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Sleep apnea may correlate with anxiety, depression in patients with PCOS
a study suggests.
This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.
“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”
Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.
OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.
PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
A cross-sectional study
To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.
Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.
The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.
Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.
On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).
The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).
In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.
In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.
Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
Various possible links
Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.
The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.
“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”
In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.
Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”
Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.
Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.
Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.
SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.
a study suggests.
This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.
“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”
Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.
OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.
PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
A cross-sectional study
To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.
Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.
The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.
Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.
On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).
The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).
In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.
In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.
Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
Various possible links
Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.
The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.
“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”
In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.
Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”
Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.
Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.
Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.
SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.
a study suggests.
This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.
“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”
Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.
OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.
PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
A cross-sectional study
To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.
Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.
The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.
Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.
On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).
The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).
In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.
In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.
Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
Various possible links
Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.
The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.
“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”
In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.
Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”
Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.
Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.
Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.
SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.
FROM ASRM 2020
COVID-19 burdens follow patients after discharge
COVID-19 patients who survive their hospitalization don’t leave the disease behind upon discharge, as a significant percentage died within 60 days of discharge, with an ICU admission heightening the risk, according to an observational study of 38 Michigan hospitals. What’s more, many of them were burdened with health and emotional challenges ranging from hospital readmission to job loss and financial problems.
“These data confirm that the toll of COVID-19 extends well beyond hospitalization, a finding consistent with long-term sequelae from sepsis and other severe respiratory viral illnesses,” wrote lead author Vineet Chopra, MBBS, of the University of Michigan, Ann Arbor, and colleagues (Ann Intern Med. 2020 Nov 11: doi: 10.7326/M20-5661)
The researchers found that 29.2% of all patients hospitalized for COVID-19 from March 16 to July 1 died. The observational cohort study included 1,648 COVID-19 patients hospitalized at 38 Michigan hospitals participating in a statewide collaborative.
The bulk of those deaths occurred during hospitalization: 24.2% of patients (n = 398). Of the 1,250 patients discharged, 78% (n = 975) went home and 12.6% (n = 158) went to a skilled nursing facility, with the remainder unaccounted for. Within 60 days of discharge, 6.7% (n = 84) of hospitalized survivors had died and 15.2% (n = 189) were readmitted. The researchers gathered 60-day postdischarge data via a telephone survey, contacting 41.8% (n = 488) of discharged patients.
Outcomes were even worse for discharged patients who spent time in the ICU. The death rate among this group was 10.4% (17 of 165) after discharge. That resulted in an overall study death rate of 63.5% (n = 257) for the 405 patients who were in the ICU.
While the study data were in the first wave of the novel coronavirus, the findings have relevance today, said Mary Jo Farmer, MD, PhD, FCCP, directory of pulmonary hypertension services at Baystate Health in Springfield, Mass.
“This is the best information we have to date,” she said. “We have to continue to have an open mind and expect that this information may change as the virus possibly mutates as it spreads, and we should continue doing these types of outcomes studies at 90 days, 120 days, etc.”
The median age of study patients was 62, with a range of 50-72. The three leading comorbidities among discharged patients were hypertension (n = 800, 64%), diabetes (34.9%, n = 436), and cardiovascular disease (24.1%, n = 301).
Poor postdischarge outcomes weren’t limited to mortality and readmission. Almost 19% (n = 92) reported new or worsening cardiopulmonary symptoms such as cough and dyspnea, 13.3% had a persistent loss of taste or smell, and 12% (n = 58) reported more difficulty with daily living tasks.
The after-effects were not only physical. Nearly half of discharged patients (48.7%, n = 238) reported emotional effects and almost 6% (n = 28) sought mental health care. Among the 40% (n = 195) employed before they were hospitalized, 36% (n = 78) couldn’t return to work because of health issues or layoffs. Sixty percent (n = 117) of the pre-employed discharged patients did return to work, but 25% (n = 30) did so with reduced hours or modified job duties because of health problems.
Financial problems were also a burden. More than a third, 36.7% (n = 179), reported some financial impact from their hospitalization. About 10% (n = 47) said they used most or all of their savings, and 7% (n = 35) said they resorted to rationing necessities such as food or medications.
The researchers noted that one in five patients had no primary care follow-up at 2 months post discharge. “Collectively, these findings suggest that better models to support COVID-19 survivors are necessary,” said Dr. Chopra and colleagues.
The postdischarge course for patients involves two humps, said Sachin Gupta, MD, FCCP a pulmonary and critical care specialist at Alameda Health System in Oakland, Calif.: Getting over the hospitalization itself and the recovery phase. “As you look at the median age of the survivors, elderly patients who survive a hospital stay are still going to have a period of recovery, and like any viral illness that leads to someone being hospitalized, when you have an elderly patient with comorbidities, not all of them can make it over that final hump.”
He echoed the study authors’ call for better postdischarge support for COVID-19 patients. “There’s typically, although not at every hospital, a one-size-fits-all discharge planning process,” Dr. Gupta said. “For older patients, particularly with comorbid conditions, close follow-up after discharge is important.”
Dr. Farmer noted that one challenge in discharge support may be a matter of personnel. “The providers of this care might be fearful of patients who have had COVID-19 – Do the patients remain contagious? What if symptoms of COVID-19 return such as dry cough, fever? – and of contracting the disease themselves,” she said.
The findings regarding the emotional status of discharged patients should factor into discharge planning, she added. “Providers of posthospital care need to be educated in the emotional impact of this disease (e.g., the patients may feel ostracized or that no one wants to be around them) to assist in their recovery.”
Dr. Chopra and Dr. Farmer have no financial relationships to disclose. Dr. Gupta is an employee and shareholder of Genentech.
SOURCE: Chopra V et al. Ann Intern Med. 2020 Nov 11. doi: 10.7326/M20-5661.
COVID-19 patients who survive their hospitalization don’t leave the disease behind upon discharge, as a significant percentage died within 60 days of discharge, with an ICU admission heightening the risk, according to an observational study of 38 Michigan hospitals. What’s more, many of them were burdened with health and emotional challenges ranging from hospital readmission to job loss and financial problems.
“These data confirm that the toll of COVID-19 extends well beyond hospitalization, a finding consistent with long-term sequelae from sepsis and other severe respiratory viral illnesses,” wrote lead author Vineet Chopra, MBBS, of the University of Michigan, Ann Arbor, and colleagues (Ann Intern Med. 2020 Nov 11: doi: 10.7326/M20-5661)
The researchers found that 29.2% of all patients hospitalized for COVID-19 from March 16 to July 1 died. The observational cohort study included 1,648 COVID-19 patients hospitalized at 38 Michigan hospitals participating in a statewide collaborative.
The bulk of those deaths occurred during hospitalization: 24.2% of patients (n = 398). Of the 1,250 patients discharged, 78% (n = 975) went home and 12.6% (n = 158) went to a skilled nursing facility, with the remainder unaccounted for. Within 60 days of discharge, 6.7% (n = 84) of hospitalized survivors had died and 15.2% (n = 189) were readmitted. The researchers gathered 60-day postdischarge data via a telephone survey, contacting 41.8% (n = 488) of discharged patients.
Outcomes were even worse for discharged patients who spent time in the ICU. The death rate among this group was 10.4% (17 of 165) after discharge. That resulted in an overall study death rate of 63.5% (n = 257) for the 405 patients who were in the ICU.
While the study data were in the first wave of the novel coronavirus, the findings have relevance today, said Mary Jo Farmer, MD, PhD, FCCP, directory of pulmonary hypertension services at Baystate Health in Springfield, Mass.
“This is the best information we have to date,” she said. “We have to continue to have an open mind and expect that this information may change as the virus possibly mutates as it spreads, and we should continue doing these types of outcomes studies at 90 days, 120 days, etc.”
The median age of study patients was 62, with a range of 50-72. The three leading comorbidities among discharged patients were hypertension (n = 800, 64%), diabetes (34.9%, n = 436), and cardiovascular disease (24.1%, n = 301).
Poor postdischarge outcomes weren’t limited to mortality and readmission. Almost 19% (n = 92) reported new or worsening cardiopulmonary symptoms such as cough and dyspnea, 13.3% had a persistent loss of taste or smell, and 12% (n = 58) reported more difficulty with daily living tasks.
The after-effects were not only physical. Nearly half of discharged patients (48.7%, n = 238) reported emotional effects and almost 6% (n = 28) sought mental health care. Among the 40% (n = 195) employed before they were hospitalized, 36% (n = 78) couldn’t return to work because of health issues or layoffs. Sixty percent (n = 117) of the pre-employed discharged patients did return to work, but 25% (n = 30) did so with reduced hours or modified job duties because of health problems.
Financial problems were also a burden. More than a third, 36.7% (n = 179), reported some financial impact from their hospitalization. About 10% (n = 47) said they used most or all of their savings, and 7% (n = 35) said they resorted to rationing necessities such as food or medications.
The researchers noted that one in five patients had no primary care follow-up at 2 months post discharge. “Collectively, these findings suggest that better models to support COVID-19 survivors are necessary,” said Dr. Chopra and colleagues.
The postdischarge course for patients involves two humps, said Sachin Gupta, MD, FCCP a pulmonary and critical care specialist at Alameda Health System in Oakland, Calif.: Getting over the hospitalization itself and the recovery phase. “As you look at the median age of the survivors, elderly patients who survive a hospital stay are still going to have a period of recovery, and like any viral illness that leads to someone being hospitalized, when you have an elderly patient with comorbidities, not all of them can make it over that final hump.”
He echoed the study authors’ call for better postdischarge support for COVID-19 patients. “There’s typically, although not at every hospital, a one-size-fits-all discharge planning process,” Dr. Gupta said. “For older patients, particularly with comorbid conditions, close follow-up after discharge is important.”
Dr. Farmer noted that one challenge in discharge support may be a matter of personnel. “The providers of this care might be fearful of patients who have had COVID-19 – Do the patients remain contagious? What if symptoms of COVID-19 return such as dry cough, fever? – and of contracting the disease themselves,” she said.
The findings regarding the emotional status of discharged patients should factor into discharge planning, she added. “Providers of posthospital care need to be educated in the emotional impact of this disease (e.g., the patients may feel ostracized or that no one wants to be around them) to assist in their recovery.”
Dr. Chopra and Dr. Farmer have no financial relationships to disclose. Dr. Gupta is an employee and shareholder of Genentech.
SOURCE: Chopra V et al. Ann Intern Med. 2020 Nov 11. doi: 10.7326/M20-5661.
COVID-19 patients who survive their hospitalization don’t leave the disease behind upon discharge, as a significant percentage died within 60 days of discharge, with an ICU admission heightening the risk, according to an observational study of 38 Michigan hospitals. What’s more, many of them were burdened with health and emotional challenges ranging from hospital readmission to job loss and financial problems.
“These data confirm that the toll of COVID-19 extends well beyond hospitalization, a finding consistent with long-term sequelae from sepsis and other severe respiratory viral illnesses,” wrote lead author Vineet Chopra, MBBS, of the University of Michigan, Ann Arbor, and colleagues (Ann Intern Med. 2020 Nov 11: doi: 10.7326/M20-5661)
The researchers found that 29.2% of all patients hospitalized for COVID-19 from March 16 to July 1 died. The observational cohort study included 1,648 COVID-19 patients hospitalized at 38 Michigan hospitals participating in a statewide collaborative.
The bulk of those deaths occurred during hospitalization: 24.2% of patients (n = 398). Of the 1,250 patients discharged, 78% (n = 975) went home and 12.6% (n = 158) went to a skilled nursing facility, with the remainder unaccounted for. Within 60 days of discharge, 6.7% (n = 84) of hospitalized survivors had died and 15.2% (n = 189) were readmitted. The researchers gathered 60-day postdischarge data via a telephone survey, contacting 41.8% (n = 488) of discharged patients.
Outcomes were even worse for discharged patients who spent time in the ICU. The death rate among this group was 10.4% (17 of 165) after discharge. That resulted in an overall study death rate of 63.5% (n = 257) for the 405 patients who were in the ICU.
While the study data were in the first wave of the novel coronavirus, the findings have relevance today, said Mary Jo Farmer, MD, PhD, FCCP, directory of pulmonary hypertension services at Baystate Health in Springfield, Mass.
“This is the best information we have to date,” she said. “We have to continue to have an open mind and expect that this information may change as the virus possibly mutates as it spreads, and we should continue doing these types of outcomes studies at 90 days, 120 days, etc.”
