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‘Affect discrepancies’ may underlie negative symptoms in schizophrenia
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
Emergency physicians take issue with AHRQ errors report
The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.
The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.
The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.
“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
Emergency medicine organizations express concerns for accuracy
The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.
The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.
The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.
Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.
All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
Misleading and inadequate evidence
“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.
“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”
The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.
“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.
The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.
“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.
“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.
Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.
“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”
Dr. Glatter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.
The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.
The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.
“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
Emergency medicine organizations express concerns for accuracy
The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.
The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.
The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.
Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.
All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
Misleading and inadequate evidence
“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.
“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”
The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.
“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.
The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.
“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.
“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.
Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.
“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”
Dr. Glatter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.
The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.
The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.
“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
Emergency medicine organizations express concerns for accuracy
The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.
The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.
The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.
Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.
All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
Misleading and inadequate evidence
“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.
“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”
The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.
“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.
The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.
“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.
“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.
Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.
“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”
Dr. Glatter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Defining six asthma subtypes may promote personalized treatment
Six subtypes of asthma that may facilitate personalized treatment were identified and confirmed in a large database review of approximately 50,000 patients, according to a recent study.
Previous studies of asthma subtypes have involved age of disease onset, the presence of allergies, and level of eosinophilic inflammation, and have been limited by factors including small sample size and lack of formal validation, Elsie M.F. Horne, MD, of the Asthma UK Centre for Applied Research, Edinburgh, and colleagues wrote.
In a study published in the International Journal of Medical Informatics, the researchers used data from two databases in the United Kingdom: the Optimum Patient Care Research Database (OPCRD) and the Secure Anonymised Information Linkage Database (SAIL). Each dataset included 50,000 randomly selected nonoverlapping adult asthma patients.
The researchers identified 45 categorical features from primary care electronic health records. The features included those directly linked to asthma, such as medications; and features indirectly linked to asthma, such as comorbidities.
The subtypes were defined by the clinically applicable features of level of inhaled corticosteroid use, level of health care use, and the presence of comorbidities, using multiple correspondence analysis and k-means cluster analysis.
The six asthma subtypes were identified in the OPCRD study population as follows: low inhaled corticosteroid use and low health care utilization (30%); low to medium ICS use (36%); low to medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high ICS use (10%); and very high ICS use (7%).
The researchers replicated the subtypes with 91%-92% accuracy in an internal dataset and 84%-86% accuracy in an external dataset. “These subtypes generalized well at two future time points, and in an additional EHR database from a different U.K. nation (the SAIL Databank),” they wrote in their discussion.
The findings were limited by several factors including the retrospective design, the possible inclusion of people without asthma because of the cohort selection criteria, and the possible biases associated with the use of EHRs; however, the results were strengthened by the large dataset and the additional validations, the researchers noted.
“Using these subtypes to summarize asthma populations could help with management and resource planning at the practice level, and could be useful for understanding regional differences in the asthma population,” they noted. For example, key clinical implications for individuals in a low health care utilization subtype could include being flagged for barriers to care and misdiagnoses, while those in a high health care utilization subtype could be considered for reassessment of medication and other options.
The study received no outside funding. Lead author Dr. Horne had no financial conflicts to disclose.
Six subtypes of asthma that may facilitate personalized treatment were identified and confirmed in a large database review of approximately 50,000 patients, according to a recent study.
Previous studies of asthma subtypes have involved age of disease onset, the presence of allergies, and level of eosinophilic inflammation, and have been limited by factors including small sample size and lack of formal validation, Elsie M.F. Horne, MD, of the Asthma UK Centre for Applied Research, Edinburgh, and colleagues wrote.
In a study published in the International Journal of Medical Informatics, the researchers used data from two databases in the United Kingdom: the Optimum Patient Care Research Database (OPCRD) and the Secure Anonymised Information Linkage Database (SAIL). Each dataset included 50,000 randomly selected nonoverlapping adult asthma patients.
