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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
New RSV vaccine will cut hospitalizations, study shows
, according to research presented at an annual scientific meeting on infectious diseases.
“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.
“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.
This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.
The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
Strong efficacy data
Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.
As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.
The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.
Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
New modeling study
Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.
According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.
With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.
Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.
Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.
Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.
Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”
In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.
The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.
A version of this article first appeared on Medscape.com.
, according to research presented at an annual scientific meeting on infectious diseases.
“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.
“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.
This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.
The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
Strong efficacy data
Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.
As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.
The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.
Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
New modeling study
Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.
According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.
With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.
Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.
Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.
Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.
Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”
In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.
The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.
A version of this article first appeared on Medscape.com.
, according to research presented at an annual scientific meeting on infectious diseases.
“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.
“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.
This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.
The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
Strong efficacy data
Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.
As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.
The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.
Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
New modeling study
Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.
According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.
With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.
Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.
Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.
Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.
Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”
In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.
The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.
A version of this article first appeared on Medscape.com.
FROM IDWEEK 2023
Hopeful insights, no overall HFpEF gains from splanchnic nerve ablation: REBALANCE-HF
It’s still early days for a potential transcatheter technique that tones down sympathetic activation mediating blood volume shifts to the heart and lungs. Such volume transfers can contribute to congestion and acute decompensation in some patients with heart failure. But a randomized trial with negative overall results still may have moved the novel procedure a modest step forward.
The procedure, right-sided splanchnic-nerve ablation for volume management (SAVM), failed to show significant effects on hemodynamics, exercise capacity, natriuretic peptides, or quality of life in a trial covering a broad population of patients with heart failure with preserved ejection fraction (HFpEF).
The study, called REBALANCE-HF, compared ablation of the right greater splanchnic nerve with a sham version of the procedure for any effects on hemodynamic or functional outcomes.
Among such “potential responders,” those undergoing SAVM trended better than patients receiving the sham procedure with respect to hemodynamic, functional, natriuretic peptide, and quality of life endpoints.
The potential predictors of SAVM success included elevated or preserved cardiac output and pulse pressure with exercise or on standing up; appropriate heart-rate exercise responses; and little or no echocardiographic evidence of diastolic dysfunction.
The panel of features might potentially identify patients more likely to respond to the procedure and perhaps sharpen entry criteria in future clinical trials, Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., said in an interview.
Dr. Fudim presented the REBALANCE-HF findings at the annual meeting of the Heart Failure Society of America.
How SAVM works
Sympathetic activation can lead to acute or chronic constriction of vessels in the splanchnic bed within the upper and lower abdomen, one of the body’s largest blood reservoirs, Dr. Fudim explained. Resulting volume shifts to the general circulation, and therefore the heart and lungs, are a normal exercise response that, in HF, can fall out of balance and excessively raise cardiac filling pressure.
Lessened sympathetic tone after unilateral GNS ablation can promote splanchnic venous dilation that reduces intrathoracic blood volume, potentially averting congestion, and decompensation, observed Kavita Sharma, MD, invited discussant for Dr. Fudim’s presentation.
The trial’s potential-responder cohort “seemed able to augment cardiac output in response to stress” and to “maintain or augment their orthostatic pulse pressure,” more effectively than the other participants, said Dr. Sharma, of Johns Hopkins University, Baltimore.
Although the trial was overall negative for 1-month change in pulmonary capillary wedge pressure (PCWP), the primary efficacy endpoint, Dr. Sharma said, it confirmed SAVM as a safe procedure in HFpEF and “ensured its replicability and technical success.”
Future studies should explore ways to characterize unlikely SAVM responders, she proposed. “I would argue these patients are probably more important than even the responders.”
Yet it’s unknown why, for example, cardiac output wouldn’t increase with exercise in a patient with HFpEF. “Is it related to preload insufficiency, right ventricular failure, atrial myopathy, perhaps more restrictive physiology, chronotropic incompetence, or medications – or a combination of the above?”
REBALANCE-HF assigned 90 patients with HFpEF to either the active or sham SAVM groups, 44 and 46 patients, respectively. To be eligible, patients were stable on HF meds and had either elevated natriuretic peptides or, within the past year, at least one HF hospitalization or escalation of intravenous diuretics for worsening HF.
The active and sham control groups fared similarly for the primary PCWP endpoint and for the secondary endpoints of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, 6-minute walk distance (6MWD), and natriuretic peptide levels at 6 and 12 months.
Predicting SAVM response
In analysis limited to potential responders, PCWP, KCCQ, 6MWD, and natriuretic peptide outcomes for patients were combined into z scores, a single metric that reflects multiple outcomes, Dr. Fudim explained.
The z scores were derived for tertiles of patients in subgroups defined by a range of parameters that included demographics, medical history, and hemodynamic and echocardiographic variables.
Four such variables were found to interact across tertiles in a way that suggested their value as SAVM outcome predictors and were then used to select the cohort of potential responders. The variables were exertion-related changes in cardiac index, pulse pressure, and heart rate, and mitral E/A ratio – the latter a measure of diastolic dysfunction.
Among potential responders, those who underwent SAVM showed a 2.9–mm Hg steeper drop in peak PCWP at 1 month (P = .02), compared with patients getting the sham procedure.
They also bested control patients at both 6 and 12 months for KCCQ score, 6MWD, and natriuretic peptide levels, the latter of which fell in the SAVM group and climbed in control patients at both follow-ups.
“Hypothetically, it makes sense” to target the splanchnic nerve in HFpEF, and indeed in HF with reduced ejection fraction, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.
And should SAVM enter the mainstream, it would definitely be important to identify “the right” patients for such an invasive procedure, those likely to show “efficacy with a good safety margin,” said Dr. Bozkurt, who was not associated with REBALANCE-HF.
But the trial, she said, “unfortunately did not give real signals of outcome benefit.”
REBALANCE-HF was supported by Axon Therapies. Dr. Fudim disclosed consulting, receiving royalties, or having ownership or equity in Axon Therapies. Dr. Sharma disclosed receiving honoraria for speaking from Novartis and Janssen and serving on an advisory board or consulting for Novartis, Janssen, and Bayer. Dr. Bozkurt disclosed receiving honoraria from AstraZeneca, Baxter Health Care, and Sanofi Aventis and having other relationships with Renovacor, Respicardia, Abbott Vascular, Liva Nova, Vifor, and Cardurion.
A version of this article first appeared on Medscape.com.
It’s still early days for a potential transcatheter technique that tones down sympathetic activation mediating blood volume shifts to the heart and lungs. Such volume transfers can contribute to congestion and acute decompensation in some patients with heart failure. But a randomized trial with negative overall results still may have moved the novel procedure a modest step forward.
The procedure, right-sided splanchnic-nerve ablation for volume management (SAVM), failed to show significant effects on hemodynamics, exercise capacity, natriuretic peptides, or quality of life in a trial covering a broad population of patients with heart failure with preserved ejection fraction (HFpEF).
The study, called REBALANCE-HF, compared ablation of the right greater splanchnic nerve with a sham version of the procedure for any effects on hemodynamic or functional outcomes.
Among such “potential responders,” those undergoing SAVM trended better than patients receiving the sham procedure with respect to hemodynamic, functional, natriuretic peptide, and quality of life endpoints.
The potential predictors of SAVM success included elevated or preserved cardiac output and pulse pressure with exercise or on standing up; appropriate heart-rate exercise responses; and little or no echocardiographic evidence of diastolic dysfunction.
The panel of features might potentially identify patients more likely to respond to the procedure and perhaps sharpen entry criteria in future clinical trials, Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., said in an interview.
Dr. Fudim presented the REBALANCE-HF findings at the annual meeting of the Heart Failure Society of America.
How SAVM works
Sympathetic activation can lead to acute or chronic constriction of vessels in the splanchnic bed within the upper and lower abdomen, one of the body’s largest blood reservoirs, Dr. Fudim explained. Resulting volume shifts to the general circulation, and therefore the heart and lungs, are a normal exercise response that, in HF, can fall out of balance and excessively raise cardiac filling pressure.
Lessened sympathetic tone after unilateral GNS ablation can promote splanchnic venous dilation that reduces intrathoracic blood volume, potentially averting congestion, and decompensation, observed Kavita Sharma, MD, invited discussant for Dr. Fudim’s presentation.
The trial’s potential-responder cohort “seemed able to augment cardiac output in response to stress” and to “maintain or augment their orthostatic pulse pressure,” more effectively than the other participants, said Dr. Sharma, of Johns Hopkins University, Baltimore.
