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AGA Clinical Practice Update: Young adult–onset colorectal cancer diagnosis and management
The rising incidence of colorectal cancer in adults younger than 50 years heightens the need to evaluate the colon and rectum of any patient, regardless of age, who presents with symptoms such as rectal bleeding, weight loss, abdominal pain, iron-deficiency anemia, or changes in bowel habits, according to a new American Gastroenterological Association clinical practice update.
In addition to receiving cancer staging or being referred to an oncologist, newly diagnosed patients should be counseled about both germline genetic testing and fertility preservation, wrote Lisa A. Boardman, MD, of Mayo Clinic in Rochester, Minn., with associates in Clinical Gastroenterology and Hepatology. “Clinicians should present the role of fertility preservation prior to [administering] cancer-directed therapy, including surgery, pelvic radiation, or chemotherapy.”
It remains unclear why the incidence of young adult–onset colorectal cancer is rising, but the trend is not limited to the United States. Implicated risk factors include inflammatory bowel disease, prior irradiation, harboring a pathogenic germline mutation for a known hereditary cancer syndrome, and having a first- or second-degree relative with colorectal cancer. Indeed, the odds of developing young adult–onset disease are nearly 4 times higher if a parent has colorectal cancer and nearly 12 times higher if a sibling is affected.
For newly diagnosed young adults, it is important to collect a family cancer history but vital, regardless of history, to discuss targeted or multiplex germline mutation testing. Detecting hereditary colorectal cancer syndromes is crucial because their nature informs surgical options for treatment. “Roughly one in five young adult–onset colorectal cancers will be caused by a germline mutation, and among those with a detectable hereditary condition, half of those patients with young adult–onset colorectal cancer will have Lynch syndrome,” the experts noted. For these patients (who have mutations involving MSH2, EPCAM, MLH1, MSH6, and PMS2), ileorectostomy (IRA) for colorectal cancer should be considered.
For patients with the classic subtype of familial adenomatous polyposis, ileal pouch anal anastomosis is recommended after the polyp burden can no longer be managed endoscopically, although initial IRA with subsequent conversion to IPAA is an option for women of child-bearing age, according to the clinical practice update. Patients with the attenuated subtype of familial adenomatous polyposis should consider IRA or colectomy if colorectal cancer develops or if the polyp burden exceeds endoscopic control. In contrast, colectomy is the only type of surgery recommended for patients with serrated polyposis syndrome requiring surgical treatment.
Finally, clinicians should offer only screening for hereditary cancer syndromes if young adults cancer have been diagnosed with a hereditary colorectal cancer syndrome. “For patients with sporadic young adult–onset colorectal cancer, extracolonic screening and colorectal cancer surveillance intervals are the same as for patients with older adult–onset colorectal cancer,” the experts wrote. For young patients without an apparent underlying genetic syndrome, molecular studies may eventually help tailor treatment options, “but at this point, more extensive surgery or more aggressive chemotherapy cannot be recommended. As cancer treatments evolve to use patient tumor specific therapeutics, our management of patients with young adult–onset colorectal cancer will improve.”
Dr. Boardman and associates reported having no relevant conflicts of interest.
SOURCE: Boardman LA et al. Clin Gastroenterol Hepatol. 2020 Jun 7. doi: 10.1016/j.cgh.2020.05.058.
The rising incidence of colorectal cancer in adults younger than 50 years heightens the need to evaluate the colon and rectum of any patient, regardless of age, who presents with symptoms such as rectal bleeding, weight loss, abdominal pain, iron-deficiency anemia, or changes in bowel habits, according to a new American Gastroenterological Association clinical practice update.
In addition to receiving cancer staging or being referred to an oncologist, newly diagnosed patients should be counseled about both germline genetic testing and fertility preservation, wrote Lisa A. Boardman, MD, of Mayo Clinic in Rochester, Minn., with associates in Clinical Gastroenterology and Hepatology. “Clinicians should present the role of fertility preservation prior to [administering] cancer-directed therapy, including surgery, pelvic radiation, or chemotherapy.”
It remains unclear why the incidence of young adult–onset colorectal cancer is rising, but the trend is not limited to the United States. Implicated risk factors include inflammatory bowel disease, prior irradiation, harboring a pathogenic germline mutation for a known hereditary cancer syndrome, and having a first- or second-degree relative with colorectal cancer. Indeed, the odds of developing young adult–onset disease are nearly 4 times higher if a parent has colorectal cancer and nearly 12 times higher if a sibling is affected.
For newly diagnosed young adults, it is important to collect a family cancer history but vital, regardless of history, to discuss targeted or multiplex germline mutation testing. Detecting hereditary colorectal cancer syndromes is crucial because their nature informs surgical options for treatment. “Roughly one in five young adult–onset colorectal cancers will be caused by a germline mutation, and among those with a detectable hereditary condition, half of those patients with young adult–onset colorectal cancer will have Lynch syndrome,” the experts noted. For these patients (who have mutations involving MSH2, EPCAM, MLH1, MSH6, and PMS2), ileorectostomy (IRA) for colorectal cancer should be considered.
For patients with the classic subtype of familial adenomatous polyposis, ileal pouch anal anastomosis is recommended after the polyp burden can no longer be managed endoscopically, although initial IRA with subsequent conversion to IPAA is an option for women of child-bearing age, according to the clinical practice update. Patients with the attenuated subtype of familial adenomatous polyposis should consider IRA or colectomy if colorectal cancer develops or if the polyp burden exceeds endoscopic control. In contrast, colectomy is the only type of surgery recommended for patients with serrated polyposis syndrome requiring surgical treatment.
Finally, clinicians should offer only screening for hereditary cancer syndromes if young adults cancer have been diagnosed with a hereditary colorectal cancer syndrome. “For patients with sporadic young adult–onset colorectal cancer, extracolonic screening and colorectal cancer surveillance intervals are the same as for patients with older adult–onset colorectal cancer,” the experts wrote. For young patients without an apparent underlying genetic syndrome, molecular studies may eventually help tailor treatment options, “but at this point, more extensive surgery or more aggressive chemotherapy cannot be recommended. As cancer treatments evolve to use patient tumor specific therapeutics, our management of patients with young adult–onset colorectal cancer will improve.”
Dr. Boardman and associates reported having no relevant conflicts of interest.
SOURCE: Boardman LA et al. Clin Gastroenterol Hepatol. 2020 Jun 7. doi: 10.1016/j.cgh.2020.05.058.
The rising incidence of colorectal cancer in adults younger than 50 years heightens the need to evaluate the colon and rectum of any patient, regardless of age, who presents with symptoms such as rectal bleeding, weight loss, abdominal pain, iron-deficiency anemia, or changes in bowel habits, according to a new American Gastroenterological Association clinical practice update.
In addition to receiving cancer staging or being referred to an oncologist, newly diagnosed patients should be counseled about both germline genetic testing and fertility preservation, wrote Lisa A. Boardman, MD, of Mayo Clinic in Rochester, Minn., with associates in Clinical Gastroenterology and Hepatology. “Clinicians should present the role of fertility preservation prior to [administering] cancer-directed therapy, including surgery, pelvic radiation, or chemotherapy.”
It remains unclear why the incidence of young adult–onset colorectal cancer is rising, but the trend is not limited to the United States. Implicated risk factors include inflammatory bowel disease, prior irradiation, harboring a pathogenic germline mutation for a known hereditary cancer syndrome, and having a first- or second-degree relative with colorectal cancer. Indeed, the odds of developing young adult–onset disease are nearly 4 times higher if a parent has colorectal cancer and nearly 12 times higher if a sibling is affected.
For newly diagnosed young adults, it is important to collect a family cancer history but vital, regardless of history, to discuss targeted or multiplex germline mutation testing. Detecting hereditary colorectal cancer syndromes is crucial because their nature informs surgical options for treatment. “Roughly one in five young adult–onset colorectal cancers will be caused by a germline mutation, and among those with a detectable hereditary condition, half of those patients with young adult–onset colorectal cancer will have Lynch syndrome,” the experts noted. For these patients (who have mutations involving MSH2, EPCAM, MLH1, MSH6, and PMS2), ileorectostomy (IRA) for colorectal cancer should be considered.
For patients with the classic subtype of familial adenomatous polyposis, ileal pouch anal anastomosis is recommended after the polyp burden can no longer be managed endoscopically, although initial IRA with subsequent conversion to IPAA is an option for women of child-bearing age, according to the clinical practice update. Patients with the attenuated subtype of familial adenomatous polyposis should consider IRA or colectomy if colorectal cancer develops or if the polyp burden exceeds endoscopic control. In contrast, colectomy is the only type of surgery recommended for patients with serrated polyposis syndrome requiring surgical treatment.
Finally, clinicians should offer only screening for hereditary cancer syndromes if young adults cancer have been diagnosed with a hereditary colorectal cancer syndrome. “For patients with sporadic young adult–onset colorectal cancer, extracolonic screening and colorectal cancer surveillance intervals are the same as for patients with older adult–onset colorectal cancer,” the experts wrote. For young patients without an apparent underlying genetic syndrome, molecular studies may eventually help tailor treatment options, “but at this point, more extensive surgery or more aggressive chemotherapy cannot be recommended. As cancer treatments evolve to use patient tumor specific therapeutics, our management of patients with young adult–onset colorectal cancer will improve.”
Dr. Boardman and associates reported having no relevant conflicts of interest.
SOURCE: Boardman LA et al. Clin Gastroenterol Hepatol. 2020 Jun 7. doi: 10.1016/j.cgh.2020.05.058.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Worry over family, friends the main driver of COVID-19 stress
Individuals are more worried about family members becoming ill with COVID-19 or about unknowingly transmitting the disease to family members than they are about contracting it themselves, results of a new survey show.
Investigators surveyed over 3,000 adults, using an online questionnaire. Of the respondents, about 20% were health care workers, and most were living in locations with active stay-at-home orders at the time of the survey.
Close to half of participants were worried about family members contracting the virus, one third were worried about unknowingly infecting others, and 20% were worried about contracting the virus themselves.
“We were a little surprised to see that people were more concerned about others than about themselves, specifically worrying about whether a family member would contract COVID-19 and whether they might unintentionally infect others,” lead author Ran Barzilay, MD, PhD, child and adolescent psychiatrist at the Children’s Hospital of Philadelphia (CHOP), told Medscape Medical News.
The study was published online August 20 in Translational Psychiatry.
Interactive platform
“The pandemic has provided a unique opportunity to study resilience in healthcare professionals and others,” said Barzilay, assistant professor at the Lifespan Brain Institute, a collaboration between CHOP and the University of Pennsylvania, under the directorship of Raquel Gur, MD, PhD.
