I am. Like most others, I wish I made more money, or that my overhead was less, but I’m overall content with my little world. I have a great staff, a relaxed office, and the majority of my patients are good people.
I have no interest in trading that to be a leader in medicine. In the game of trying to make the world a better place, I’ve found my calling. I can do good for others far more effectively at my second-floor office than in a corporate tower.
And if doing my best for patients day in and day out doesn’t make me a leader in medicine, I don’t know what does.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
About once a week, along with all the other junk mail, I get a glossy brochure for some university’s online courses to “become a leader in medicine.”
They extol the virtues of their programs: How they equip me to “change the health care system,” “harness market forces to improve medical care,” “empower the next generation of physicians,” and other statements that were almost certainly not written by a doctor.
I’m sure some people are interested in this sort of thing. Maybe they’re ready for a career change from the exam room to the boardroom. But me? I have, pretty much, zero desire to do that. I don’t want to be a corporate leader in medicine. I didn’t come here to sit at a table and watch PowerPoint slides. I didn’t work to get into, and through, medical school, residency, and fellowship to debate earnings ratios and procedure costs with accountants.
I’m here for the patients. I’m sure there are some who became attending physicians, realized this wasn’t for them, and went off to do something else. That’s fine. I have nothing against it.
But, after 20 years in practice, I’m happy where I am. Like most others, I wish I made more money, or that my overhead was less, but I’m overall content with my little world. I have a great staff, a relaxed office, and the majority of my patients are good people.
I have no interest in trading that to be a leader in medicine. In the game of trying to make the world a better place, I’ve found my calling. I can do good for others far more effectively at my second-floor office than in a corporate tower.
And if doing my best for patients day in and day out doesn’t make me a leader in medicine, I don’t know what does.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Patients with focal epilepsy have progressive cortical thinning
, according to research published online July 1 in JAMA Neurology. Methods for preventing this thinning are unknown. “Our findings appear to highlight the need for longitudinal studies to develop disease-modifying treatments for epilepsy,” said Marian Galovic, MD, a doctoral student at University College London, and colleagues.
To date, neurologists have not found a definitive answer to the question of whether epilepsy is a static or progressive disease. Few longitudinal studies have examined patients with structural neuroimaging to determine whether the brain changes over time. The studies that have taken this approach have had small populations or have lacked control populations.
Comparing brain changes in patients and controls
Dr. Galovic and colleagues analyzed data for consecutive patients with focal epilepsy who underwent follow-up at the National Hospital for Neurology and Neurosurgery in London. The data were collected from Aug. 3, 2004, to Jan. 26, 2016. The researchers chose individuals who had at least 2 high-resolution T1-weighted MRI scans performed on the same scanner more than 6 months apart. They excluded patients with brain lesions other than hippocampal sclerosis, those with inadequate MRI scan quality, and those for whom clinical data were missing. To match these patients with controls, Dr. Galovic and colleagues chose three longitudinal data sets with data for healthy volunteers between ages 20 and 70 years. Each control participant had two high-resolution T1-weighted scans taken more than 6 months apart. The investigators matched patients and controls on age and sex. The automated and validated Computational Anatomy Toolbox (CAT12) estimated cortical thickness.
Dr. Galovic’s group included 190 patients with focal epilepsy, who had had 396 MRI scans, and 141 healthy controls, who had had 282 MRI scans, in their analysis. Age, sex, and image quality did not differ significantly between the two groups. Mean age was 36 years for patients and 35 years for controls. The proportion of women was 52.1% among patients and 53.9% among controls.
The rate of atrophy was doubled in patients
Approximately 77% of people with epilepsy had progressive cortical thinning that was distinct from that associated with normal aging. The mean overall annual rate of global cortical thinning was higher among patients with epilepsy (0.024) than among controls (0.011). The mean annual rate of cortical thinning increased among people with epilepsy who were older than 55 years. This rate was 0.021 in patients aged 18 to less than 35 years, compared with 0.023 in patients aged 35 to less than 55 years. Seizure frequency, number of antiepileptic drugs (AEDs) taken, and history of secondarily generalized seizures did not differ between age groups.
Compared with healthy controls, patients with focal epilepsy had widespread areas of greater progressive atrophy. Bilaterally affected areas included the lateral and posterior temporal lobes, posterior cingulate gyri, occipital lobes, pericentral gyri, and opercula. The distribution of progressive thinning in all patients with epilepsy was similar to regions connected to both hippocampi. Healthy controls had no areas of greater cortical thinning, compared with patients with epilepsy.
Progressive thinning in the left postcentral gyrus was greater in patients with left temporal lobe epilepsy (TLE) than in those with right TLE. Cortical thinning was more progressive in patients with right frontal lobe epilepsy (FLE) than in those with left FLE, particularly in right parietotemporal and right frontal areas.
Dr. Galovic and colleagues found no association between the rate of cortical thinning and seizure frequency, history of secondarily generalized seizures, or number of AEDs taken between MRIs. They found no difference in the rate of atrophy between patients with epilepsy with ongoing seizures and those without. The annual mean rate of cortical thinning was higher in people with a short duration of epilepsy (i.e., less than 5 years), compared with patients with a longer duration of epilepsy (i.e., 5 years or more).
A surrogate marker for neurodegeneration?
“The most likely cause of cortical thinning is neuronal loss, suggesting that these measurements are a surrogate marker for neurodegeneration,” said Dr. Galovic and colleagues. The finding that progressive morphologic changes were most pronounced in the first 5 years after epilepsy onset “supports the need for early diagnosis, rapid treatment, and reduction of delays of surgical referral in people with epilepsy,” they added.
One limitation of the current study is the fact that data from patients and controls were acquired using different MRI scanners. In addition, the patients included in the study had been referred to the center because their cases were more complicated, thus introducing the possibility of referral bias. The findings thus cannot be generalized readily to the overall population, said Dr. Galovic and colleagues.
Future studies should examine whether particular AEDs have differential influences on the progressive morphologic changes observed in epilepsy, said the investigators. “Future research should also address whether progressive changes in cortical morphologic characteristics correlate with deficits on serial cognitive testing or spreading of the irritative zone on EEG recordings,” they concluded.
The study and the authors received support from the Medical Research Council, the Wellcome Trust, and the University College London Hospital.
SOURCE: Galovic M et al. JAMA Neurol. 2019 Jul 1. doi: 10.1001/jamaneurol.2019.1708.
, according to research published online July 1 in JAMA Neurology. Methods for preventing this thinning are unknown. “Our findings appear to highlight the need for longitudinal studies to develop disease-modifying treatments for epilepsy,” said Marian Galovic, MD, a doctoral student at University College London, and colleagues.
To date, neurologists have not found a definitive answer to the question of whether epilepsy is a static or progressive disease. Few longitudinal studies have examined patients with structural neuroimaging to determine whether the brain changes over time. The studies that have taken this approach have had small populations or have lacked control populations.
Comparing brain changes in patients and controls
Dr. Galovic and colleagues analyzed data for consecutive patients with focal epilepsy who underwent follow-up at the National Hospital for Neurology and Neurosurgery in London. The data were collected from Aug. 3, 2004, to Jan. 26, 2016. The researchers chose individuals who had at least 2 high-resolution T1-weighted MRI scans performed on the same scanner more than 6 months apart. They excluded patients with brain lesions other than hippocampal sclerosis, those with inadequate MRI scan quality, and those for whom clinical data were missing. To match these patients with controls, Dr. Galovic and colleagues chose three longitudinal data sets with data for healthy volunteers between ages 20 and 70 years. Each control participant had two high-resolution T1-weighted scans taken more than 6 months apart. The investigators matched patients and controls on age and sex. The automated and validated Computational Anatomy Toolbox (CAT12) estimated cortical thickness.
Dr. Galovic’s group included 190 patients with focal epilepsy, who had had 396 MRI scans, and 141 healthy controls, who had had 282 MRI scans, in their analysis. Age, sex, and image quality did not differ significantly between the two groups. Mean age was 36 years for patients and 35 years for controls. The proportion of women was 52.1% among patients and 53.9% among controls.
The rate of atrophy was doubled in patients
Approximately 77% of people with epilepsy had progressive cortical thinning that was distinct from that associated with normal aging. The mean overall annual rate of global cortical thinning was higher among patients with epilepsy (0.024) than among controls (0.011). The mean annual rate of cortical thinning increased among people with epilepsy who were older than 55 years. This rate was 0.021 in patients aged 18 to less than 35 years, compared with 0.023 in patients aged 35 to less than 55 years. Seizure frequency, number of antiepileptic drugs (AEDs) taken, and history of secondarily generalized seizures did not differ between age groups.
Compared with healthy controls, patients with focal epilepsy had widespread areas of greater progressive atrophy. Bilaterally affected areas included the lateral and posterior temporal lobes, posterior cingulate gyri, occipital lobes, pericentral gyri, and opercula. The distribution of progressive thinning in all patients with epilepsy was similar to regions connected to both hippocampi. Healthy controls had no areas of greater cortical thinning, compared with patients with epilepsy.
Progressive thinning in the left postcentral gyrus was greater in patients with left temporal lobe epilepsy (TLE) than in those with right TLE. Cortical thinning was more progressive in patients with right frontal lobe epilepsy (FLE) than in those with left FLE, particularly in right parietotemporal and right frontal areas.
Dr. Galovic and colleagues found no association between the rate of cortical thinning and seizure frequency, history of secondarily generalized seizures, or number of AEDs taken between MRIs. They found no difference in the rate of atrophy between patients with epilepsy with ongoing seizures and those without. The annual mean rate of cortical thinning was higher in people with a short duration of epilepsy (i.e., less than 5 years), compared with patients with a longer duration of epilepsy (i.e., 5 years or more).
A surrogate marker for neurodegeneration?
“The most likely cause of cortical thinning is neuronal loss, suggesting that these measurements are a surrogate marker for neurodegeneration,” said Dr. Galovic and colleagues. The finding that progressive morphologic changes were most pronounced in the first 5 years after epilepsy onset “supports the need for early diagnosis, rapid treatment, and reduction of delays of surgical referral in people with epilepsy,” they added.
One limitation of the current study is the fact that data from patients and controls were acquired using different MRI scanners. In addition, the patients included in the study had been referred to the center because their cases were more complicated, thus introducing the possibility of referral bias. The findings thus cannot be generalized readily to the overall population, said Dr. Galovic and colleagues.