Although the trial was overall negative for 1-month change in pulmonary capillary wedge pressure (PCWP), the primary efficacy endpoint, Dr. Sharma said, it confirmed SAVM as a safe procedure in HFpEF and “ensured its replicability and technical success.”
Future studies should explore ways to characterize unlikely SAVM responders, she proposed. “I would argue these patients are probably more important than even the responders.”
Yet it’s unknown why, for example, cardiac output wouldn’t increase with exercise in a patient with HFpEF. “Is it related to preload insufficiency, right ventricular failure, atrial myopathy, perhaps more restrictive physiology, chronotropic incompetence, or medications – or a combination of the above?”
REBALANCE-HF assigned 90 patients with HFpEF to either the active or sham SAVM groups, 44 and 46 patients, respectively. To be eligible, patients were stable on HF meds and had either elevated natriuretic peptides or, within the past year, at least one HF hospitalization or escalation of intravenous diuretics for worsening HF.
The active and sham control groups fared similarly for the primary PCWP endpoint and for the secondary endpoints of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, 6-minute walk distance (6MWD), and natriuretic peptide levels at 6 and 12 months.
Predicting SAVM response
In analysis limited to potential responders, PCWP, KCCQ, 6MWD, and natriuretic peptide outcomes for patients were combined into z scores, a single metric that reflects multiple outcomes, Dr. Fudim explained.
The z scores were derived for tertiles of patients in subgroups defined by a range of parameters that included demographics, medical history, and hemodynamic and echocardiographic variables.
Four such variables were found to interact across tertiles in a way that suggested their value as SAVM outcome predictors and were then used to select the cohort of potential responders. The variables were exertion-related changes in cardiac index, pulse pressure, and heart rate, and mitral E/A ratio – the latter a measure of diastolic dysfunction.
Among potential responders, those who underwent SAVM showed a 2.9–mm Hg steeper drop in peak PCWP at 1 month (P = .02), compared with patients getting the sham procedure.
They also bested control patients at both 6 and 12 months for KCCQ score, 6MWD, and natriuretic peptide levels, the latter of which fell in the SAVM group and climbed in control patients at both follow-ups.
“Hypothetically, it makes sense” to target the splanchnic nerve in HFpEF, and indeed in HF with reduced ejection fraction, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.
And should SAVM enter the mainstream, it would definitely be important to identify “the right” patients for such an invasive procedure, those likely to show “efficacy with a good safety margin,” said Dr. Bozkurt, who was not associated with REBALANCE-HF.
But the trial, she said, “unfortunately did not give real signals of outcome benefit.”
REBALANCE-HF was supported by Axon Therapies. Dr. Fudim disclosed consulting, receiving royalties, or having ownership or equity in Axon Therapies. Dr. Sharma disclosed receiving honoraria for speaking from Novartis and Janssen and serving on an advisory board or consulting for Novartis, Janssen, and Bayer. Dr. Bozkurt disclosed receiving honoraria from AstraZeneca, Baxter Health Care, and Sanofi Aventis and having other relationships with Renovacor, Respicardia, Abbott Vascular, Liva Nova, Vifor, and Cardurion.
A version of this article first appeared on Medscape.com.
It’s still early days for a potential transcatheter technique that tones down sympathetic activation mediating blood volume shifts to the heart and lungs. Such volume transfers can contribute to congestion and acute decompensation in some patients with heart failure. But a randomized trial with negative overall results still may have moved the novel procedure a modest step forward.
The procedure, right-sided splanchnic-nerve ablation for volume management (SAVM), failed to show significant effects on hemodynamics, exercise capacity, natriuretic peptides, or quality of life in a trial covering a broad population of patients with heart failure with preserved ejection fraction (HFpEF).
The study, called REBALANCE-HF, compared ablation of the right greater splanchnic nerve with a sham version of the procedure for any effects on hemodynamic or functional outcomes.
Among such “potential responders,” those undergoing SAVM trended better than patients receiving the sham procedure with respect to hemodynamic, functional, natriuretic peptide, and quality of life endpoints.
The potential predictors of SAVM success included elevated or preserved cardiac output and pulse pressure with exercise or on standing up; appropriate heart-rate exercise responses; and little or no echocardiographic evidence of diastolic dysfunction.
The panel of features might potentially identify patients more likely to respond to the procedure and perhaps sharpen entry criteria in future clinical trials, Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., said in an interview.
Dr. Fudim presented the REBALANCE-HF findings at the annual meeting of the Heart Failure Society of America.
How SAVM works
Sympathetic activation can lead to acute or chronic constriction of vessels in the splanchnic bed within the upper and lower abdomen, one of the body’s largest blood reservoirs, Dr. Fudim explained. Resulting volume shifts to the general circulation, and therefore the heart and lungs, are a normal exercise response that, in HF, can fall out of balance and excessively raise cardiac filling pressure.
Lessened sympathetic tone after unilateral GNS ablation can promote splanchnic venous dilation that reduces intrathoracic blood volume, potentially averting congestion, and decompensation, observed Kavita Sharma, MD, invited discussant for Dr. Fudim’s presentation.
The trial’s potential-responder cohort “seemed able to augment cardiac output in response to stress” and to “maintain or augment their orthostatic pulse pressure,” more effectively than the other participants, said Dr. Sharma, of Johns Hopkins University, Baltimore.
Although the trial was overall negative for 1-month change in pulmonary capillary wedge pressure (PCWP), the primary efficacy endpoint, Dr. Sharma said, it confirmed SAVM as a safe procedure in HFpEF and “ensured its replicability and technical success.”
Future studies should explore ways to characterize unlikely SAVM responders, she proposed. “I would argue these patients are probably more important than even the responders.”
Yet it’s unknown why, for example, cardiac output wouldn’t increase with exercise in a patient with HFpEF. “Is it related to preload insufficiency, right ventricular failure, atrial myopathy, perhaps more restrictive physiology, chronotropic incompetence, or medications – or a combination of the above?”
REBALANCE-HF assigned 90 patients with HFpEF to either the active or sham SAVM groups, 44 and 46 patients, respectively. To be eligible, patients were stable on HF meds and had either elevated natriuretic peptides or, within the past year, at least one HF hospitalization or escalation of intravenous diuretics for worsening HF.
The active and sham control groups fared similarly for the primary PCWP endpoint and for the secondary endpoints of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, 6-minute walk distance (6MWD), and natriuretic peptide levels at 6 and 12 months.
Predicting SAVM response
In analysis limited to potential responders, PCWP, KCCQ, 6MWD, and natriuretic peptide outcomes for patients were combined into z scores, a single metric that reflects multiple outcomes, Dr. Fudim explained.
The z scores were derived for tertiles of patients in subgroups defined by a range of parameters that included demographics, medical history, and hemodynamic and echocardiographic variables.
Four such variables were found to interact across tertiles in a way that suggested their value as SAVM outcome predictors and were then used to select the cohort of potential responders. The variables were exertion-related changes in cardiac index, pulse pressure, and heart rate, and mitral E/A ratio – the latter a measure of diastolic dysfunction.
Among potential responders, those who underwent SAVM showed a 2.9–mm Hg steeper drop in peak PCWP at 1 month (P = .02), compared with patients getting the sham procedure.
They also bested control patients at both 6 and 12 months for KCCQ score, 6MWD, and natriuretic peptide levels, the latter of which fell in the SAVM group and climbed in control patients at both follow-ups.
“Hypothetically, it makes sense” to target the splanchnic nerve in HFpEF, and indeed in HF with reduced ejection fraction, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.
And should SAVM enter the mainstream, it would definitely be important to identify “the right” patients for such an invasive procedure, those likely to show “efficacy with a good safety margin,” said Dr. Bozkurt, who was not associated with REBALANCE-HF.
But the trial, she said, “unfortunately did not give real signals of outcome benefit.”
REBALANCE-HF was supported by Axon Therapies. Dr. Fudim disclosed consulting, receiving royalties, or having ownership or equity in Axon Therapies. Dr. Sharma disclosed receiving honoraria for speaking from Novartis and Janssen and serving on an advisory board or consulting for Novartis, Janssen, and Bayer. Dr. Bozkurt disclosed receiving honoraria from AstraZeneca, Baxter Health Care, and Sanofi Aventis and having other relationships with Renovacor, Respicardia, Abbott Vascular, Liva Nova, Vifor, and Cardurion.