“After the pandemic broke out in March, we launched a website in early April where we surveyed people for levels of resilience, mental health, and well-being during the outbreak,” he added.
Survey participants then shared it with their contacts.
“To date, over 7000 people have completed it – mostly from the US but also from Israel,” Barzilay said.
The survey was anonymous, but participants could choose to have follow-up contact. The survey included an interactive 21-item resilience questionnaire and an assessment of COVID-19-related items related to worries concerning the following: contracting, dying from, or currently having the illness; having a family member contract the illness; unknowingly infecting others; and experiencing significant financial burden.
A total of 1350 participants took a second survey on anxiety and depression that utilized the Generalized Anxiety Disorder–7 and the Patient Health Questionnaire–2.
“What makes the survey unique is that it’s not just a means of collecting data but also an interactive platform that gives participants immediate personalized feedback, based on their responses to the resilience and well-being surveys, with practical tips and recommendations for stress management and ways of boosting resilience,” Barzilay said.
Tend and befriend
Ten days into the survey, data were available on 3,042 participants (64% women, 54% with advanced education, 20.5% health care providers), who ranged in age from 18 to 70 years (mean [SD], 38.9 [11.9] years).
After accounting for covariates, the researchers found that participants reported more distress about family members contracting COVID-19 and about unknowingly infecting others than about getting COVID-19 themselves (48.5% and 36% vs. 19.9%, respectively; P < .0005).
Increased COVID-19-related worries were associated with 22% higher anxiety and 16.1% higher depression scores; women had higher scores than men on both.
Each 1-SD increase in the composite score of COVID-19 worries was associated with over twice the increased probability of generalized anxiety and depression (odds ratio, 2.23; 95% confidence interval, 1.88-2.65; and OR, 1.67; 95% CI, 1.41-1.98, respectively; for both, P < .001).
On the other hand, for every 1-SD increase in the resilience score, there was a 64.9% decrease in the possibility of screening positive for generalized anxiety disorder and a 69.3% decrease in the possibility of screening positive for depression (for both, P < .0001).
Compared to participants from Israel, US participants were “more stressed” about contracting, dying from, and currently having COVID-19 themselves. Overall, Israeli participants scored higher than US participants on the resilience scale.
Rates of anxiety and depression did not differ significantly between healthcare providers and others. Health care providers worried more about contracting COVID-19 themselves and worried less about finances after COVID-19.
The authors propose that survey participants were more worried about others than about themselves because of “prosocial behavior under stress” and “tend-and-befriend,” whereby, “in response to threat, humans tend to protect their close ones (tending) and seek out their social group for mutual defense (befriending).”
This type of altruistic behavior has been “described in acute situations throughout history” and has been “linked to mechanisms of resilience for overcoming adversity,” the authors indicate.
Demographic biases
Commenting on the findings for Medscape Medical News, Golnaz Tabibnia, PhD, a neuroscientist at the University of California, Irvine, who was not involved in the research, suggested that although higher resilience scores were associated with lower COVID-related worries, it is possible, “as the authors suggest, that having more resilience resources makes you less worried, but the causality could go the other direction as well, and less worry/rumination may lead to more resilience.”
Also commenting on the study for Medscape Medical News, Christiaan Vinkers, MD, PhD, a psychiatrist at the Amsterdam University Medical Center, Amsterdam, the Netherlands, said it was noteworthy that healthcare providers reported similar levels of mood and anxiety symptoms, compared to others.
“This is encouraging, as it suggests adequate resilience levels in professionals who work in the front lines of the COVID-19 pandemic,” he said.
Resilience occurs not only at the individual level but also at the community level, which may help explain the striking differences in COVID-19-related worries and anxiety between participants from the United States and Israel, Vinkers added.
E. Alison Holman, PhD, professor, Sue and Bill Gross School of Nursing, University of California, Irvine, noted that respondents were predominantly white, female, and had relatively high incomes, “suggesting strong demographic biases in those who chose to participate.”
Holman, who was not involved with the study, told Medscape Medical News that the “findings do not address the real impact of COVID-19 on the hardest-hit communities in America – poor, Black, and Latinx communities, where a large proportion of essential workers live.”
Barzilay acknowledged that, “unfortunately, because of the way the study was circulated, it did not reach minorities, which is one of the things we want to improve.”
The study is ongoing and has been translated into Spanish, French, and Hebrew. The team plans to collect data on diverse populations.
The study was supported by grants from the National Institute of Mental Health, the Lifespan Brain Institute of Children’s Hospital of Philadelphia, Penn Medicine, the University of Pennsylvania, and in part by the Zuckerman STEM Leadership Program. Barzilay serves on the scientific board and reports stock ownership in Taliaz Health. The other authors, Golnaz, Vinkers, and Holman have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Individuals are more worried about family members becoming ill with COVID-19 or about unknowingly transmitting the disease to family members than they are about contracting it themselves, results of a new survey show.
Investigators surveyed over 3,000 adults, using an online questionnaire. Of the respondents, about 20% were health care workers, and most were living in locations with active stay-at-home orders at the time of the survey.
Close to half of participants were worried about family members contracting the virus, one third were worried about unknowingly infecting others, and 20% were worried about contracting the virus themselves.
“We were a little surprised to see that people were more concerned about others than about themselves, specifically worrying about whether a family member would contract COVID-19 and whether they might unintentionally infect others,” lead author Ran Barzilay, MD, PhD, child and adolescent psychiatrist at the Children’s Hospital of Philadelphia (CHOP), told Medscape Medical News.
The study was published online August 20 in Translational Psychiatry.
Interactive platform
“The pandemic has provided a unique opportunity to study resilience in healthcare professionals and others,” said Barzilay, assistant professor at the Lifespan Brain Institute, a collaboration between CHOP and the University of Pennsylvania, under the directorship of Raquel Gur, MD, PhD.
“After the pandemic broke out in March, we launched a website in early April where we surveyed people for levels of resilience, mental health, and well-being during the outbreak,” he added.
Survey participants then shared it with their contacts.
“To date, over 7000 people have completed it – mostly from the US but also from Israel,” Barzilay said.
The survey was anonymous, but participants could choose to have follow-up contact. The survey included an interactive 21-item resilience questionnaire and an assessment of COVID-19-related items related to worries concerning the following: contracting, dying from, or currently having the illness; having a family member contract the illness; unknowingly infecting others; and experiencing significant financial burden.
A total of 1350 participants took a second survey on anxiety and depression that utilized the Generalized Anxiety Disorder–7 and the Patient Health Questionnaire–2.
“What makes the survey unique is that it’s not just a means of collecting data but also an interactive platform that gives participants immediate personalized feedback, based on their responses to the resilience and well-being surveys, with practical tips and recommendations for stress management and ways of boosting resilience,” Barzilay said.
Tend and befriend
Ten days into the survey, data were available on 3,042 participants (64% women, 54% with advanced education, 20.5% health care providers), who ranged in age from 18 to 70 years (mean [SD], 38.9 [11.9] years).
After accounting for covariates, the researchers found that participants reported more distress about family members contracting COVID-19 and about unknowingly infecting others than about getting COVID-19 themselves (48.5% and 36% vs. 19.9%, respectively; P < .0005).
Increased COVID-19-related worries were associated with 22% higher anxiety and 16.1% higher depression scores; women had higher scores than men on both.
Each 1-SD increase in the composite score of COVID-19 worries was associated with over twice the increased probability of generalized anxiety and depression (odds ratio, 2.23; 95% confidence interval, 1.88-2.65; and OR, 1.67; 95% CI, 1.41-1.98, respectively; for both, P < .001).
On the other hand, for every 1-SD increase in the resilience score, there was a 64.9% decrease in the possibility of screening positive for generalized anxiety disorder and a 69.3% decrease in the possibility of screening positive for depression (for both, P < .0001).
Compared to participants from Israel, US participants were “more stressed” about contracting, dying from, and currently having COVID-19 themselves. Overall, Israeli participants scored higher than US participants on the resilience scale.
Rates of anxiety and depression did not differ significantly between healthcare providers and others. Health care providers worried more about contracting COVID-19 themselves and worried less about finances after COVID-19.
The authors propose that survey participants were more worried about others than about themselves because of “prosocial behavior under stress” and “tend-and-befriend,” whereby, “in response to threat, humans tend to protect their close ones (tending) and seek out their social group for mutual defense (befriending).”
This type of altruistic behavior has been “described in acute situations throughout history” and has been “linked to mechanisms of resilience for overcoming adversity,” the authors indicate.
Demographic biases
Commenting on the findings for Medscape Medical News, Golnaz Tabibnia, PhD, a neuroscientist at the University of California, Irvine, who was not involved in the research, suggested that although higher resilience scores were associated with lower COVID-related worries, it is possible, “as the authors suggest, that having more resilience resources makes you less worried, but the causality could go the other direction as well, and less worry/rumination may lead to more resilience.”
Also commenting on the study for Medscape Medical News, Christiaan Vinkers, MD, PhD, a psychiatrist at the Amsterdam University Medical Center, Amsterdam, the Netherlands, said it was noteworthy that healthcare providers reported similar levels of mood and anxiety symptoms, compared to others.
“This is encouraging, as it suggests adequate resilience levels in professionals who work in the front lines of the COVID-19 pandemic,” he said.
Resilience occurs not only at the individual level but also at the community level, which may help explain the striking differences in COVID-19-related worries and anxiety between participants from the United States and Israel, Vinkers added.
E. Alison Holman, PhD, professor, Sue and Bill Gross School of Nursing, University of California, Irvine, noted that respondents were predominantly white, female, and had relatively high incomes, “suggesting strong demographic biases in those who chose to participate.”
Holman, who was not involved with the study, told Medscape Medical News that the “findings do not address the real impact of COVID-19 on the hardest-hit communities in America – poor, Black, and Latinx communities, where a large proportion of essential workers live.”
Barzilay acknowledged that, “unfortunately, because of the way the study was circulated, it did not reach minorities, which is one of the things we want to improve.”
The study is ongoing and has been translated into Spanish, French, and Hebrew. The team plans to collect data on diverse populations.
The study was supported by grants from the National Institute of Mental Health, the Lifespan Brain Institute of Children’s Hospital of Philadelphia, Penn Medicine, the University of Pennsylvania, and in part by the Zuckerman STEM Leadership Program. Barzilay serves on the scientific board and reports stock ownership in Taliaz Health. The other authors, Golnaz, Vinkers, and Holman have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Individuals are more worried about family members becoming ill with COVID-19 or about unknowingly transmitting the disease to family members than they are about contracting it themselves, results of a new survey show.