The median age of study patients was 62, with a range of 50-72. The three leading comorbidities among discharged patients were hypertension (n = 800, 64%), diabetes (34.9%, n = 436), and cardiovascular disease (24.1%, n = 301).
Poor postdischarge outcomes weren’t limited to mortality and readmission. Almost 19% (n = 92) reported new or worsening cardiopulmonary symptoms such as cough and dyspnea, 13.3% had a persistent loss of taste or smell, and 12% (n = 58) reported more difficulty with daily living tasks.
The after-effects were not only physical. Nearly half of discharged patients (48.7%, n = 238) reported emotional effects and almost 6% (n = 28) sought mental health care. Among the 40% (n = 195) employed before they were hospitalized, 36% (n = 78) couldn’t return to work because of health issues or layoffs. Sixty percent (n = 117) of the pre-employed discharged patients did return to work, but 25% (n = 30) did so with reduced hours or modified job duties because of health problems.
Financial problems were also a burden. More than a third, 36.7% (n = 179), reported some financial impact from their hospitalization. About 10% (n = 47) said they used most or all of their savings, and 7% (n = 35) said they resorted to rationing necessities such as food or medications.
The researchers noted that one in five patients had no primary care follow-up at 2 months post discharge. “Collectively, these findings suggest that better models to support COVID-19 survivors are necessary,” said Dr. Chopra and colleagues.
The postdischarge course for patients involves two humps, said Sachin Gupta, MD, FCCP a pulmonary and critical care specialist at Alameda Health System in Oakland, Calif.: Getting over the hospitalization itself and the recovery phase. “As you look at the median age of the survivors, elderly patients who survive a hospital stay are still going to have a period of recovery, and like any viral illness that leads to someone being hospitalized, when you have an elderly patient with comorbidities, not all of them can make it over that final hump.”
He echoed the study authors’ call for better postdischarge support for COVID-19 patients. “There’s typically, although not at every hospital, a one-size-fits-all discharge planning process,” Dr. Gupta said. “For older patients, particularly with comorbid conditions, close follow-up after discharge is important.”
Dr. Farmer noted that one challenge in discharge support may be a matter of personnel. “The providers of this care might be fearful of patients who have had COVID-19 – Do the patients remain contagious? What if symptoms of COVID-19 return such as dry cough, fever? – and of contracting the disease themselves,” she said.
The findings regarding the emotional status of discharged patients should factor into discharge planning, she added. “Providers of posthospital care need to be educated in the emotional impact of this disease (e.g., the patients may feel ostracized or that no one wants to be around them) to assist in their recovery.”
Dr. Chopra and Dr. Farmer have no financial relationships to disclose. Dr. Gupta is an employee and shareholder of Genentech.
SOURCE: Chopra V et al. Ann Intern Med. 2020 Nov 11. doi: 10.7326/M20-5661.
FROM ANNALS OF INTERNAL MEDICINE
Metapneumovirus infections clinically indistinguishable from flu, RSV
The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).
“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.
“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.
The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.
HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.
Relative newcomer
Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.
Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.
A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.
“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.
Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.
In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.
“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
Fatalities among older adults
As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.
In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.
Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
Supportive care only
“Do we have anything for treatment? The short answer is, No,” Dr. Williams.
Supportive care is currently the only effective approach for patients with severe HMPV infection.
Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.
“It really can’t be recommended, and I don’t recommend it,” he said.
Virology may still help
Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.
“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.
“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.
Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.
Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.
The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).
“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.
“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.
The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.
HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.
Relative newcomer
Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.
Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.
A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.
“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.
Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.
In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.
“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
Fatalities among older adults
As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.
In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.
Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
Supportive care only
“Do we have anything for treatment? The short answer is, No,” Dr. Williams.
Supportive care is currently the only effective approach for patients with severe HMPV infection.
Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.
“It really can’t be recommended, and I don’t recommend it,” he said.
Virology may still help
Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.
“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.
“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.
Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.
Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.
The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).
“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.
“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.
The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.
HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.
Relative newcomer
Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.
Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.
A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.
“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.
Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.
In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.
“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
Fatalities among older adults
As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.
In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.
Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
Supportive care only
“Do we have anything for treatment? The short answer is, No,” Dr. Williams.
Supportive care is currently the only effective approach for patients with severe HMPV infection.
Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.
“It really can’t be recommended, and I don’t recommend it,” he said.
Virology may still help
Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.
“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.
“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.
Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.
Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.
FROM IDWEEK 2020
VTEs tied to immune checkpoint inhibitor cancer treatment
Cancer patients who receive an immune checkpoint inhibitor have more than a doubled rate of venous thromboembolism during the subsequent 2 years, compared with their rate during the 2 years before treatment, according to a retrospective analysis of more than 2,800 patients treated at a single U.S. center.
The study focused on cancer patients treated with an immune checkpoint inhibitor (ICI) at Massachusetts General Hospital in Boston. It showed that during the 2 years prior to treatment with any type of ICI, the incidence of venous thromboembolic events (VTE) was 4.85/100 patient-years that then jumped to 11.75/100 patient-years during the 2 years following treatment. This translated into an incidence rate ratio of 2.43 during posttreatment follow-up, compared with pretreatment, Jingyi Gong, MD, said at the virtual American Heart Association scientific sessions.
The increased VTE rate resulted from rises in both the rate of deep vein thrombosis, which had an IRR of 3.23 during the posttreatment period, and for pulmonary embolism, which showed an IRR of 2.24, said Dr. Gong, a physician at Brigham and Women’s Hospital in Boston. She hypothesized that this effect may result from a procoagulant effect of the immune activation and inflammation triggered by ICIs.
Hypothesis-generating results
Cardiologists cautioned that these findings should only be considered hypothesis generating, but raise an important alert for clinicians to have heightened awareness of the potential for VTE following ICI treatment.
“A clear message is to be aware that there is this signal, and be vigilant for patients who might present with VTE following ICI treatment,” commented Richard J. Kovacs, MD, a cardiologist and professor at Indiana University, Indianapolis. The data that Dr. Gong reported are “moderately convincing,” he added in an interview.
“Awareness that patients who receive ICI may be at increased VTE risk is very important,” agreed Umberto Campia, MD, a cardiologist, vascular specialist, and member of the cardio-oncology group at Brigham and Women’s Hospital, who was not involved in the new study.
The potential impact of ICI treatment on VTE risk is slowly emerging, added Dr. Campia. Until recently, the literature primarily was case reports, but recently another retrospective, single-center study came out that reported a 13% incidence of VTE in cancer patients following ICI treatment. On the other hand, a recently published meta-analysis of more than 20,000 patients from 68 ICI studies failed to find a suggestion of increased VTE incidence following ICI interventions.
Attempting to assess the impact of treatment on VTE risk in cancer patients is challenging because cancer itself boosts the risk. Recommendations on the use of VTE prophylaxis in cancer patients most recently came out in 2014 from the American Society of Clinical Oncology, which said that VTE prophylaxis for ambulatory cancer patients “may be considered for highly select high-risk patients.” The impact of cancer therapy on VTE risk and the need for prophylaxis is usually assessed by applying the Khorana score, Dr. Campia said in an interview.
VTE spikes acutely after ICI treatment
Dr. Gong analyzed VTE incidence rates by time during the total 4-year period studied, and found that the rate gradually and steadily rose with time throughout the 2 years preceding treatment, spiked immediately following ICI treatment, and then gradually and steadily fell back to roughly the rate seen just before treatment, reaching that level about a year after treatment. She ran a sensitivity analysis that excluded patients who died during the first year following their ICI treatment, and in this calculation an acute spike in VTE following ICI treatment still occurred but with reduced magnitude.
She also reported the results of several subgroup analyses. The IRRs remained consistent among women and men, among patients who were aged over or under 65 years, and regardless of cancer type or treatment with corticosteroids. But the subgroup analyses identified two parameters that seemed to clearly split VTE rates.
Among patients on treatment with an anticoagulant agent at the time of their ICI treatment, roughly 10% of the patients, the IRR was 0.56, compared with a ratio of 3.86 among the other patients, suggesting possible protection. A second factor that seemed linked with VTE incidence was the number of ICI treatment cycles a patient received. Those who received more than five cycles had a risk ratio of 3.95, while those who received five or fewer cycles had a RR of 1.66.
Her analysis included 2,842 cancer patients who received treatment with an ICI at Massachusetts General Hospital. Patients averaged 64 years of age, slightly more than half were men, and 13% had a prior history of VTE. Patients received an average of 5 ICI treatment cycles, but a quarter of the patients received more than 10 cycles.
During the 2-year follow-up, 244 patients (9%) developed VTE. The patients who developed VTE were significantly younger than those who did not, with an average age of 63 years, compared with 65. And the patients who eventually developed VTE had a significantly higher prevalence of prior VTE at 18%, compared with 12% among the patients who stayed VTE free.
The cancer types patients had were non–small cell lung, 29%; melanoma, 28%; head and neck, 12%; renal genitourinary, 6%; and other, 25%. ICIs have been available for routine U.S. practice since 2011. The class includes agents such as pembrolizumab (Keytruda) and durvalumab (Imfinzi).
Researchers would need to perform a prospective, randomized study to determine whether anticoagulant prophylaxis is clearly beneficial for patients receiving ICI treatment, Dr. Gong said. But both Dr. Kovacs and Dr. Campia said that more data on this topic are first needed.
“We need to confirm that treatment with ICI is associated with VTEs. Retrospective data are not definitive,” said Dr. Campia. “We would need to prospectively assess the impact of ICI,” which will not be easy, as it’s quickly become a cornerstone for treating many cancers. “We need to become more familiar with the adverse effects of these drugs. We are still learning about their toxicities.”
The study had no commercial funding. Dr. Gong, Dr. Kovacs, and Dr. Campia had no disclosures.
Cancer patients who receive an immune checkpoint inhibitor have more than a doubled rate of venous thromboembolism during the subsequent 2 years, compared with their rate during the 2 years before treatment, according to a retrospective analysis of more than 2,800 patients treated at a single U.S. center.
The study focused on cancer patients treated with an immune checkpoint inhibitor (ICI) at Massachusetts General Hospital in Boston. It showed that during the 2 years prior to treatment with any type of ICI, the incidence of venous thromboembolic events (VTE) was 4.85/100 patient-years that then jumped to 11.75/100 patient-years during the 2 years following treatment. This translated into an incidence rate ratio of 2.43 during posttreatment follow-up, compared with pretreatment, Jingyi Gong, MD, said at the virtual American Heart Association scientific sessions.
The increased VTE rate resulted from rises in both the rate of deep vein thrombosis, which had an IRR of 3.23 during the posttreatment period, and for pulmonary embolism, which showed an IRR of 2.24, said Dr. Gong, a physician at Brigham and Women’s Hospital in Boston. She hypothesized that this effect may result from a procoagulant effect of the immune activation and inflammation triggered by ICIs.
Hypothesis-generating results
Cardiologists cautioned that these findings should only be considered hypothesis generating, but raise an important alert for clinicians to have heightened awareness of the potential for VTE following ICI treatment.
“A clear message is to be aware that there is this signal, and be vigilant for patients who might present with VTE following ICI treatment,” commented Richard J. Kovacs, MD, a cardiologist and professor at Indiana University, Indianapolis. The data that Dr. Gong reported are “moderately convincing,” he added in an interview.
“Awareness that patients who receive ICI may be at increased VTE risk is very important,” agreed Umberto Campia, MD, a cardiologist, vascular specialist, and member of the cardio-oncology group at Brigham and Women’s Hospital, who was not involved in the new study.
The potential impact of ICI treatment on VTE risk is slowly emerging, added Dr. Campia. Until recently, the literature primarily was case reports, but recently another retrospective, single-center study came out that reported a 13% incidence of VTE in cancer patients following ICI treatment. On the other hand, a recently published meta-analysis of more than 20,000 patients from 68 ICI studies failed to find a suggestion of increased VTE incidence following ICI interventions.
Attempting to assess the impact of treatment on VTE risk in cancer patients is challenging because cancer itself boosts the risk. Recommendations on the use of VTE prophylaxis in cancer patients most recently came out in 2014 from the American Society of Clinical Oncology, which said that VTE prophylaxis for ambulatory cancer patients “may be considered for highly select high-risk patients.” The impact of cancer therapy on VTE risk and the need for prophylaxis is usually assessed by applying the Khorana score, Dr. Campia said in an interview.