A version of this article first appeared on Medscape.com.
FROM HFSA 2023
Ocrelizumab benefit confirmed in older patients with MS
MILAN – they say.
The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.
“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Lack of data in older patients
Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.
“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.
This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”
One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.
To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.
They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.
The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
Only relapse rates reduced
With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.
The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.
They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).
The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.
Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).
Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.
He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
Muddling the data
Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.
“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.
This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.
The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.
The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.
“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”
Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.
No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
MILAN – they say.
The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.
“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Lack of data in older patients
Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.
“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.
This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”
One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.
To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.
They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.
The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
Only relapse rates reduced
With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.
The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.
They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).
The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.
Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).
Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.
He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
Muddling the data
Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.
“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.
This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.
The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.
The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.
“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”
Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.
No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
MILAN – they say.
The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.
“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Lack of data in older patients
Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.
“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.
This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”
One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.
To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.
They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.
The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
Only relapse rates reduced
With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.
The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.
They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).
The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.
Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).
Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.
He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
Muddling the data
Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.
“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.
This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.
The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.
The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.
“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”
Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.
No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
AT ECTRIMS 2023
Obesity linked to multiple ills in MS study
MILAN – Swedish researchers reported at the 9th Joint ECTRIMS-ACTRIMS meeting.
In a group of 3,249 subjects tracked for up to 5 years (74% female; mean age, 37.8 years), patients who were obese at diagnosis were 1.41 times more likely than normal-weight patients to reach an Expanded Disability Status Scale (EDSS) score of 3. About 35% of 355 obese subjects (body mass index > 30 kg/m2) reached that level versus 29% of 713 overweight patients (BMI, 25-30) and 28% of 1,475 normal-weight patients (BMI, 18.5-24.99).
Among subjects whose BMI category didn’t change over follow-up, those who were obese at diagnosis were more likely to develop cognitive worsening than those who weren’t obese (hazard ratio, 1.47, 95% confidence interval, 1.08-2.01).
Lars Alfredsson, PhD, a professor at the Karolinska Institutet, Stockholm, who presented the study findings, said in an interview that they fill a gap in knowledge about obesity and MS. “It is known that obesity around the age of 20 or in adolescence is a risk factor for developing MS. But much less is known in regard to progression, and the studies have been very inconclusive.”
The researchers tracked patients via the Swedish MS registry: 1,475 of normal weight, 713 overweight, and 355 obese. Before adjustment for factors such as age, gender, and baseline EDSS, obese subjects were 1.51 times more likely to reach EDSS score 3 than normal-weight subjects.
Obese subjects whose BMI level didn’t change over time were 1.70 times more likely than the nonobese to develop physical worsening as measured by an increased Multiple Sclerosis Impact Scale physical score of 7.5 points or more, and they were 1.36 times more likely to have psychological worsening as measured by increased MSIS-28 psychological score of 7.5 points or more.
Also, among subjects whose BMI didn’t change over time, the likelihood of cognitive disability worsening was 1.47 times higher among obese participants versus nonobese participants. Worsening was defined as an increased Symbol Digit Modalities Test score of 8 points or more.
The level of excess cognitive decline “will affect people significantly,” Dr. Alfredsson said.
While obesity can counterintuitively provide a protective effect in some diseases, he said there’s no sign of such an effect in the subjects.
As for limitations, Dr. Alfredsson noted in his presentation that BMI data is self-reported, and it’s possible that the researchers didn’t adjust their statistics to reflect important confounders.
A 2023 German study of outcomes in MS patients with obesity came to similar conclusions. It tracked 1,066 subjects for up to 6 years and found that “median time to reach EDSS 3 was 0.99 years for patients with BMI of 30 or higher and 1.46 years for nonobese patients. Risk to reach EDSS 3 over 6 years was significantly increased in patients with BMI of at least 30, compared with patients with BMI less than 30 after adjustment for sex, age, smoking (HR, 1.87; 95% CI, 1.3-2.6; P < .001), and independent of disease-modifying therapies.”
However, the German researchers found no link between obesity and higher levels of relapse, contrast-enhancing MRI lesions, or MRI T2 lesion burden.
Interpretation and commentary
Could obesity be causing worse outcomes? The new study doesn’t provide insight into cause and effect. However, obesity may speed up progression via low-grade inflammation, Dr. Alfredsson said.
What can clinicians do with the information from the study? If patients are obese, it can be a good idea to more carefully monitor them and use reliable tools to improve their progression, Dr. Alfredsson said.
In an interview, Michael D. Kornberg, MD, PhD, an assistant professor of neurology at Johns Hopkins University, Baltimore, who was not involved with the study, agreed with Dr. Alfredsson that other research has linked obesity early in life to higher rates of MS. He added that “a number of studies have shown that comorbidities in general are usually associated with a higher rate of disability.”
Dr. Kornberg said the new research is important, and he noted that it has a “robust” cohort because of its larger size.
Could patients with MS reverse the risk of progression and other poor outcomes by losing weight? “It’s hard to say,” Dr. Kornberg said. “We have to be cautious when we assume causation. There’s a plausible rationale that obesity might worsen progression in MS, but it could just be a marker of some other factor that reflects a different phenotype of MS.”
He doesn’t think it’s likely that weight loss would “dramatically reverse the biology of MS,” but he said reversing the obesity epidemic would still be a good thing. An interventional study could examine the effects of weight-loss intervention on disability measures, he said, “and that’s the next step.”
Also contacted for commentary, Adil Harroud, MD, a neurologist at McGill University who studies obesity in MS, said research suggests that “obesity seems to exacerbate MS disability. While some studies show no effect, the majority indicate a detrimental impact.”
However, “the effect of obesity on MS progression remains unclear. Animal studies suggest that shifts in immune cell subsets and functions may play a role, but the relevance to humans is yet to be determined,” he said.
Dr. Harroud, who did not take part in the new study, said it’s “one of the largest examining the impact of obesity on MS disability.” He added that “the cohort was relatively early in their disease course, suggesting that obesity impacts even the early stages of MS. This underscores the importance of obesity as a modifiable risk factor for disability accumulation.”
As for why obesity affects MS, he said one theory is that obesity plays a role through its impact on vitamin D levels. “However, using a genetic approach, we have demonstrated that, at least for MS risk, the effect of obesity is independent of vitamin D. This is also likely true for MS progression, as recent trials of vitamin D supplementation have not shown a meaningful impact on MS outcomes.”
According to Dr. Harroud, “other theories suggest that obesity leads to a pro-inflammatory immune shift. Additionally, it has been proposed that obesity may influence the response to disease-modifying therapy by reducing drug bioavailability, potentially necessitating weight-based dosing for some therapies.”
Dr. Alfredsson reported receiving grants from the Swedish Research Council, the Swedish Research Council for Health Working Life and Welfare, and the Swedish Brain Foundation and personal fees from Teva and Biogene Idec. Some of the other study authors reported various disclosures. Dr. Kornberg and Dr. Harroud reported no relevant disclosures.
This article was updated 10/20/23.
MILAN – Swedish researchers reported at the 9th Joint ECTRIMS-ACTRIMS meeting.
In a group of 3,249 subjects tracked for up to 5 years (74% female; mean age, 37.8 years), patients who were obese at diagnosis were 1.41 times more likely than normal-weight patients to reach an Expanded Disability Status Scale (EDSS) score of 3. About 35% of 355 obese subjects (body mass index > 30 kg/m2) reached that level versus 29% of 713 overweight patients (BMI, 25-30) and 28% of 1,475 normal-weight patients (BMI, 18.5-24.99).
Among subjects whose BMI category didn’t change over follow-up, those who were obese at diagnosis were more likely to develop cognitive worsening than those who weren’t obese (hazard ratio, 1.47, 95% confidence interval, 1.08-2.01).
Lars Alfredsson, PhD, a professor at the Karolinska Institutet, Stockholm, who presented the study findings, said in an interview that they fill a gap in knowledge about obesity and MS. “It is known that obesity around the age of 20 or in adolescence is a risk factor for developing MS. But much less is known in regard to progression, and the studies have been very inconclusive.”
The researchers tracked patients via the Swedish MS registry: 1,475 of normal weight, 713 overweight, and 355 obese. Before adjustment for factors such as age, gender, and baseline EDSS, obese subjects were 1.51 times more likely to reach EDSS score 3 than normal-weight subjects.