Investigators surveyed over 3,000 adults, using an online questionnaire. Of the respondents, about 20% were health care workers, and most were living in locations with active stay-at-home orders at the time of the survey.
Close to half of participants were worried about family members contracting the virus, one third were worried about unknowingly infecting others, and 20% were worried about contracting the virus themselves.
“We were a little surprised to see that people were more concerned about others than about themselves, specifically worrying about whether a family member would contract COVID-19 and whether they might unintentionally infect others,” lead author Ran Barzilay, MD, PhD, child and adolescent psychiatrist at the Children’s Hospital of Philadelphia (CHOP), told Medscape Medical News.
The study was published online August 20 in Translational Psychiatry.
Interactive platform
“The pandemic has provided a unique opportunity to study resilience in healthcare professionals and others,” said Barzilay, assistant professor at the Lifespan Brain Institute, a collaboration between CHOP and the University of Pennsylvania, under the directorship of Raquel Gur, MD, PhD.
“After the pandemic broke out in March, we launched a website in early April where we surveyed people for levels of resilience, mental health, and well-being during the outbreak,” he added.
Survey participants then shared it with their contacts.
“To date, over 7000 people have completed it – mostly from the US but also from Israel,” Barzilay said.
The survey was anonymous, but participants could choose to have follow-up contact. The survey included an interactive 21-item resilience questionnaire and an assessment of COVID-19-related items related to worries concerning the following: contracting, dying from, or currently having the illness; having a family member contract the illness; unknowingly infecting others; and experiencing significant financial burden.
A total of 1350 participants took a second survey on anxiety and depression that utilized the Generalized Anxiety Disorder–7 and the Patient Health Questionnaire–2.
“What makes the survey unique is that it’s not just a means of collecting data but also an interactive platform that gives participants immediate personalized feedback, based on their responses to the resilience and well-being surveys, with practical tips and recommendations for stress management and ways of boosting resilience,” Barzilay said.
Tend and befriend
Ten days into the survey, data were available on 3,042 participants (64% women, 54% with advanced education, 20.5% health care providers), who ranged in age from 18 to 70 years (mean [SD], 38.9 [11.9] years).
After accounting for covariates, the researchers found that participants reported more distress about family members contracting COVID-19 and about unknowingly infecting others than about getting COVID-19 themselves (48.5% and 36% vs. 19.9%, respectively; P < .0005).
Increased COVID-19-related worries were associated with 22% higher anxiety and 16.1% higher depression scores; women had higher scores than men on both.
Each 1-SD increase in the composite score of COVID-19 worries was associated with over twice the increased probability of generalized anxiety and depression (odds ratio, 2.23; 95% confidence interval, 1.88-2.65; and OR, 1.67; 95% CI, 1.41-1.98, respectively; for both, P < .001).
On the other hand, for every 1-SD increase in the resilience score, there was a 64.9% decrease in the possibility of screening positive for generalized anxiety disorder and a 69.3% decrease in the possibility of screening positive for depression (for both, P < .0001).
Compared to participants from Israel, US participants were “more stressed” about contracting, dying from, and currently having COVID-19 themselves. Overall, Israeli participants scored higher than US participants on the resilience scale.
Rates of anxiety and depression did not differ significantly between healthcare providers and others. Health care providers worried more about contracting COVID-19 themselves and worried less about finances after COVID-19.
The authors propose that survey participants were more worried about others than about themselves because of “prosocial behavior under stress” and “tend-and-befriend,” whereby, “in response to threat, humans tend to protect their close ones (tending) and seek out their social group for mutual defense (befriending).”
This type of altruistic behavior has been “described in acute situations throughout history” and has been “linked to mechanisms of resilience for overcoming adversity,” the authors indicate.
Demographic biases
Commenting on the findings for Medscape Medical News, Golnaz Tabibnia, PhD, a neuroscientist at the University of California, Irvine, who was not involved in the research, suggested that although higher resilience scores were associated with lower COVID-related worries, it is possible, “as the authors suggest, that having more resilience resources makes you less worried, but the causality could go the other direction as well, and less worry/rumination may lead to more resilience.”
Also commenting on the study for Medscape Medical News, Christiaan Vinkers, MD, PhD, a psychiatrist at the Amsterdam University Medical Center, Amsterdam, the Netherlands, said it was noteworthy that healthcare providers reported similar levels of mood and anxiety symptoms, compared to others.
“This is encouraging, as it suggests adequate resilience levels in professionals who work in the front lines of the COVID-19 pandemic,” he said.
Resilience occurs not only at the individual level but also at the community level, which may help explain the striking differences in COVID-19-related worries and anxiety between participants from the United States and Israel, Vinkers added.
E. Alison Holman, PhD, professor, Sue and Bill Gross School of Nursing, University of California, Irvine, noted that respondents were predominantly white, female, and had relatively high incomes, “suggesting strong demographic biases in those who chose to participate.”
Holman, who was not involved with the study, told Medscape Medical News that the “findings do not address the real impact of COVID-19 on the hardest-hit communities in America – poor, Black, and Latinx communities, where a large proportion of essential workers live.”
Barzilay acknowledged that, “unfortunately, because of the way the study was circulated, it did not reach minorities, which is one of the things we want to improve.”
The study is ongoing and has been translated into Spanish, French, and Hebrew. The team plans to collect data on diverse populations.
The study was supported by grants from the National Institute of Mental Health, the Lifespan Brain Institute of Children’s Hospital of Philadelphia, Penn Medicine, the University of Pennsylvania, and in part by the Zuckerman STEM Leadership Program. Barzilay serves on the scientific board and reports stock ownership in Taliaz Health. The other authors, Golnaz, Vinkers, and Holman have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Sleep EEG may predict later antidepressant response
A change in rapid eye movement sleeping pattern as measured by quantitative EEG in patients with major depressive disorder after just a single week on a first-line antidepressant predicts eventual clinical response or nonresponse to the medication weeks later, Thorsten Mikoteit, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
This finding from a small, randomized, controlled trial opens the door to a novel biomarker-based treatment strategy: namely, an immediate switch to a different antidepressant in predicted nonresponders to the first agent. The goal is to improve the final treatment response rate while collapsing the time required to get there, explained Dr. Mikoteit, a psychiatrist affiliated with the University of Basel (Switzerland).
“In real terms, it means that patients, often in the depths of despair, might not need to wait weeks to see if their therapy is working before modifying their treatment,” he observed.
There is a huge unmet need for a biomarker predictive of response to antidepressant medication in patients with major depression, the psychiatrist added. At present, the treatment response rate is unsatisfactory. Moreover, clinical improvement takes a long time to achieve, often requiring several rounds of therapeutic trials during which patients are exposed to weeks of unpleasant side effects of drugs that are ultimately switched out for lack of efficacy or poor tolerance.
The quantitative EEG biomarker under investigation is prefrontal theta cordance (PTC) during REM sleep. It is computed from the absolute and relative theta power in tonic REM sleep. PTC has been shown to correlate with frontocingulate brain activity and cerebral blood perfusion. In an earlier pilot study, Dr. Mikoteit and coinvestigators demonstrated in 33 patients who were experiencing a depressive episode that an increase in PTC after their first week on an antidepressant was associated a significantly increased treatment response rate at the end of the fourth week on the drug, while nonresponders failed to show such increase (J Psychiatr Res. 2017 Sep;92:64-73).
At ECNP 2020, Dr. Mikoteit presented preliminary results from an ongoing randomized, controlled trial including 37 patients hospitalized for major depressive disorder. All underwent baseline evaluation using the Hamilton Depression Rating Scale (HAMD) and were placed on the first-line antidepressant of their psychiatrist’s choice. After 1 week of therapy, participants underwent polysomnography with PTC measurement during tonic REM sleep.
Twenty-two patients were randomized to the intervention arm, in which investigators informed treating psychiatrists of the PTC results. The clinicians were instructed to change to another antidepressant if the biomarker predicted nonresponse or stay the course if the PTC results were favorable. Polysomnography was repeated 1 week later in the intervention arm, and the second-line antidepressant was either continued or switched out depending on the PTC findings. In the control arm, psychiatrists weren’t informed of the PTC results and patients continued on their initial antidepressant. The intervention and control groups were comparable in terms of age, sex, and severity of depression, with an average baseline HAMD score of 22.
A treatment response was defined as at least a 50% reduction in HAMD score from baseline to week 5. About 86% of patients who switched antidepressants based upon their 1-week quantitative EEG findings were categorized as treatment responders at week 5, compared with 20% of controls.
The overall 5-week response rate in the intervention group was 73%, compared with 60% in the control arm. This favorable trend didn’t achieve statistical significance, presumably because of the study’s sample size; however, the study is continuing to enroll participants in order to achieve a definitive result.
Dr. Mikoteit noted that the cost and inconvenience of spending a night in a sleep laboratory would be worthwhile if it resulted in the ability to give effective treatment much sooner. This would be particularly advantageous in patients at increased risk for suicide.
he said.
Study could have “enormous implications”
Of note, in the landmark National Institute of Mental Health–sponsored Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, slightly less than half of patients with major depressive disorder achieved a treatment response to their first-line antidepressant, and it took an average of 6 weeks of therapy to do. About one in four nonresponders who chose to switch to a different antidepressant got better.
“The STAR*D trial is still the gold standard for understanding antidepressant response, and so being able to see if an antidepressant works within 1 week would be a real breakthrough,” Catherine Harmer, DPhil, said in an interview.
“Most of the time, patients need to wait for around 4 weeks before they can tell if they are responding to a particular antidepressant or not. This is a hugely disabling and lengthy process, and often a different treatment then needs to be started,” added Dr. Harmer, professor of cognitive neuroscience and director of the Psychopharmacology and Emotional Research Lab at the University of Oxford (England).
“If the study results presented by Dr. Mikoteit are replicated in a larger blinded study, then it would have enormous implications for the future treatment of individuals with depression,” according to Dr. Harmer, who was not involved in the study and has no conflicts of interest related to it.
Dr. Mikoteit reported having no financial conflicts regarding the study, funded by the Psychiatric University Hospital of Basel.
SOURCE: Mikoteit T et al. ECNP 2020, Abstract P.733.
A change in rapid eye movement sleeping pattern as measured by quantitative EEG in patients with major depressive disorder after just a single week on a first-line antidepressant predicts eventual clinical response or nonresponse to the medication weeks later, Thorsten Mikoteit, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
This finding from a small, randomized, controlled trial opens the door to a novel biomarker-based treatment strategy: namely, an immediate switch to a different antidepressant in predicted nonresponders to the first agent. The goal is to improve the final treatment response rate while collapsing the time required to get there, explained Dr. Mikoteit, a psychiatrist affiliated with the University of Basel (Switzerland).