The researchers identified 45 categorical features from primary care electronic health records. The features included those directly linked to asthma, such as medications; and features indirectly linked to asthma, such as comorbidities.
The subtypes were defined by the clinically applicable features of level of inhaled corticosteroid use, level of health care use, and the presence of comorbidities, using multiple correspondence analysis and k-means cluster analysis.
The six asthma subtypes were identified in the OPCRD study population as follows: low inhaled corticosteroid use and low health care utilization (30%); low to medium ICS use (36%); low to medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high ICS use (10%); and very high ICS use (7%).
The researchers replicated the subtypes with 91%-92% accuracy in an internal dataset and 84%-86% accuracy in an external dataset. “These subtypes generalized well at two future time points, and in an additional EHR database from a different U.K. nation (the SAIL Databank),” they wrote in their discussion.
The findings were limited by several factors including the retrospective design, the possible inclusion of people without asthma because of the cohort selection criteria, and the possible biases associated with the use of EHRs; however, the results were strengthened by the large dataset and the additional validations, the researchers noted.
“Using these subtypes to summarize asthma populations could help with management and resource planning at the practice level, and could be useful for understanding regional differences in the asthma population,” they noted. For example, key clinical implications for individuals in a low health care utilization subtype could include being flagged for barriers to care and misdiagnoses, while those in a high health care utilization subtype could be considered for reassessment of medication and other options.
The study received no outside funding. Lead author Dr. Horne had no financial conflicts to disclose.
Six subtypes of asthma that may facilitate personalized treatment were identified and confirmed in a large database review of approximately 50,000 patients, according to a recent study.
Previous studies of asthma subtypes have involved age of disease onset, the presence of allergies, and level of eosinophilic inflammation, and have been limited by factors including small sample size and lack of formal validation, Elsie M.F. Horne, MD, of the Asthma UK Centre for Applied Research, Edinburgh, and colleagues wrote.
In a study published in the International Journal of Medical Informatics, the researchers used data from two databases in the United Kingdom: the Optimum Patient Care Research Database (OPCRD) and the Secure Anonymised Information Linkage Database (SAIL). Each dataset included 50,000 randomly selected nonoverlapping adult asthma patients.
The researchers identified 45 categorical features from primary care electronic health records. The features included those directly linked to asthma, such as medications; and features indirectly linked to asthma, such as comorbidities.
The subtypes were defined by the clinically applicable features of level of inhaled corticosteroid use, level of health care use, and the presence of comorbidities, using multiple correspondence analysis and k-means cluster analysis.
The six asthma subtypes were identified in the OPCRD study population as follows: low inhaled corticosteroid use and low health care utilization (30%); low to medium ICS use (36%); low to medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high ICS use (10%); and very high ICS use (7%).
The researchers replicated the subtypes with 91%-92% accuracy in an internal dataset and 84%-86% accuracy in an external dataset. “These subtypes generalized well at two future time points, and in an additional EHR database from a different U.K. nation (the SAIL Databank),” they wrote in their discussion.
The findings were limited by several factors including the retrospective design, the possible inclusion of people without asthma because of the cohort selection criteria, and the possible biases associated with the use of EHRs; however, the results were strengthened by the large dataset and the additional validations, the researchers noted.
“Using these subtypes to summarize asthma populations could help with management and resource planning at the practice level, and could be useful for understanding regional differences in the asthma population,” they noted. For example, key clinical implications for individuals in a low health care utilization subtype could include being flagged for barriers to care and misdiagnoses, while those in a high health care utilization subtype could be considered for reassessment of medication and other options.
The study received no outside funding. Lead author Dr. Horne had no financial conflicts to disclose.
FROM THE INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS
New treatments aim to tame vitiligo
LAS VEGAS – in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.
Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.
The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.
Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.
Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.
In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.
Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.
In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.
In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.
Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.
Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.
JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.
Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.
An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.
Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.
Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.
Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.
The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.
Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.
Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.
In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.
Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.
In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.
In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.
Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.
Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.
JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.
Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.
An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.
Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.
Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.
Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.
The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.
Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.
Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.
In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.
Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.
In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.
In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.
Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.
Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.
JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.
Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.
An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.
Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.
Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.
MedscapeLive and this news organization are owned by the same parent company.
AT INNOVATIONS IN DERMATOLOGY
Dapper homolog 2 shows promise for pulmonary fibrosis
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
FROM THE INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Topical psoriasis treatments
LAS VEGAS – ,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.
However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.
Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.
The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.
In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.
Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
Get proactive to maintain results
With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.
Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,
She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.
What’s new and approved
Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.
Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.
In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.
Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.
Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.
Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.
Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – ,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.
However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.
Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.
The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.
In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.
Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
Get proactive to maintain results
With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.
Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,
She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.
What’s new and approved
Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.
Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.
In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.
Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.
Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.
Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.
Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – ,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.
However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.
Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.
The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.
In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.
Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
Get proactive to maintain results
With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.
Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,
She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.
What’s new and approved
Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.
Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.
In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.
Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.
Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.
Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.
Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.
MedscapeLive and this news organization are owned by the same parent company.
AT INNOVATIONS IN DERMATOLOGY
Fat-free mass index tied to outcomes in underweight COPD patients
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
From the Journal CHEST
Serum trace metals relate to lower risk of sleep disorders
, based on data from 3,660 individuals.
Previous research has shown an association between trace metals and sleep and sleep patterns, but data on the impact of serum trace metals on sleep disorders have been limited, wrote Ming-Gang Deng, MD, of Wuhan (China) University and colleagues.
In a study published in the Journal of Affective Disorders, the researchers reviewed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to calculate the odds ratios of sleep disorders and serum zinc (Zn), copper (Cu), and selenium (Se). The study population included adults aged 18 years and older, with an average age of 47.6 years. Approximately half of the participants were men, and the majority was non-Hispanic white. Serum Zn, Cu, and Se were identified at the Environmental Health Sciences Laboratory of the Centers for Disease Control and Prevention National Center for Environmental Health. The lower limits of detection for Zn, Cu, and Se were 2.9 mcg/dL, 2.5 mcg/dL, and 4.5 mcg/L, respectively. Sleep disorders were assessed based on self-reports of discussions with health professionals about sleep disorders, and via the Sleep Disorder Questionnaire.
After adjusting for sociodemographic, behavioral characteristics, and health characteristics, adults in the highest tertiles of serum Zn had a 30% reduced risk of sleep disorders, compared with those in the lowest tertiles of serum Zn (odds ratio, 0.70; P = .035). In measures of trace metals ratios, serum Zn/Cu and Zn/Se also were significantly associated with reduced risk of sleep disorders for individuals in the highest tertiles, compared with those in the lowest tertiles (OR, 0.62 and OR, 0.68, respectively).
However, serum Cu, Se and Cu/Se were not associated with sleep disorder risk.
Sociodemographic factors included age, sex, race, education level, family income level; behavioral characteristics included smoking, alcohol consumption, physical activity, and caffeine intake.
The researchers also used a restricted cubic spline model to examine the dose-response relationships between serum trace metals, serum trace metals ratios, and sleep disorders. In this analysis, higher levels of serum Zn, Zn/Cu, and Zn/Se were related to reduced risk of sleep disorders, while no significant association appeared between serum Cu, Se, or Cu/Se and sleep disorders risk.
The findings showing a lack of association between Se and sleep disorders were not consistent with previous studies, the researchers wrote in their discussion. Previous research has shown that a higher Se was less likely to be associated with trouble falling asleep, and has shown a potential treatment effect of Se on obstructive sleep apnea, they said.
“Although serum Cu and Se levels were not correlated to sleep disorders in our study, the Zn/Cu and Zn/Se may provide some novel insights,” they wrote. For example, Zn/Cu has been used as a predictor of several clinical complications related to an increased risk of sleep disorders including cardiovascular disease, cancer, and major depressive disorder, they noted.
The findings were limited by several factors including the cross-sectional design, use of self-reports, and the inability to examine relationships between trace metals and specific sleep disorder symptoms, such as restless legs syndrome, insomnia, and obstructive sleep apnea, the researchers noted.