Obese subjects whose BMI level didn’t change over time were 1.70 times more likely than the nonobese to develop physical worsening as measured by an increased Multiple Sclerosis Impact Scale physical score of 7.5 points or more, and they were 1.36 times more likely to have psychological worsening as measured by increased MSIS-28 psychological score of 7.5 points or more.
Also, among subjects whose BMI didn’t change over time, the likelihood of cognitive disability worsening was 1.47 times higher among obese participants versus nonobese participants. Worsening was defined as an increased Symbol Digit Modalities Test score of 8 points or more.
The level of excess cognitive decline “will affect people significantly,” Dr. Alfredsson said.
While obesity can counterintuitively provide a protective effect in some diseases, he said there’s no sign of such an effect in the subjects.
As for limitations, Dr. Alfredsson noted in his presentation that BMI data is self-reported, and it’s possible that the researchers didn’t adjust their statistics to reflect important confounders.
A 2023 German study of outcomes in MS patients with obesity came to similar conclusions. It tracked 1,066 subjects for up to 6 years and found that “median time to reach EDSS 3 was 0.99 years for patients with BMI of 30 or higher and 1.46 years for nonobese patients. Risk to reach EDSS 3 over 6 years was significantly increased in patients with BMI of at least 30, compared with patients with BMI less than 30 after adjustment for sex, age, smoking (HR, 1.87; 95% CI, 1.3-2.6; P < .001), and independent of disease-modifying therapies.”
However, the German researchers found no link between obesity and higher levels of relapse, contrast-enhancing MRI lesions, or MRI T2 lesion burden.
Interpretation and commentary
Could obesity be causing worse outcomes? The new study doesn’t provide insight into cause and effect. However, obesity may speed up progression via low-grade inflammation, Dr. Alfredsson said.
What can clinicians do with the information from the study? If patients are obese, it can be a good idea to more carefully monitor them and use reliable tools to improve their progression, Dr. Alfredsson said.
In an interview, Michael D. Kornberg, MD, PhD, an assistant professor of neurology at Johns Hopkins University, Baltimore, who was not involved with the study, agreed with Dr. Alfredsson that other research has linked obesity early in life to higher rates of MS. He added that “a number of studies have shown that comorbidities in general are usually associated with a higher rate of disability.”
Dr. Kornberg said the new research is important, and he noted that it has a “robust” cohort because of its larger size.
Could patients with MS reverse the risk of progression and other poor outcomes by losing weight? “It’s hard to say,” Dr. Kornberg said. “We have to be cautious when we assume causation. There’s a plausible rationale that obesity might worsen progression in MS, but it could just be a marker of some other factor that reflects a different phenotype of MS.”
He doesn’t think it’s likely that weight loss would “dramatically reverse the biology of MS,” but he said reversing the obesity epidemic would still be a good thing. An interventional study could examine the effects of weight-loss intervention on disability measures, he said, “and that’s the next step.”
Also contacted for commentary, Adil Harroud, MD, a neurologist at McGill University who studies obesity in MS, said research suggests that “obesity seems to exacerbate MS disability. While some studies show no effect, the majority indicate a detrimental impact.”
However, “the effect of obesity on MS progression remains unclear. Animal studies suggest that shifts in immune cell subsets and functions may play a role, but the relevance to humans is yet to be determined,” he said.
Dr. Harroud, who did not take part in the new study, said it’s “one of the largest examining the impact of obesity on MS disability.” He added that “the cohort was relatively early in their disease course, suggesting that obesity impacts even the early stages of MS. This underscores the importance of obesity as a modifiable risk factor for disability accumulation.”
As for why obesity affects MS, he said one theory is that obesity plays a role through its impact on vitamin D levels. “However, using a genetic approach, we have demonstrated that, at least for MS risk, the effect of obesity is independent of vitamin D. This is also likely true for MS progression, as recent trials of vitamin D supplementation have not shown a meaningful impact on MS outcomes.”
According to Dr. Harroud, “other theories suggest that obesity leads to a pro-inflammatory immune shift. Additionally, it has been proposed that obesity may influence the response to disease-modifying therapy by reducing drug bioavailability, potentially necessitating weight-based dosing for some therapies.”
Dr. Alfredsson reported receiving grants from the Swedish Research Council, the Swedish Research Council for Health Working Life and Welfare, and the Swedish Brain Foundation and personal fees from Teva and Biogene Idec. Some of the other study authors reported various disclosures. Dr. Kornberg and Dr. Harroud reported no relevant disclosures.
This article was updated 10/20/23.
MILAN – Swedish researchers reported at the 9th Joint ECTRIMS-ACTRIMS meeting.
In a group of 3,249 subjects tracked for up to 5 years (74% female; mean age, 37.8 years), patients who were obese at diagnosis were 1.41 times more likely than normal-weight patients to reach an Expanded Disability Status Scale (EDSS) score of 3. About 35% of 355 obese subjects (body mass index > 30 kg/m2) reached that level versus 29% of 713 overweight patients (BMI, 25-30) and 28% of 1,475 normal-weight patients (BMI, 18.5-24.99).
Among subjects whose BMI category didn’t change over follow-up, those who were obese at diagnosis were more likely to develop cognitive worsening than those who weren’t obese (hazard ratio, 1.47, 95% confidence interval, 1.08-2.01).
Lars Alfredsson, PhD, a professor at the Karolinska Institutet, Stockholm, who presented the study findings, said in an interview that they fill a gap in knowledge about obesity and MS. “It is known that obesity around the age of 20 or in adolescence is a risk factor for developing MS. But much less is known in regard to progression, and the studies have been very inconclusive.”
The researchers tracked patients via the Swedish MS registry: 1,475 of normal weight, 713 overweight, and 355 obese. Before adjustment for factors such as age, gender, and baseline EDSS, obese subjects were 1.51 times more likely to reach EDSS score 3 than normal-weight subjects.
Obese subjects whose BMI level didn’t change over time were 1.70 times more likely than the nonobese to develop physical worsening as measured by an increased Multiple Sclerosis Impact Scale physical score of 7.5 points or more, and they were 1.36 times more likely to have psychological worsening as measured by increased MSIS-28 psychological score of 7.5 points or more.
Also, among subjects whose BMI didn’t change over time, the likelihood of cognitive disability worsening was 1.47 times higher among obese participants versus nonobese participants. Worsening was defined as an increased Symbol Digit Modalities Test score of 8 points or more.
The level of excess cognitive decline “will affect people significantly,” Dr. Alfredsson said.
While obesity can counterintuitively provide a protective effect in some diseases, he said there’s no sign of such an effect in the subjects.
As for limitations, Dr. Alfredsson noted in his presentation that BMI data is self-reported, and it’s possible that the researchers didn’t adjust their statistics to reflect important confounders.
A 2023 German study of outcomes in MS patients with obesity came to similar conclusions. It tracked 1,066 subjects for up to 6 years and found that “median time to reach EDSS 3 was 0.99 years for patients with BMI of 30 or higher and 1.46 years for nonobese patients. Risk to reach EDSS 3 over 6 years was significantly increased in patients with BMI of at least 30, compared with patients with BMI less than 30 after adjustment for sex, age, smoking (HR, 1.87; 95% CI, 1.3-2.6; P < .001), and independent of disease-modifying therapies.”
However, the German researchers found no link between obesity and higher levels of relapse, contrast-enhancing MRI lesions, or MRI T2 lesion burden.
Interpretation and commentary
Could obesity be causing worse outcomes? The new study doesn’t provide insight into cause and effect. However, obesity may speed up progression via low-grade inflammation, Dr. Alfredsson said.
What can clinicians do with the information from the study? If patients are obese, it can be a good idea to more carefully monitor them and use reliable tools to improve their progression, Dr. Alfredsson said.
In an interview, Michael D. Kornberg, MD, PhD, an assistant professor of neurology at Johns Hopkins University, Baltimore, who was not involved with the study, agreed with Dr. Alfredsson that other research has linked obesity early in life to higher rates of MS. He added that “a number of studies have shown that comorbidities in general are usually associated with a higher rate of disability.”
Dr. Kornberg said the new research is important, and he noted that it has a “robust” cohort because of its larger size.
Could patients with MS reverse the risk of progression and other poor outcomes by losing weight? “It’s hard to say,” Dr. Kornberg said. “We have to be cautious when we assume causation. There’s a plausible rationale that obesity might worsen progression in MS, but it could just be a marker of some other factor that reflects a different phenotype of MS.”