“In real terms, it means that patients, often in the depths of despair, might not need to wait weeks to see if their therapy is working before modifying their treatment,” he observed.
There is a huge unmet need for a biomarker predictive of response to antidepressant medication in patients with major depression, the psychiatrist added. At present, the treatment response rate is unsatisfactory. Moreover, clinical improvement takes a long time to achieve, often requiring several rounds of therapeutic trials during which patients are exposed to weeks of unpleasant side effects of drugs that are ultimately switched out for lack of efficacy or poor tolerance.
The quantitative EEG biomarker under investigation is prefrontal theta cordance (PTC) during REM sleep. It is computed from the absolute and relative theta power in tonic REM sleep. PTC has been shown to correlate with frontocingulate brain activity and cerebral blood perfusion. In an earlier pilot study, Dr. Mikoteit and coinvestigators demonstrated in 33 patients who were experiencing a depressive episode that an increase in PTC after their first week on an antidepressant was associated a significantly increased treatment response rate at the end of the fourth week on the drug, while nonresponders failed to show such increase (J Psychiatr Res. 2017 Sep;92:64-73).
At ECNP 2020, Dr. Mikoteit presented preliminary results from an ongoing randomized, controlled trial including 37 patients hospitalized for major depressive disorder. All underwent baseline evaluation using the Hamilton Depression Rating Scale (HAMD) and were placed on the first-line antidepressant of their psychiatrist’s choice. After 1 week of therapy, participants underwent polysomnography with PTC measurement during tonic REM sleep.
Twenty-two patients were randomized to the intervention arm, in which investigators informed treating psychiatrists of the PTC results. The clinicians were instructed to change to another antidepressant if the biomarker predicted nonresponse or stay the course if the PTC results were favorable. Polysomnography was repeated 1 week later in the intervention arm, and the second-line antidepressant was either continued or switched out depending on the PTC findings. In the control arm, psychiatrists weren’t informed of the PTC results and patients continued on their initial antidepressant. The intervention and control groups were comparable in terms of age, sex, and severity of depression, with an average baseline HAMD score of 22.
A treatment response was defined as at least a 50% reduction in HAMD score from baseline to week 5. About 86% of patients who switched antidepressants based upon their 1-week quantitative EEG findings were categorized as treatment responders at week 5, compared with 20% of controls.
The overall 5-week response rate in the intervention group was 73%, compared with 60% in the control arm. This favorable trend didn’t achieve statistical significance, presumably because of the study’s sample size; however, the study is continuing to enroll participants in order to achieve a definitive result.
Dr. Mikoteit noted that the cost and inconvenience of spending a night in a sleep laboratory would be worthwhile if it resulted in the ability to give effective treatment much sooner. This would be particularly advantageous in patients at increased risk for suicide.
he said.
Study could have “enormous implications”
Of note, in the landmark National Institute of Mental Health–sponsored Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, slightly less than half of patients with major depressive disorder achieved a treatment response to their first-line antidepressant, and it took an average of 6 weeks of therapy to do. About one in four nonresponders who chose to switch to a different antidepressant got better.
“The STAR*D trial is still the gold standard for understanding antidepressant response, and so being able to see if an antidepressant works within 1 week would be a real breakthrough,” Catherine Harmer, DPhil, said in an interview.
“Most of the time, patients need to wait for around 4 weeks before they can tell if they are responding to a particular antidepressant or not. This is a hugely disabling and lengthy process, and often a different treatment then needs to be started,” added Dr. Harmer, professor of cognitive neuroscience and director of the Psychopharmacology and Emotional Research Lab at the University of Oxford (England).
“If the study results presented by Dr. Mikoteit are replicated in a larger blinded study, then it would have enormous implications for the future treatment of individuals with depression,” according to Dr. Harmer, who was not involved in the study and has no conflicts of interest related to it.
Dr. Mikoteit reported having no financial conflicts regarding the study, funded by the Psychiatric University Hospital of Basel.
SOURCE: Mikoteit T et al. ECNP 2020, Abstract P.733.
A change in rapid eye movement sleeping pattern as measured by quantitative EEG in patients with major depressive disorder after just a single week on a first-line antidepressant predicts eventual clinical response or nonresponse to the medication weeks later, Thorsten Mikoteit, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
This finding from a small, randomized, controlled trial opens the door to a novel biomarker-based treatment strategy: namely, an immediate switch to a different antidepressant in predicted nonresponders to the first agent. The goal is to improve the final treatment response rate while collapsing the time required to get there, explained Dr. Mikoteit, a psychiatrist affiliated with the University of Basel (Switzerland).
“In real terms, it means that patients, often in the depths of despair, might not need to wait weeks to see if their therapy is working before modifying their treatment,” he observed.
There is a huge unmet need for a biomarker predictive of response to antidepressant medication in patients with major depression, the psychiatrist added. At present, the treatment response rate is unsatisfactory. Moreover, clinical improvement takes a long time to achieve, often requiring several rounds of therapeutic trials during which patients are exposed to weeks of unpleasant side effects of drugs that are ultimately switched out for lack of efficacy or poor tolerance.
The quantitative EEG biomarker under investigation is prefrontal theta cordance (PTC) during REM sleep. It is computed from the absolute and relative theta power in tonic REM sleep. PTC has been shown to correlate with frontocingulate brain activity and cerebral blood perfusion. In an earlier pilot study, Dr. Mikoteit and coinvestigators demonstrated in 33 patients who were experiencing a depressive episode that an increase in PTC after their first week on an antidepressant was associated a significantly increased treatment response rate at the end of the fourth week on the drug, while nonresponders failed to show such increase (J Psychiatr Res. 2017 Sep;92:64-73).
At ECNP 2020, Dr. Mikoteit presented preliminary results from an ongoing randomized, controlled trial including 37 patients hospitalized for major depressive disorder. All underwent baseline evaluation using the Hamilton Depression Rating Scale (HAMD) and were placed on the first-line antidepressant of their psychiatrist’s choice. After 1 week of therapy, participants underwent polysomnography with PTC measurement during tonic REM sleep.
Twenty-two patients were randomized to the intervention arm, in which investigators informed treating psychiatrists of the PTC results. The clinicians were instructed to change to another antidepressant if the biomarker predicted nonresponse or stay the course if the PTC results were favorable. Polysomnography was repeated 1 week later in the intervention arm, and the second-line antidepressant was either continued or switched out depending on the PTC findings. In the control arm, psychiatrists weren’t informed of the PTC results and patients continued on their initial antidepressant. The intervention and control groups were comparable in terms of age, sex, and severity of depression, with an average baseline HAMD score of 22.
A treatment response was defined as at least a 50% reduction in HAMD score from baseline to week 5. About 86% of patients who switched antidepressants based upon their 1-week quantitative EEG findings were categorized as treatment responders at week 5, compared with 20% of controls.
The overall 5-week response rate in the intervention group was 73%, compared with 60% in the control arm. This favorable trend didn’t achieve statistical significance, presumably because of the study’s sample size; however, the study is continuing to enroll participants in order to achieve a definitive result.
Dr. Mikoteit noted that the cost and inconvenience of spending a night in a sleep laboratory would be worthwhile if it resulted in the ability to give effective treatment much sooner. This would be particularly advantageous in patients at increased risk for suicide.
he said.
Study could have “enormous implications”
Of note, in the landmark National Institute of Mental Health–sponsored Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, slightly less than half of patients with major depressive disorder achieved a treatment response to their first-line antidepressant, and it took an average of 6 weeks of therapy to do. About one in four nonresponders who chose to switch to a different antidepressant got better.
“The STAR*D trial is still the gold standard for understanding antidepressant response, and so being able to see if an antidepressant works within 1 week would be a real breakthrough,” Catherine Harmer, DPhil, said in an interview.
“Most of the time, patients need to wait for around 4 weeks before they can tell if they are responding to a particular antidepressant or not. This is a hugely disabling and lengthy process, and often a different treatment then needs to be started,” added Dr. Harmer, professor of cognitive neuroscience and director of the Psychopharmacology and Emotional Research Lab at the University of Oxford (England).
“If the study results presented by Dr. Mikoteit are replicated in a larger blinded study, then it would have enormous implications for the future treatment of individuals with depression,” according to Dr. Harmer, who was not involved in the study and has no conflicts of interest related to it.
Dr. Mikoteit reported having no financial conflicts regarding the study, funded by the Psychiatric University Hospital of Basel.
SOURCE: Mikoteit T et al. ECNP 2020, Abstract P.733.
FROM ECNP 2020
App for MS aims to capture elusive signals of progression
At the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020, researchers at the University Hospital and University of Basel in Switzerland, presented data on their dreaMS app. The investigators are validating the app in a nonblinded cohort of 30 people with MS in the early to middle stages of progression and 30 controls without MS.
The application comprises a series of active tests measuring movement, fine motor skills, cognition, and vision, as well as questionnaires to assess quality of life, walking ability, and fatigue in people with Expanded Disability Status Scale (EDSS) scores of 6.5 or lower. A wrist device, used concurrently with the app, passively monitors subjects’ step count, heart rate, and different measures of activity.
If validated, such smartphone-based “digital biomarkers” will provide clinicians and investigators with a steadier flow of information for assessing MS disease progression and informing clinical decision-making. In June, Ludwig Kappos, MD, the app study’s senior researcher, co-authored an analysis of randomized trial data that argued for discarding the standard categories of relapsing and progressive MS in favor of seeing the disease as a continuum, in which progression can and does occur in the absence of relapses.
The digital biomarker work builds on that more unified view of the disease, Dr. Kappos said in an interview.
Outside of disease exacerbations or relapses, “progression can be very difficult to capture, especially in the first stage of the disease because of compensation in the central nervous system,” he said. “Our ability to see these very slight changes during a neurological examination is limited even if we do it very thoroughly. But by having these more frequent assessments we may be able to.”
Smartphone-gleaned biomarkers may have implications for prognosis and for choice of therapy, Dr. Kappos added. “We expect that these digital biomarkers will be even more sensitive and to be able to recognize before severe deficits are evident who is a candidate for a more intensive treatment and who is not.”
At the MSVirtual2020 congress, Dr. Kappos’s colleagues at the university Johannes Lorscheider, MD, and Yvonne Naegelin, MD, presented their feasibility and acceptance study currently underway in 60 volunteers. One of the concerns the investigators have had was whether engaged users would remain with the app. “We have designed the tests as little challenges to help keep people interested—we want to make these tests as appealing as possible,” Dr. Kappos said.