VTE spikes acutely after ICI treatment
Dr. Gong analyzed VTE incidence rates by time during the total 4-year period studied, and found that the rate gradually and steadily rose with time throughout the 2 years preceding treatment, spiked immediately following ICI treatment, and then gradually and steadily fell back to roughly the rate seen just before treatment, reaching that level about a year after treatment. She ran a sensitivity analysis that excluded patients who died during the first year following their ICI treatment, and in this calculation an acute spike in VTE following ICI treatment still occurred but with reduced magnitude.
She also reported the results of several subgroup analyses. The IRRs remained consistent among women and men, among patients who were aged over or under 65 years, and regardless of cancer type or treatment with corticosteroids. But the subgroup analyses identified two parameters that seemed to clearly split VTE rates.
Among patients on treatment with an anticoagulant agent at the time of their ICI treatment, roughly 10% of the patients, the IRR was 0.56, compared with a ratio of 3.86 among the other patients, suggesting possible protection. A second factor that seemed linked with VTE incidence was the number of ICI treatment cycles a patient received. Those who received more than five cycles had a risk ratio of 3.95, while those who received five or fewer cycles had a RR of 1.66.
Her analysis included 2,842 cancer patients who received treatment with an ICI at Massachusetts General Hospital. Patients averaged 64 years of age, slightly more than half were men, and 13% had a prior history of VTE. Patients received an average of 5 ICI treatment cycles, but a quarter of the patients received more than 10 cycles.
During the 2-year follow-up, 244 patients (9%) developed VTE. The patients who developed VTE were significantly younger than those who did not, with an average age of 63 years, compared with 65. And the patients who eventually developed VTE had a significantly higher prevalence of prior VTE at 18%, compared with 12% among the patients who stayed VTE free.
The cancer types patients had were non–small cell lung, 29%; melanoma, 28%; head and neck, 12%; renal genitourinary, 6%; and other, 25%. ICIs have been available for routine U.S. practice since 2011. The class includes agents such as pembrolizumab (Keytruda) and durvalumab (Imfinzi).
Researchers would need to perform a prospective, randomized study to determine whether anticoagulant prophylaxis is clearly beneficial for patients receiving ICI treatment, Dr. Gong said. But both Dr. Kovacs and Dr. Campia said that more data on this topic are first needed.
“We need to confirm that treatment with ICI is associated with VTEs. Retrospective data are not definitive,” said Dr. Campia. “We would need to prospectively assess the impact of ICI,” which will not be easy, as it’s quickly become a cornerstone for treating many cancers. “We need to become more familiar with the adverse effects of these drugs. We are still learning about their toxicities.”
The study had no commercial funding. Dr. Gong, Dr. Kovacs, and Dr. Campia had no disclosures.
Cancer patients who receive an immune checkpoint inhibitor have more than a doubled rate of venous thromboembolism during the subsequent 2 years, compared with their rate during the 2 years before treatment, according to a retrospective analysis of more than 2,800 patients treated at a single U.S. center.
The study focused on cancer patients treated with an immune checkpoint inhibitor (ICI) at Massachusetts General Hospital in Boston. It showed that during the 2 years prior to treatment with any type of ICI, the incidence of venous thromboembolic events (VTE) was 4.85/100 patient-years that then jumped to 11.75/100 patient-years during the 2 years following treatment. This translated into an incidence rate ratio of 2.43 during posttreatment follow-up, compared with pretreatment, Jingyi Gong, MD, said at the virtual American Heart Association scientific sessions.
The increased VTE rate resulted from rises in both the rate of deep vein thrombosis, which had an IRR of 3.23 during the posttreatment period, and for pulmonary embolism, which showed an IRR of 2.24, said Dr. Gong, a physician at Brigham and Women’s Hospital in Boston. She hypothesized that this effect may result from a procoagulant effect of the immune activation and inflammation triggered by ICIs.
Hypothesis-generating results
Cardiologists cautioned that these findings should only be considered hypothesis generating, but raise an important alert for clinicians to have heightened awareness of the potential for VTE following ICI treatment.
“A clear message is to be aware that there is this signal, and be vigilant for patients who might present with VTE following ICI treatment,” commented Richard J. Kovacs, MD, a cardiologist and professor at Indiana University, Indianapolis. The data that Dr. Gong reported are “moderately convincing,” he added in an interview.
“Awareness that patients who receive ICI may be at increased VTE risk is very important,” agreed Umberto Campia, MD, a cardiologist, vascular specialist, and member of the cardio-oncology group at Brigham and Women’s Hospital, who was not involved in the new study.
The potential impact of ICI treatment on VTE risk is slowly emerging, added Dr. Campia. Until recently, the literature primarily was case reports, but recently another retrospective, single-center study came out that reported a 13% incidence of VTE in cancer patients following ICI treatment. On the other hand, a recently published meta-analysis of more than 20,000 patients from 68 ICI studies failed to find a suggestion of increased VTE incidence following ICI interventions.
Attempting to assess the impact of treatment on VTE risk in cancer patients is challenging because cancer itself boosts the risk. Recommendations on the use of VTE prophylaxis in cancer patients most recently came out in 2014 from the American Society of Clinical Oncology, which said that VTE prophylaxis for ambulatory cancer patients “may be considered for highly select high-risk patients.” The impact of cancer therapy on VTE risk and the need for prophylaxis is usually assessed by applying the Khorana score, Dr. Campia said in an interview.
VTE spikes acutely after ICI treatment
Dr. Gong analyzed VTE incidence rates by time during the total 4-year period studied, and found that the rate gradually and steadily rose with time throughout the 2 years preceding treatment, spiked immediately following ICI treatment, and then gradually and steadily fell back to roughly the rate seen just before treatment, reaching that level about a year after treatment. She ran a sensitivity analysis that excluded patients who died during the first year following their ICI treatment, and in this calculation an acute spike in VTE following ICI treatment still occurred but with reduced magnitude.
She also reported the results of several subgroup analyses. The IRRs remained consistent among women and men, among patients who were aged over or under 65 years, and regardless of cancer type or treatment with corticosteroids. But the subgroup analyses identified two parameters that seemed to clearly split VTE rates.
Among patients on treatment with an anticoagulant agent at the time of their ICI treatment, roughly 10% of the patients, the IRR was 0.56, compared with a ratio of 3.86 among the other patients, suggesting possible protection. A second factor that seemed linked with VTE incidence was the number of ICI treatment cycles a patient received. Those who received more than five cycles had a risk ratio of 3.95, while those who received five or fewer cycles had a RR of 1.66.
Her analysis included 2,842 cancer patients who received treatment with an ICI at Massachusetts General Hospital. Patients averaged 64 years of age, slightly more than half were men, and 13% had a prior history of VTE. Patients received an average of 5 ICI treatment cycles, but a quarter of the patients received more than 10 cycles.
During the 2-year follow-up, 244 patients (9%) developed VTE. The patients who developed VTE were significantly younger than those who did not, with an average age of 63 years, compared with 65. And the patients who eventually developed VTE had a significantly higher prevalence of prior VTE at 18%, compared with 12% among the patients who stayed VTE free.
The cancer types patients had were non–small cell lung, 29%; melanoma, 28%; head and neck, 12%; renal genitourinary, 6%; and other, 25%. ICIs have been available for routine U.S. practice since 2011. The class includes agents such as pembrolizumab (Keytruda) and durvalumab (Imfinzi).
Researchers would need to perform a prospective, randomized study to determine whether anticoagulant prophylaxis is clearly beneficial for patients receiving ICI treatment, Dr. Gong said. But both Dr. Kovacs and Dr. Campia said that more data on this topic are first needed.
“We need to confirm that treatment with ICI is associated with VTEs. Retrospective data are not definitive,” said Dr. Campia. “We would need to prospectively assess the impact of ICI,” which will not be easy, as it’s quickly become a cornerstone for treating many cancers. “We need to become more familiar with the adverse effects of these drugs. We are still learning about their toxicities.”
The study had no commercial funding. Dr. Gong, Dr. Kovacs, and Dr. Campia had no disclosures.
FROM AHA 2020
Options grow for interstitial lung disease other than idiopathic pulmonary fibrosis
Care of the patient with a fibrosing interstitial lung disease (ILD) presents constant challenges not just in the diagnosis of ILD but in the choice of treatment. Since the FDA approval of both nintedanib and pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in 2014, interest has grown for their employ in treating other non-IPF ILDs. This is especially true in cases with the pattern of radiographic or histopathological disease is similar to IPF – a usual interstitial pneumonia (UIP) pattern – despite not meeting criteria for an IPF diagnosis due to the identification of a predisposing etiology. As research evolves, clinicians may have more options to fight the vast variety of fibrosing ILDs encountered in practice.
In 2014, the publication of separate clinical trials of nintedanib and pirfenidone in patients with IPF marked a new beginning in the treatment of this disease. Nintedanib, a tyrosine kinase inhibitor with multiple targets, was shown to decrease progression of disease as measured by the annual rate of decline in forced vital capacity (FVC) (Richeldi L, et al. N Engl J Med. 2014 May;370[22]:2071-82). Pirfenidone, whose antifibrotic mechanisms are not completely understood, similarly slowed disease progression via a decrease in the percent change of predicted FVC (Lederer DJ, et al. N Engl J Med. 2014 May;370[19]:2083-92). Clinicians were now armed with two therapeutic options following the subsequent FDA approval of both drugs for the treatment of IPF. This represented a giant leap forward in the management of the disease, as prior to 2014 the only available options were supportive care and lung transplant for appropriate candidates.
As IPF represents but 20% of ILDs in the United States, a significant proportion of diseases were left without an antifibrotic option after the arrival of nintedanib and pirfenidone. (Lederer DJ. N Engl J Med. 2018 May;378:1811-23). For the others, such as chronic hypersensitivity pneumonitis and the many connective tissue disease-associated ILDs, treatment revolved around a variety of anti-inflammatory pharmaceuticals. Common treatment choices include corticosteroids, mycophenolate, and azathioprine. The data in support of these treatments for non-IPF ILD is comparatively lean in contrast to the more robust pirfenidone and nintedanib IPF trials.
One notable exception includes the Scleroderma Lung Studies. In Scleroderma Lung Study II (SLS II), 142 patients with scleroderma-related interstitial lung disease were randomized to oral mycophenolate for 24 months vs oral cyclophosphamide for 12 months plus placebo for 12 months (Tashkin DP, et al. Lancet Respir Med. 2016 Sep;4(9):708-19). The 2006 Scleroderma Lung Study established oral cyclophosphamide in scleroderma lung disease as a reasonable standard of care after demonstrating a slowing of disease progression after 12 months of therapy (Tashkin DP, et al. N Engl J Med. 2006 Jun;354[25]:2655-66). In SLS II, both cyclophosphamide and mycophenolate improved lung function at 24 months, but mycophenolate was better tolerated with less toxicity.
Other supportive data for immunosuppressive treatments for non-IPF ILD rely heavily on smaller studies, case reports, and retrospective reviews. Choices of who and when to treat are often unclear and typically come from physician preferences and patient values discussions. In the cases of connective tissue disease-associated ILD, patients may already require treatment for the underlying condition. And, while some therapies could be beneficial in a concurrent manner for a patient’s lung disease, many others are not (TNF-alpha antibody therapy, for example).
A major step forward for patients with scleroderma lung disease came with the publication of the SENSCIS trial (Oliver D, et al. N Engl J Med. 2019 Jun;380:2518-28). A total of 576 patients with scleroderma of recent onset (< 7 years) and at least 10% fibrosis on chest CT were randomized to receive either nintedanib or placebo. Patients were allowed to be supported by other therapies at stable doses prior to enrollment, and as such almost half of the patients were receiving mycophenolate. A significant improvement in annual FVC decline was reported in the treatment group, although the effect was tempered in the subgroup analysis when considering patients already on mycophenolate. Thus, the role of nintedanib in patients taking mycophenolate is less clear.
An ongoing study may clarify the role of mycophenolate and antifibrotic therapy in these patients. The phase 2 Scleroderma Lung Study III has a planned enrollment of 150 patients who are either treatment-naïve or only recently started on therapy (www.clinicaltrials.gov; NCT03221257). Patients are randomized to mycophenolate plus pirfenidone vs mycophenolate plus placebo, and the treatment phase will last 18 months. The primary outcome is change in baseline FVC. This trial design will hopefully answer whether the combination of an antifibrotic with an anti-inflammatory medication is superior to the anti-inflammatory therapy alone, in patients with at least some evidence of inflammation (ground-glass opacifications) on high-resolution CT scan (HRCT).