Future studies should examine whether particular AEDs have differential influences on the progressive morphologic changes observed in epilepsy, said the investigators. “Future research should also address whether progressive changes in cortical morphologic characteristics correlate with deficits on serial cognitive testing or spreading of the irritative zone on EEG recordings,” they concluded.
The study and the authors received support from the Medical Research Council, the Wellcome Trust, and the University College London Hospital.
SOURCE: Galovic M et al. JAMA Neurol. 2019 Jul 1. doi: 10.1001/jamaneurol.2019.1708.
, according to research published online July 1 in JAMA Neurology. Methods for preventing this thinning are unknown. “Our findings appear to highlight the need for longitudinal studies to develop disease-modifying treatments for epilepsy,” said Marian Galovic, MD, a doctoral student at University College London, and colleagues.
To date, neurologists have not found a definitive answer to the question of whether epilepsy is a static or progressive disease. Few longitudinal studies have examined patients with structural neuroimaging to determine whether the brain changes over time. The studies that have taken this approach have had small populations or have lacked control populations.
Comparing brain changes in patients and controls
Dr. Galovic and colleagues analyzed data for consecutive patients with focal epilepsy who underwent follow-up at the National Hospital for Neurology and Neurosurgery in London. The data were collected from Aug. 3, 2004, to Jan. 26, 2016. The researchers chose individuals who had at least 2 high-resolution T1-weighted MRI scans performed on the same scanner more than 6 months apart. They excluded patients with brain lesions other than hippocampal sclerosis, those with inadequate MRI scan quality, and those for whom clinical data were missing. To match these patients with controls, Dr. Galovic and colleagues chose three longitudinal data sets with data for healthy volunteers between ages 20 and 70 years. Each control participant had two high-resolution T1-weighted scans taken more than 6 months apart. The investigators matched patients and controls on age and sex. The automated and validated Computational Anatomy Toolbox (CAT12) estimated cortical thickness.
Dr. Galovic’s group included 190 patients with focal epilepsy, who had had 396 MRI scans, and 141 healthy controls, who had had 282 MRI scans, in their analysis. Age, sex, and image quality did not differ significantly between the two groups. Mean age was 36 years for patients and 35 years for controls. The proportion of women was 52.1% among patients and 53.9% among controls.
The rate of atrophy was doubled in patients
Approximately 77% of people with epilepsy had progressive cortical thinning that was distinct from that associated with normal aging. The mean overall annual rate of global cortical thinning was higher among patients with epilepsy (0.024) than among controls (0.011). The mean annual rate of cortical thinning increased among people with epilepsy who were older than 55 years. This rate was 0.021 in patients aged 18 to less than 35 years, compared with 0.023 in patients aged 35 to less than 55 years. Seizure frequency, number of antiepileptic drugs (AEDs) taken, and history of secondarily generalized seizures did not differ between age groups.
Compared with healthy controls, patients with focal epilepsy had widespread areas of greater progressive atrophy. Bilaterally affected areas included the lateral and posterior temporal lobes, posterior cingulate gyri, occipital lobes, pericentral gyri, and opercula. The distribution of progressive thinning in all patients with epilepsy was similar to regions connected to both hippocampi. Healthy controls had no areas of greater cortical thinning, compared with patients with epilepsy.
Progressive thinning in the left postcentral gyrus was greater in patients with left temporal lobe epilepsy (TLE) than in those with right TLE. Cortical thinning was more progressive in patients with right frontal lobe epilepsy (FLE) than in those with left FLE, particularly in right parietotemporal and right frontal areas.
Dr. Galovic and colleagues found no association between the rate of cortical thinning and seizure frequency, history of secondarily generalized seizures, or number of AEDs taken between MRIs. They found no difference in the rate of atrophy between patients with epilepsy with ongoing seizures and those without. The annual mean rate of cortical thinning was higher in people with a short duration of epilepsy (i.e., less than 5 years), compared with patients with a longer duration of epilepsy (i.e., 5 years or more).
A surrogate marker for neurodegeneration?
“The most likely cause of cortical thinning is neuronal loss, suggesting that these measurements are a surrogate marker for neurodegeneration,” said Dr. Galovic and colleagues. The finding that progressive morphologic changes were most pronounced in the first 5 years after epilepsy onset “supports the need for early diagnosis, rapid treatment, and reduction of delays of surgical referral in people with epilepsy,” they added.
One limitation of the current study is the fact that data from patients and controls were acquired using different MRI scanners. In addition, the patients included in the study had been referred to the center because their cases were more complicated, thus introducing the possibility of referral bias. The findings thus cannot be generalized readily to the overall population, said Dr. Galovic and colleagues.
Future studies should examine whether particular AEDs have differential influences on the progressive morphologic changes observed in epilepsy, said the investigators. “Future research should also address whether progressive changes in cortical morphologic characteristics correlate with deficits on serial cognitive testing or spreading of the irritative zone on EEG recordings,” they concluded.
The study and the authors received support from the Medical Research Council, the Wellcome Trust, and the University College London Hospital.
SOURCE: Galovic M et al. JAMA Neurol. 2019 Jul 1. doi: 10.1001/jamaneurol.2019.1708.
FROM JAMA NEUROLOGY
Lipoprotein(a) levels tied to higher ischemic stroke risk
High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.
Anne Langsted, MD, with Copenhagen University Hospital and the University of Copenhagen in Denmark, and her co-researchers evaluated the impact of high Lp(a) levels in a large contemporary cohort of 49,699 individuals in the Copenhagen General Population Study, and another 10,813 individuals in the Copenhagen City Heart Study.
Measurements assessed included plasma lipoprotein(a) levels and carrier or noncarrier status for LPA rs10455872. The endpoint of ischemic stroke was ascertained from Danish national health registries and confirmed by physicians.
Although risk estimates were less pronounced than what was reported before regarding the link between Lp(a) for ischemic heart disease and aortic valve stenosis, the risk of stroke was increased by a factor of 1.6 among individuals with high Lp(a) levels as compared to those with lower levels, the investigators said.
Compared with noncarriers of LPA rs1045572, the hazard ratio for ischemic stroke was 1.23 for carriers of LPA rs1045572, which was associated with high levels plasma lipoprotein(a) levels, according to the researchers.
“Our results indicate a causal association of Lp(a) with risk of ischemic stroke, and emphasize the need for randomized, controlled clinical trials on the effect of Lp(a)-lowering to prevent cardiovascular disease including ischemic stroke,” About 20% of the general population have high Lp(a) levels, and some individuals have extremely high levels, Dr. Langsted and co-authors said in their report.
Interest in Lp(a) as a risk factor for cardiovascular disease has been reignited following large studies showing that high Lp(a) levels were linked to increased risk of myocardial infarction and aortic valve stenosis, according to the investigators.
However, results of various studies are conflicting as to whether high Lp(a) levels increase risk of hemorrhagic or ischemic stroke, they said.
Both cohort studies used in the analysis were supported by sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures. One co-author reported disclosures related to Akcea, Amgen, Sanofi, Regeneron, and AstraZeneca.
SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
This study linking high lipoprotein(a) [Lp(a)] levels to stroke risk, taken together with previous research, provide a sound basis to routinely perform one-time screening so that individuals with inherited high levels can try to avoid adverse cardiovascular outcomes, according to Christie M. Ballantyne, MD.
“As someone in the dual role of preventive cardiologist and patient with a strong family history of cardiovascular disease, I think that we have sufficient evidence that high Lp(a) is strongly associated with an increased risk of myocardial infarction, stroke, and aortic valve stenosis,” Dr. Ballantyne wrote in an editorial comment on the study.
Evidence is now “overwhelming” that high Lp(a) is linked to myocardial infarction and stroke, and it’s known that statins and aspirin reduce risk of these outcomes, he said in the commentary.
Despite that, scientific statements do not recommend routine Lp(a) testing due to a lack of clinical trials evidence; as a result, clinical trials are not including Lp(a) as a routine measurement: “We thus have a loop of futility—lack of routine measurement leads to lack of data,” he said.
This most recent study from Langsted and colleagues demonstrates that high Lp(a) levels, and genetic variants associated with Lp(a), are associated with increased ischemic stroke risk. “The genetics strongly supported that high Lp(a) levels were in the causal pathway for ischemic stroke and coronary heart disease,” Dr. Ballantyne said.
One major strength and weakness of the study is its large and relatively homogeneous European population—that bolstered the genetic analyses, but also means the data can’t be extrapolated to other populations, such as Africans and East Asians, who have higher stroke rates compared with Europeans, Dr. Ballantyne said.
Dr. Ballantyne is with the Department of Medicine and Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Tex. His editorial comment appears in the Journal of the American College of Cardiology (2019;74[1]:67-9. doi:10.1016/j.jacc.2019.05.029 . Dr. Ballantyne reported disclosures related to Akcea, Amgen, and Novartis.
This study linking high lipoprotein(a) [Lp(a)] levels to stroke risk, taken together with previous research, provide a sound basis to routinely perform one-time screening so that individuals with inherited high levels can try to avoid adverse cardiovascular outcomes, according to Christie M. Ballantyne, MD.
“As someone in the dual role of preventive cardiologist and patient with a strong family history of cardiovascular disease, I think that we have sufficient evidence that high Lp(a) is strongly associated with an increased risk of myocardial infarction, stroke, and aortic valve stenosis,” Dr. Ballantyne wrote in an editorial comment on the study.
Evidence is now “overwhelming” that high Lp(a) is linked to myocardial infarction and stroke, and it’s known that statins and aspirin reduce risk of these outcomes, he said in the commentary.
Despite that, scientific statements do not recommend routine Lp(a) testing due to a lack of clinical trials evidence; as a result, clinical trials are not including Lp(a) as a routine measurement: “We thus have a loop of futility—lack of routine measurement leads to lack of data,” he said.
This most recent study from Langsted and colleagues demonstrates that high Lp(a) levels, and genetic variants associated with Lp(a), are associated with increased ischemic stroke risk. “The genetics strongly supported that high Lp(a) levels were in the causal pathway for ischemic stroke and coronary heart disease,” Dr. Ballantyne said.
One major strength and weakness of the study is its large and relatively homogeneous European population—that bolstered the genetic analyses, but also means the data can’t be extrapolated to other populations, such as Africans and East Asians, who have higher stroke rates compared with Europeans, Dr. Ballantyne said.