In this study, the reliability of each test is determined by intra-class correlation and median coefficient of variation. Preliminary reliability testing with healthy controls showed intra-class correlation coefficients of greater than 60% for the digital biomarkers and greater than 80% for at least one in every domain.
Once the best tests are selected and the app is fine-tuned, the group intends to embark on larger studies of the digital biomarkers. The next, planned for 2021, will recruit approximately 400 patients from the Swiss MS cohort, whose 1,000-some MS participants are followed with standardized examination and imaging protocols across healthcare centers.
“This is a very well characterized group of patients who are followed continuously with state-of-the-art neurological examinations, high-end MRI, and blood biomarkers,” Dr. Kappos said. “We want to see if we can add value by using digital biomarkers.”
The dreaMS app project is an independent investigator-initiated venture in cooperation with a technological partner. The study was supported by the Swiss Innovation Agency. The University Hospital Basel has received research funding for clinical trials from a number of pharmaceutical manufacturers.
SOURCE: Lorscheider J, et al. MSVirtual2020. Abstract P0069.
At the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020, researchers at the University Hospital and University of Basel in Switzerland, presented data on their dreaMS app. The investigators are validating the app in a nonblinded cohort of 30 people with MS in the early to middle stages of progression and 30 controls without MS.
The application comprises a series of active tests measuring movement, fine motor skills, cognition, and vision, as well as questionnaires to assess quality of life, walking ability, and fatigue in people with Expanded Disability Status Scale (EDSS) scores of 6.5 or lower. A wrist device, used concurrently with the app, passively monitors subjects’ step count, heart rate, and different measures of activity.
If validated, such smartphone-based “digital biomarkers” will provide clinicians and investigators with a steadier flow of information for assessing MS disease progression and informing clinical decision-making. In June, Ludwig Kappos, MD, the app study’s senior researcher, co-authored an analysis of randomized trial data that argued for discarding the standard categories of relapsing and progressive MS in favor of seeing the disease as a continuum, in which progression can and does occur in the absence of relapses.
The digital biomarker work builds on that more unified view of the disease, Dr. Kappos said in an interview.
Outside of disease exacerbations or relapses, “progression can be very difficult to capture, especially in the first stage of the disease because of compensation in the central nervous system,” he said. “Our ability to see these very slight changes during a neurological examination is limited even if we do it very thoroughly. But by having these more frequent assessments we may be able to.”
Smartphone-gleaned biomarkers may have implications for prognosis and for choice of therapy, Dr. Kappos added. “We expect that these digital biomarkers will be even more sensitive and to be able to recognize before severe deficits are evident who is a candidate for a more intensive treatment and who is not.”
At the MSVirtual2020 congress, Dr. Kappos’s colleagues at the university Johannes Lorscheider, MD, and Yvonne Naegelin, MD, presented their feasibility and acceptance study currently underway in 60 volunteers. One of the concerns the investigators have had was whether engaged users would remain with the app. “We have designed the tests as little challenges to help keep people interested—we want to make these tests as appealing as possible,” Dr. Kappos said.
In this study, the reliability of each test is determined by intra-class correlation and median coefficient of variation. Preliminary reliability testing with healthy controls showed intra-class correlation coefficients of greater than 60% for the digital biomarkers and greater than 80% for at least one in every domain.
Once the best tests are selected and the app is fine-tuned, the group intends to embark on larger studies of the digital biomarkers. The next, planned for 2021, will recruit approximately 400 patients from the Swiss MS cohort, whose 1,000-some MS participants are followed with standardized examination and imaging protocols across healthcare centers.
“This is a very well characterized group of patients who are followed continuously with state-of-the-art neurological examinations, high-end MRI, and blood biomarkers,” Dr. Kappos said. “We want to see if we can add value by using digital biomarkers.”
The dreaMS app project is an independent investigator-initiated venture in cooperation with a technological partner. The study was supported by the Swiss Innovation Agency. The University Hospital Basel has received research funding for clinical trials from a number of pharmaceutical manufacturers.
SOURCE: Lorscheider J, et al. MSVirtual2020. Abstract P0069.
At the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020, researchers at the University Hospital and University of Basel in Switzerland, presented data on their dreaMS app. The investigators are validating the app in a nonblinded cohort of 30 people with MS in the early to middle stages of progression and 30 controls without MS.
The application comprises a series of active tests measuring movement, fine motor skills, cognition, and vision, as well as questionnaires to assess quality of life, walking ability, and fatigue in people with Expanded Disability Status Scale (EDSS) scores of 6.5 or lower. A wrist device, used concurrently with the app, passively monitors subjects’ step count, heart rate, and different measures of activity.
If validated, such smartphone-based “digital biomarkers” will provide clinicians and investigators with a steadier flow of information for assessing MS disease progression and informing clinical decision-making. In June, Ludwig Kappos, MD, the app study’s senior researcher, co-authored an analysis of randomized trial data that argued for discarding the standard categories of relapsing and progressive MS in favor of seeing the disease as a continuum, in which progression can and does occur in the absence of relapses.
The digital biomarker work builds on that more unified view of the disease, Dr. Kappos said in an interview.
Outside of disease exacerbations or relapses, “progression can be very difficult to capture, especially in the first stage of the disease because of compensation in the central nervous system,” he said. “Our ability to see these very slight changes during a neurological examination is limited even if we do it very thoroughly. But by having these more frequent assessments we may be able to.”
Smartphone-gleaned biomarkers may have implications for prognosis and for choice of therapy, Dr. Kappos added. “We expect that these digital biomarkers will be even more sensitive and to be able to recognize before severe deficits are evident who is a candidate for a more intensive treatment and who is not.”
At the MSVirtual2020 congress, Dr. Kappos’s colleagues at the university Johannes Lorscheider, MD, and Yvonne Naegelin, MD, presented their feasibility and acceptance study currently underway in 60 volunteers. One of the concerns the investigators have had was whether engaged users would remain with the app. “We have designed the tests as little challenges to help keep people interested—we want to make these tests as appealing as possible,” Dr. Kappos said.
In this study, the reliability of each test is determined by intra-class correlation and median coefficient of variation. Preliminary reliability testing with healthy controls showed intra-class correlation coefficients of greater than 60% for the digital biomarkers and greater than 80% for at least one in every domain.
Once the best tests are selected and the app is fine-tuned, the group intends to embark on larger studies of the digital biomarkers. The next, planned for 2021, will recruit approximately 400 patients from the Swiss MS cohort, whose 1,000-some MS participants are followed with standardized examination and imaging protocols across healthcare centers.
“This is a very well characterized group of patients who are followed continuously with state-of-the-art neurological examinations, high-end MRI, and blood biomarkers,” Dr. Kappos said. “We want to see if we can add value by using digital biomarkers.”
The dreaMS app project is an independent investigator-initiated venture in cooperation with a technological partner. The study was supported by the Swiss Innovation Agency. The University Hospital Basel has received research funding for clinical trials from a number of pharmaceutical manufacturers.
SOURCE: Lorscheider J, et al. MSVirtual2020. Abstract P0069.
FROM MSVirtual2020
Satralizumab reduces risk of severe NMOSD relapse
(NMOSD), according to investigators. The drug also was associated with a lower likelihood of using acute relapse therapy.
These results were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
NMOSD is characterized by acute relapses that are unpredictable and lead to the accumulation of disability. “Patients with NMOSD often recover poorly from relapses, therefore, the primary goal for disease management is to reduce attack frequency,” said Ingo Kleiter, MD, medical director of Marianne-Strauß-Klinik in Berg, Germany. “In the two phase 3 trials SAkuraSky and SAkuraStar, the IL-6 receptor inhibitor satralizumab was found to significantly reduce the risk of relapses versus placebo.” Satralizumab is a humanized, monoclonal, recycling antibody that targets the interleukin-6 receptor.
Dr. Kleiter and colleagues examined pooled data from the two phase 3 trials of satralizumab to determine the treatment’s effect on relapse severity in patients with NMOSD. Participants in those trials received placebo or 120 mg of satralizumab at weeks 0, 2, 4, and every 4 weeks thereafter.
For their research, the investigators analyzed data from the pooled intention-to-treat population in the double-blind periods of both studies. To evaluate the severity of protocol-defined relapses, they compared patients’ Expanded Disability Status Scale (EDSS) scores at the time of relapse with their scores before the relapse (i.e., their scores at the last scheduled study visit). Using the visual Functional Systems Score (FSS), Dr. Kleiter and colleagues performed a similar analysis on optic neuritis relapses. They categorized a protocol-defined relapse as severe if it entailed a change of two or more points on the EDSS or visual FSS. The investigators conducted Kaplan-Meier analyses to evaluate the time to first severe protocol-defined relapse. They also compared the number of patients receiving acute therapy for any relapse between treatment groups.
Safety profile confirmed
Dr. Kleiter and colleagues included 178 patients in their analyses. A total of 27 of 104 patients (26%) who received satralizumab had a protocol-defined relapse, compared with 34 of 74 patients (46%) who received placebo. The number and proportion of severe protocol-defined relapses were lower in the satralizumab group (5 of 27 events [19%]), compared with the placebo group (12 of 34 events [35%]). In addition, the number and proportion of severe protocol-defined optic neuritis relapses were lower in patients receiving satralizumab (2 of 8 events [25%]), compared with those receiving placebo (5 of 13 events [39%]). Compared with placebo, satralizumab was associated with a 79% reduction in the risk of severe protocol-defined relapse (hazard ratio, 0.21).
A lower proportion of patients receiving satralizumab was prescribed acute relapse therapy (38%), compared with patients receiving placebo (58%). The odds ratio of receiving a prescription of acute relapse therapy was 0.46 among patients receiving satralizumab.
The activity of IL-6 may cause neurologic damage in patients with NMOSD through astrocytic damage, disruption of the blood–brain barrier, and T cell polarization. “It is proposed that through inhibiting IL-6 across these multiple mechanisms, satralizumab reduces the risk and severity of NMOSD attacks,” Dr. Kleiter said.
To date, the rates of infection and serious infection for patients treated with satralizumab in the combined double-blind and open-label extension periods have been consistent with those for patients treated with satralizumab in the double-blind portion. These rates have not increased over time. Satralizumab is administered as a subcutaneous injection every 4 weeks, and treatment can be self-administered at the discretion of the managing physician. “These data provide reassurance to physicians about the overall profile of satralizumab, with respect to efficacy and safety in the longer term,” said Dr. Kleiter.
Does satralizumab differ from other new agents?