In ILD other than that associated with scleroderma, nintedanib was again explored in a large randomized controlled clinical trial. In INBUILD, 663 patients with progressive ILD not caused by IPF or scleroderma were randomized to nintedanib vs placebo for one year (Flaherty KR. N Engl J Med. 2019 Sep;381:1718-27). A majority of the patients (62%) had a UIP pattern on CT scan. There was overall improvement in the annual rate of decline in FVC in the treatment group, especially in the pr-determined subgroup of patients with a UIP pattern. The most common ILDs in the study were chronic hypersensitivity pneumonitis and that associated with connective tissue disease.
Pirfenidone is also being studied in multiple trials for various types of non-IPF ILD. Studies are either completed and nearing publication, or are ongoing. Some examples include the TRAIL1 study examining pirfenidone vs placebo in patients with rheumatoid arthritis (www.clinicaltrials.gov; NCT02808871), and the phase 2 RELIEF study that explores pirfenidone vs placebo in patients with progressive ILD from a variety of etiologies.
As more clinical trials are published, clinicians are now facing a different dilemma. Whereas the options for treatment were limited to only various anti-inflammatory medications in past years for patients with non-IPF ILDs, the growing body of literature supporting antifibrotics present a new therapeutic avenue to explore. Which patients should be started on anti-inflammatory medications, and which should start antifibrotics? Those questions may never be answered satisfactorily in clinical trials. Mycophenolate has become so entrenched in many treatment plans, enrollment into such a study comparing the two therapeutic classes head-to-head would be challenging.
However, a consideration of the specific phenotype of the patient’s ILD is a suggested approach that comes from clinical experience. Patients with more inflammatory changes on CT scan, such as more ground glass opacifications or a non-UIP pattern, might benefit from initiation of anti-inflammatory therapies such as a combination of corticosteroids and mycophenolate. Conversely, initiating antifibrotic therapy upfront, with or without concomitant mycophenolate, is a consideration if the pattern of disease is consistent with UIP on CT scan.
Ultimately, referral to a dedicated interstitial lung disease center for expert evaluation and multidisciplinary discussion may be warranted to sift through these difficult situations, especially as the field of research grows more robust. In any event, the future for patients with these diseases, though still challenged, is brighter than before.
Dr. Kershaw is Associate Professor of Medicine, Division of Pulmonary & Critical Care Medicine, University of Texas Southwestern Medical Center. He is the current section editor for Pulmonary
Perpsectives®and Vice Chair of the Interstitial and Diffuse Lung Disease NetWork at CHEST.
Care of the patient with a fibrosing interstitial lung disease (ILD) presents constant challenges not just in the diagnosis of ILD but in the choice of treatment. Since the FDA approval of both nintedanib and pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in 2014, interest has grown for their employ in treating other non-IPF ILDs. This is especially true in cases with the pattern of radiographic or histopathological disease is similar to IPF – a usual interstitial pneumonia (UIP) pattern – despite not meeting criteria for an IPF diagnosis due to the identification of a predisposing etiology. As research evolves, clinicians may have more options to fight the vast variety of fibrosing ILDs encountered in practice.
In 2014, the publication of separate clinical trials of nintedanib and pirfenidone in patients with IPF marked a new beginning in the treatment of this disease. Nintedanib, a tyrosine kinase inhibitor with multiple targets, was shown to decrease progression of disease as measured by the annual rate of decline in forced vital capacity (FVC) (Richeldi L, et al. N Engl J Med. 2014 May;370[22]:2071-82). Pirfenidone, whose antifibrotic mechanisms are not completely understood, similarly slowed disease progression via a decrease in the percent change of predicted FVC (Lederer DJ, et al. N Engl J Med. 2014 May;370[19]:2083-92). Clinicians were now armed with two therapeutic options following the subsequent FDA approval of both drugs for the treatment of IPF. This represented a giant leap forward in the management of the disease, as prior to 2014 the only available options were supportive care and lung transplant for appropriate candidates.
As IPF represents but 20% of ILDs in the United States, a significant proportion of diseases were left without an antifibrotic option after the arrival of nintedanib and pirfenidone. (Lederer DJ. N Engl J Med. 2018 May;378:1811-23). For the others, such as chronic hypersensitivity pneumonitis and the many connective tissue disease-associated ILDs, treatment revolved around a variety of anti-inflammatory pharmaceuticals. Common treatment choices include corticosteroids, mycophenolate, and azathioprine. The data in support of these treatments for non-IPF ILD is comparatively lean in contrast to the more robust pirfenidone and nintedanib IPF trials.
One notable exception includes the Scleroderma Lung Studies. In Scleroderma Lung Study II (SLS II), 142 patients with scleroderma-related interstitial lung disease were randomized to oral mycophenolate for 24 months vs oral cyclophosphamide for 12 months plus placebo for 12 months (Tashkin DP, et al. Lancet Respir Med. 2016 Sep;4(9):708-19). The 2006 Scleroderma Lung Study established oral cyclophosphamide in scleroderma lung disease as a reasonable standard of care after demonstrating a slowing of disease progression after 12 months of therapy (Tashkin DP, et al. N Engl J Med. 2006 Jun;354[25]:2655-66). In SLS II, both cyclophosphamide and mycophenolate improved lung function at 24 months, but mycophenolate was better tolerated with less toxicity.
Other supportive data for immunosuppressive treatments for non-IPF ILD rely heavily on smaller studies, case reports, and retrospective reviews. Choices of who and when to treat are often unclear and typically come from physician preferences and patient values discussions. In the cases of connective tissue disease-associated ILD, patients may already require treatment for the underlying condition. And, while some therapies could be beneficial in a concurrent manner for a patient’s lung disease, many others are not (TNF-alpha antibody therapy, for example).
A major step forward for patients with scleroderma lung disease came with the publication of the SENSCIS trial (Oliver D, et al. N Engl J Med. 2019 Jun;380:2518-28). A total of 576 patients with scleroderma of recent onset (< 7 years) and at least 10% fibrosis on chest CT were randomized to receive either nintedanib or placebo. Patients were allowed to be supported by other therapies at stable doses prior to enrollment, and as such almost half of the patients were receiving mycophenolate. A significant improvement in annual FVC decline was reported in the treatment group, although the effect was tempered in the subgroup analysis when considering patients already on mycophenolate. Thus, the role of nintedanib in patients taking mycophenolate is less clear.
An ongoing study may clarify the role of mycophenolate and antifibrotic therapy in these patients. The phase 2 Scleroderma Lung Study III has a planned enrollment of 150 patients who are either treatment-naïve or only recently started on therapy (www.clinicaltrials.gov; NCT03221257). Patients are randomized to mycophenolate plus pirfenidone vs mycophenolate plus placebo, and the treatment phase will last 18 months. The primary outcome is change in baseline FVC. This trial design will hopefully answer whether the combination of an antifibrotic with an anti-inflammatory medication is superior to the anti-inflammatory therapy alone, in patients with at least some evidence of inflammation (ground-glass opacifications) on high-resolution CT scan (HRCT).
In ILD other than that associated with scleroderma, nintedanib was again explored in a large randomized controlled clinical trial. In INBUILD, 663 patients with progressive ILD not caused by IPF or scleroderma were randomized to nintedanib vs placebo for one year (Flaherty KR. N Engl J Med. 2019 Sep;381:1718-27). A majority of the patients (62%) had a UIP pattern on CT scan. There was overall improvement in the annual rate of decline in FVC in the treatment group, especially in the pr-determined subgroup of patients with a UIP pattern. The most common ILDs in the study were chronic hypersensitivity pneumonitis and that associated with connective tissue disease.
Pirfenidone is also being studied in multiple trials for various types of non-IPF ILD. Studies are either completed and nearing publication, or are ongoing. Some examples include the TRAIL1 study examining pirfenidone vs placebo in patients with rheumatoid arthritis (www.clinicaltrials.gov; NCT02808871), and the phase 2 RELIEF study that explores pirfenidone vs placebo in patients with progressive ILD from a variety of etiologies.
As more clinical trials are published, clinicians are now facing a different dilemma. Whereas the options for treatment were limited to only various anti-inflammatory medications in past years for patients with non-IPF ILDs, the growing body of literature supporting antifibrotics present a new therapeutic avenue to explore. Which patients should be started on anti-inflammatory medications, and which should start antifibrotics? Those questions may never be answered satisfactorily in clinical trials. Mycophenolate has become so entrenched in many treatment plans, enrollment into such a study comparing the two therapeutic classes head-to-head would be challenging.
However, a consideration of the specific phenotype of the patient’s ILD is a suggested approach that comes from clinical experience. Patients with more inflammatory changes on CT scan, such as more ground glass opacifications or a non-UIP pattern, might benefit from initiation of anti-inflammatory therapies such as a combination of corticosteroids and mycophenolate. Conversely, initiating antifibrotic therapy upfront, with or without concomitant mycophenolate, is a consideration if the pattern of disease is consistent with UIP on CT scan.
Ultimately, referral to a dedicated interstitial lung disease center for expert evaluation and multidisciplinary discussion may be warranted to sift through these difficult situations, especially as the field of research grows more robust. In any event, the future for patients with these diseases, though still challenged, is brighter than before.
Dr. Kershaw is Associate Professor of Medicine, Division of Pulmonary & Critical Care Medicine, University of Texas Southwestern Medical Center. He is the current section editor for Pulmonary
Perpsectives®and Vice Chair of the Interstitial and Diffuse Lung Disease NetWork at CHEST.
Care of the patient with a fibrosing interstitial lung disease (ILD) presents constant challenges not just in the diagnosis of ILD but in the choice of treatment. Since the FDA approval of both nintedanib and pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in 2014, interest has grown for their employ in treating other non-IPF ILDs. This is especially true in cases with the pattern of radiographic or histopathological disease is similar to IPF – a usual interstitial pneumonia (UIP) pattern – despite not meeting criteria for an IPF diagnosis due to the identification of a predisposing etiology. As research evolves, clinicians may have more options to fight the vast variety of fibrosing ILDs encountered in practice.
In 2014, the publication of separate clinical trials of nintedanib and pirfenidone in patients with IPF marked a new beginning in the treatment of this disease. Nintedanib, a tyrosine kinase inhibitor with multiple targets, was shown to decrease progression of disease as measured by the annual rate of decline in forced vital capacity (FVC) (Richeldi L, et al. N Engl J Med. 2014 May;370[22]:2071-82). Pirfenidone, whose antifibrotic mechanisms are not completely understood, similarly slowed disease progression via a decrease in the percent change of predicted FVC (Lederer DJ, et al. N Engl J Med. 2014 May;370[19]:2083-92). Clinicians were now armed with two therapeutic options following the subsequent FDA approval of both drugs for the treatment of IPF. This represented a giant leap forward in the management of the disease, as prior to 2014 the only available options were supportive care and lung transplant for appropriate candidates.
As IPF represents but 20% of ILDs in the United States, a significant proportion of diseases were left without an antifibrotic option after the arrival of nintedanib and pirfenidone. (Lederer DJ. N Engl J Med. 2018 May;378:1811-23). For the others, such as chronic hypersensitivity pneumonitis and the many connective tissue disease-associated ILDs, treatment revolved around a variety of anti-inflammatory pharmaceuticals. Common treatment choices include corticosteroids, mycophenolate, and azathioprine. The data in support of these treatments for non-IPF ILD is comparatively lean in contrast to the more robust pirfenidone and nintedanib IPF trials.
One notable exception includes the Scleroderma Lung Studies. In Scleroderma Lung Study II (SLS II), 142 patients with scleroderma-related interstitial lung disease were randomized to oral mycophenolate for 24 months vs oral cyclophosphamide for 12 months plus placebo for 12 months (Tashkin DP, et al. Lancet Respir Med. 2016 Sep;4(9):708-19). The 2006 Scleroderma Lung Study established oral cyclophosphamide in scleroderma lung disease as a reasonable standard of care after demonstrating a slowing of disease progression after 12 months of therapy (Tashkin DP, et al. N Engl J Med. 2006 Jun;354[25]:2655-66). In SLS II, both cyclophosphamide and mycophenolate improved lung function at 24 months, but mycophenolate was better tolerated with less toxicity.