Dr. Ballantyne is with the Department of Medicine and Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Tex. His editorial comment appears in the Journal of the American College of Cardiology (2019;74[1]:67-9. doi:10.1016/j.jacc.2019.05.029 . Dr. Ballantyne reported disclosures related to Akcea, Amgen, and Novartis.
This study linking high lipoprotein(a) [Lp(a)] levels to stroke risk, taken together with previous research, provide a sound basis to routinely perform one-time screening so that individuals with inherited high levels can try to avoid adverse cardiovascular outcomes, according to Christie M. Ballantyne, MD.
“As someone in the dual role of preventive cardiologist and patient with a strong family history of cardiovascular disease, I think that we have sufficient evidence that high Lp(a) is strongly associated with an increased risk of myocardial infarction, stroke, and aortic valve stenosis,” Dr. Ballantyne wrote in an editorial comment on the study.
Evidence is now “overwhelming” that high Lp(a) is linked to myocardial infarction and stroke, and it’s known that statins and aspirin reduce risk of these outcomes, he said in the commentary.
Despite that, scientific statements do not recommend routine Lp(a) testing due to a lack of clinical trials evidence; as a result, clinical trials are not including Lp(a) as a routine measurement: “We thus have a loop of futility—lack of routine measurement leads to lack of data,” he said.
This most recent study from Langsted and colleagues demonstrates that high Lp(a) levels, and genetic variants associated with Lp(a), are associated with increased ischemic stroke risk. “The genetics strongly supported that high Lp(a) levels were in the causal pathway for ischemic stroke and coronary heart disease,” Dr. Ballantyne said.
One major strength and weakness of the study is its large and relatively homogeneous European population—that bolstered the genetic analyses, but also means the data can’t be extrapolated to other populations, such as Africans and East Asians, who have higher stroke rates compared with Europeans, Dr. Ballantyne said.
Dr. Ballantyne is with the Department of Medicine and Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Tex. His editorial comment appears in the Journal of the American College of Cardiology (2019;74[1]:67-9. doi:10.1016/j.jacc.2019.05.029 . Dr. Ballantyne reported disclosures related to Akcea, Amgen, and Novartis.
High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.
Anne Langsted, MD, with Copenhagen University Hospital and the University of Copenhagen in Denmark, and her co-researchers evaluated the impact of high Lp(a) levels in a large contemporary cohort of 49,699 individuals in the Copenhagen General Population Study, and another 10,813 individuals in the Copenhagen City Heart Study.
Measurements assessed included plasma lipoprotein(a) levels and carrier or noncarrier status for LPA rs10455872. The endpoint of ischemic stroke was ascertained from Danish national health registries and confirmed by physicians.
Although risk estimates were less pronounced than what was reported before regarding the link between Lp(a) for ischemic heart disease and aortic valve stenosis, the risk of stroke was increased by a factor of 1.6 among individuals with high Lp(a) levels as compared to those with lower levels, the investigators said.
Compared with noncarriers of LPA rs1045572, the hazard ratio for ischemic stroke was 1.23 for carriers of LPA rs1045572, which was associated with high levels plasma lipoprotein(a) levels, according to the researchers.
“Our results indicate a causal association of Lp(a) with risk of ischemic stroke, and emphasize the need for randomized, controlled clinical trials on the effect of Lp(a)-lowering to prevent cardiovascular disease including ischemic stroke,” About 20% of the general population have high Lp(a) levels, and some individuals have extremely high levels, Dr. Langsted and co-authors said in their report.
Interest in Lp(a) as a risk factor for cardiovascular disease has been reignited following large studies showing that high Lp(a) levels were linked to increased risk of myocardial infarction and aortic valve stenosis, according to the investigators.
However, results of various studies are conflicting as to whether high Lp(a) levels increase risk of hemorrhagic or ischemic stroke, they said.
Both cohort studies used in the analysis were supported by sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures. One co-author reported disclosures related to Akcea, Amgen, Sanofi, Regeneron, and AstraZeneca.
SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.
Anne Langsted, MD, with Copenhagen University Hospital and the University of Copenhagen in Denmark, and her co-researchers evaluated the impact of high Lp(a) levels in a large contemporary cohort of 49,699 individuals in the Copenhagen General Population Study, and another 10,813 individuals in the Copenhagen City Heart Study.
Measurements assessed included plasma lipoprotein(a) levels and carrier or noncarrier status for LPA rs10455872. The endpoint of ischemic stroke was ascertained from Danish national health registries and confirmed by physicians.
Although risk estimates were less pronounced than what was reported before regarding the link between Lp(a) for ischemic heart disease and aortic valve stenosis, the risk of stroke was increased by a factor of 1.6 among individuals with high Lp(a) levels as compared to those with lower levels, the investigators said.
Compared with noncarriers of LPA rs1045572, the hazard ratio for ischemic stroke was 1.23 for carriers of LPA rs1045572, which was associated with high levels plasma lipoprotein(a) levels, according to the researchers.
“Our results indicate a causal association of Lp(a) with risk of ischemic stroke, and emphasize the need for randomized, controlled clinical trials on the effect of Lp(a)-lowering to prevent cardiovascular disease including ischemic stroke,” About 20% of the general population have high Lp(a) levels, and some individuals have extremely high levels, Dr. Langsted and co-authors said in their report.
Interest in Lp(a) as a risk factor for cardiovascular disease has been reignited following large studies showing that high Lp(a) levels were linked to increased risk of myocardial infarction and aortic valve stenosis, according to the investigators.
However, results of various studies are conflicting as to whether high Lp(a) levels increase risk of hemorrhagic or ischemic stroke, they said.
Both cohort studies used in the analysis were supported by sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures. One co-author reported disclosures related to Akcea, Amgen, Sanofi, Regeneron, and AstraZeneca.
SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point:
Major finding: Stroke risk was 1.6X higher with high Lp(a) levels.
Study details: Analysis of 49,699 individuals in the Copenhagen General Population Study, and 10,813 individuals in the Copenhagen City Heart Study.
Disclosures: Both studies were supported by the sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures.
Source: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
Study eyes narcolepsy’s impact on patient quality of life
SAN ANTONIO – Narcolepsy adversely impacts one’s health-related quality of life in a variety of ways, from elevated levels of depression to negative social stigma, results from a mixed methods study suggest.
“Despite established pharmacological treatments to reduce narcolepsy symptoms, health-related quality of life remains poor,” the study’s first author, Jason C. Ong, PhD, said at the annual meeting of the Associated Professional Sleep Societies. “The impact these symptoms have on functioning, the disease burden, and psychosocial functioning in particular is very important. Psychosocial functioning is particularly poor.”
Previous research has shown that people with narcolepsy have two- to four times the rate of psychiatric comorbidities and that health-related stigma is a predictor of depression and poor functioning, said Dr. Ong, a psychologist with the Center for Circadian and Sleep Medicine at the Northwestern University Feinberg School of Medicine, Chicago. In an effort to assess current practices for addressing the psychosocial needs of persons with narcolepsy and to identify potential strategies that could be used to develop a psychosocial intervention, he and his associates conducted a mixed methods study to examine how narcolepsy symptoms impact health-related quality of life and the appropriateness of different health-related quality of life measures for the disorder. “Our long-term goal is to see if we can use this information to help inform the feasibility of a psychosocial intervention to improve health-related quality of life,” he said.
For the study, 29 adults with an established diagnosis of narcolepsy completed online versions of the Patient Health Questionnaire-9 (PHQ-9), the Patient Reported Outcomes Measurement Information System (PROMIS), the 36-item Short Form Survey (SF-36), and the Epworth Sleepiness Scale (ESS). They also participated in a focus group, which consisted of questions pertaining to quality of life for persons with narcolepsy, current practices for addressing psychosocial health of affected individuals, and suggestions for developing a psychosocial intervention. The researchers used thematic analysis to reduce the qualitative data to key themes.
Most of the study participants (93%) were female, 90% were white, their mean age was 31, and their mean time since narcolepsy diagnosis was 4.3 years. Clinically significant elevations on the PROMIS scale, defined as a t-score of greater than 60, were reported for depression (t-score of 64.8), anxiety (66.3), fatigue (68.3), and sleep impairment (66.9). Elevations in depressive symptoms were reported on the PHQ-9 (a mean of 15.79), “which corresponds to moderately severe levels,” Dr. Ong said. “The ESS was highly elevated and fit well with the scales for sleep impairment as well as fatigue on the PROMIS. Overall, there was nice congruence across these measures.”
On the SF-36, the researchers observed that there were deficits in physical and emotional aspects of role limitations, and in energy/fatigue. “One thing we did find was a significant difference in general functioning, where patients with type 1 narcolepsy were worse off than those with type 2 narcolepsy (P less than .05).”
Qualitative data from focus groups revealed several key themes, including the perception that narcolepsy is poorly understood by the public and health care providers.
“People have the perception that if you have narcolepsy, you just feel fine and then you fall asleep,” Dr. Ong said. “They don’t understand that it’s a constant thing. Negative social stigma was also common. As a result, we found a lot of negative impact on self-esteem and self-efficacy. People talked about being hesitant to tell other people about their diagnosis, feeling that they’re ashamed of having narcolepsy. They felt less capable. One person said, ‘I get tired trying to explain why I’m tired.’”
Another common theme that emerged was the challenge of optimal treatment for their narcolepsy. Most patients met with sleep doctors or clinics every 3-6 months. “They said that this was generally good for discussing medications and symptom management, but there didn’t seem to be much time to talk about psychosocial aspects,” Dr. Ong said. “That seemed to be one area of need. There was also a strong dissatisfaction with mental health providers. People talked about how their mental health provider really didn’t understand narcolepsy. It did seem to reduce rapport and the ability to trust their therapist. Some talked about the challenges of accessibility. In some cases, people said their narcolepsy symptoms created challenges with appointment attendance.”
In terms of preferences for a psychosocial intervention, respondents generally “preferred some kind of online or Internet delivery,” he said. “They prefer a team approach with a clinician who’s knowledgeable about both sleep and mental health.”
Dr. Ong acknowledged certain limitations of the study, including its small sample size and the fact that it was not adequately powered to detect differences between type 1 and type 2 narcolepsy.
The study was funded by a grant from Wake Up Narcolepsy. Dr. Ong reported having no relevant financial disclosures.
SOURCE: Ong J et al., SLEEP 2019, abstract 0624.