The main strength of the study is that sufficient numbers of relapses were available for analysis in the active and control groups, said Achim Berthele, MD, associate professor of neurology at the Technical University of Munich. This allowed the researchers to examine whether satralizumab led to a better outcome after each relapse, which it did. “A weakness is how the severity of relapses was quantified,” said Dr. Berthele. “The EDSS as a measure is not linear, and its functional systems are not clinically equivalent. However, the whole NMOSD community is struggling with this problem.”
The study’s implications for neurologists’ clinical practice are unclear, however. “Although the results presented are encouraging, the data are still too small to say with certainty that satralizumab does indeed improve the outcome of relapses,” said Dr. Berthele. “It is also an open question whether satralizumab differs in this respect from the other new immunotherapeutic agents.”
Investigators must collect further data on the outcome of relapses that occur during treatment with modern immunomodulatory therapy, Dr. Berthele added. Future research could examine whether the new anti-inflammatory immunotherapeutic agents also are suitable drugs for relapse therapy. Another salient question is whether clinical vigilance or relapse therapy in NMOSD has improved in general. “This is what Kleiter and colleagues show as well: The number of severe relapses under placebo was much lower than expected,” said Dr. Berthele.
Chugai/Roche funded the study. Dr. Kleiter has received compensation for consulting, speaking, or serving on advisory boards for Alexion, Biogen, Celgene, Merck, and Roche. Dr. Berthele was not involved in any of the satralizumab trials, but is an investigator and coauthor of the PREVENT trial of eculizumab.
SOURCE: Kleiter I, et al. MSVirtual2020. Abstract FC01.03.
(NMOSD), according to investigators. The drug also was associated with a lower likelihood of using acute relapse therapy.
These results were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
NMOSD is characterized by acute relapses that are unpredictable and lead to the accumulation of disability. “Patients with NMOSD often recover poorly from relapses, therefore, the primary goal for disease management is to reduce attack frequency,” said Ingo Kleiter, MD, medical director of Marianne-Strauß-Klinik in Berg, Germany. “In the two phase 3 trials SAkuraSky and SAkuraStar, the IL-6 receptor inhibitor satralizumab was found to significantly reduce the risk of relapses versus placebo.” Satralizumab is a humanized, monoclonal, recycling antibody that targets the interleukin-6 receptor.
Dr. Kleiter and colleagues examined pooled data from the two phase 3 trials of satralizumab to determine the treatment’s effect on relapse severity in patients with NMOSD. Participants in those trials received placebo or 120 mg of satralizumab at weeks 0, 2, 4, and every 4 weeks thereafter.
For their research, the investigators analyzed data from the pooled intention-to-treat population in the double-blind periods of both studies. To evaluate the severity of protocol-defined relapses, they compared patients’ Expanded Disability Status Scale (EDSS) scores at the time of relapse with their scores before the relapse (i.e., their scores at the last scheduled study visit). Using the visual Functional Systems Score (FSS), Dr. Kleiter and colleagues performed a similar analysis on optic neuritis relapses. They categorized a protocol-defined relapse as severe if it entailed a change of two or more points on the EDSS or visual FSS. The investigators conducted Kaplan-Meier analyses to evaluate the time to first severe protocol-defined relapse. They also compared the number of patients receiving acute therapy for any relapse between treatment groups.
Safety profile confirmed
Dr. Kleiter and colleagues included 178 patients in their analyses. A total of 27 of 104 patients (26%) who received satralizumab had a protocol-defined relapse, compared with 34 of 74 patients (46%) who received placebo. The number and proportion of severe protocol-defined relapses were lower in the satralizumab group (5 of 27 events [19%]), compared with the placebo group (12 of 34 events [35%]). In addition, the number and proportion of severe protocol-defined optic neuritis relapses were lower in patients receiving satralizumab (2 of 8 events [25%]), compared with those receiving placebo (5 of 13 events [39%]). Compared with placebo, satralizumab was associated with a 79% reduction in the risk of severe protocol-defined relapse (hazard ratio, 0.21).
A lower proportion of patients receiving satralizumab was prescribed acute relapse therapy (38%), compared with patients receiving placebo (58%). The odds ratio of receiving a prescription of acute relapse therapy was 0.46 among patients receiving satralizumab.
The activity of IL-6 may cause neurologic damage in patients with NMOSD through astrocytic damage, disruption of the blood–brain barrier, and T cell polarization. “It is proposed that through inhibiting IL-6 across these multiple mechanisms, satralizumab reduces the risk and severity of NMOSD attacks,” Dr. Kleiter said.
To date, the rates of infection and serious infection for patients treated with satralizumab in the combined double-blind and open-label extension periods have been consistent with those for patients treated with satralizumab in the double-blind portion. These rates have not increased over time. Satralizumab is administered as a subcutaneous injection every 4 weeks, and treatment can be self-administered at the discretion of the managing physician. “These data provide reassurance to physicians about the overall profile of satralizumab, with respect to efficacy and safety in the longer term,” said Dr. Kleiter.
Does satralizumab differ from other new agents?
The main strength of the study is that sufficient numbers of relapses were available for analysis in the active and control groups, said Achim Berthele, MD, associate professor of neurology at the Technical University of Munich. This allowed the researchers to examine whether satralizumab led to a better outcome after each relapse, which it did. “A weakness is how the severity of relapses was quantified,” said Dr. Berthele. “The EDSS as a measure is not linear, and its functional systems are not clinically equivalent. However, the whole NMOSD community is struggling with this problem.”
The study’s implications for neurologists’ clinical practice are unclear, however. “Although the results presented are encouraging, the data are still too small to say with certainty that satralizumab does indeed improve the outcome of relapses,” said Dr. Berthele. “It is also an open question whether satralizumab differs in this respect from the other new immunotherapeutic agents.”
Investigators must collect further data on the outcome of relapses that occur during treatment with modern immunomodulatory therapy, Dr. Berthele added. Future research could examine whether the new anti-inflammatory immunotherapeutic agents also are suitable drugs for relapse therapy. Another salient question is whether clinical vigilance or relapse therapy in NMOSD has improved in general. “This is what Kleiter and colleagues show as well: The number of severe relapses under placebo was much lower than expected,” said Dr. Berthele.
Chugai/Roche funded the study. Dr. Kleiter has received compensation for consulting, speaking, or serving on advisory boards for Alexion, Biogen, Celgene, Merck, and Roche. Dr. Berthele was not involved in any of the satralizumab trials, but is an investigator and coauthor of the PREVENT trial of eculizumab.
SOURCE: Kleiter I, et al. MSVirtual2020. Abstract FC01.03.
(NMOSD), according to investigators. The drug also was associated with a lower likelihood of using acute relapse therapy.
These results were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
NMOSD is characterized by acute relapses that are unpredictable and lead to the accumulation of disability. “Patients with NMOSD often recover poorly from relapses, therefore, the primary goal for disease management is to reduce attack frequency,” said Ingo Kleiter, MD, medical director of Marianne-Strauß-Klinik in Berg, Germany. “In the two phase 3 trials SAkuraSky and SAkuraStar, the IL-6 receptor inhibitor satralizumab was found to significantly reduce the risk of relapses versus placebo.” Satralizumab is a humanized, monoclonal, recycling antibody that targets the interleukin-6 receptor.
Dr. Kleiter and colleagues examined pooled data from the two phase 3 trials of satralizumab to determine the treatment’s effect on relapse severity in patients with NMOSD. Participants in those trials received placebo or 120 mg of satralizumab at weeks 0, 2, 4, and every 4 weeks thereafter.
For their research, the investigators analyzed data from the pooled intention-to-treat population in the double-blind periods of both studies. To evaluate the severity of protocol-defined relapses, they compared patients’ Expanded Disability Status Scale (EDSS) scores at the time of relapse with their scores before the relapse (i.e., their scores at the last scheduled study visit). Using the visual Functional Systems Score (FSS), Dr. Kleiter and colleagues performed a similar analysis on optic neuritis relapses. They categorized a protocol-defined relapse as severe if it entailed a change of two or more points on the EDSS or visual FSS. The investigators conducted Kaplan-Meier analyses to evaluate the time to first severe protocol-defined relapse. They also compared the number of patients receiving acute therapy for any relapse between treatment groups.
Safety profile confirmed
Dr. Kleiter and colleagues included 178 patients in their analyses. A total of 27 of 104 patients (26%) who received satralizumab had a protocol-defined relapse, compared with 34 of 74 patients (46%) who received placebo. The number and proportion of severe protocol-defined relapses were lower in the satralizumab group (5 of 27 events [19%]), compared with the placebo group (12 of 34 events [35%]). In addition, the number and proportion of severe protocol-defined optic neuritis relapses were lower in patients receiving satralizumab (2 of 8 events [25%]), compared with those receiving placebo (5 of 13 events [39%]). Compared with placebo, satralizumab was associated with a 79% reduction in the risk of severe protocol-defined relapse (hazard ratio, 0.21).
A lower proportion of patients receiving satralizumab was prescribed acute relapse therapy (38%), compared with patients receiving placebo (58%). The odds ratio of receiving a prescription of acute relapse therapy was 0.46 among patients receiving satralizumab.
The activity of IL-6 may cause neurologic damage in patients with NMOSD through astrocytic damage, disruption of the blood–brain barrier, and T cell polarization. “It is proposed that through inhibiting IL-6 across these multiple mechanisms, satralizumab reduces the risk and severity of NMOSD attacks,” Dr. Kleiter said.
To date, the rates of infection and serious infection for patients treated with satralizumab in the combined double-blind and open-label extension periods have been consistent with those for patients treated with satralizumab in the double-blind portion. These rates have not increased over time. Satralizumab is administered as a subcutaneous injection every 4 weeks, and treatment can be self-administered at the discretion of the managing physician. “These data provide reassurance to physicians about the overall profile of satralizumab, with respect to efficacy and safety in the longer term,” said Dr. Kleiter.
Does satralizumab differ from other new agents?
The main strength of the study is that sufficient numbers of relapses were available for analysis in the active and control groups, said Achim Berthele, MD, associate professor of neurology at the Technical University of Munich. This allowed the researchers to examine whether satralizumab led to a better outcome after each relapse, which it did. “A weakness is how the severity of relapses was quantified,” said Dr. Berthele. “The EDSS as a measure is not linear, and its functional systems are not clinically equivalent. However, the whole NMOSD community is struggling with this problem.”
The study’s implications for neurologists’ clinical practice are unclear, however. “Although the results presented are encouraging, the data are still too small to say with certainty that satralizumab does indeed improve the outcome of relapses,” said Dr. Berthele. “It is also an open question whether satralizumab differs in this respect from the other new immunotherapeutic agents.”