Other supportive data for immunosuppressive treatments for non-IPF ILD rely heavily on smaller studies, case reports, and retrospective reviews. Choices of who and when to treat are often unclear and typically come from physician preferences and patient values discussions. In the cases of connective tissue disease-associated ILD, patients may already require treatment for the underlying condition. And, while some therapies could be beneficial in a concurrent manner for a patient’s lung disease, many others are not (TNF-alpha antibody therapy, for example).
A major step forward for patients with scleroderma lung disease came with the publication of the SENSCIS trial (Oliver D, et al. N Engl J Med. 2019 Jun;380:2518-28). A total of 576 patients with scleroderma of recent onset (< 7 years) and at least 10% fibrosis on chest CT were randomized to receive either nintedanib or placebo. Patients were allowed to be supported by other therapies at stable doses prior to enrollment, and as such almost half of the patients were receiving mycophenolate. A significant improvement in annual FVC decline was reported in the treatment group, although the effect was tempered in the subgroup analysis when considering patients already on mycophenolate. Thus, the role of nintedanib in patients taking mycophenolate is less clear.
An ongoing study may clarify the role of mycophenolate and antifibrotic therapy in these patients. The phase 2 Scleroderma Lung Study III has a planned enrollment of 150 patients who are either treatment-naïve or only recently started on therapy (www.clinicaltrials.gov; NCT03221257). Patients are randomized to mycophenolate plus pirfenidone vs mycophenolate plus placebo, and the treatment phase will last 18 months. The primary outcome is change in baseline FVC. This trial design will hopefully answer whether the combination of an antifibrotic with an anti-inflammatory medication is superior to the anti-inflammatory therapy alone, in patients with at least some evidence of inflammation (ground-glass opacifications) on high-resolution CT scan (HRCT).
In ILD other than that associated with scleroderma, nintedanib was again explored in a large randomized controlled clinical trial. In INBUILD, 663 patients with progressive ILD not caused by IPF or scleroderma were randomized to nintedanib vs placebo for one year (Flaherty KR. N Engl J Med. 2019 Sep;381:1718-27). A majority of the patients (62%) had a UIP pattern on CT scan. There was overall improvement in the annual rate of decline in FVC in the treatment group, especially in the pr-determined subgroup of patients with a UIP pattern. The most common ILDs in the study were chronic hypersensitivity pneumonitis and that associated with connective tissue disease.
Pirfenidone is also being studied in multiple trials for various types of non-IPF ILD. Studies are either completed and nearing publication, or are ongoing. Some examples include the TRAIL1 study examining pirfenidone vs placebo in patients with rheumatoid arthritis (www.clinicaltrials.gov; NCT02808871), and the phase 2 RELIEF study that explores pirfenidone vs placebo in patients with progressive ILD from a variety of etiologies.
As more clinical trials are published, clinicians are now facing a different dilemma. Whereas the options for treatment were limited to only various anti-inflammatory medications in past years for patients with non-IPF ILDs, the growing body of literature supporting antifibrotics present a new therapeutic avenue to explore. Which patients should be started on anti-inflammatory medications, and which should start antifibrotics? Those questions may never be answered satisfactorily in clinical trials. Mycophenolate has become so entrenched in many treatment plans, enrollment into such a study comparing the two therapeutic classes head-to-head would be challenging.
However, a consideration of the specific phenotype of the patient’s ILD is a suggested approach that comes from clinical experience. Patients with more inflammatory changes on CT scan, such as more ground glass opacifications or a non-UIP pattern, might benefit from initiation of anti-inflammatory therapies such as a combination of corticosteroids and mycophenolate. Conversely, initiating antifibrotic therapy upfront, with or without concomitant mycophenolate, is a consideration if the pattern of disease is consistent with UIP on CT scan.
Ultimately, referral to a dedicated interstitial lung disease center for expert evaluation and multidisciplinary discussion may be warranted to sift through these difficult situations, especially as the field of research grows more robust. In any event, the future for patients with these diseases, though still challenged, is brighter than before.
Dr. Kershaw is Associate Professor of Medicine, Division of Pulmonary & Critical Care Medicine, University of Texas Southwestern Medical Center. He is the current section editor for Pulmonary
Perpsectives®and Vice Chair of the Interstitial and Diffuse Lung Disease NetWork at CHEST.
FDA-approved peanut immunotherapy protocol comes with a cost
Peanut allergy immunotherapy now comes with approval from the US Food and Drug Administration (FDA), but it also comes with protocols, standards, and paperwork. Whether it will be widely adopted has yet to be determined.
A few dozen allergists around the world have been offering food allergy immunotherapy for many years, having developed their own measuring techniques using store-bought food.
But the vast majority of allergists are not interested in developing home-grown treatments, not only because it involves research and development, but also because it comes with legal risks.
“Finally we have another treatment option,” said Edwin Kim, MD, from the UNC Allergy and Immunology Clinic in Chapel Hill, N.C. “This is what we were waiting for. It’s not cowboy stuff; this works.”
In January, the FDA approved peanut allergen powder (Palforzia) for patients 4-17 years of age, as reported by Medscape Medical News.
The pill contains measured doses of peanut flour and comes with a protocol that will allow allergists to bring patients to a peanut tolerance of 300 mg (about one peanut) and a black-box warning about anaphylaxis risk.
And before allergists can prescribe it, they must take a Risk Evaluation and Mitigation Strategy course to learn about dosing and the allergic reaction protocol.
“That may scare some away,” said Dr. Kim, who discussed the FDA-approved option during his presentation at the American College of Allergy, Asthma & Immunology 2020 Annual Scientific Meeting.
Allergic reaction, including the potential for anaphylaxis, has always been an issue with immunotherapy.
“People make the argument that there is a difference” between an expected allergic reaction – such as one that occurs after the administration of immunotherapy – and an unexpected reaction, he said. Because an expected reaction can be treated quickly, “some feel these expected reactions don’t matter so much.”
“Others say a reaction is a reaction” and argue that if, a treatment causes reaction, then it doesn’t make sense, he explained.
It comes down to patients – they must be willing to take a risk to develop tolerance and improve their quality of life – and the allergists willing to treat them.
The peanut powder involves paperwork, preauthorization forms, denials of care, a higher price tag, regimented procedures, and a prerequisite number of visits with patients. “Not everyone will want to do this,” said Dr. Kim.
The regimen involves three phases. During initial dose escalation, five doses are administered in the office on day 1. Then, over the next 6 months, updoses are administered during 11 in-office sessions and a 300-mg tolerance is achieved. Finally, to maintain tolerance to one peanut, daily doses are administered at home.
The drug cost alone is about $4,200 a year, according to Institute for Clinical and Economic Review. Peanut flour from the grocery store is cheaper, but comes with the risk of bacteria or other contamination.
“This product offers some reassurance, and that matters,” Dr. Kim said.
It’s good to have more options for food allergy treatment. “We need a more proactive way to treat food allergy; avoidance is not good enough,” he explained. “And presumably, at some point, the patient will be able to eat a grocery-store peanut instead of buying the pills.”
The art of medicine
But not all allergists will be able to make the protocol work. And it’s not clear whether there is room to alter treatment and offer patients with a higher tolerance a higher starting dose. What we do know, though, is that “the product leaves little room for ‘the art of medicine,’ ” Kim said.
That art is practiced by Arnon Elizur, MD, from the Shamir Medical Center in Tzrifin, Israel, but it’s backed by a rigid home-grown protocol.
Since 2010, he has treated 1,800 patients for peanut allergy, updosing slowly to a tolerance of 3,000 mg of peanut, the equivalent of 10 peanuts. He keeps the maintenance dose at four peanuts (1,200 mg). His center takes a personalized approach, starting patients on the highest dose they can tolerate and working up, with daily patient check-ins from home and a staff available around the clock to answer questions and deal with reactions.
“We aim for full sensitization,” Dr. Elizur said in an interview.
The peanut pill is “a big step forward” for immunotherapy, he said. It is “a standardized product, checked for bacteria and allergen content, which is available to a wide community of physicians.”
But, he pointed out, “it’s expensive.” And it’s only for peanut. “There are millions of food-allergic patients around the world dying from adverse reactions to many different kinds of food. We don’t want to wait for years for a product for all of them. We can use the actual food.”
He questions the lifelong maintenance protocol with a daily 300-mg pill. “If you can’t eat a peanut, why would you buy a drug that’s a peanut?” he asked.
He also said he’s disappointed that the product is not indicated for adults.
At the Shamir clinic, reactions are closely monitored. “Some are mild, others we treat with autoinjectors, epinephrine,” he reported. “Those are the most undesirable.”
Data from his center show that reactions occur in about 15% of patients. But his treatment success rates are good. In an average of 8 months, he is able to get 80% of his adult patients to full sensitization.
But it’s not for all patients or for all clinics, he acknowledged. “We continue to look at this balance in quality of life throughout the process. Our goal is to improve the quality of life threshold.”
Treatment that involves “native food” is “a lot of work” and requires “a lot of investment,” Dr. Elizur said. His center uses a web reporting system to maintain a 24/7 dialogue with patients, “and we look at the reports every day.” They also have a physician on call at all times. “Not everyone can commit to providing care throughout the day and night.”
His center charges the equivalent of $US3,000 per food allergy treated. “That’s whether it takes 6 months or 2 years,” he said.
There are more than 1,000 people on his 3-year waiting list.
“This is the first year that the American College of Allergy, Asthma, and Immunology is not hosting a pro–con debate on oral immunotherapy,” Dr. Kim pointed out. “We have a therapy now.”
However, the pandemic has slowed treatment uptake. “Immunotherapy is not easy to do, whether it’s FDA approved or not,” he explained. With at least 11 doctor visits in the first 6 months – each visit is between 30 minutes and 2-3 hours long – it hasn’t been possible to set up this year. “It’s not ideal.”
It will be interesting to see “how this will roll out and how it will be adopted,” Dr. Kim said. “From a food allergy point of view, the next 12 months are going to be very interesting.”
Dr. Kim reports receiving consulting honorarium from Aimmune, the maker of Palforzia; being on the clinical medical advisory board for DBV Technologies; and consulting for Aimmune, Allakos, Allergenis, DBV, Duke Clinical Research Institute, Ukko Incorporated, Vibrant America, and Kenota Health. Dr. Elizur has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Peanut allergy immunotherapy now comes with approval from the US Food and Drug Administration (FDA), but it also comes with protocols, standards, and paperwork. Whether it will be widely adopted has yet to be determined.
A few dozen allergists around the world have been offering food allergy immunotherapy for many years, having developed their own measuring techniques using store-bought food.
But the vast majority of allergists are not interested in developing home-grown treatments, not only because it involves research and development, but also because it comes with legal risks.
“Finally we have another treatment option,” said Edwin Kim, MD, from the UNC Allergy and Immunology Clinic in Chapel Hill, N.C. “This is what we were waiting for. It’s not cowboy stuff; this works.”
In January, the FDA approved peanut allergen powder (Palforzia) for patients 4-17 years of age, as reported by Medscape Medical News.
The pill contains measured doses of peanut flour and comes with a protocol that will allow allergists to bring patients to a peanut tolerance of 300 mg (about one peanut) and a black-box warning about anaphylaxis risk.
And before allergists can prescribe it, they must take a Risk Evaluation and Mitigation Strategy course to learn about dosing and the allergic reaction protocol.
“That may scare some away,” said Dr. Kim, who discussed the FDA-approved option during his presentation at the American College of Allergy, Asthma & Immunology 2020 Annual Scientific Meeting.
Allergic reaction, including the potential for anaphylaxis, has always been an issue with immunotherapy.
“People make the argument that there is a difference” between an expected allergic reaction – such as one that occurs after the administration of immunotherapy – and an unexpected reaction, he said. Because an expected reaction can be treated quickly, “some feel these expected reactions don’t matter so much.”
“Others say a reaction is a reaction” and argue that if, a treatment causes reaction, then it doesn’t make sense, he explained.
It comes down to patients – they must be willing to take a risk to develop tolerance and improve their quality of life – and the allergists willing to treat them.
The peanut powder involves paperwork, preauthorization forms, denials of care, a higher price tag, regimented procedures, and a prerequisite number of visits with patients. “Not everyone will want to do this,” said Dr. Kim.
The regimen involves three phases. During initial dose escalation, five doses are administered in the office on day 1. Then, over the next 6 months, updoses are administered during 11 in-office sessions and a 300-mg tolerance is achieved. Finally, to maintain tolerance to one peanut, daily doses are administered at home.
The drug cost alone is about $4,200 a year, according to Institute for Clinical and Economic Review. Peanut flour from the grocery store is cheaper, but comes with the risk of bacteria or other contamination.