SAN ANTONIO – Narcolepsy adversely impacts one’s health-related quality of life in a variety of ways, from elevated levels of depression to negative social stigma, results from a mixed methods study suggest.
“Despite established pharmacological treatments to reduce narcolepsy symptoms, health-related quality of life remains poor,” the study’s first author, Jason C. Ong, PhD, said at the annual meeting of the Associated Professional Sleep Societies. “The impact these symptoms have on functioning, the disease burden, and psychosocial functioning in particular is very important. Psychosocial functioning is particularly poor.”
Previous research has shown that people with narcolepsy have two- to four times the rate of psychiatric comorbidities and that health-related stigma is a predictor of depression and poor functioning, said Dr. Ong, a psychologist with the Center for Circadian and Sleep Medicine at the Northwestern University Feinberg School of Medicine, Chicago. In an effort to assess current practices for addressing the psychosocial needs of persons with narcolepsy and to identify potential strategies that could be used to develop a psychosocial intervention, he and his associates conducted a mixed methods study to examine how narcolepsy symptoms impact health-related quality of life and the appropriateness of different health-related quality of life measures for the disorder. “Our long-term goal is to see if we can use this information to help inform the feasibility of a psychosocial intervention to improve health-related quality of life,” he said.
For the study, 29 adults with an established diagnosis of narcolepsy completed online versions of the Patient Health Questionnaire-9 (PHQ-9), the Patient Reported Outcomes Measurement Information System (PROMIS), the 36-item Short Form Survey (SF-36), and the Epworth Sleepiness Scale (ESS). They also participated in a focus group, which consisted of questions pertaining to quality of life for persons with narcolepsy, current practices for addressing psychosocial health of affected individuals, and suggestions for developing a psychosocial intervention. The researchers used thematic analysis to reduce the qualitative data to key themes.
Most of the study participants (93%) were female, 90% were white, their mean age was 31, and their mean time since narcolepsy diagnosis was 4.3 years. Clinically significant elevations on the PROMIS scale, defined as a t-score of greater than 60, were reported for depression (t-score of 64.8), anxiety (66.3), fatigue (68.3), and sleep impairment (66.9). Elevations in depressive symptoms were reported on the PHQ-9 (a mean of 15.79), “which corresponds to moderately severe levels,” Dr. Ong said. “The ESS was highly elevated and fit well with the scales for sleep impairment as well as fatigue on the PROMIS. Overall, there was nice congruence across these measures.”
On the SF-36, the researchers observed that there were deficits in physical and emotional aspects of role limitations, and in energy/fatigue. “One thing we did find was a significant difference in general functioning, where patients with type 1 narcolepsy were worse off than those with type 2 narcolepsy (P less than .05).”
Qualitative data from focus groups revealed several key themes, including the perception that narcolepsy is poorly understood by the public and health care providers.
“People have the perception that if you have narcolepsy, you just feel fine and then you fall asleep,” Dr. Ong said. “They don’t understand that it’s a constant thing. Negative social stigma was also common. As a result, we found a lot of negative impact on self-esteem and self-efficacy. People talked about being hesitant to tell other people about their diagnosis, feeling that they’re ashamed of having narcolepsy. They felt less capable. One person said, ‘I get tired trying to explain why I’m tired.’”
Another common theme that emerged was the challenge of optimal treatment for their narcolepsy. Most patients met with sleep doctors or clinics every 3-6 months. “They said that this was generally good for discussing medications and symptom management, but there didn’t seem to be much time to talk about psychosocial aspects,” Dr. Ong said. “That seemed to be one area of need. There was also a strong dissatisfaction with mental health providers. People talked about how their mental health provider really didn’t understand narcolepsy. It did seem to reduce rapport and the ability to trust their therapist. Some talked about the challenges of accessibility. In some cases, people said their narcolepsy symptoms created challenges with appointment attendance.”
In terms of preferences for a psychosocial intervention, respondents generally “preferred some kind of online or Internet delivery,” he said. “They prefer a team approach with a clinician who’s knowledgeable about both sleep and mental health.”
Dr. Ong acknowledged certain limitations of the study, including its small sample size and the fact that it was not adequately powered to detect differences between type 1 and type 2 narcolepsy.
The study was funded by a grant from Wake Up Narcolepsy. Dr. Ong reported having no relevant financial disclosures.
SOURCE: Ong J et al., SLEEP 2019, abstract 0624.
SAN ANTONIO – Narcolepsy adversely impacts one’s health-related quality of life in a variety of ways, from elevated levels of depression to negative social stigma, results from a mixed methods study suggest.
“Despite established pharmacological treatments to reduce narcolepsy symptoms, health-related quality of life remains poor,” the study’s first author, Jason C. Ong, PhD, said at the annual meeting of the Associated Professional Sleep Societies. “The impact these symptoms have on functioning, the disease burden, and psychosocial functioning in particular is very important. Psychosocial functioning is particularly poor.”
Previous research has shown that people with narcolepsy have two- to four times the rate of psychiatric comorbidities and that health-related stigma is a predictor of depression and poor functioning, said Dr. Ong, a psychologist with the Center for Circadian and Sleep Medicine at the Northwestern University Feinberg School of Medicine, Chicago. In an effort to assess current practices for addressing the psychosocial needs of persons with narcolepsy and to identify potential strategies that could be used to develop a psychosocial intervention, he and his associates conducted a mixed methods study to examine how narcolepsy symptoms impact health-related quality of life and the appropriateness of different health-related quality of life measures for the disorder. “Our long-term goal is to see if we can use this information to help inform the feasibility of a psychosocial intervention to improve health-related quality of life,” he said.
For the study, 29 adults with an established diagnosis of narcolepsy completed online versions of the Patient Health Questionnaire-9 (PHQ-9), the Patient Reported Outcomes Measurement Information System (PROMIS), the 36-item Short Form Survey (SF-36), and the Epworth Sleepiness Scale (ESS). They also participated in a focus group, which consisted of questions pertaining to quality of life for persons with narcolepsy, current practices for addressing psychosocial health of affected individuals, and suggestions for developing a psychosocial intervention. The researchers used thematic analysis to reduce the qualitative data to key themes.
Most of the study participants (93%) were female, 90% were white, their mean age was 31, and their mean time since narcolepsy diagnosis was 4.3 years. Clinically significant elevations on the PROMIS scale, defined as a t-score of greater than 60, were reported for depression (t-score of 64.8), anxiety (66.3), fatigue (68.3), and sleep impairment (66.9). Elevations in depressive symptoms were reported on the PHQ-9 (a mean of 15.79), “which corresponds to moderately severe levels,” Dr. Ong said. “The ESS was highly elevated and fit well with the scales for sleep impairment as well as fatigue on the PROMIS. Overall, there was nice congruence across these measures.”
On the SF-36, the researchers observed that there were deficits in physical and emotional aspects of role limitations, and in energy/fatigue. “One thing we did find was a significant difference in general functioning, where patients with type 1 narcolepsy were worse off than those with type 2 narcolepsy (P less than .05).”
Qualitative data from focus groups revealed several key themes, including the perception that narcolepsy is poorly understood by the public and health care providers.
“People have the perception that if you have narcolepsy, you just feel fine and then you fall asleep,” Dr. Ong said. “They don’t understand that it’s a constant thing. Negative social stigma was also common. As a result, we found a lot of negative impact on self-esteem and self-efficacy. People talked about being hesitant to tell other people about their diagnosis, feeling that they’re ashamed of having narcolepsy. They felt less capable. One person said, ‘I get tired trying to explain why I’m tired.’”
Another common theme that emerged was the challenge of optimal treatment for their narcolepsy. Most patients met with sleep doctors or clinics every 3-6 months. “They said that this was generally good for discussing medications and symptom management, but there didn’t seem to be much time to talk about psychosocial aspects,” Dr. Ong said. “That seemed to be one area of need. There was also a strong dissatisfaction with mental health providers. People talked about how their mental health provider really didn’t understand narcolepsy. It did seem to reduce rapport and the ability to trust their therapist. Some talked about the challenges of accessibility. In some cases, people said their narcolepsy symptoms created challenges with appointment attendance.”
In terms of preferences for a psychosocial intervention, respondents generally “preferred some kind of online or Internet delivery,” he said. “They prefer a team approach with a clinician who’s knowledgeable about both sleep and mental health.”
Dr. Ong acknowledged certain limitations of the study, including its small sample size and the fact that it was not adequately powered to detect differences between type 1 and type 2 narcolepsy.
The study was funded by a grant from Wake Up Narcolepsy. Dr. Ong reported having no relevant financial disclosures.
SOURCE: Ong J et al., SLEEP 2019, abstract 0624.
REPORTING FROM SLEEP 2019
Treatment for pediatric low-grade glioma is associated with poor cognitive and socioeconomic outcomes
Children who underwent surgery alone had better neuropsychologic and socioeconomic outcomes than those who also underwent radiotherapy, but their outcomes were worse than those of unaffected siblings. These findings were published online June 24 in Cancer.
“Late effects in adulthood are evident even for children with the least malignant types of brain tumors who were treated with the least toxic therapies available at the time,” said M. Douglas Ris, PhD, professor of pediatrics and psychology at Baylor College of Medicine in Houston, in a press release. “As pediatric brain tumors become more survivable with continued advances in treatments, we need to improve surveillance of these populations so that survivors continue to receive the best interventions during their transition to adulthood and well beyond.”
Clinicians generally have assumed that children with low-grade CNS tumors who receive less toxic treatment will have fewer long-term effects than survivors of more malignant tumors who undergo neurotoxic therapies. Yet research has indicated that the former patients can have lasting neurobehavioral or functional morbidity.
Dr. Ris and colleagues invited survivors of pediatric low-grade gliomas participating in the Childhood Cancer Survivor Study (CCSS) and a sibling comparison group to undergo a direct, comprehensive neurocognitive assessment. Of 495 eligible survivors, 257 participated. Seventy-six patients did not travel to a study site, but completed a questionnaire, and the researchers did not include data for this group in their analysis. Dr. Ris and colleagues obtained information about surgery and radiotherapy from participants’ medical records. Patients underwent standardized, age-normed neuropsychologic tests. The primary neuropsychologic outcomes were the Composite Neuropsychological Index (CNI) and estimated IQ. To evaluate socioeconomic outcomes, Dr. Ris and colleagues measured participants’ educational attainment, income, and occupational prestige.