He doesn’t think it’s likely that weight loss would “dramatically reverse the biology of MS,” but he said reversing the obesity epidemic would still be a good thing. An interventional study could examine the effects of weight-loss intervention on disability measures, he said, “and that’s the next step.”
Also contacted for commentary, Adil Harroud, MD, a neurologist at McGill University who studies obesity in MS, said research suggests that “obesity seems to exacerbate MS disability. While some studies show no effect, the majority indicate a detrimental impact.”
However, “the effect of obesity on MS progression remains unclear. Animal studies suggest that shifts in immune cell subsets and functions may play a role, but the relevance to humans is yet to be determined,” he said.
Dr. Harroud, who did not take part in the new study, said it’s “one of the largest examining the impact of obesity on MS disability.” He added that “the cohort was relatively early in their disease course, suggesting that obesity impacts even the early stages of MS. This underscores the importance of obesity as a modifiable risk factor for disability accumulation.”
As for why obesity affects MS, he said one theory is that obesity plays a role through its impact on vitamin D levels. “However, using a genetic approach, we have demonstrated that, at least for MS risk, the effect of obesity is independent of vitamin D. This is also likely true for MS progression, as recent trials of vitamin D supplementation have not shown a meaningful impact on MS outcomes.”
According to Dr. Harroud, “other theories suggest that obesity leads to a pro-inflammatory immune shift. Additionally, it has been proposed that obesity may influence the response to disease-modifying therapy by reducing drug bioavailability, potentially necessitating weight-based dosing for some therapies.”
Dr. Alfredsson reported receiving grants from the Swedish Research Council, the Swedish Research Council for Health Working Life and Welfare, and the Swedish Brain Foundation and personal fees from Teva and Biogene Idec. Some of the other study authors reported various disclosures. Dr. Kornberg and Dr. Harroud reported no relevant disclosures.
This article was updated 10/20/23.
AT ECTRIMS 2023
DMT discontinuation trial halted; MS returned in 17.8%
MILAN –
In the multicenter, randomized, controlled, noninferiority DOT-MS trial, inflammatory activity came back in 17.8% of 45 participants who discontinued DMT, researchers reported at the 9th Joint ECTRIMS-ACTRIMS Meeting.
“Because the number of participants with active disease – relapse or MRI activity – was higher in the discontinuation group, and this difference between the groups exceeded our predefined threshold, we prematurely terminated the trial in its current form,” said Eline Coerver, a graduate student with VU University Amsterdam, in an interview.
Previous studies have offered a mixed picture about whether stopping DMT is a good idea when patients with MS are doing well.
“Observational studies suggest that discontinuation of first-line DMTs, or platform therapies, might be safe in patients with MS who have been stable for a long period of time, meaning they did not have any clinical relapses or inflammatory MRI activity – new or contrast-enhancing lesions on MRI,” Ms. Coerver said. “These studies also suggest that patients with higher age have a lower risk of disease activity after DMT discontinuation.”
Discontinuation of DMTs can spare patients from side effects and the cost of the drugs. However, a phase 4 trial published earlier this year in The Lancet Neurology could not determine that stopping DMTs is noninferior to continuing treatment in patients with MS aged 55 and older.
“Six (4.7%) of 128 participants in the continue group and 16 (12.2%) of 131 in the discontinue group had a relapse or a new or expanding brain MRI lesion within 2 years,” the researchers reported.
For the new study, Ms. Coerver and colleagues recruited patients with relapse-onset MS aged 18 years or older who hadn’t had any relapses or substantial MRI activity in the last 5 years. The subjects were randomly assigned to discontinue DMT (interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate) or continue taking the therapy for 2 years.
At pre-set interim analyses, the researchers would look for signs of inflammatory disease activity, which they defined as a confirmed relapse or three or more new T2-lesions or two or more contrast-enhancing lesions detected via MRI.
At the time of cessation in March 2023 (median follow-up = 12.0 months, interquartile range 7.0-20.0), the study had recruited 89 subjects: 67.4% female, mean age 53 (SD, 7.8). Just over half (50.6%) were randomized to discontinue treatment. Of the 45 in the discontinuation group, 8 (17.8%) developed inflammatory activity (7 significant MRI activity, 2 relapses) versus none of the 44 who continued therapy.
Interpreting the results
Two MS clinicians who are familiar with the study findings but weren’t involved with the research were reached for comment.
Katherine Knox, MD, a physiatrist and associate professor who specializes in MS care at the University of Saskatchewan, Saskatoon, said in an interview that the new study is useful “because it affirms that an appropriate stopping recommendation cannot be made primarily on the basis of a standard number of years without disease activity.”
In regard to the percentage of patients who had a recurrence of inflammatory activity (17.8%), Dr. Knox said “ideally patients can be triaged for stopping therapy appropriately with a much lower risk for return of disease activity based on their individual risk factors – i.e., under 2%.”
Michael J. Olek, DO, associate professor of neurology at Touro University Nevada, Henderson, took a different view. He said he does not discontinue medication in patients with MS even if they’re stable for 5 years.
“I am waiting for trials that show that discontinuing medication is OK for the patient. To date, there are no studies showing that stopping medication is a good idea,” he said. “The immune systems slows as people age, so there may be a point in a person’s lifetime when medication used to slow the immune system is no longer needed. But until then I will continue medication for all multiple sclerosis patients.”
Moving forward, study lead author Ms. Coerver said “there are large differences between patients, and there is still room for discussion regarding what percentage of disease activity can be accepted after DMT discontinuation. The most important point is to inform patients about the risks of discontinuation so that each individual patient can make a well-informed decision.”
The study was funded by the Netherlands Organization for Health Research and Development and Stichting MS Research. Ms. Coerver reports no disclosures; some other study authors report various disclosures. Dr. Olek reports no disclosures. Dr. Knox discloses research funding from the Saskatchewan Ministry of Health to evaluate and monitor long-term outcomes in MS.
MILAN –
In the multicenter, randomized, controlled, noninferiority DOT-MS trial, inflammatory activity came back in 17.8% of 45 participants who discontinued DMT, researchers reported at the 9th Joint ECTRIMS-ACTRIMS Meeting.
“Because the number of participants with active disease – relapse or MRI activity – was higher in the discontinuation group, and this difference between the groups exceeded our predefined threshold, we prematurely terminated the trial in its current form,” said Eline Coerver, a graduate student with VU University Amsterdam, in an interview.
Previous studies have offered a mixed picture about whether stopping DMT is a good idea when patients with MS are doing well.
“Observational studies suggest that discontinuation of first-line DMTs, or platform therapies, might be safe in patients with MS who have been stable for a long period of time, meaning they did not have any clinical relapses or inflammatory MRI activity – new or contrast-enhancing lesions on MRI,” Ms. Coerver said. “These studies also suggest that patients with higher age have a lower risk of disease activity after DMT discontinuation.”
Discontinuation of DMTs can spare patients from side effects and the cost of the drugs. However, a phase 4 trial published earlier this year in The Lancet Neurology could not determine that stopping DMTs is noninferior to continuing treatment in patients with MS aged 55 and older.
“Six (4.7%) of 128 participants in the continue group and 16 (12.2%) of 131 in the discontinue group had a relapse or a new or expanding brain MRI lesion within 2 years,” the researchers reported.
For the new study, Ms. Coerver and colleagues recruited patients with relapse-onset MS aged 18 years or older who hadn’t had any relapses or substantial MRI activity in the last 5 years. The subjects were randomly assigned to discontinue DMT (interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate) or continue taking the therapy for 2 years.
At pre-set interim analyses, the researchers would look for signs of inflammatory disease activity, which they defined as a confirmed relapse or three or more new T2-lesions or two or more contrast-enhancing lesions detected via MRI.
At the time of cessation in March 2023 (median follow-up = 12.0 months, interquartile range 7.0-20.0), the study had recruited 89 subjects: 67.4% female, mean age 53 (SD, 7.8). Just over half (50.6%) were randomized to discontinue treatment. Of the 45 in the discontinuation group, 8 (17.8%) developed inflammatory activity (7 significant MRI activity, 2 relapses) versus none of the 44 who continued therapy.
Interpreting the results
Two MS clinicians who are familiar with the study findings but weren’t involved with the research were reached for comment.
Katherine Knox, MD, a physiatrist and associate professor who specializes in MS care at the University of Saskatchewan, Saskatoon, said in an interview that the new study is useful “because it affirms that an appropriate stopping recommendation cannot be made primarily on the basis of a standard number of years without disease activity.”