“This product offers some reassurance, and that matters,” Dr. Kim said.
It’s good to have more options for food allergy treatment. “We need a more proactive way to treat food allergy; avoidance is not good enough,” he explained. “And presumably, at some point, the patient will be able to eat a grocery-store peanut instead of buying the pills.”
The art of medicine
But not all allergists will be able to make the protocol work. And it’s not clear whether there is room to alter treatment and offer patients with a higher tolerance a higher starting dose. What we do know, though, is that “the product leaves little room for ‘the art of medicine,’ ” Kim said.
That art is practiced by Arnon Elizur, MD, from the Shamir Medical Center in Tzrifin, Israel, but it’s backed by a rigid home-grown protocol.
Since 2010, he has treated 1,800 patients for peanut allergy, updosing slowly to a tolerance of 3,000 mg of peanut, the equivalent of 10 peanuts. He keeps the maintenance dose at four peanuts (1,200 mg). His center takes a personalized approach, starting patients on the highest dose they can tolerate and working up, with daily patient check-ins from home and a staff available around the clock to answer questions and deal with reactions.
“We aim for full sensitization,” Dr. Elizur said in an interview.
The peanut pill is “a big step forward” for immunotherapy, he said. It is “a standardized product, checked for bacteria and allergen content, which is available to a wide community of physicians.”
But, he pointed out, “it’s expensive.” And it’s only for peanut. “There are millions of food-allergic patients around the world dying from adverse reactions to many different kinds of food. We don’t want to wait for years for a product for all of them. We can use the actual food.”
He questions the lifelong maintenance protocol with a daily 300-mg pill. “If you can’t eat a peanut, why would you buy a drug that’s a peanut?” he asked.
He also said he’s disappointed that the product is not indicated for adults.
At the Shamir clinic, reactions are closely monitored. “Some are mild, others we treat with autoinjectors, epinephrine,” he reported. “Those are the most undesirable.”
Data from his center show that reactions occur in about 15% of patients. But his treatment success rates are good. In an average of 8 months, he is able to get 80% of his adult patients to full sensitization.
But it’s not for all patients or for all clinics, he acknowledged. “We continue to look at this balance in quality of life throughout the process. Our goal is to improve the quality of life threshold.”
Treatment that involves “native food” is “a lot of work” and requires “a lot of investment,” Dr. Elizur said. His center uses a web reporting system to maintain a 24/7 dialogue with patients, “and we look at the reports every day.” They also have a physician on call at all times. “Not everyone can commit to providing care throughout the day and night.”
His center charges the equivalent of $US3,000 per food allergy treated. “That’s whether it takes 6 months or 2 years,” he said.
There are more than 1,000 people on his 3-year waiting list.
“This is the first year that the American College of Allergy, Asthma, and Immunology is not hosting a pro–con debate on oral immunotherapy,” Dr. Kim pointed out. “We have a therapy now.”
However, the pandemic has slowed treatment uptake. “Immunotherapy is not easy to do, whether it’s FDA approved or not,” he explained. With at least 11 doctor visits in the first 6 months – each visit is between 30 minutes and 2-3 hours long – it hasn’t been possible to set up this year. “It’s not ideal.”
It will be interesting to see “how this will roll out and how it will be adopted,” Dr. Kim said. “From a food allergy point of view, the next 12 months are going to be very interesting.”
Dr. Kim reports receiving consulting honorarium from Aimmune, the maker of Palforzia; being on the clinical medical advisory board for DBV Technologies; and consulting for Aimmune, Allakos, Allergenis, DBV, Duke Clinical Research Institute, Ukko Incorporated, Vibrant America, and Kenota Health. Dr. Elizur has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Peanut allergy immunotherapy now comes with approval from the US Food and Drug Administration (FDA), but it also comes with protocols, standards, and paperwork. Whether it will be widely adopted has yet to be determined.
A few dozen allergists around the world have been offering food allergy immunotherapy for many years, having developed their own measuring techniques using store-bought food.
But the vast majority of allergists are not interested in developing home-grown treatments, not only because it involves research and development, but also because it comes with legal risks.
“Finally we have another treatment option,” said Edwin Kim, MD, from the UNC Allergy and Immunology Clinic in Chapel Hill, N.C. “This is what we were waiting for. It’s not cowboy stuff; this works.”
In January, the FDA approved peanut allergen powder (Palforzia) for patients 4-17 years of age, as reported by Medscape Medical News.
The pill contains measured doses of peanut flour and comes with a protocol that will allow allergists to bring patients to a peanut tolerance of 300 mg (about one peanut) and a black-box warning about anaphylaxis risk.
And before allergists can prescribe it, they must take a Risk Evaluation and Mitigation Strategy course to learn about dosing and the allergic reaction protocol.
“That may scare some away,” said Dr. Kim, who discussed the FDA-approved option during his presentation at the American College of Allergy, Asthma & Immunology 2020 Annual Scientific Meeting.
Allergic reaction, including the potential for anaphylaxis, has always been an issue with immunotherapy.
“People make the argument that there is a difference” between an expected allergic reaction – such as one that occurs after the administration of immunotherapy – and an unexpected reaction, he said. Because an expected reaction can be treated quickly, “some feel these expected reactions don’t matter so much.”
“Others say a reaction is a reaction” and argue that if, a treatment causes reaction, then it doesn’t make sense, he explained.
It comes down to patients – they must be willing to take a risk to develop tolerance and improve their quality of life – and the allergists willing to treat them.
The peanut powder involves paperwork, preauthorization forms, denials of care, a higher price tag, regimented procedures, and a prerequisite number of visits with patients. “Not everyone will want to do this,” said Dr. Kim.
The regimen involves three phases. During initial dose escalation, five doses are administered in the office on day 1. Then, over the next 6 months, updoses are administered during 11 in-office sessions and a 300-mg tolerance is achieved. Finally, to maintain tolerance to one peanut, daily doses are administered at home.
The drug cost alone is about $4,200 a year, according to Institute for Clinical and Economic Review. Peanut flour from the grocery store is cheaper, but comes with the risk of bacteria or other contamination.
“This product offers some reassurance, and that matters,” Dr. Kim said.
It’s good to have more options for food allergy treatment. “We need a more proactive way to treat food allergy; avoidance is not good enough,” he explained. “And presumably, at some point, the patient will be able to eat a grocery-store peanut instead of buying the pills.”
The art of medicine
But not all allergists will be able to make the protocol work. And it’s not clear whether there is room to alter treatment and offer patients with a higher tolerance a higher starting dose. What we do know, though, is that “the product leaves little room for ‘the art of medicine,’ ” Kim said.
That art is practiced by Arnon Elizur, MD, from the Shamir Medical Center in Tzrifin, Israel, but it’s backed by a rigid home-grown protocol.
Since 2010, he has treated 1,800 patients for peanut allergy, updosing slowly to a tolerance of 3,000 mg of peanut, the equivalent of 10 peanuts. He keeps the maintenance dose at four peanuts (1,200 mg). His center takes a personalized approach, starting patients on the highest dose they can tolerate and working up, with daily patient check-ins from home and a staff available around the clock to answer questions and deal with reactions.
“We aim for full sensitization,” Dr. Elizur said in an interview.
The peanut pill is “a big step forward” for immunotherapy, he said. It is “a standardized product, checked for bacteria and allergen content, which is available to a wide community of physicians.”
But, he pointed out, “it’s expensive.” And it’s only for peanut. “There are millions of food-allergic patients around the world dying from adverse reactions to many different kinds of food. We don’t want to wait for years for a product for all of them. We can use the actual food.”
He questions the lifelong maintenance protocol with a daily 300-mg pill. “If you can’t eat a peanut, why would you buy a drug that’s a peanut?” he asked.
He also said he’s disappointed that the product is not indicated for adults.
At the Shamir clinic, reactions are closely monitored. “Some are mild, others we treat with autoinjectors, epinephrine,” he reported. “Those are the most undesirable.”
Data from his center show that reactions occur in about 15% of patients. But his treatment success rates are good. In an average of 8 months, he is able to get 80% of his adult patients to full sensitization.
But it’s not for all patients or for all clinics, he acknowledged. “We continue to look at this balance in quality of life throughout the process. Our goal is to improve the quality of life threshold.”
Treatment that involves “native food” is “a lot of work” and requires “a lot of investment,” Dr. Elizur said. His center uses a web reporting system to maintain a 24/7 dialogue with patients, “and we look at the reports every day.” They also have a physician on call at all times. “Not everyone can commit to providing care throughout the day and night.”
His center charges the equivalent of $US3,000 per food allergy treated. “That’s whether it takes 6 months or 2 years,” he said.
There are more than 1,000 people on his 3-year waiting list.
“This is the first year that the American College of Allergy, Asthma, and Immunology is not hosting a pro–con debate on oral immunotherapy,” Dr. Kim pointed out. “We have a therapy now.”
However, the pandemic has slowed treatment uptake. “Immunotherapy is not easy to do, whether it’s FDA approved or not,” he explained. With at least 11 doctor visits in the first 6 months – each visit is between 30 minutes and 2-3 hours long – it hasn’t been possible to set up this year. “It’s not ideal.”
It will be interesting to see “how this will roll out and how it will be adopted,” Dr. Kim said. “From a food allergy point of view, the next 12 months are going to be very interesting.”
Dr. Kim reports receiving consulting honorarium from Aimmune, the maker of Palforzia; being on the clinical medical advisory board for DBV Technologies; and consulting for Aimmune, Allakos, Allergenis, DBV, Duke Clinical Research Institute, Ukko Incorporated, Vibrant America, and Kenota Health. Dr. Elizur has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Poverty raises depression risk in patients with cystic fibrosis
Poor people with chronic illness have greater difficulty managing their disease than do their better-off counterparts, and a new study confirms this reality for patients with cystic fibrosis.
and anxiety symptoms, according to a new cross-sectional study. The data were drawn from the Cystic Fibrosis Foundation’s Success with Therapies Research Consortium.
“Assessing the special challenges that individuals with lower SES face, including financial barriers, is essential to understand how we can address the unique combinations of adherence barriers. In other chronic disorders, financial barriers or lower socioeconomic status is associated with nonadherence, but this relationship has not been well established in cystic fibrosis,” said Kimberly Dickinson, MD, MPH, of Johns Hopkins University, Baltimore, during her presentation of the results at the virtual North American Cystic Fibrosis Conference.
“I’ve always thought that my patients in the poorer population were doing worse, and I think this demonstrates that that’s true,” said Robert Giusti, MD, in an interview. Dr. Giusti is a clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center in New York. He was not involved in the study.
“These are very pertinent issues, especially if you think about the pandemic, and some of the issues related to mental health. It just highlights the importance of socioeconomic status and screening for some of the known risk factors so that we can develop interventions or programs to provide equitable care to all of our cystic fibrosis patients,” said Ryan Perkins, MD, who moderated the session where the study was presented. He is a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, also in Boston.
The researchers looked retrospectively at 1 year’s worth of pharmacy refill receipts and number of times prescriptions were refilled versus the number of times prescribed, then calculated medicinal possession ratios. This was cross-referenced with annual household income and insurance status of patients with CF at 12 pediatric and 9 adult CF care centers, for a total of 376 patients (128 pediatric and 248 adult).
In this population, 32% of participants had public or no insurance, 68% had private or military insurance. The public/no insurance group was more likely than the private/military insurance group to report having trouble paying for treatments, food, or critical expenses related to CF care (23.3% vs. 12.1%, respectively); feeling symptoms on most days of depression (42.5% vs. 31.3%) or anxiety (40.0% vs. 28.5%); and experiencing conflict or stress with loved ones over treatments (30.0% vs. 20.3%) (P < .05 for all).
In all, 35% had a household income less than $40,000 per year, 33% between $44,000 and $100,000, and 32% higher than $100,000. The low-income group had a lower composite medication possession ratio (0.41) than the middle- (0.44) or high-income (0.52) groups, were more likely to have trouble paying for treatments, food, or treatment-related expenses (25%, 18%, 4%, respectively); were more likely most days to report symptoms of depression (43%, 34%, 26%) or anxiety (40%, 32%, 24%), and to have concerns about whether treatments were effective (42%, 27%, 29%). They were more likely to not be able to maintain a daily schedule or routine for treatments (28%, 22%, 14%).