After the researchers adjusted the data for age and sex, they found that siblings had higher mean scores than survivors treated with surgery plus radiotherapy or surgery alone on all neuropsychologic outcomes, including the CNI (siblings, 106.8; surgery only, 95.6; surgery plus radiotherapy, 88.3) and estimated IQ. Survivors who had been diagnosed at younger ages had low scores for all outcomes except for attention/processing speed.
Furthermore, surgery plus radiotherapy was associated with a 7.7-fold higher risk of having an occupation in the lowest sibling quartile, compared with siblings. Survivors who underwent surgery alone had a 2.8-fold higher risk than siblings of having an occupation in the lowest quartile. Surgery plus radiotherapy was associated with a 2.6-fold increased risk of a low occupation score, compared with survivors who underwent surgery alone.
Compared with siblings, surgery plus radiotherapy was associated with a 4.5-fold risk of an annual income of less than $20,000, while the risk for survivors who underwent surgery alone did not differ significantly from that for siblings. Surgery plus radiotherapy was associated with a 2.6-fold higher risk than surgery alone. Surgery plus radiotherapy was also associated with a significantly increased risk for an education level lower than a bachelor’s degree, compared with siblings, but surgery alone was not.
The National Cancer Institute supported the study. The authors had no disclosures.
SOURCE: Ris MD et al. Cancer. 2019 Jun 24. doi: 10.1002/cncr.32186.
Children who underwent surgery alone had better neuropsychologic and socioeconomic outcomes than those who also underwent radiotherapy, but their outcomes were worse than those of unaffected siblings. These findings were published online June 24 in Cancer.
“Late effects in adulthood are evident even for children with the least malignant types of brain tumors who were treated with the least toxic therapies available at the time,” said M. Douglas Ris, PhD, professor of pediatrics and psychology at Baylor College of Medicine in Houston, in a press release. “As pediatric brain tumors become more survivable with continued advances in treatments, we need to improve surveillance of these populations so that survivors continue to receive the best interventions during their transition to adulthood and well beyond.”
Clinicians generally have assumed that children with low-grade CNS tumors who receive less toxic treatment will have fewer long-term effects than survivors of more malignant tumors who undergo neurotoxic therapies. Yet research has indicated that the former patients can have lasting neurobehavioral or functional morbidity.
Dr. Ris and colleagues invited survivors of pediatric low-grade gliomas participating in the Childhood Cancer Survivor Study (CCSS) and a sibling comparison group to undergo a direct, comprehensive neurocognitive assessment. Of 495 eligible survivors, 257 participated. Seventy-six patients did not travel to a study site, but completed a questionnaire, and the researchers did not include data for this group in their analysis. Dr. Ris and colleagues obtained information about surgery and radiotherapy from participants’ medical records. Patients underwent standardized, age-normed neuropsychologic tests. The primary neuropsychologic outcomes were the Composite Neuropsychological Index (CNI) and estimated IQ. To evaluate socioeconomic outcomes, Dr. Ris and colleagues measured participants’ educational attainment, income, and occupational prestige.
After the researchers adjusted the data for age and sex, they found that siblings had higher mean scores than survivors treated with surgery plus radiotherapy or surgery alone on all neuropsychologic outcomes, including the CNI (siblings, 106.8; surgery only, 95.6; surgery plus radiotherapy, 88.3) and estimated IQ. Survivors who had been diagnosed at younger ages had low scores for all outcomes except for attention/processing speed.
Furthermore, surgery plus radiotherapy was associated with a 7.7-fold higher risk of having an occupation in the lowest sibling quartile, compared with siblings. Survivors who underwent surgery alone had a 2.8-fold higher risk than siblings of having an occupation in the lowest quartile. Surgery plus radiotherapy was associated with a 2.6-fold increased risk of a low occupation score, compared with survivors who underwent surgery alone.
Compared with siblings, surgery plus radiotherapy was associated with a 4.5-fold risk of an annual income of less than $20,000, while the risk for survivors who underwent surgery alone did not differ significantly from that for siblings. Surgery plus radiotherapy was associated with a 2.6-fold higher risk than surgery alone. Surgery plus radiotherapy was also associated with a significantly increased risk for an education level lower than a bachelor’s degree, compared with siblings, but surgery alone was not.
The National Cancer Institute supported the study. The authors had no disclosures.
SOURCE: Ris MD et al. Cancer. 2019 Jun 24. doi: 10.1002/cncr.32186.
Children who underwent surgery alone had better neuropsychologic and socioeconomic outcomes than those who also underwent radiotherapy, but their outcomes were worse than those of unaffected siblings. These findings were published online June 24 in Cancer.
“Late effects in adulthood are evident even for children with the least malignant types of brain tumors who were treated with the least toxic therapies available at the time,” said M. Douglas Ris, PhD, professor of pediatrics and psychology at Baylor College of Medicine in Houston, in a press release. “As pediatric brain tumors become more survivable with continued advances in treatments, we need to improve surveillance of these populations so that survivors continue to receive the best interventions during their transition to adulthood and well beyond.”
Clinicians generally have assumed that children with low-grade CNS tumors who receive less toxic treatment will have fewer long-term effects than survivors of more malignant tumors who undergo neurotoxic therapies. Yet research has indicated that the former patients can have lasting neurobehavioral or functional morbidity.
Dr. Ris and colleagues invited survivors of pediatric low-grade gliomas participating in the Childhood Cancer Survivor Study (CCSS) and a sibling comparison group to undergo a direct, comprehensive neurocognitive assessment. Of 495 eligible survivors, 257 participated. Seventy-six patients did not travel to a study site, but completed a questionnaire, and the researchers did not include data for this group in their analysis. Dr. Ris and colleagues obtained information about surgery and radiotherapy from participants’ medical records. Patients underwent standardized, age-normed neuropsychologic tests. The primary neuropsychologic outcomes were the Composite Neuropsychological Index (CNI) and estimated IQ. To evaluate socioeconomic outcomes, Dr. Ris and colleagues measured participants’ educational attainment, income, and occupational prestige.
After the researchers adjusted the data for age and sex, they found that siblings had higher mean scores than survivors treated with surgery plus radiotherapy or surgery alone on all neuropsychologic outcomes, including the CNI (siblings, 106.8; surgery only, 95.6; surgery plus radiotherapy, 88.3) and estimated IQ. Survivors who had been diagnosed at younger ages had low scores for all outcomes except for attention/processing speed.
Furthermore, surgery plus radiotherapy was associated with a 7.7-fold higher risk of having an occupation in the lowest sibling quartile, compared with siblings. Survivors who underwent surgery alone had a 2.8-fold higher risk than siblings of having an occupation in the lowest quartile. Surgery plus radiotherapy was associated with a 2.6-fold increased risk of a low occupation score, compared with survivors who underwent surgery alone.
Compared with siblings, surgery plus radiotherapy was associated with a 4.5-fold risk of an annual income of less than $20,000, while the risk for survivors who underwent surgery alone did not differ significantly from that for siblings. Surgery plus radiotherapy was associated with a 2.6-fold higher risk than surgery alone. Surgery plus radiotherapy was also associated with a significantly increased risk for an education level lower than a bachelor’s degree, compared with siblings, but surgery alone was not.
The National Cancer Institute supported the study. The authors had no disclosures.
SOURCE: Ris MD et al. Cancer. 2019 Jun 24. doi: 10.1002/cncr.32186.
FROM CANCER
Age does not influence cladribine’s efficacy in MS
SEATTLE – In addition, age does not affect the likelihood that a patient who receives cladribine will achieve no evidence of disease activity (NEDA), according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In the phase 3 CLARITY study, a cumulative dose of 3.5 mg/kg of cladribine over 2 years was associated with significantly reduced relapse rate and disability progression and improved MRI outcomes, compared with placebo. The drug’s efficacy persisted in patients who were switched to placebo in a 96-week extension study.
A post hoc analysis
A 2017 study by Weideman et al. suggested that disease-modifying treatment (DMT) is less effective in older patients. For this reason, Gavin Giovannoni, MBBCh, PhD, professor of neurology at Queen Mary University of London, and colleagues decided to investigate the effect of age on the efficacy of treatment with 3.5 mg/kg of cladribine. The investigators performed a post hoc analysis of the CLARITY and CLARITY extension studies of patients with relapsing-remitting MS. They categorized patients as older than 45 years or age 45 years or younger.
Patients enrolled in CLARITY were between ages 18 years and 65 years. They underwent MRI at pretrial assessment and at weeks 24, 48, and 96 or early termination. The investigators defined a qualifying relapse as one associated with changes in Kurtzke Functional Systems score and other specified clinical parameters. Qualifying relapses were confirmed by an independent evaluating physician who was blinded to treatment assignment.
In the CLARITY extension study, 98 participants who had received cladribine tablets 3.5 mg/kg in CLARITY were randomized to placebo for 2 additional years. Participants who continued on placebo in the CLARITY extension were evaluated according to age at entry into CLARITY.
Dr. Giovannoni and colleagues performed efficacy analyses for qualifying relapses; all relapses; and mean and cumulative numbers of new T1 gadolinium-enhancing lesions, active T2 lesions, and combined unique lesions. They defined NEDA as freedom from qualifying relapses, 6-month confirmed disability progression (as measured by the Expanded Disability Status Scale [EDSS] score), T1 gadolinium-enhancing lesions, and active T2 lesions. The investigators performed equivalent analyses for patients who received placebo in the CLARITY extension.
Age did not influence efficacy
Within each age group, participants in both treatment arms had similar baseline demographic and disease characteristics. In CLARITY, 221 patients were older than 45 years, and 649 were age 45 years or younger. In the CLARITY extension, 22 patients were older than 45 years, and 76 were age 45 years or younger. In CLARITY, but not the extension, the proportion of women was higher in the older group than in the younger group (77.7% vs. 66.1%). In CLARITY, patients aged 45 years or younger had a higher number of T1 gadolinium-enhancing lesions at baseline, compared with older patients.
At week 96 in CLARITY, the annual rate of qualifying relapses among patients older than 45 years was 0.14 for cladribine and 0.28 for placebo. Among patients aged 45 or younger, the annual rate of qualifying relapses was 0.15 for cladribine and 0.37 for placebo. For patients older than 45 years, the annual rate of all relapses was 0.28 for cladribine and 0.55 for placebo. For patients aged 45 years or younger, the annual rate of all relapses was 0.26 for cladribine and 0.65 for placebo. The treatment effect of cladribine, compared with placebo, on qualifying relapses and all relapses was similar for both age groups. In the CLARITY extension, the annualized relapse rate (ARR) was 0.17 in patients aged 45 years or younger and 0.05 in patients older than 45 years.