In regard to the percentage of patients who had a recurrence of inflammatory activity (17.8%), Dr. Knox said “ideally patients can be triaged for stopping therapy appropriately with a much lower risk for return of disease activity based on their individual risk factors – i.e., under 2%.”
Michael J. Olek, DO, associate professor of neurology at Touro University Nevada, Henderson, took a different view. He said he does not discontinue medication in patients with MS even if they’re stable for 5 years.
“I am waiting for trials that show that discontinuing medication is OK for the patient. To date, there are no studies showing that stopping medication is a good idea,” he said. “The immune systems slows as people age, so there may be a point in a person’s lifetime when medication used to slow the immune system is no longer needed. But until then I will continue medication for all multiple sclerosis patients.”
Moving forward, study lead author Ms. Coerver said “there are large differences between patients, and there is still room for discussion regarding what percentage of disease activity can be accepted after DMT discontinuation. The most important point is to inform patients about the risks of discontinuation so that each individual patient can make a well-informed decision.”
The study was funded by the Netherlands Organization for Health Research and Development and Stichting MS Research. Ms. Coerver reports no disclosures; some other study authors report various disclosures. Dr. Olek reports no disclosures. Dr. Knox discloses research funding from the Saskatchewan Ministry of Health to evaluate and monitor long-term outcomes in MS.
MILAN –
In the multicenter, randomized, controlled, noninferiority DOT-MS trial, inflammatory activity came back in 17.8% of 45 participants who discontinued DMT, researchers reported at the 9th Joint ECTRIMS-ACTRIMS Meeting.
“Because the number of participants with active disease – relapse or MRI activity – was higher in the discontinuation group, and this difference between the groups exceeded our predefined threshold, we prematurely terminated the trial in its current form,” said Eline Coerver, a graduate student with VU University Amsterdam, in an interview.
Previous studies have offered a mixed picture about whether stopping DMT is a good idea when patients with MS are doing well.
“Observational studies suggest that discontinuation of first-line DMTs, or platform therapies, might be safe in patients with MS who have been stable for a long period of time, meaning they did not have any clinical relapses or inflammatory MRI activity – new or contrast-enhancing lesions on MRI,” Ms. Coerver said. “These studies also suggest that patients with higher age have a lower risk of disease activity after DMT discontinuation.”
Discontinuation of DMTs can spare patients from side effects and the cost of the drugs. However, a phase 4 trial published earlier this year in The Lancet Neurology could not determine that stopping DMTs is noninferior to continuing treatment in patients with MS aged 55 and older.
“Six (4.7%) of 128 participants in the continue group and 16 (12.2%) of 131 in the discontinue group had a relapse or a new or expanding brain MRI lesion within 2 years,” the researchers reported.
For the new study, Ms. Coerver and colleagues recruited patients with relapse-onset MS aged 18 years or older who hadn’t had any relapses or substantial MRI activity in the last 5 years. The subjects were randomly assigned to discontinue DMT (interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate) or continue taking the therapy for 2 years.
At pre-set interim analyses, the researchers would look for signs of inflammatory disease activity, which they defined as a confirmed relapse or three or more new T2-lesions or two or more contrast-enhancing lesions detected via MRI.
At the time of cessation in March 2023 (median follow-up = 12.0 months, interquartile range 7.0-20.0), the study had recruited 89 subjects: 67.4% female, mean age 53 (SD, 7.8). Just over half (50.6%) were randomized to discontinue treatment. Of the 45 in the discontinuation group, 8 (17.8%) developed inflammatory activity (7 significant MRI activity, 2 relapses) versus none of the 44 who continued therapy.
Interpreting the results
Two MS clinicians who are familiar with the study findings but weren’t involved with the research were reached for comment.
Katherine Knox, MD, a physiatrist and associate professor who specializes in MS care at the University of Saskatchewan, Saskatoon, said in an interview that the new study is useful “because it affirms that an appropriate stopping recommendation cannot be made primarily on the basis of a standard number of years without disease activity.”
In regard to the percentage of patients who had a recurrence of inflammatory activity (17.8%), Dr. Knox said “ideally patients can be triaged for stopping therapy appropriately with a much lower risk for return of disease activity based on their individual risk factors – i.e., under 2%.”
Michael J. Olek, DO, associate professor of neurology at Touro University Nevada, Henderson, took a different view. He said he does not discontinue medication in patients with MS even if they’re stable for 5 years.
“I am waiting for trials that show that discontinuing medication is OK for the patient. To date, there are no studies showing that stopping medication is a good idea,” he said. “The immune systems slows as people age, so there may be a point in a person’s lifetime when medication used to slow the immune system is no longer needed. But until then I will continue medication for all multiple sclerosis patients.”
Moving forward, study lead author Ms. Coerver said “there are large differences between patients, and there is still room for discussion regarding what percentage of disease activity can be accepted after DMT discontinuation. The most important point is to inform patients about the risks of discontinuation so that each individual patient can make a well-informed decision.”
The study was funded by the Netherlands Organization for Health Research and Development and Stichting MS Research. Ms. Coerver reports no disclosures; some other study authors report various disclosures. Dr. Olek reports no disclosures. Dr. Knox discloses research funding from the Saskatchewan Ministry of Health to evaluate and monitor long-term outcomes in MS.
FROM ECTRIMS 2023
Wastewater can signal upswing in flu, RSV
according to new research reported at an annual scientific meeting on infectious diseases.
The analysis of wastewater in Calgary (Alta.) found a “positive correlation” between positivity rates for these three viruses in wastewater and weekly laboratory-confirmed clinical cases and test positivity rates, study investigator Kristine Du, with Cumming School of Medicine, University of Calgary, told this news organization.
Wastewater monitoring of viral activity has become an established tool for COVID-19 pandemic monitoring, providing a leading indicator to cases and hospitalizations. However, less is known about its potential for monitoring endemic respiratory viruses.
The new study shows that wastewater-based surveillance is a “robust and adaptable” tool for community-level surveillance of seasonal respiratory viruses – “one that can complement health care clinical testing because it’s independent from testing biases, and we can actually correlate our cases very well with it,” Ms. Du said during a preconference media briefing.
Tracking community trends
For the study, Ms. Du and colleagues assessed the occurrence of influenza A, influenza B, and RSV RNA in all three wastewater treatment plants in Calgary between March 2022 and April 2023 and its correlation with clinical disease.
They found that viral signals in Calgary’s wastewater for influenza A and B and RSV correlated significantly with weekly confirmed clinical cases in Calgary residents.
Influenza A peaked in Calgary’s wastewater between November and December 2022; influenza B peaked between February and April 2023; and RSV between November 2022 and February 2023.
“Wastewater gives us unbiased, objective, and comprehensive data. It can be used in addition to other testing for assessing the community burden that disease may have, and it is complementary to clinical testing,” Ms. Du said.
Their team, Ms. Du said, is continuing to proactively monitor wastewater for influenza and RSV, as well as other agents of “pandemic potential to make sure we know what could affect humans – and make sure everyone is aware of that.”
Commenting on the research, briefing moderator Belinda Ostrowsky, MD, MPH, Albert Einstein College of Medicine, New York, said, “Wastewater surveillance illustrates how understanding community levels of viral trends can identify hotspots, inform local public health decision-making, and prepare clinicians and hospitals for potential outreach. This topic is particularly timely as we head into the flu and RSV season.”
The study had no commercial funding. Ms. Du and Dr. Ostrowsky report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new research reported at an annual scientific meeting on infectious diseases.
The analysis of wastewater in Calgary (Alta.) found a “positive correlation” between positivity rates for these three viruses in wastewater and weekly laboratory-confirmed clinical cases and test positivity rates, study investigator Kristine Du, with Cumming School of Medicine, University of Calgary, told this news organization.
Wastewater monitoring of viral activity has become an established tool for COVID-19 pandemic monitoring, providing a leading indicator to cases and hospitalizations. However, less is known about its potential for monitoring endemic respiratory viruses.
The new study shows that wastewater-based surveillance is a “robust and adaptable” tool for community-level surveillance of seasonal respiratory viruses – “one that can complement health care clinical testing because it’s independent from testing biases, and we can actually correlate our cases very well with it,” Ms. Du said during a preconference media briefing.
Tracking community trends
For the study, Ms. Du and colleagues assessed the occurrence of influenza A, influenza B, and RSV RNA in all three wastewater treatment plants in Calgary between March 2022 and April 2023 and its correlation with clinical disease.