The study showed that adherence barriers and suboptimal adherence are issues that cross all socioeconomic categories, though they were more problematic in the lowest bracket. Greater anxiety and depression among lower income individuals and those with private or no insurance was a key finding, according to Dr. Dickinson. “It highlights the importance of screening for mental health comorbidities that may impact non-adherence,” she said.
The study received funding from the Cystic Fibrosis Foundation. Dr. Dickinson, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.
Poor people with chronic illness have greater difficulty managing their disease than do their better-off counterparts, and a new study confirms this reality for patients with cystic fibrosis.
and anxiety symptoms, according to a new cross-sectional study. The data were drawn from the Cystic Fibrosis Foundation’s Success with Therapies Research Consortium.
“Assessing the special challenges that individuals with lower SES face, including financial barriers, is essential to understand how we can address the unique combinations of adherence barriers. In other chronic disorders, financial barriers or lower socioeconomic status is associated with nonadherence, but this relationship has not been well established in cystic fibrosis,” said Kimberly Dickinson, MD, MPH, of Johns Hopkins University, Baltimore, during her presentation of the results at the virtual North American Cystic Fibrosis Conference.
“I’ve always thought that my patients in the poorer population were doing worse, and I think this demonstrates that that’s true,” said Robert Giusti, MD, in an interview. Dr. Giusti is a clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center in New York. He was not involved in the study.
“These are very pertinent issues, especially if you think about the pandemic, and some of the issues related to mental health. It just highlights the importance of socioeconomic status and screening for some of the known risk factors so that we can develop interventions or programs to provide equitable care to all of our cystic fibrosis patients,” said Ryan Perkins, MD, who moderated the session where the study was presented. He is a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, also in Boston.
The researchers looked retrospectively at 1 year’s worth of pharmacy refill receipts and number of times prescriptions were refilled versus the number of times prescribed, then calculated medicinal possession ratios. This was cross-referenced with annual household income and insurance status of patients with CF at 12 pediatric and 9 adult CF care centers, for a total of 376 patients (128 pediatric and 248 adult).
In this population, 32% of participants had public or no insurance, 68% had private or military insurance. The public/no insurance group was more likely than the private/military insurance group to report having trouble paying for treatments, food, or critical expenses related to CF care (23.3% vs. 12.1%, respectively); feeling symptoms on most days of depression (42.5% vs. 31.3%) or anxiety (40.0% vs. 28.5%); and experiencing conflict or stress with loved ones over treatments (30.0% vs. 20.3%) (P < .05 for all).
In all, 35% had a household income less than $40,000 per year, 33% between $44,000 and $100,000, and 32% higher than $100,000. The low-income group had a lower composite medication possession ratio (0.41) than the middle- (0.44) or high-income (0.52) groups, were more likely to have trouble paying for treatments, food, or treatment-related expenses (25%, 18%, 4%, respectively); were more likely most days to report symptoms of depression (43%, 34%, 26%) or anxiety (40%, 32%, 24%), and to have concerns about whether treatments were effective (42%, 27%, 29%). They were more likely to not be able to maintain a daily schedule or routine for treatments (28%, 22%, 14%).
The study showed that adherence barriers and suboptimal adherence are issues that cross all socioeconomic categories, though they were more problematic in the lowest bracket. Greater anxiety and depression among lower income individuals and those with private or no insurance was a key finding, according to Dr. Dickinson. “It highlights the importance of screening for mental health comorbidities that may impact non-adherence,” she said.
The study received funding from the Cystic Fibrosis Foundation. Dr. Dickinson, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.
Poor people with chronic illness have greater difficulty managing their disease than do their better-off counterparts, and a new study confirms this reality for patients with cystic fibrosis.
and anxiety symptoms, according to a new cross-sectional study. The data were drawn from the Cystic Fibrosis Foundation’s Success with Therapies Research Consortium.
“Assessing the special challenges that individuals with lower SES face, including financial barriers, is essential to understand how we can address the unique combinations of adherence barriers. In other chronic disorders, financial barriers or lower socioeconomic status is associated with nonadherence, but this relationship has not been well established in cystic fibrosis,” said Kimberly Dickinson, MD, MPH, of Johns Hopkins University, Baltimore, during her presentation of the results at the virtual North American Cystic Fibrosis Conference.
“I’ve always thought that my patients in the poorer population were doing worse, and I think this demonstrates that that’s true,” said Robert Giusti, MD, in an interview. Dr. Giusti is a clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center in New York. He was not involved in the study.
“These are very pertinent issues, especially if you think about the pandemic, and some of the issues related to mental health. It just highlights the importance of socioeconomic status and screening for some of the known risk factors so that we can develop interventions or programs to provide equitable care to all of our cystic fibrosis patients,” said Ryan Perkins, MD, who moderated the session where the study was presented. He is a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, also in Boston.
The researchers looked retrospectively at 1 year’s worth of pharmacy refill receipts and number of times prescriptions were refilled versus the number of times prescribed, then calculated medicinal possession ratios. This was cross-referenced with annual household income and insurance status of patients with CF at 12 pediatric and 9 adult CF care centers, for a total of 376 patients (128 pediatric and 248 adult).
In this population, 32% of participants had public or no insurance, 68% had private or military insurance. The public/no insurance group was more likely than the private/military insurance group to report having trouble paying for treatments, food, or critical expenses related to CF care (23.3% vs. 12.1%, respectively); feeling symptoms on most days of depression (42.5% vs. 31.3%) or anxiety (40.0% vs. 28.5%); and experiencing conflict or stress with loved ones over treatments (30.0% vs. 20.3%) (P < .05 for all).
In all, 35% had a household income less than $40,000 per year, 33% between $44,000 and $100,000, and 32% higher than $100,000. The low-income group had a lower composite medication possession ratio (0.41) than the middle- (0.44) or high-income (0.52) groups, were more likely to have trouble paying for treatments, food, or treatment-related expenses (25%, 18%, 4%, respectively); were more likely most days to report symptoms of depression (43%, 34%, 26%) or anxiety (40%, 32%, 24%), and to have concerns about whether treatments were effective (42%, 27%, 29%). They were more likely to not be able to maintain a daily schedule or routine for treatments (28%, 22%, 14%).
The study showed that adherence barriers and suboptimal adherence are issues that cross all socioeconomic categories, though they were more problematic in the lowest bracket. Greater anxiety and depression among lower income individuals and those with private or no insurance was a key finding, according to Dr. Dickinson. “It highlights the importance of screening for mental health comorbidities that may impact non-adherence,” she said.
The study received funding from the Cystic Fibrosis Foundation. Dr. Dickinson, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.
FROM NACFC 2020
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Dripping, dabbing, and bongs: Can’t tell the players without a scorecard
E-cigarettes may be synonymous with vaping to most physicians, but there are other ways for patients to inhale nicotine or tetrahydrocannabinol-containing aerosols, according to investigators at the Cleveland Clinic. 
Humberto Choi, MD, and associates wrote in the Annals of the American Thoracic Society.
These “alternate aerosol inhalation methods” have been poorly described thus far, so little is known about their scope of use and potential health impact, they noted.
Dripping involves an e-cigarette modified to expose the heating coil. The e-cigarette liquid is dripped directly onto the hot coil, which produces immediate aerosolization and results in a thicker cloud.
Dripping “may expose users to higher levels of nicotine compared to e-cigarette inhalation” and lead to “increased release of volatile aldehydes as a result of the higher heating potential of direct atomizer exposure,” the investigators suggested.
Water pipes, or bongs, produce both smoke and vapor, although an electronic vaporizer can be attached to create a “vape bong.” About 21% of daily cannabis users report using a bong, but tobacco inhalation is less common. Cases of severe pulmonary infections have been associated with bong use, along with a couple of tuberculosis clusters, Dr. Choi and associates said.
Dabbing uses butane-extracted, concentrated cannabis oil inhaled through a modified water pipe or bong or a smaller device called a “dab pen.” A small amount, or “dab,” of the product is placed on the “nail,” which replaces the bowl of the water pipe, heated with a blowtorch, and inhaled through the pipe, the researchers explained.
The prevalence of dabbing is unknown, but “the most recent Monitoring the Future survey of high school seniors shows that 11.9% of students have used a marijuana vaporizer at some point in their life,” they said.
Besides the fire risks involved in creating the material needed for dabbing – use of heating plates, ovens, and devices for removing butane vapors – inhalation of residual butane vapors could lead to vomiting, cardiac arrhythmias, acute encephalopathy, and respiratory depression, Dr. Choi and associates said.
Nicotine dependence is also a concern, as is the possibility of withdrawal symptoms. “Patients presenting with prolonged and severe vomiting, psychotic symptoms, or other acute neuropsychiatric symptoms should raise the suspicion of [tetrahydrocannabinol]-containing products especially synthetic cannabinoids,” they wrote.
SOURCE: Choi H et al. Ann Am Thorac Soc. 2020 Oct 14. doi: 10.1513/AnnalsATS.202005-511CME.
E-cigarettes may be synonymous with vaping to most physicians, but there are other ways for patients to inhale nicotine or tetrahydrocannabinol-containing aerosols, according to investigators at the Cleveland Clinic.
Humberto Choi, MD, and associates wrote in the Annals of the American Thoracic Society.
These “alternate aerosol inhalation methods” have been poorly described thus far, so little is known about their scope of use and potential health impact, they noted.
Dripping involves an e-cigarette modified to expose the heating coil. The e-cigarette liquid is dripped directly onto the hot coil, which produces immediate aerosolization and results in a thicker cloud.
Dripping “may expose users to higher levels of nicotine compared to e-cigarette inhalation” and lead to “increased release of volatile aldehydes as a result of the higher heating potential of direct atomizer exposure,” the investigators suggested.
Water pipes, or bongs, produce both smoke and vapor, although an electronic vaporizer can be attached to create a “vape bong.” About 21% of daily cannabis users report using a bong, but tobacco inhalation is less common. Cases of severe pulmonary infections have been associated with bong use, along with a couple of tuberculosis clusters, Dr. Choi and associates said.
Dabbing uses butane-extracted, concentrated cannabis oil inhaled through a modified water pipe or bong or a smaller device called a “dab pen.” A small amount, or “dab,” of the product is placed on the “nail,” which replaces the bowl of the water pipe, heated with a blowtorch, and inhaled through the pipe, the researchers explained.
The prevalence of dabbing is unknown, but “the most recent Monitoring the Future survey of high school seniors shows that 11.9% of students have used a marijuana vaporizer at some point in their life,” they said.
Besides the fire risks involved in creating the material needed for dabbing – use of heating plates, ovens, and devices for removing butane vapors – inhalation of residual butane vapors could lead to vomiting, cardiac arrhythmias, acute encephalopathy, and respiratory depression, Dr. Choi and associates said.
Nicotine dependence is also a concern, as is the possibility of withdrawal symptoms. “Patients presenting with prolonged and severe vomiting, psychotic symptoms, or other acute neuropsychiatric symptoms should raise the suspicion of [tetrahydrocannabinol]-containing products especially synthetic cannabinoids,” they wrote.
SOURCE: Choi H et al. Ann Am Thorac Soc. 2020 Oct 14. doi: 10.1513/AnnalsATS.202005-511CME.
E-cigarettes may be synonymous with vaping to most physicians, but there are other ways for patients to inhale nicotine or tetrahydrocannabinol-containing aerosols, according to investigators at the Cleveland Clinic.
Humberto Choi, MD, and associates wrote in the Annals of the American Thoracic Society.
These “alternate aerosol inhalation methods” have been poorly described thus far, so little is known about their scope of use and potential health impact, they noted.
Dripping involves an e-cigarette modified to expose the heating coil. The e-cigarette liquid is dripped directly onto the hot coil, which produces immediate aerosolization and results in a thicker cloud.
Dripping “may expose users to higher levels of nicotine compared to e-cigarette inhalation” and lead to “increased release of volatile aldehydes as a result of the higher heating potential of direct atomizer exposure,” the investigators suggested.
Water pipes, or bongs, produce both smoke and vapor, although an electronic vaporizer can be attached to create a “vape bong.” About 21% of daily cannabis users report using a bong, but tobacco inhalation is less common. Cases of severe pulmonary infections have been associated with bong use, along with a couple of tuberculosis clusters, Dr. Choi and associates said.
Dabbing uses butane-extracted, concentrated cannabis oil inhaled through a modified water pipe or bong or a smaller device called a “dab pen.” A small amount, or “dab,” of the product is placed on the “nail,” which replaces the bowl of the water pipe, heated with a blowtorch, and inhaled through the pipe, the researchers explained.