The mean number of new T1 gadolinium-enhancing lesions and cumulative new T1 gadolinium-enhancing lesions was reduced with cladribine, compared with placebo, in both age groups at week 96 in CLARITY. The mean number of active T2 lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.167 in patients older than 45 years and 0.667 in patients aged 45 years and younger. In addition, the mean number of combined unique lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.333 in patients older than 45 years and 0.667 in patients aged 45 years or younger.
The proportion of participants who achieved NEDA in CLARITY was 55.6% among patients older than 45 years who received cladribine, 39.6% among patients aged 45 years or younger who received cladribine, 28.2% among patients older than 45 years who received placebo, and 9.5% of patients aged 45 years or younger who received placebo. The odds ratio for achieving NEDA was significantly more favorable for the cladribine group, compared with the placebo group, in both age groups (3.19 for patients older than 45 years and 6.23 for patients aged 45 years or younger). In the CLARITY extension, the proportion of participants who achieved NEDA was 40.9% among patients older than 45 years and 28.2% among patients aged 45 years or younger.
“These data are consistent with previous analyses from CLARITY using a different age cutoff and with results from the overall study population,” said Dr. Giovannoni and colleagues.
Merck KGaA, which manufactures and markets cladribine, supported the study. Dr. Giovannoni and several of his coinvestigators have received speaker honoraria, consulting fees, or other funding from companies including Merck KGaA.
SEATTLE – In addition, age does not affect the likelihood that a patient who receives cladribine will achieve no evidence of disease activity (NEDA), according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In the phase 3 CLARITY study, a cumulative dose of 3.5 mg/kg of cladribine over 2 years was associated with significantly reduced relapse rate and disability progression and improved MRI outcomes, compared with placebo. The drug’s efficacy persisted in patients who were switched to placebo in a 96-week extension study.
A post hoc analysis
A 2017 study by Weideman et al. suggested that disease-modifying treatment (DMT) is less effective in older patients. For this reason, Gavin Giovannoni, MBBCh, PhD, professor of neurology at Queen Mary University of London, and colleagues decided to investigate the effect of age on the efficacy of treatment with 3.5 mg/kg of cladribine. The investigators performed a post hoc analysis of the CLARITY and CLARITY extension studies of patients with relapsing-remitting MS. They categorized patients as older than 45 years or age 45 years or younger.
Patients enrolled in CLARITY were between ages 18 years and 65 years. They underwent MRI at pretrial assessment and at weeks 24, 48, and 96 or early termination. The investigators defined a qualifying relapse as one associated with changes in Kurtzke Functional Systems score and other specified clinical parameters. Qualifying relapses were confirmed by an independent evaluating physician who was blinded to treatment assignment.
In the CLARITY extension study, 98 participants who had received cladribine tablets 3.5 mg/kg in CLARITY were randomized to placebo for 2 additional years. Participants who continued on placebo in the CLARITY extension were evaluated according to age at entry into CLARITY.
Dr. Giovannoni and colleagues performed efficacy analyses for qualifying relapses; all relapses; and mean and cumulative numbers of new T1 gadolinium-enhancing lesions, active T2 lesions, and combined unique lesions. They defined NEDA as freedom from qualifying relapses, 6-month confirmed disability progression (as measured by the Expanded Disability Status Scale [EDSS] score), T1 gadolinium-enhancing lesions, and active T2 lesions. The investigators performed equivalent analyses for patients who received placebo in the CLARITY extension.
Age did not influence efficacy
Within each age group, participants in both treatment arms had similar baseline demographic and disease characteristics. In CLARITY, 221 patients were older than 45 years, and 649 were age 45 years or younger. In the CLARITY extension, 22 patients were older than 45 years, and 76 were age 45 years or younger. In CLARITY, but not the extension, the proportion of women was higher in the older group than in the younger group (77.7% vs. 66.1%). In CLARITY, patients aged 45 years or younger had a higher number of T1 gadolinium-enhancing lesions at baseline, compared with older patients.
At week 96 in CLARITY, the annual rate of qualifying relapses among patients older than 45 years was 0.14 for cladribine and 0.28 for placebo. Among patients aged 45 or younger, the annual rate of qualifying relapses was 0.15 for cladribine and 0.37 for placebo. For patients older than 45 years, the annual rate of all relapses was 0.28 for cladribine and 0.55 for placebo. For patients aged 45 years or younger, the annual rate of all relapses was 0.26 for cladribine and 0.65 for placebo. The treatment effect of cladribine, compared with placebo, on qualifying relapses and all relapses was similar for both age groups. In the CLARITY extension, the annualized relapse rate (ARR) was 0.17 in patients aged 45 years or younger and 0.05 in patients older than 45 years.
The mean number of new T1 gadolinium-enhancing lesions and cumulative new T1 gadolinium-enhancing lesions was reduced with cladribine, compared with placebo, in both age groups at week 96 in CLARITY. The mean number of active T2 lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.167 in patients older than 45 years and 0.667 in patients aged 45 years and younger. In addition, the mean number of combined unique lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.333 in patients older than 45 years and 0.667 in patients aged 45 years or younger.
The proportion of participants who achieved NEDA in CLARITY was 55.6% among patients older than 45 years who received cladribine, 39.6% among patients aged 45 years or younger who received cladribine, 28.2% among patients older than 45 years who received placebo, and 9.5% of patients aged 45 years or younger who received placebo. The odds ratio for achieving NEDA was significantly more favorable for the cladribine group, compared with the placebo group, in both age groups (3.19 for patients older than 45 years and 6.23 for patients aged 45 years or younger). In the CLARITY extension, the proportion of participants who achieved NEDA was 40.9% among patients older than 45 years and 28.2% among patients aged 45 years or younger.
“These data are consistent with previous analyses from CLARITY using a different age cutoff and with results from the overall study population,” said Dr. Giovannoni and colleagues.
Merck KGaA, which manufactures and markets cladribine, supported the study. Dr. Giovannoni and several of his coinvestigators have received speaker honoraria, consulting fees, or other funding from companies including Merck KGaA.
SEATTLE – In addition, age does not affect the likelihood that a patient who receives cladribine will achieve no evidence of disease activity (NEDA), according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In the phase 3 CLARITY study, a cumulative dose of 3.5 mg/kg of cladribine over 2 years was associated with significantly reduced relapse rate and disability progression and improved MRI outcomes, compared with placebo. The drug’s efficacy persisted in patients who were switched to placebo in a 96-week extension study.
A post hoc analysis
A 2017 study by Weideman et al. suggested that disease-modifying treatment (DMT) is less effective in older patients. For this reason, Gavin Giovannoni, MBBCh, PhD, professor of neurology at Queen Mary University of London, and colleagues decided to investigate the effect of age on the efficacy of treatment with 3.5 mg/kg of cladribine. The investigators performed a post hoc analysis of the CLARITY and CLARITY extension studies of patients with relapsing-remitting MS. They categorized patients as older than 45 years or age 45 years or younger.
Patients enrolled in CLARITY were between ages 18 years and 65 years. They underwent MRI at pretrial assessment and at weeks 24, 48, and 96 or early termination. The investigators defined a qualifying relapse as one associated with changes in Kurtzke Functional Systems score and other specified clinical parameters. Qualifying relapses were confirmed by an independent evaluating physician who was blinded to treatment assignment.
In the CLARITY extension study, 98 participants who had received cladribine tablets 3.5 mg/kg in CLARITY were randomized to placebo for 2 additional years. Participants who continued on placebo in the CLARITY extension were evaluated according to age at entry into CLARITY.
Dr. Giovannoni and colleagues performed efficacy analyses for qualifying relapses; all relapses; and mean and cumulative numbers of new T1 gadolinium-enhancing lesions, active T2 lesions, and combined unique lesions. They defined NEDA as freedom from qualifying relapses, 6-month confirmed disability progression (as measured by the Expanded Disability Status Scale [EDSS] score), T1 gadolinium-enhancing lesions, and active T2 lesions. The investigators performed equivalent analyses for patients who received placebo in the CLARITY extension.
Age did not influence efficacy
Within each age group, participants in both treatment arms had similar baseline demographic and disease characteristics. In CLARITY, 221 patients were older than 45 years, and 649 were age 45 years or younger. In the CLARITY extension, 22 patients were older than 45 years, and 76 were age 45 years or younger. In CLARITY, but not the extension, the proportion of women was higher in the older group than in the younger group (77.7% vs. 66.1%). In CLARITY, patients aged 45 years or younger had a higher number of T1 gadolinium-enhancing lesions at baseline, compared with older patients.
At week 96 in CLARITY, the annual rate of qualifying relapses among patients older than 45 years was 0.14 for cladribine and 0.28 for placebo. Among patients aged 45 or younger, the annual rate of qualifying relapses was 0.15 for cladribine and 0.37 for placebo. For patients older than 45 years, the annual rate of all relapses was 0.28 for cladribine and 0.55 for placebo. For patients aged 45 years or younger, the annual rate of all relapses was 0.26 for cladribine and 0.65 for placebo. The treatment effect of cladribine, compared with placebo, on qualifying relapses and all relapses was similar for both age groups. In the CLARITY extension, the annualized relapse rate (ARR) was 0.17 in patients aged 45 years or younger and 0.05 in patients older than 45 years.
The mean number of new T1 gadolinium-enhancing lesions and cumulative new T1 gadolinium-enhancing lesions was reduced with cladribine, compared with placebo, in both age groups at week 96 in CLARITY. The mean number of active T2 lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.167 in patients older than 45 years and 0.667 in patients aged 45 years and younger. In addition, the mean number of combined unique lesions per patient per scan also was significantly reduced with cladribine, compared with placebo, in both age groups. The reduction was 0.333 in patients older than 45 years and 0.667 in patients aged 45 years or younger.
The proportion of participants who achieved NEDA in CLARITY was 55.6% among patients older than 45 years who received cladribine, 39.6% among patients aged 45 years or younger who received cladribine, 28.2% among patients older than 45 years who received placebo, and 9.5% of patients aged 45 years or younger who received placebo. The odds ratio for achieving NEDA was significantly more favorable for the cladribine group, compared with the placebo group, in both age groups (3.19 for patients older than 45 years and 6.23 for patients aged 45 years or younger). In the CLARITY extension, the proportion of participants who achieved NEDA was 40.9% among patients older than 45 years and 28.2% among patients aged 45 years or younger.