They found that viral signals in Calgary’s wastewater for influenza A and B and RSV correlated significantly with weekly confirmed clinical cases in Calgary residents.
Influenza A peaked in Calgary’s wastewater between November and December 2022; influenza B peaked between February and April 2023; and RSV between November 2022 and February 2023.
“Wastewater gives us unbiased, objective, and comprehensive data. It can be used in addition to other testing for assessing the community burden that disease may have, and it is complementary to clinical testing,” Ms. Du said.
Their team, Ms. Du said, is continuing to proactively monitor wastewater for influenza and RSV, as well as other agents of “pandemic potential to make sure we know what could affect humans – and make sure everyone is aware of that.”
Commenting on the research, briefing moderator Belinda Ostrowsky, MD, MPH, Albert Einstein College of Medicine, New York, said, “Wastewater surveillance illustrates how understanding community levels of viral trends can identify hotspots, inform local public health decision-making, and prepare clinicians and hospitals for potential outreach. This topic is particularly timely as we head into the flu and RSV season.”
The study had no commercial funding. Ms. Du and Dr. Ostrowsky report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new research reported at an annual scientific meeting on infectious diseases.
The analysis of wastewater in Calgary (Alta.) found a “positive correlation” between positivity rates for these three viruses in wastewater and weekly laboratory-confirmed clinical cases and test positivity rates, study investigator Kristine Du, with Cumming School of Medicine, University of Calgary, told this news organization.
Wastewater monitoring of viral activity has become an established tool for COVID-19 pandemic monitoring, providing a leading indicator to cases and hospitalizations. However, less is known about its potential for monitoring endemic respiratory viruses.
The new study shows that wastewater-based surveillance is a “robust and adaptable” tool for community-level surveillance of seasonal respiratory viruses – “one that can complement health care clinical testing because it’s independent from testing biases, and we can actually correlate our cases very well with it,” Ms. Du said during a preconference media briefing.
Tracking community trends
For the study, Ms. Du and colleagues assessed the occurrence of influenza A, influenza B, and RSV RNA in all three wastewater treatment plants in Calgary between March 2022 and April 2023 and its correlation with clinical disease.
They found that viral signals in Calgary’s wastewater for influenza A and B and RSV correlated significantly with weekly confirmed clinical cases in Calgary residents.
Influenza A peaked in Calgary’s wastewater between November and December 2022; influenza B peaked between February and April 2023; and RSV between November 2022 and February 2023.
“Wastewater gives us unbiased, objective, and comprehensive data. It can be used in addition to other testing for assessing the community burden that disease may have, and it is complementary to clinical testing,” Ms. Du said.
Their team, Ms. Du said, is continuing to proactively monitor wastewater for influenza and RSV, as well as other agents of “pandemic potential to make sure we know what could affect humans – and make sure everyone is aware of that.”
Commenting on the research, briefing moderator Belinda Ostrowsky, MD, MPH, Albert Einstein College of Medicine, New York, said, “Wastewater surveillance illustrates how understanding community levels of viral trends can identify hotspots, inform local public health decision-making, and prepare clinicians and hospitals for potential outreach. This topic is particularly timely as we head into the flu and RSV season.”
The study had no commercial funding. Ms. Du and Dr. Ostrowsky report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM IDWEEK 2023
Confirmed: Intermittent use of benzodiazepines is the safest option
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
AT ECNP 2023
Esketamine bests quetiapine for severe depression in head-to-head trial
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
AT ECNP 2023
Are they ‘antiobesity medications’ or ‘weight-loss drugs’?
A simple Google search for the terms “weight-loss pens,” “weight-loss drugs,” and “weight-loss medications” displays seven times more results than a search for terms like “antiobesity medications,” “antiobesity drugs,” or “drugs (or medications) to treat obesity.” The same search applied to academic databases yields the opposite results: fewer than 500 results for “weight-loss drugs/agents/medications” and 19,000 results for “antiobesity agents,” for example.
To highlight the importance of the language used to talk about obesity treatment, researchers affiliated with the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) released a statement on the subject at the Brazilian Congress of Update in Endocrinology and Metabolism 2023. On the basis of the study by the ABESO and the SBEM, the statement proposes abandoning the use of the term “weight-loss medications” in scientific publications and, most importantly, in the media.
“Put together, we believe that the common use of the term ‘weight-loss medications’ by media and the public, as well as by doctors and the scientific community, contributes to stigma, and certainly that language matters,” study author Paulo Augusto Carvalho Miranda, MD, PhD, chair of SBEM, said in an interview.
“When we refer to these medications as ‘weight-loss drugs,’ we are using derogatory terms to refer to medications that were extensively studied before their launch onto the market and approved by a regulatory authority to treat a disease called obesity,” said study author Márcio Mancini, MD, PhD, deputy chair of the SBEM’s Obesity Department.
Beyond semantics
Another article published by this news organization presents the initiative of a global task force comprising 60 leaders in the clinical management of obesity, who proposed a new name for the disease. According to the leader of the project, Francesco Rubino, MD, “The word is so stigmatized, with so much misunderstanding and misperception, that some might say the only solution is to change the name.” Following this same logic, the authors of the Brazilian study believe that changing how we refer to medications may improve perceptions of health care professionals and patients toward prevention and treatment strategies for obesity.
According to Dr. Miranda, the first step is “remembering that how we refer to people, diseases, and treatments makes all the difference, especially in situations like obesity, a stigmatized disease loaded with misconceptions. It is not merely an issue of semantics, but also an issue of reducing the stigma surrounding the subject.”
According to Dr. Miranda, the primary purpose of the statement is to highlight the uniqueness of the situation and the importance of encouraging the use of the expressions “antiobesity medications” and “medications to treat obesity” to help reduce the stigma and improve adherence and persistence in obesity treatment.
Impact in practice
The statement also emphasizes that obesity pharmacotherapy is widely underused in patients with obesity and that, in the United States, it is prescribed only for approximately 3% of adults with the disease. Weight management programs for this patient population stress implementing lifestyle changes, and only 1.1% of participants are prescribed medications.
According to the statement, the term “weight-loss medications” contributes to the concept that their use has an aesthetic goal and can be consumed by anyone who desires to lose weight.
In addition to ensuring the correct use of language, Dr. Mancini adds that it is essential for doctors to seek and present pharmacologic treatment for obesity as something that will improve patient health. This means stressing that obesity can be controlled with a 10% loss in body weight, just as other chronic diseases, such as diabetes, can be controlled. Moreover, it is important to point out that medications also have a crucial role in optimizing weight maintenance in the long term.
Another issue Dr. Mancini raised is the prejudice that many doctors have against people with obesity. Health professionals should recognize they are also subject to weight bias and that the way they communicate with patients could have a profound effect on health-related outcomes.
“The stigma surrounding obesity can lead to bullying, even in the patient’s home by their relatives; this is very common. Weight stigma is so strong that it hinders patient health and decreases the likelihood of the patient seeking specialized care,” Dr. Mancini warned.
According to the authors, it is of utmost importance to understand that an individual should not be defined by his or disease (as by the use of the terms “obese” or “diabetic”) but rather understood to live with this disease (“individual with obesity” or “with diabetes”). Dr. Mancini suggests the following strategies that health care professionals can adopt while caring for patients with obesity:
- Speak to patients with empathy and respect, avoiding the use of judgmental words.
- Ask if they would like to discuss the “weight issue,” “BMI issue,” terms that are better received by the public, instead of saying “excess fat” or “excess weight.”
- If the patient agrees to talk about the subject, reinforce that this is a chronic health problem that requires longterm treatment and give him or her short, medium, and longterm options.
Lastly, the authors highlighted the importance of differentiating between regulatory agency–approved medications and over-the-counter drugs and supplements that are often sold as “weight-loss agents” and are responsible for an unacceptably high rate of emergency visits.
This article was translated from the Medscape Portuguese Edition. A version appeared on Medscape.com.
A simple Google search for the terms “weight-loss pens,” “weight-loss drugs,” and “weight-loss medications” displays seven times more results than a search for terms like “antiobesity medications,” “antiobesity drugs,” or “drugs (or medications) to treat obesity.” The same search applied to academic databases yields the opposite results: fewer than 500 results for “weight-loss drugs/agents/medications” and 19,000 results for “antiobesity agents,” for example.