The prevalence of dabbing is unknown, but “the most recent Monitoring the Future survey of high school seniors shows that 11.9% of students have used a marijuana vaporizer at some point in their life,” they said.
Besides the fire risks involved in creating the material needed for dabbing – use of heating plates, ovens, and devices for removing butane vapors – inhalation of residual butane vapors could lead to vomiting, cardiac arrhythmias, acute encephalopathy, and respiratory depression, Dr. Choi and associates said.
Nicotine dependence is also a concern, as is the possibility of withdrawal symptoms. “Patients presenting with prolonged and severe vomiting, psychotic symptoms, or other acute neuropsychiatric symptoms should raise the suspicion of [tetrahydrocannabinol]-containing products especially synthetic cannabinoids,” they wrote.
SOURCE: Choi H et al. Ann Am Thorac Soc. 2020 Oct 14. doi: 10.1513/AnnalsATS.202005-511CME.
FROM ANNALS OF THE AMERICAN THORACIC SOCIETY
Triple combination therapy for cystic fibrosis linked to plunging hospitalizations
.
The triple combination therapy elexacaftor/tezacaftor/ivacaftor was associated with a near elimination of hospital stays in one hospital in Oregon, according to a new report. The hospital savings still weren’t nearly enough to pay for the cost of therapy, but the study underscores what many institutions have observed and adds a new layer to the view of quality of life improvements that the new therapy brings.
“After we started prescribing it, we noticed pretty quickly that hospitalizations appeared to be declining after patients started triple combination therapy, and we were hearing [similar reports] from other centers as well. We wanted to quantify this,” Eric C. Walter, MD, a pulmonologist at the Kaiser Permanente Cystic Fibrosis Clinic in Portland, Ore., said during a presentation of the results at the virtual North American Cystic Fibrosis Conference.
“We’re seeing that across the board in real practice, the number of cystic fibrosis patients that have to be hospitalized since starting this triple combination has gone down,” Robert Giusti, MD, said in an interview. “When they’ve had pulmonary exacerbations in the past, it was frequently because they failed outpatient antibiotics, but I think with triple combination therapy, if they do get sick, the likelihood is they will respond to oral antibiotics, so they may not need that prolonged IV course in the hospital.” Dr. Giusti is clinical professor of pediatrics at New York University and director of the Pediatric Cystic Fibrosis Center. He was not involved in the study.
The therapy gained Food and Drug Administration approval in 2019 for the treatment of individuals with CF who are aged 12 years and older, and who have at least one copy of the F508del mutation. Its cost is about $317,000 per year within the Kaiser Permanente system, according to Dr. Walter. His group compared hospitalization days for CF-related diagnoses from Jan. 1 through Aug. 31, 2020, before and after initiation of triple combination therapy.
Of 47 eligible patients, 32 initiated therapy during the study period; 38% had severe lung disease, defined by forced expiratory volume in 1 second (FEV1) value less than 40%. In 2020, before initiation of therapy, there were an average of 27 hospital days per month, all among patients with severe lung disease.
Among the therapy group, there were no hospitalizations after initiation of therapy through Aug. 31. Dr. Walter noted that the first hospitalization of a patient on triple combination therapy didn’t occur until early October.
At an average daily cost of $6,700, the researchers calculated that triple combination therapy saved about $189,000 per month in this group of patients. Comparing numbers to previous years, in which some patients with FEV1 greater than 40% were hospitalized, the researchers calculated that the therapy saved about $151,000 per month among individuals with severe lung disease: Patients with severe lung disease contributed about 80% to total hospital costs.
The drug itself for the whole group cost $845,000, dwarfing the $189,000 savings overall. But among patients with severe disease, hospitalization savings were about $151,000 per month, while the drug cost in this group was $316,800 per month.
Cost savings are important, but the improvement in quality of life for a patient – avoiding hospitalization, fewer impacts on work and education – should not be overlooked, according to Ryan Perkins, MD, a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, who moderated the session. “Some of these aren’t things people typically quantify and assign a price tag to,” Dr. Perkins said in an interview.
A big limitation of the work is that it was conducted during the COVID-19 pandemic, which may have reduced hospitalizations. “We did have patients that called in, told us they were sick, that they needed to be treated for an exacerbation but didn’t want to go to the hospital,” said Dr. Walter. To help adjust for this, Dr. Walter’s team plans to compare intravenous antibiotic exposure before and after triple combination therapy, reasoning that it could help clarify the pandemic’s impact on hospitalizations.
Dr. Walter, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.
SOURCE: Walter E et al. NACFC 2020. Abstract 795.
.
The triple combination therapy elexacaftor/tezacaftor/ivacaftor was associated with a near elimination of hospital stays in one hospital in Oregon, according to a new report. The hospital savings still weren’t nearly enough to pay for the cost of therapy, but the study underscores what many institutions have observed and adds a new layer to the view of quality of life improvements that the new therapy brings.
“After we started prescribing it, we noticed pretty quickly that hospitalizations appeared to be declining after patients started triple combination therapy, and we were hearing [similar reports] from other centers as well. We wanted to quantify this,” Eric C. Walter, MD, a pulmonologist at the Kaiser Permanente Cystic Fibrosis Clinic in Portland, Ore., said during a presentation of the results at the virtual North American Cystic Fibrosis Conference.
“We’re seeing that across the board in real practice, the number of cystic fibrosis patients that have to be hospitalized since starting this triple combination has gone down,” Robert Giusti, MD, said in an interview. “When they’ve had pulmonary exacerbations in the past, it was frequently because they failed outpatient antibiotics, but I think with triple combination therapy, if they do get sick, the likelihood is they will respond to oral antibiotics, so they may not need that prolonged IV course in the hospital.” Dr. Giusti is clinical professor of pediatrics at New York University and director of the Pediatric Cystic Fibrosis Center. He was not involved in the study.
The therapy gained Food and Drug Administration approval in 2019 for the treatment of individuals with CF who are aged 12 years and older, and who have at least one copy of the F508del mutation. Its cost is about $317,000 per year within the Kaiser Permanente system, according to Dr. Walter. His group compared hospitalization days for CF-related diagnoses from Jan. 1 through Aug. 31, 2020, before and after initiation of triple combination therapy.
Of 47 eligible patients, 32 initiated therapy during the study period; 38% had severe lung disease, defined by forced expiratory volume in 1 second (FEV1) value less than 40%. In 2020, before initiation of therapy, there were an average of 27 hospital days per month, all among patients with severe lung disease.
Among the therapy group, there were no hospitalizations after initiation of therapy through Aug. 31. Dr. Walter noted that the first hospitalization of a patient on triple combination therapy didn’t occur until early October.
At an average daily cost of $6,700, the researchers calculated that triple combination therapy saved about $189,000 per month in this group of patients. Comparing numbers to previous years, in which some patients with FEV1 greater than 40% were hospitalized, the researchers calculated that the therapy saved about $151,000 per month among individuals with severe lung disease: Patients with severe lung disease contributed about 80% to total hospital costs.
The drug itself for the whole group cost $845,000, dwarfing the $189,000 savings overall. But among patients with severe disease, hospitalization savings were about $151,000 per month, while the drug cost in this group was $316,800 per month.
Cost savings are important, but the improvement in quality of life for a patient – avoiding hospitalization, fewer impacts on work and education – should not be overlooked, according to Ryan Perkins, MD, a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, who moderated the session. “Some of these aren’t things people typically quantify and assign a price tag to,” Dr. Perkins said in an interview.
A big limitation of the work is that it was conducted during the COVID-19 pandemic, which may have reduced hospitalizations. “We did have patients that called in, told us they were sick, that they needed to be treated for an exacerbation but didn’t want to go to the hospital,” said Dr. Walter. To help adjust for this, Dr. Walter’s team plans to compare intravenous antibiotic exposure before and after triple combination therapy, reasoning that it could help clarify the pandemic’s impact on hospitalizations.
Dr. Walter, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.
SOURCE: Walter E et al. NACFC 2020. Abstract 795.
.
The triple combination therapy elexacaftor/tezacaftor/ivacaftor was associated with a near elimination of hospital stays in one hospital in Oregon, according to a new report. The hospital savings still weren’t nearly enough to pay for the cost of therapy, but the study underscores what many institutions have observed and adds a new layer to the view of quality of life improvements that the new therapy brings.
“After we started prescribing it, we noticed pretty quickly that hospitalizations appeared to be declining after patients started triple combination therapy, and we were hearing [similar reports] from other centers as well. We wanted to quantify this,” Eric C. Walter, MD, a pulmonologist at the Kaiser Permanente Cystic Fibrosis Clinic in Portland, Ore., said during a presentation of the results at the virtual North American Cystic Fibrosis Conference.
“We’re seeing that across the board in real practice, the number of cystic fibrosis patients that have to be hospitalized since starting this triple combination has gone down,” Robert Giusti, MD, said in an interview. “When they’ve had pulmonary exacerbations in the past, it was frequently because they failed outpatient antibiotics, but I think with triple combination therapy, if they do get sick, the likelihood is they will respond to oral antibiotics, so they may not need that prolonged IV course in the hospital.” Dr. Giusti is clinical professor of pediatrics at New York University and director of the Pediatric Cystic Fibrosis Center. He was not involved in the study.
The therapy gained Food and Drug Administration approval in 2019 for the treatment of individuals with CF who are aged 12 years and older, and who have at least one copy of the F508del mutation. Its cost is about $317,000 per year within the Kaiser Permanente system, according to Dr. Walter. His group compared hospitalization days for CF-related diagnoses from Jan. 1 through Aug. 31, 2020, before and after initiation of triple combination therapy.
Of 47 eligible patients, 32 initiated therapy during the study period; 38% had severe lung disease, defined by forced expiratory volume in 1 second (FEV1) value less than 40%. In 2020, before initiation of therapy, there were an average of 27 hospital days per month, all among patients with severe lung disease.
Among the therapy group, there were no hospitalizations after initiation of therapy through Aug. 31. Dr. Walter noted that the first hospitalization of a patient on triple combination therapy didn’t occur until early October.
At an average daily cost of $6,700, the researchers calculated that triple combination therapy saved about $189,000 per month in this group of patients. Comparing numbers to previous years, in which some patients with FEV1 greater than 40% were hospitalized, the researchers calculated that the therapy saved about $151,000 per month among individuals with severe lung disease: Patients with severe lung disease contributed about 80% to total hospital costs.
The drug itself for the whole group cost $845,000, dwarfing the $189,000 savings overall. But among patients with severe disease, hospitalization savings were about $151,000 per month, while the drug cost in this group was $316,800 per month.
Cost savings are important, but the improvement in quality of life for a patient – avoiding hospitalization, fewer impacts on work and education – should not be overlooked, according to Ryan Perkins, MD, a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, who moderated the session. “Some of these aren’t things people typically quantify and assign a price tag to,” Dr. Perkins said in an interview.
A big limitation of the work is that it was conducted during the COVID-19 pandemic, which may have reduced hospitalizations. “We did have patients that called in, told us they were sick, that they needed to be treated for an exacerbation but didn’t want to go to the hospital,” said Dr. Walter. To help adjust for this, Dr. Walter’s team plans to compare intravenous antibiotic exposure before and after triple combination therapy, reasoning that it could help clarify the pandemic’s impact on hospitalizations.
Dr. Walter, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.
SOURCE: Walter E et al. NACFC 2020. Abstract 795.
FROM NACFC 2020
Cystic fibrosis patients’ vulnerability to COVID-19 infection: Preliminary data ease fears
But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.
Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.
D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV1) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.
As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.
Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV1 value less than 40% predicted (14% vs. 8%).
As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.
One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.
At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.
Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV1 measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.
Across all age groups, hospitalizations were more common in patients with best FEV1 percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.
There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV1 than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.
Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.
Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.
But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.
Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.
D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV1) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.
As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.
Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV1 value less than 40% predicted (14% vs. 8%).
As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.
One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.
At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.
Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV1 measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.
Across all age groups, hospitalizations were more common in patients with best FEV1 percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.
There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV1 than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.
Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.
Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.
But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.
Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.
D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV1) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.
As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.
Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV1 value less than 40% predicted (14% vs. 8%).
As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.
One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.
At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.
Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV1 measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.
Across all age groups, hospitalizations were more common in patients with best FEV1 percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.
There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV1 than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.
Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.
Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.
FROM NACFC 2020