“These data are consistent with previous analyses from CLARITY using a different age cutoff and with results from the overall study population,” said Dr. Giovannoni and colleagues.
Merck KGaA, which manufactures and markets cladribine, supported the study. Dr. Giovannoni and several of his coinvestigators have received speaker honoraria, consulting fees, or other funding from companies including Merck KGaA.
REPORTING FROM CMSC 2019
ACIP approves meningococcal booster for persons at increased risk
according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
The committee voted unanimously in favor of a booster dose of MenB vaccine 1 year after completion of the primary series, with additional boosters every 2-3 years “for as long as risk remains” for high-risk persons, including microbiologists and persons with complement deficiency, complement inhibitor use, or asplenia.
The committee also voted unanimously in favor of a one-time MenB booster for individuals aged 10 years and older who are at least a year beyond completion of a MenB primary series and deemed at increased risk by public health officials in an outbreak situation.
In addition, “a booster dose interval of 6 months or more may be considered by public health officials depending on the specific outbreak, vaccine strategy, and projected duration of elevated risk” according to the language, which was included in the unanimously approved statement “Meningococcal Vaccination: Recommendations of The Advisory Committee on Immunization Practices.”
The updated statement on meningococcal vaccination was developed in 2019 “to consolidate all existing ACIP recommendations for MenACWY and MenB vaccines in a single document,” said Sarah Mbaeyi, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, who presented immunogenicity data and the proposed recommendations.
The statement includes the recommendation of a MenB primary series for individuals aged 16-23 years based on shared clinical decision making. Kelly Moore, MD, of Vanderbilt University, Nashville, Tenn., noted the importance of ongoing data collection, and said clinicians must make clear to patients that, “if they want protection, they need the booster.”
Approximately 7% of serogroup B cases in the United States are related to disease outbreaks, mainly among college students, Dr. Mbaeyi said. All 13 universities that experienced outbreaks between 2013 and 2019 have implemented a MenB primary series, and one university has implemented an off-label booster program.
The work group concluded that a MenB booster dose is necessary to sustain protection against serogroup B disease in persons at increased risk during an outbreak, and that the potential benefits outweighed the harms given the seriousness of meningococcal disease.
Paul Hunter, MD, of the City of Milwaukee Health Department, noted that “the booster recommendation gives more flexibility” in an outbreak response.
The committee also voted unanimously to approve the Vaccines for Children resolution for the meningococcal vaccine that updates language to align with the new recommendations.
The ACIP members had no financial conflicts to disclose.
according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
The committee voted unanimously in favor of a booster dose of MenB vaccine 1 year after completion of the primary series, with additional boosters every 2-3 years “for as long as risk remains” for high-risk persons, including microbiologists and persons with complement deficiency, complement inhibitor use, or asplenia.
The committee also voted unanimously in favor of a one-time MenB booster for individuals aged 10 years and older who are at least a year beyond completion of a MenB primary series and deemed at increased risk by public health officials in an outbreak situation.
In addition, “a booster dose interval of 6 months or more may be considered by public health officials depending on the specific outbreak, vaccine strategy, and projected duration of elevated risk” according to the language, which was included in the unanimously approved statement “Meningococcal Vaccination: Recommendations of The Advisory Committee on Immunization Practices.”
The updated statement on meningococcal vaccination was developed in 2019 “to consolidate all existing ACIP recommendations for MenACWY and MenB vaccines in a single document,” said Sarah Mbaeyi, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, who presented immunogenicity data and the proposed recommendations.
The statement includes the recommendation of a MenB primary series for individuals aged 16-23 years based on shared clinical decision making. Kelly Moore, MD, of Vanderbilt University, Nashville, Tenn., noted the importance of ongoing data collection, and said clinicians must make clear to patients that, “if they want protection, they need the booster.”
Approximately 7% of serogroup B cases in the United States are related to disease outbreaks, mainly among college students, Dr. Mbaeyi said. All 13 universities that experienced outbreaks between 2013 and 2019 have implemented a MenB primary series, and one university has implemented an off-label booster program.
The work group concluded that a MenB booster dose is necessary to sustain protection against serogroup B disease in persons at increased risk during an outbreak, and that the potential benefits outweighed the harms given the seriousness of meningococcal disease.
Paul Hunter, MD, of the City of Milwaukee Health Department, noted that “the booster recommendation gives more flexibility” in an outbreak response.
The committee also voted unanimously to approve the Vaccines for Children resolution for the meningococcal vaccine that updates language to align with the new recommendations.
The ACIP members had no financial conflicts to disclose.
according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
The committee voted unanimously in favor of a booster dose of MenB vaccine 1 year after completion of the primary series, with additional boosters every 2-3 years “for as long as risk remains” for high-risk persons, including microbiologists and persons with complement deficiency, complement inhibitor use, or asplenia.
The committee also voted unanimously in favor of a one-time MenB booster for individuals aged 10 years and older who are at least a year beyond completion of a MenB primary series and deemed at increased risk by public health officials in an outbreak situation.
In addition, “a booster dose interval of 6 months or more may be considered by public health officials depending on the specific outbreak, vaccine strategy, and projected duration of elevated risk” according to the language, which was included in the unanimously approved statement “Meningococcal Vaccination: Recommendations of The Advisory Committee on Immunization Practices.”
The updated statement on meningococcal vaccination was developed in 2019 “to consolidate all existing ACIP recommendations for MenACWY and MenB vaccines in a single document,” said Sarah Mbaeyi, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, who presented immunogenicity data and the proposed recommendations.
The statement includes the recommendation of a MenB primary series for individuals aged 16-23 years based on shared clinical decision making. Kelly Moore, MD, of Vanderbilt University, Nashville, Tenn., noted the importance of ongoing data collection, and said clinicians must make clear to patients that, “if they want protection, they need the booster.”
Approximately 7% of serogroup B cases in the United States are related to disease outbreaks, mainly among college students, Dr. Mbaeyi said. All 13 universities that experienced outbreaks between 2013 and 2019 have implemented a MenB primary series, and one university has implemented an off-label booster program.
The work group concluded that a MenB booster dose is necessary to sustain protection against serogroup B disease in persons at increased risk during an outbreak, and that the potential benefits outweighed the harms given the seriousness of meningococcal disease.
Paul Hunter, MD, of the City of Milwaukee Health Department, noted that “the booster recommendation gives more flexibility” in an outbreak response.
The committee also voted unanimously to approve the Vaccines for Children resolution for the meningococcal vaccine that updates language to align with the new recommendations.
The ACIP members had no financial conflicts to disclose.
REPORTING FROM AN ACIP MEETING
FDA approves bevacizumab-bvzr for several cancers
The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.
Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.
Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.
Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.
The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
Specific indications for the biosimilar are as follows:
Metastatic colorectal cancer
Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.
Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.
Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.
First-line nonsquamous non–small cell lung cancer
Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.
Recurrent glioblastoma
Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.
Metastatic renal cell carcinoma
Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.
Persistent, recurrent, or metastatic cervical cancer
Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.
Complete prescribing information can be found on the FDA website.
The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.
Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.
Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.
Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.
The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
Specific indications for the biosimilar are as follows:
Metastatic colorectal cancer
Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.
Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.
Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.
First-line nonsquamous non–small cell lung cancer
Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.
Recurrent glioblastoma
Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.
Metastatic renal cell carcinoma
Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.
Persistent, recurrent, or metastatic cervical cancer
Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.
Complete prescribing information can be found on the FDA website.
The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.
Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.
Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.
Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.
The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
Specific indications for the biosimilar are as follows:
Metastatic colorectal cancer
Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.
Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.
Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.
First-line nonsquamous non–small cell lung cancer
Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.
Recurrent glioblastoma
Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.
Metastatic renal cell carcinoma
Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.
Persistent, recurrent, or metastatic cervical cancer
Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.
Complete prescribing information can be found on the FDA website.
Health care gets heated on Night 2 of the Democratic presidential debate
Just as on Wednesday night, moderators asked candidates who would support abolishing private insurance under a single-payer system. Again, only two candidates — this time Sen. Sanders and Sen. Kamala Harris of California— raised their hands.
Former Vice President Joe Biden also jumped on health care, saying Americans “need to have insurance that is covered, and that they can afford.”
But he offered a different view of how to achieve the goal, saying the fastest way would be to “build on Obamacare. To build on what we did.” He also drew a line in the sand, promising to oppose any Democrat or Republican who tried to take down Obamacare.
Candidates including South Bend, Ind., Mayor Pete Buttigieg, New York Sen. Kristen Gillibrand and Colorado Sen. Michael Bennet offered their takes on universal coverage, each underscoring the importance of a transition from the current system and suggesting that a public option approach, something that would allow people to buy into a program like Medicare, would offer a “glide path” to the ultimate goal of universal coverage. Sen. Gillibrand noted that she ran on such a proposal in 2005. (This is true.)
Meanwhile, former Colorado Gov. John Hickenlooper used the issue of Medicare for All to say that it is important to not allow Republicans to paint the Democratic Party as socialist but also to claim his own successes in implementing coverage expansions to reach “near universal coverage” Colorado. PolitiFact examined this claim and found it Mostly True.“You don’t need big government to do big things. I know that because I’m the one person up here who’s actually done the big progressive things everyone else is talking about,” he said.
But still, while candidates were quick to make their differences clear, not all of their claims fully stood up to scrutiny.
We fact-checked some of those remarks.
Sen. Sanders: “President Trump, you’re not standing up for working families when you try to throw 32 million people off the health care that they have.”
This is one of Sanders’ favorite lines, but it falls short of giving the full story of the Republican effort to repeal and replace Obamacare. We rated a similar claim Half True.
Scrapping the Affordable Care Act was a key campaign promise for President Donald Trump. In 2017, as the Republican-led Congress struggled to deliver, Trump tweeted “Republicans should just REPEAL failing Obamacare now and work on a new health care plan that will start from a clean slate.”
The Congressional Budget Office estimated that would lead to 32 million more people without insurance by 2026. But some portion of that 32 million would have chosen not to buy insurance due to the end of the individual mandate, which would happen under repeal. (It happened anyway, when the 2017 tax law repealed the fine for the individual mandate.)
In the end, full repeal didn’t happen. Instead, Trump was only able to zero out the fines for people who didn’t have insurance. Coverage has eroded. The latest survey shows about 1.3 million people have lost insurance since Trump took office.