To highlight the importance of the language used to talk about obesity treatment, researchers affiliated with the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) released a statement on the subject at the Brazilian Congress of Update in Endocrinology and Metabolism 2023. On the basis of the study by the ABESO and the SBEM, the statement proposes abandoning the use of the term “weight-loss medications” in scientific publications and, most importantly, in the media.
“Put together, we believe that the common use of the term ‘weight-loss medications’ by media and the public, as well as by doctors and the scientific community, contributes to stigma, and certainly that language matters,” study author Paulo Augusto Carvalho Miranda, MD, PhD, chair of SBEM, said in an interview.
“When we refer to these medications as ‘weight-loss drugs,’ we are using derogatory terms to refer to medications that were extensively studied before their launch onto the market and approved by a regulatory authority to treat a disease called obesity,” said study author Márcio Mancini, MD, PhD, deputy chair of the SBEM’s Obesity Department.
Beyond semantics
Another article published by this news organization presents the initiative of a global task force comprising 60 leaders in the clinical management of obesity, who proposed a new name for the disease. According to the leader of the project, Francesco Rubino, MD, “The word is so stigmatized, with so much misunderstanding and misperception, that some might say the only solution is to change the name.” Following this same logic, the authors of the Brazilian study believe that changing how we refer to medications may improve perceptions of health care professionals and patients toward prevention and treatment strategies for obesity.
According to Dr. Miranda, the first step is “remembering that how we refer to people, diseases, and treatments makes all the difference, especially in situations like obesity, a stigmatized disease loaded with misconceptions. It is not merely an issue of semantics, but also an issue of reducing the stigma surrounding the subject.”
According to Dr. Miranda, the primary purpose of the statement is to highlight the uniqueness of the situation and the importance of encouraging the use of the expressions “antiobesity medications” and “medications to treat obesity” to help reduce the stigma and improve adherence and persistence in obesity treatment.
Impact in practice
The statement also emphasizes that obesity pharmacotherapy is widely underused in patients with obesity and that, in the United States, it is prescribed only for approximately 3% of adults with the disease. Weight management programs for this patient population stress implementing lifestyle changes, and only 1.1% of participants are prescribed medications.
According to the statement, the term “weight-loss medications” contributes to the concept that their use has an aesthetic goal and can be consumed by anyone who desires to lose weight.
In addition to ensuring the correct use of language, Dr. Mancini adds that it is essential for doctors to seek and present pharmacologic treatment for obesity as something that will improve patient health. This means stressing that obesity can be controlled with a 10% loss in body weight, just as other chronic diseases, such as diabetes, can be controlled. Moreover, it is important to point out that medications also have a crucial role in optimizing weight maintenance in the long term.
Another issue Dr. Mancini raised is the prejudice that many doctors have against people with obesity. Health professionals should recognize they are also subject to weight bias and that the way they communicate with patients could have a profound effect on health-related outcomes.
“The stigma surrounding obesity can lead to bullying, even in the patient’s home by their relatives; this is very common. Weight stigma is so strong that it hinders patient health and decreases the likelihood of the patient seeking specialized care,” Dr. Mancini warned.
According to the authors, it is of utmost importance to understand that an individual should not be defined by his or disease (as by the use of the terms “obese” or “diabetic”) but rather understood to live with this disease (“individual with obesity” or “with diabetes”). Dr. Mancini suggests the following strategies that health care professionals can adopt while caring for patients with obesity:
- Speak to patients with empathy and respect, avoiding the use of judgmental words.
- Ask if they would like to discuss the “weight issue,” “BMI issue,” terms that are better received by the public, instead of saying “excess fat” or “excess weight.”
- If the patient agrees to talk about the subject, reinforce that this is a chronic health problem that requires longterm treatment and give him or her short, medium, and longterm options.
Lastly, the authors highlighted the importance of differentiating between regulatory agency–approved medications and over-the-counter drugs and supplements that are often sold as “weight-loss agents” and are responsible for an unacceptably high rate of emergency visits.
This article was translated from the Medscape Portuguese Edition. A version appeared on Medscape.com.
A simple Google search for the terms “weight-loss pens,” “weight-loss drugs,” and “weight-loss medications” displays seven times more results than a search for terms like “antiobesity medications,” “antiobesity drugs,” or “drugs (or medications) to treat obesity.” The same search applied to academic databases yields the opposite results: fewer than 500 results for “weight-loss drugs/agents/medications” and 19,000 results for “antiobesity agents,” for example.
To highlight the importance of the language used to talk about obesity treatment, researchers affiliated with the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) released a statement on the subject at the Brazilian Congress of Update in Endocrinology and Metabolism 2023. On the basis of the study by the ABESO and the SBEM, the statement proposes abandoning the use of the term “weight-loss medications” in scientific publications and, most importantly, in the media.
“Put together, we believe that the common use of the term ‘weight-loss medications’ by media and the public, as well as by doctors and the scientific community, contributes to stigma, and certainly that language matters,” study author Paulo Augusto Carvalho Miranda, MD, PhD, chair of SBEM, said in an interview.
“When we refer to these medications as ‘weight-loss drugs,’ we are using derogatory terms to refer to medications that were extensively studied before their launch onto the market and approved by a regulatory authority to treat a disease called obesity,” said study author Márcio Mancini, MD, PhD, deputy chair of the SBEM’s Obesity Department.
Beyond semantics
Another article published by this news organization presents the initiative of a global task force comprising 60 leaders in the clinical management of obesity, who proposed a new name for the disease. According to the leader of the project, Francesco Rubino, MD, “The word is so stigmatized, with so much misunderstanding and misperception, that some might say the only solution is to change the name.” Following this same logic, the authors of the Brazilian study believe that changing how we refer to medications may improve perceptions of health care professionals and patients toward prevention and treatment strategies for obesity.
According to Dr. Miranda, the first step is “remembering that how we refer to people, diseases, and treatments makes all the difference, especially in situations like obesity, a stigmatized disease loaded with misconceptions. It is not merely an issue of semantics, but also an issue of reducing the stigma surrounding the subject.”
According to Dr. Miranda, the primary purpose of the statement is to highlight the uniqueness of the situation and the importance of encouraging the use of the expressions “antiobesity medications” and “medications to treat obesity” to help reduce the stigma and improve adherence and persistence in obesity treatment.
Impact in practice
The statement also emphasizes that obesity pharmacotherapy is widely underused in patients with obesity and that, in the United States, it is prescribed only for approximately 3% of adults with the disease. Weight management programs for this patient population stress implementing lifestyle changes, and only 1.1% of participants are prescribed medications.
According to the statement, the term “weight-loss medications” contributes to the concept that their use has an aesthetic goal and can be consumed by anyone who desires to lose weight.
In addition to ensuring the correct use of language, Dr. Mancini adds that it is essential for doctors to seek and present pharmacologic treatment for obesity as something that will improve patient health. This means stressing that obesity can be controlled with a 10% loss in body weight, just as other chronic diseases, such as diabetes, can be controlled. Moreover, it is important to point out that medications also have a crucial role in optimizing weight maintenance in the long term.
Another issue Dr. Mancini raised is the prejudice that many doctors have against people with obesity. Health professionals should recognize they are also subject to weight bias and that the way they communicate with patients could have a profound effect on health-related outcomes.
“The stigma surrounding obesity can lead to bullying, even in the patient’s home by their relatives; this is very common. Weight stigma is so strong that it hinders patient health and decreases the likelihood of the patient seeking specialized care,” Dr. Mancini warned.
According to the authors, it is of utmost importance to understand that an individual should not be defined by his or disease (as by the use of the terms “obese” or “diabetic”) but rather understood to live with this disease (“individual with obesity” or “with diabetes”). Dr. Mancini suggests the following strategies that health care professionals can adopt while caring for patients with obesity:
- Speak to patients with empathy and respect, avoiding the use of judgmental words.
- Ask if they would like to discuss the “weight issue,” “BMI issue,” terms that are better received by the public, instead of saying “excess fat” or “excess weight.”
- If the patient agrees to talk about the subject, reinforce that this is a chronic health problem that requires longterm treatment and give him or her short, medium, and longterm options.
Lastly, the authors highlighted the importance of differentiating between regulatory agency–approved medications and over-the-counter drugs and supplements that are often sold as “weight-loss agents” and are responsible for an unacceptably high rate of emergency visits.
This article was translated from the Medscape Portuguese Edition. A version appeared on Medscape.com.
Nonsurgical option for more large thyroid nodule patients?
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ATA 2023