Investigators must collect further data on the outcome of relapses that occur during treatment with modern immunomodulatory therapy, Dr. Berthele added. Future research could examine whether the new anti-inflammatory immunotherapeutic agents also are suitable drugs for relapse therapy. Another salient question is whether clinical vigilance or relapse therapy in NMOSD has improved in general. “This is what Kleiter and colleagues show as well: The number of severe relapses under placebo was much lower than expected,” said Dr. Berthele.
Chugai/Roche funded the study. Dr. Kleiter has received compensation for consulting, speaking, or serving on advisory boards for Alexion, Biogen, Celgene, Merck, and Roche. Dr. Berthele was not involved in any of the satralizumab trials, but is an investigator and coauthor of the PREVENT trial of eculizumab.
SOURCE: Kleiter I, et al. MSVirtual2020. Abstract FC01.03.
FROM MSVirtual2020
Cardiovascular risk factors linked to brain atrophy in MS
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
FROM MSVirtual2020
Lessons for patients with MS and COVID-19
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
FROM MSVirtual2020
Exposure to DMT may delay disability accumulation in primary progressive MS
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
FROM MSVirtual 2020
New billing code for added COVID practice expense
The American Medical Association on Sept. 8 announced that a new code, 99072, is intended to cover additional supplies, materials, and clinical staff time over and above those usually included in an office visit when performed during a declared public health emergency, as defined by law, attributable to respiratory-transmitted infectious disease, the AMA said in a release.
Fifty national medical specialty societies and other organizations worked with the AMA’s Specialty Society RVS Update Committee over the summer to collect data on the costs of maintaining safe medical offices during the public health emergency. It has submitted recommendations to the Centers for Medicare & Medicaid Services seeking to persuade the federal agencies to recognize the new 99072 payment code.
The intention is to recognize the extra expenses involved in steps now routinely taken to reduce the risk for COVID transmission from office visits, Current Procedural Terminology Editorial Panel Chair Mark S. Synovec, MD, said in an interview. Some practices have adapted by having staff screen patients before they enter offices and making arrangements to keep patients at a safe distance from others during their visits, he said.
“Everyone’s life has significantly changed because of COVID and the health care system has dramatically changed,” Dr. Synovec said. “It was pretty clear that the status quo was not going to work.”
Physician practices will welcome this change, said Veronica Bradley, CPC, a senior industry adviser to the Medical Group Management Association. An office visit that in the past may have involved only basic infection control measures, such as donning a pair of gloves, now may involve clinicians taking the time to put on more extensive protective gear, she said.
“Now they are taking a heck of a lot more precautions, and there’s more time and more supplies being consumed,” Ms. Bradley said in an interview.
Code looks ahead to future use
The AMA explained how this new code differs from CPT code 99070, which is typically reported for supplies and materials that may be used or provided to patients during an office visit.
The new 99072 code applies only during declared public health emergencies and applies only to additional items required to support “a safe in-person provision” of evaluation, treatment, and procedures, the AMA said.
“These items contrast with those typically reported with code 99070, which focuses on additional supplies provided over and above those usually included with a specific service, such as drugs, intravenous catheters, or trays,” the AMA said.
The CPT panel sought to structure the new code for covering COVID practice expenses so that it could not be abused, and also looked ahead to the future, Dr. Synovec said.
“It’s a code that you would put on during a public health emergency as defined by law that would be related to a respiratory-transmitted infectious disease. Obviously we meant it for SARS-CoV-2,” he said. “Hopefully we can go another 100 years before we have another pandemic, but we also wanted to prepare something where if we have another airborne respiratory virus that requires additional practice expenses as seen this time, it would be available for use.”
The AMA also announced a second addition, CPT code 86413, that anticipates greater use of quantitative measurements of SARS-CoV-2 antibodies, as opposed to a qualitative assessment (positive/negative) provided by laboratory tests reported by other CPT codes.
More information is available on the AMA website.
A version of this article originally appeared on Medscape.com.
The American Medical Association on Sept. 8 announced that a new code, 99072, is intended to cover additional supplies, materials, and clinical staff time over and above those usually included in an office visit when performed during a declared public health emergency, as defined by law, attributable to respiratory-transmitted infectious disease, the AMA said in a release.
Fifty national medical specialty societies and other organizations worked with the AMA’s Specialty Society RVS Update Committee over the summer to collect data on the costs of maintaining safe medical offices during the public health emergency. It has submitted recommendations to the Centers for Medicare & Medicaid Services seeking to persuade the federal agencies to recognize the new 99072 payment code.
The intention is to recognize the extra expenses involved in steps now routinely taken to reduce the risk for COVID transmission from office visits, Current Procedural Terminology Editorial Panel Chair Mark S. Synovec, MD, said in an interview. Some practices have adapted by having staff screen patients before they enter offices and making arrangements to keep patients at a safe distance from others during their visits, he said.
“Everyone’s life has significantly changed because of COVID and the health care system has dramatically changed,” Dr. Synovec said. “It was pretty clear that the status quo was not going to work.”
Physician practices will welcome this change, said Veronica Bradley, CPC, a senior industry adviser to the Medical Group Management Association. An office visit that in the past may have involved only basic infection control measures, such as donning a pair of gloves, now may involve clinicians taking the time to put on more extensive protective gear, she said.
“Now they are taking a heck of a lot more precautions, and there’s more time and more supplies being consumed,” Ms. Bradley said in an interview.
Code looks ahead to future use
The AMA explained how this new code differs from CPT code 99070, which is typically reported for supplies and materials that may be used or provided to patients during an office visit.
The new 99072 code applies only during declared public health emergencies and applies only to additional items required to support “a safe in-person provision” of evaluation, treatment, and procedures, the AMA said.
“These items contrast with those typically reported with code 99070, which focuses on additional supplies provided over and above those usually included with a specific service, such as drugs, intravenous catheters, or trays,” the AMA said.
The CPT panel sought to structure the new code for covering COVID practice expenses so that it could not be abused, and also looked ahead to the future, Dr. Synovec said.
“It’s a code that you would put on during a public health emergency as defined by law that would be related to a respiratory-transmitted infectious disease. Obviously we meant it for SARS-CoV-2,” he said. “Hopefully we can go another 100 years before we have another pandemic, but we also wanted to prepare something where if we have another airborne respiratory virus that requires additional practice expenses as seen this time, it would be available for use.”
The AMA also announced a second addition, CPT code 86413, that anticipates greater use of quantitative measurements of SARS-CoV-2 antibodies, as opposed to a qualitative assessment (positive/negative) provided by laboratory tests reported by other CPT codes.
More information is available on the AMA website.
A version of this article originally appeared on Medscape.com.
The American Medical Association on Sept. 8 announced that a new code, 99072, is intended to cover additional supplies, materials, and clinical staff time over and above those usually included in an office visit when performed during a declared public health emergency, as defined by law, attributable to respiratory-transmitted infectious disease, the AMA said in a release.
Fifty national medical specialty societies and other organizations worked with the AMA’s Specialty Society RVS Update Committee over the summer to collect data on the costs of maintaining safe medical offices during the public health emergency. It has submitted recommendations to the Centers for Medicare & Medicaid Services seeking to persuade the federal agencies to recognize the new 99072 payment code.
The intention is to recognize the extra expenses involved in steps now routinely taken to reduce the risk for COVID transmission from office visits, Current Procedural Terminology Editorial Panel Chair Mark S. Synovec, MD, said in an interview. Some practices have adapted by having staff screen patients before they enter offices and making arrangements to keep patients at a safe distance from others during their visits, he said.
“Everyone’s life has significantly changed because of COVID and the health care system has dramatically changed,” Dr. Synovec said. “It was pretty clear that the status quo was not going to work.”
Physician practices will welcome this change, said Veronica Bradley, CPC, a senior industry adviser to the Medical Group Management Association. An office visit that in the past may have involved only basic infection control measures, such as donning a pair of gloves, now may involve clinicians taking the time to put on more extensive protective gear, she said.
“Now they are taking a heck of a lot more precautions, and there’s more time and more supplies being consumed,” Ms. Bradley said in an interview.
Code looks ahead to future use
The AMA explained how this new code differs from CPT code 99070, which is typically reported for supplies and materials that may be used or provided to patients during an office visit.
The new 99072 code applies only during declared public health emergencies and applies only to additional items required to support “a safe in-person provision” of evaluation, treatment, and procedures, the AMA said.
“These items contrast with those typically reported with code 99070, which focuses on additional supplies provided over and above those usually included with a specific service, such as drugs, intravenous catheters, or trays,” the AMA said.
The CPT panel sought to structure the new code for covering COVID practice expenses so that it could not be abused, and also looked ahead to the future, Dr. Synovec said.
“It’s a code that you would put on during a public health emergency as defined by law that would be related to a respiratory-transmitted infectious disease. Obviously we meant it for SARS-CoV-2,” he said. “Hopefully we can go another 100 years before we have another pandemic, but we also wanted to prepare something where if we have another airborne respiratory virus that requires additional practice expenses as seen this time, it would be available for use.”
The AMA also announced a second addition, CPT code 86413, that anticipates greater use of quantitative measurements of SARS-CoV-2 antibodies, as opposed to a qualitative assessment (positive/negative) provided by laboratory tests reported by other CPT codes.
More information is available on the AMA website.
A version of this article originally appeared on Medscape.com.
In MS, serious adverse effects are more common in rituximab versus ocrelizumab
, a new postmarketing analysis finds, and AE-related deaths were not unusual. Serious AEs, and those linked to death, were more common in the rituximab group, although the reported infection rate was higher in the ocrelizumab group.
The analysis, published Aug. 21 in the Multiple Sclerosis Journal, highlights the importance of monitoring patients for infections and encouraging them to do the same, the authors said.
“This report points out the impact of treatments in terms of unrecognized or underappreciated complications,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y., who reviewed the study findings. “These medications have a significant downside.”
Lead author Natalia Gonzalez Caldito, MD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues analyzed AEs for the drugs in the Food and Drug Administration’s Adverse Event Reporting System. They only included cases in which the drugs were solely used to treat MS and were indicated as the cause of the AEs.
Rituximab (Rituxan) and ocrelizumab (Ocrevus) are both monoclonal antibodies. Rituximab is not FDA approved for MS but is used off label; ocrelizumab is approved for the relapsing forms of MS and primary progressive MS.
The researchers found 623 AE reports and 1,466 total AEs for rituximab and 7,948 and 23,613, respectively, for ocrelizumab. The average ages for the groups were 48.76 versus 43.89, respectively, (P < .001), and 71% in each group were women.