Sen. Bennet, meanwhile, used his time to attack Medicare for All on a feasibility standpoint.
Sen. Bennet: “Bernie mentioned that the taxes that we would have to pay — because of those taxes, Vermont rejected Medicare for All.”
This is true, although it could use some context.
Vermont’s effort to pass a state-based single-payer health plan — which the state legislature approved in 2011 — officially fell flat in December 2014. Financing the plan ultimately would have required an 11.5% payroll tax on all employers, plus raising the income tax by as much as 9.5%. The governor at the time, Democrat Peter Shumlin, declared this politically untenable.
That said, some analysts suggest other political factors may have played a role, too — for instance, fallout after the state launched its Affordable Care Act health insurance website, which faced technical difficulties.
Nationally, when voters are told Medicare for All could result in higher taxes, support declines.
And a point was made by author Marianne Williamson about the nation’s high burden of chronic disease.
Ms. Williamson: “So many Americans have unnecessary chronic illnesses — so many more compared to other countries.”
There is evidence for this, at least for older Americans.
A November 2014 study by the Commonwealth Fund found that 68% of Americans 65 and older had two or more chronic conditions, and an additional 20% had one chronic condition.
No other country studied — the United Kingdom, New Zealand, Sweden, Norway, France, Switzerland, the Netherlands, Germany, Austria, or Canada — had a higher rate of older residents with at least two chronic conditions. The percentages ranged from 33 percent in the United Kingdom to 56 percent in Canada.
An earlier study published in the journal Health Affairs in 2007 found that “for many of the most costly chronic conditions, diagnosed disease prevalence and treatment rates were higher in the United States than in a sample of European countries in 2004.”
PolitiFact’s Jon Greenberg and Louis Jacobson contributed to this story. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. Politifact is owned by the nonprofit Poynter Institute for Media Studies.
Just as on Wednesday night, moderators asked candidates who would support abolishing private insurance under a single-payer system. Again, only two candidates — this time Sen. Sanders and Sen. Kamala Harris of California— raised their hands.
Former Vice President Joe Biden also jumped on health care, saying Americans “need to have insurance that is covered, and that they can afford.”
But he offered a different view of how to achieve the goal, saying the fastest way would be to “build on Obamacare. To build on what we did.” He also drew a line in the sand, promising to oppose any Democrat or Republican who tried to take down Obamacare.
Candidates including South Bend, Ind., Mayor Pete Buttigieg, New York Sen. Kristen Gillibrand and Colorado Sen. Michael Bennet offered their takes on universal coverage, each underscoring the importance of a transition from the current system and suggesting that a public option approach, something that would allow people to buy into a program like Medicare, would offer a “glide path” to the ultimate goal of universal coverage. Sen. Gillibrand noted that she ran on such a proposal in 2005. (This is true.)
Meanwhile, former Colorado Gov. John Hickenlooper used the issue of Medicare for All to say that it is important to not allow Republicans to paint the Democratic Party as socialist but also to claim his own successes in implementing coverage expansions to reach “near universal coverage” Colorado. PolitiFact examined this claim and found it Mostly True.“You don’t need big government to do big things. I know that because I’m the one person up here who’s actually done the big progressive things everyone else is talking about,” he said.
But still, while candidates were quick to make their differences clear, not all of their claims fully stood up to scrutiny.
We fact-checked some of those remarks.
Sen. Sanders: “President Trump, you’re not standing up for working families when you try to throw 32 million people off the health care that they have.”
This is one of Sanders’ favorite lines, but it falls short of giving the full story of the Republican effort to repeal and replace Obamacare. We rated a similar claim Half True.
Scrapping the Affordable Care Act was a key campaign promise for President Donald Trump. In 2017, as the Republican-led Congress struggled to deliver, Trump tweeted “Republicans should just REPEAL failing Obamacare now and work on a new health care plan that will start from a clean slate.”
The Congressional Budget Office estimated that would lead to 32 million more people without insurance by 2026. But some portion of that 32 million would have chosen not to buy insurance due to the end of the individual mandate, which would happen under repeal. (It happened anyway, when the 2017 tax law repealed the fine for the individual mandate.)
In the end, full repeal didn’t happen. Instead, Trump was only able to zero out the fines for people who didn’t have insurance. Coverage has eroded. The latest survey shows about 1.3 million people have lost insurance since Trump took office.
Sen. Bennet, meanwhile, used his time to attack Medicare for All on a feasibility standpoint.
Sen. Bennet: “Bernie mentioned that the taxes that we would have to pay — because of those taxes, Vermont rejected Medicare for All.”
This is true, although it could use some context.
Vermont’s effort to pass a state-based single-payer health plan — which the state legislature approved in 2011 — officially fell flat in December 2014. Financing the plan ultimately would have required an 11.5% payroll tax on all employers, plus raising the income tax by as much as 9.5%. The governor at the time, Democrat Peter Shumlin, declared this politically untenable.
That said, some analysts suggest other political factors may have played a role, too — for instance, fallout after the state launched its Affordable Care Act health insurance website, which faced technical difficulties.
Nationally, when voters are told Medicare for All could result in higher taxes, support declines.
And a point was made by author Marianne Williamson about the nation’s high burden of chronic disease.
Ms. Williamson: “So many Americans have unnecessary chronic illnesses — so many more compared to other countries.”
There is evidence for this, at least for older Americans.
A November 2014 study by the Commonwealth Fund found that 68% of Americans 65 and older had two or more chronic conditions, and an additional 20% had one chronic condition.
No other country studied — the United Kingdom, New Zealand, Sweden, Norway, France, Switzerland, the Netherlands, Germany, Austria, or Canada — had a higher rate of older residents with at least two chronic conditions. The percentages ranged from 33 percent in the United Kingdom to 56 percent in Canada.
An earlier study published in the journal Health Affairs in 2007 found that “for many of the most costly chronic conditions, diagnosed disease prevalence and treatment rates were higher in the United States than in a sample of European countries in 2004.”
PolitiFact’s Jon Greenberg and Louis Jacobson contributed to this story. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. Politifact is owned by the nonprofit Poynter Institute for Media Studies.
Just as on Wednesday night, moderators asked candidates who would support abolishing private insurance under a single-payer system. Again, only two candidates — this time Sen. Sanders and Sen. Kamala Harris of California— raised their hands.
Former Vice President Joe Biden also jumped on health care, saying Americans “need to have insurance that is covered, and that they can afford.”
But he offered a different view of how to achieve the goal, saying the fastest way would be to “build on Obamacare. To build on what we did.” He also drew a line in the sand, promising to oppose any Democrat or Republican who tried to take down Obamacare.
Candidates including South Bend, Ind., Mayor Pete Buttigieg, New York Sen. Kristen Gillibrand and Colorado Sen. Michael Bennet offered their takes on universal coverage, each underscoring the importance of a transition from the current system and suggesting that a public option approach, something that would allow people to buy into a program like Medicare, would offer a “glide path” to the ultimate goal of universal coverage. Sen. Gillibrand noted that she ran on such a proposal in 2005. (This is true.)
Meanwhile, former Colorado Gov. John Hickenlooper used the issue of Medicare for All to say that it is important to not allow Republicans to paint the Democratic Party as socialist but also to claim his own successes in implementing coverage expansions to reach “near universal coverage” Colorado. PolitiFact examined this claim and found it Mostly True.“You don’t need big government to do big things. I know that because I’m the one person up here who’s actually done the big progressive things everyone else is talking about,” he said.
But still, while candidates were quick to make their differences clear, not all of their claims fully stood up to scrutiny.
We fact-checked some of those remarks.
Sen. Sanders: “President Trump, you’re not standing up for working families when you try to throw 32 million people off the health care that they have.”
This is one of Sanders’ favorite lines, but it falls short of giving the full story of the Republican effort to repeal and replace Obamacare. We rated a similar claim Half True.
Scrapping the Affordable Care Act was a key campaign promise for President Donald Trump. In 2017, as the Republican-led Congress struggled to deliver, Trump tweeted “Republicans should just REPEAL failing Obamacare now and work on a new health care plan that will start from a clean slate.”
The Congressional Budget Office estimated that would lead to 32 million more people without insurance by 2026. But some portion of that 32 million would have chosen not to buy insurance due to the end of the individual mandate, which would happen under repeal. (It happened anyway, when the 2017 tax law repealed the fine for the individual mandate.)
In the end, full repeal didn’t happen. Instead, Trump was only able to zero out the fines for people who didn’t have insurance. Coverage has eroded. The latest survey shows about 1.3 million people have lost insurance since Trump took office.
Sen. Bennet, meanwhile, used his time to attack Medicare for All on a feasibility standpoint.
Sen. Bennet: “Bernie mentioned that the taxes that we would have to pay — because of those taxes, Vermont rejected Medicare for All.”
This is true, although it could use some context.
Vermont’s effort to pass a state-based single-payer health plan — which the state legislature approved in 2011 — officially fell flat in December 2014. Financing the plan ultimately would have required an 11.5% payroll tax on all employers, plus raising the income tax by as much as 9.5%. The governor at the time, Democrat Peter Shumlin, declared this politically untenable.
That said, some analysts suggest other political factors may have played a role, too — for instance, fallout after the state launched its Affordable Care Act health insurance website, which faced technical difficulties.
Nationally, when voters are told Medicare for All could result in higher taxes, support declines.
And a point was made by author Marianne Williamson about the nation’s high burden of chronic disease.
Ms. Williamson: “So many Americans have unnecessary chronic illnesses — so many more compared to other countries.”
There is evidence for this, at least for older Americans.
A November 2014 study by the Commonwealth Fund found that 68% of Americans 65 and older had two or more chronic conditions, and an additional 20% had one chronic condition.
No other country studied — the United Kingdom, New Zealand, Sweden, Norway, France, Switzerland, the Netherlands, Germany, Austria, or Canada — had a higher rate of older residents with at least two chronic conditions. The percentages ranged from 33 percent in the United Kingdom to 56 percent in Canada.
An earlier study published in the journal Health Affairs in 2007 found that “for many of the most costly chronic conditions, diagnosed disease prevalence and treatment rates were higher in the United States than in a sample of European countries in 2004.”
PolitiFact’s Jon Greenberg and Louis Jacobson contributed to this story. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. Politifact is owned by the nonprofit Poynter Institute for Media Studies.