Among total AEs, serious AEs were more common in the rituximab group versus the ocrelizumab group (64.8% vs. 56.3%, respectively, P < .001). Adverse events that caused death were also more common in the rituximab group versus the ocrelizumab group (5.75% vs. 2.11%, P < .001).
Infections and infestations were more common in the ocrelizumab group than the rituximab group (21.93% vs. 11.05%, respectively, P < .001). However, certain AEs were more common in the rituximab group than the ocrelizumab group: Those in the blood and lymphatic system category (2.86% vs. 0.91%, respectively, P < .001), and those in the neoplasms category (4.02% vs. 1.28%, P < .001, respectively).
Researchers found a highly strong association between rituximab and a rare side effects – ear pruritus (itching, 0.8%). They also identified signals for infusion-related reaction (4.82%), throat irritation (4.01%) and throat tightness (1.44%), malignant melanoma (0.8%), breast cancer (1.77%) and neutropenia (2.57%).
Among the ocrelizumab AEs, researchers found the strongest association with oral herpes (2.21%), and they found other signals for herpes zoster (2.89%), urinary tract infection (10.52%), nasopharyngitis (9.79%), infusion-related reaction (4.76%), throat irritation (3.08%), and notably MS relapses (4.1%).
“Additional pharmacovigilance studies are needed to explore and further characterize these findings,” the researchers wrote. “Furthermore, these observations suggest that the AE profile of other second-generation anti-CD20 [monoclonal antibodies] may also differ from those of rituximab and ocrelizumab.”
Dr. Gudesblatt praised the analysis and said the findings make sense. “Use of B-cell–depleting agents lead to accumulative immune deficiency in routine care, which leads to higher rates of infection,” he said. He added that, “in the clinical trials for ocrelizumab, patients with IgG and IgM deficiency were excluded, but there is no advisement to exclude such patients in real care. The rates of infection in those patients with MS who have preexisting immune deficiencies and who are treated with these agents are unknown.”
The prospect of AEs is especially worrisome, he said, since “this information is only short term. Who knows what effect the prolonged use of unopposed B-cell depletion will have on infections in the long run?”
Neurologist Mitchell Wallin, MD, MPH, of George Washington University, Washington, and the University of Maryland, Baltimore County, said in an interview that the analysis is rigorous and especially useful because it includes a wider array of subjects – including those who are older and sicker – than took part in earlier clinical trials. “It’s really important to look at this real-world evidence,” he said, “and basically put this in the back of your head when you follow up with your patients.”
No study funding was reported. The corresponding author reported various disclosures. Dr. Gudesblatt and Dr. Wallin reported no disclosures.
SOURCE: Gonzalez Caldito N et al. Mult Scler J. 2020 Aug 21. doi: 10.1177/1352458520949986.
, a new postmarketing analysis finds, and AE-related deaths were not unusual. Serious AEs, and those linked to death, were more common in the rituximab group, although the reported infection rate was higher in the ocrelizumab group.
The analysis, published Aug. 21 in the Multiple Sclerosis Journal, highlights the importance of monitoring patients for infections and encouraging them to do the same, the authors said.
“This report points out the impact of treatments in terms of unrecognized or underappreciated complications,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y., who reviewed the study findings. “These medications have a significant downside.”
Lead author Natalia Gonzalez Caldito, MD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues analyzed AEs for the drugs in the Food and Drug Administration’s Adverse Event Reporting System. They only included cases in which the drugs were solely used to treat MS and were indicated as the cause of the AEs.
Rituximab (Rituxan) and ocrelizumab (Ocrevus) are both monoclonal antibodies. Rituximab is not FDA approved for MS but is used off label; ocrelizumab is approved for the relapsing forms of MS and primary progressive MS.
The researchers found 623 AE reports and 1,466 total AEs for rituximab and 7,948 and 23,613, respectively, for ocrelizumab. The average ages for the groups were 48.76 versus 43.89, respectively, (P < .001), and 71% in each group were women.
Among total AEs, serious AEs were more common in the rituximab group versus the ocrelizumab group (64.8% vs. 56.3%, respectively, P < .001). Adverse events that caused death were also more common in the rituximab group versus the ocrelizumab group (5.75% vs. 2.11%, P < .001).
Infections and infestations were more common in the ocrelizumab group than the rituximab group (21.93% vs. 11.05%, respectively, P < .001). However, certain AEs were more common in the rituximab group than the ocrelizumab group: Those in the blood and lymphatic system category (2.86% vs. 0.91%, respectively, P < .001), and those in the neoplasms category (4.02% vs. 1.28%, P < .001, respectively).
Researchers found a highly strong association between rituximab and a rare side effects – ear pruritus (itching, 0.8%). They also identified signals for infusion-related reaction (4.82%), throat irritation (4.01%) and throat tightness (1.44%), malignant melanoma (0.8%), breast cancer (1.77%) and neutropenia (2.57%).
Among the ocrelizumab AEs, researchers found the strongest association with oral herpes (2.21%), and they found other signals for herpes zoster (2.89%), urinary tract infection (10.52%), nasopharyngitis (9.79%), infusion-related reaction (4.76%), throat irritation (3.08%), and notably MS relapses (4.1%).
“Additional pharmacovigilance studies are needed to explore and further characterize these findings,” the researchers wrote. “Furthermore, these observations suggest that the AE profile of other second-generation anti-CD20 [monoclonal antibodies] may also differ from those of rituximab and ocrelizumab.”
Dr. Gudesblatt praised the analysis and said the findings make sense. “Use of B-cell–depleting agents lead to accumulative immune deficiency in routine care, which leads to higher rates of infection,” he said. He added that, “in the clinical trials for ocrelizumab, patients with IgG and IgM deficiency were excluded, but there is no advisement to exclude such patients in real care. The rates of infection in those patients with MS who have preexisting immune deficiencies and who are treated with these agents are unknown.”
The prospect of AEs is especially worrisome, he said, since “this information is only short term. Who knows what effect the prolonged use of unopposed B-cell depletion will have on infections in the long run?”
Neurologist Mitchell Wallin, MD, MPH, of George Washington University, Washington, and the University of Maryland, Baltimore County, said in an interview that the analysis is rigorous and especially useful because it includes a wider array of subjects – including those who are older and sicker – than took part in earlier clinical trials. “It’s really important to look at this real-world evidence,” he said, “and basically put this in the back of your head when you follow up with your patients.”
No study funding was reported. The corresponding author reported various disclosures. Dr. Gudesblatt and Dr. Wallin reported no disclosures.
SOURCE: Gonzalez Caldito N et al. Mult Scler J. 2020 Aug 21. doi: 10.1177/1352458520949986.
, a new postmarketing analysis finds, and AE-related deaths were not unusual. Serious AEs, and those linked to death, were more common in the rituximab group, although the reported infection rate was higher in the ocrelizumab group.
The analysis, published Aug. 21 in the Multiple Sclerosis Journal, highlights the importance of monitoring patients for infections and encouraging them to do the same, the authors said.
“This report points out the impact of treatments in terms of unrecognized or underappreciated complications,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y., who reviewed the study findings. “These medications have a significant downside.”
Lead author Natalia Gonzalez Caldito, MD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues analyzed AEs for the drugs in the Food and Drug Administration’s Adverse Event Reporting System. They only included cases in which the drugs were solely used to treat MS and were indicated as the cause of the AEs.
Rituximab (Rituxan) and ocrelizumab (Ocrevus) are both monoclonal antibodies. Rituximab is not FDA approved for MS but is used off label; ocrelizumab is approved for the relapsing forms of MS and primary progressive MS.
The researchers found 623 AE reports and 1,466 total AEs for rituximab and 7,948 and 23,613, respectively, for ocrelizumab. The average ages for the groups were 48.76 versus 43.89, respectively, (P < .001), and 71% in each group were women.
Among total AEs, serious AEs were more common in the rituximab group versus the ocrelizumab group (64.8% vs. 56.3%, respectively, P < .001). Adverse events that caused death were also more common in the rituximab group versus the ocrelizumab group (5.75% vs. 2.11%, P < .001).
Infections and infestations were more common in the ocrelizumab group than the rituximab group (21.93% vs. 11.05%, respectively, P < .001). However, certain AEs were more common in the rituximab group than the ocrelizumab group: Those in the blood and lymphatic system category (2.86% vs. 0.91%, respectively, P < .001), and those in the neoplasms category (4.02% vs. 1.28%, P < .001, respectively).
Researchers found a highly strong association between rituximab and a rare side effects – ear pruritus (itching, 0.8%). They also identified signals for infusion-related reaction (4.82%), throat irritation (4.01%) and throat tightness (1.44%), malignant melanoma (0.8%), breast cancer (1.77%) and neutropenia (2.57%).
Among the ocrelizumab AEs, researchers found the strongest association with oral herpes (2.21%), and they found other signals for herpes zoster (2.89%), urinary tract infection (10.52%), nasopharyngitis (9.79%), infusion-related reaction (4.76%), throat irritation (3.08%), and notably MS relapses (4.1%).
“Additional pharmacovigilance studies are needed to explore and further characterize these findings,” the researchers wrote. “Furthermore, these observations suggest that the AE profile of other second-generation anti-CD20 [monoclonal antibodies] may also differ from those of rituximab and ocrelizumab.”
Dr. Gudesblatt praised the analysis and said the findings make sense. “Use of B-cell–depleting agents lead to accumulative immune deficiency in routine care, which leads to higher rates of infection,” he said. He added that, “in the clinical trials for ocrelizumab, patients with IgG and IgM deficiency were excluded, but there is no advisement to exclude such patients in real care. The rates of infection in those patients with MS who have preexisting immune deficiencies and who are treated with these agents are unknown.”
The prospect of AEs is especially worrisome, he said, since “this information is only short term. Who knows what effect the prolonged use of unopposed B-cell depletion will have on infections in the long run?”
Neurologist Mitchell Wallin, MD, MPH, of George Washington University, Washington, and the University of Maryland, Baltimore County, said in an interview that the analysis is rigorous and especially useful because it includes a wider array of subjects – including those who are older and sicker – than took part in earlier clinical trials. “It’s really important to look at this real-world evidence,” he said, “and basically put this in the back of your head when you follow up with your patients.”
No study funding was reported. The corresponding author reported various disclosures. Dr. Gudesblatt and Dr. Wallin reported no disclosures.
SOURCE: Gonzalez Caldito N et al. Mult Scler J. 2020 Aug 21. doi: 10.1177/1352458520949986.
FROM MULTIPLE SCLEROSIS JOURNAL