However, the results were strengthened by the large national sample, and support data from previous studies, they said.
“The inverse associations of serum Zn, and Zn/Cu, Zn/Se with sleep disorders enlightened us that increasing Zn intake may be an excellent approach to prevent sleep disorders due to its benefits from these three aspects,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
, based on data from 3,660 individuals.
Previous research has shown an association between trace metals and sleep and sleep patterns, but data on the impact of serum trace metals on sleep disorders have been limited, wrote Ming-Gang Deng, MD, of Wuhan (China) University and colleagues.
In a study published in the Journal of Affective Disorders, the researchers reviewed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to calculate the odds ratios of sleep disorders and serum zinc (Zn), copper (Cu), and selenium (Se). The study population included adults aged 18 years and older, with an average age of 47.6 years. Approximately half of the participants were men, and the majority was non-Hispanic white. Serum Zn, Cu, and Se were identified at the Environmental Health Sciences Laboratory of the Centers for Disease Control and Prevention National Center for Environmental Health. The lower limits of detection for Zn, Cu, and Se were 2.9 mcg/dL, 2.5 mcg/dL, and 4.5 mcg/L, respectively. Sleep disorders were assessed based on self-reports of discussions with health professionals about sleep disorders, and via the Sleep Disorder Questionnaire.
After adjusting for sociodemographic, behavioral characteristics, and health characteristics, adults in the highest tertiles of serum Zn had a 30% reduced risk of sleep disorders, compared with those in the lowest tertiles of serum Zn (odds ratio, 0.70; P = .035). In measures of trace metals ratios, serum Zn/Cu and Zn/Se also were significantly associated with reduced risk of sleep disorders for individuals in the highest tertiles, compared with those in the lowest tertiles (OR, 0.62 and OR, 0.68, respectively).
However, serum Cu, Se and Cu/Se were not associated with sleep disorder risk.
Sociodemographic factors included age, sex, race, education level, family income level; behavioral characteristics included smoking, alcohol consumption, physical activity, and caffeine intake.
The researchers also used a restricted cubic spline model to examine the dose-response relationships between serum trace metals, serum trace metals ratios, and sleep disorders. In this analysis, higher levels of serum Zn, Zn/Cu, and Zn/Se were related to reduced risk of sleep disorders, while no significant association appeared between serum Cu, Se, or Cu/Se and sleep disorders risk.
The findings showing a lack of association between Se and sleep disorders were not consistent with previous studies, the researchers wrote in their discussion. Previous research has shown that a higher Se was less likely to be associated with trouble falling asleep, and has shown a potential treatment effect of Se on obstructive sleep apnea, they said.
“Although serum Cu and Se levels were not correlated to sleep disorders in our study, the Zn/Cu and Zn/Se may provide some novel insights,” they wrote. For example, Zn/Cu has been used as a predictor of several clinical complications related to an increased risk of sleep disorders including cardiovascular disease, cancer, and major depressive disorder, they noted.
The findings were limited by several factors including the cross-sectional design, use of self-reports, and the inability to examine relationships between trace metals and specific sleep disorder symptoms, such as restless legs syndrome, insomnia, and obstructive sleep apnea, the researchers noted.
However, the results were strengthened by the large national sample, and support data from previous studies, they said.
“The inverse associations of serum Zn, and Zn/Cu, Zn/Se with sleep disorders enlightened us that increasing Zn intake may be an excellent approach to prevent sleep disorders due to its benefits from these three aspects,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
, based on data from 3,660 individuals.
Previous research has shown an association between trace metals and sleep and sleep patterns, but data on the impact of serum trace metals on sleep disorders have been limited, wrote Ming-Gang Deng, MD, of Wuhan (China) University and colleagues.
In a study published in the Journal of Affective Disorders, the researchers reviewed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to calculate the odds ratios of sleep disorders and serum zinc (Zn), copper (Cu), and selenium (Se). The study population included adults aged 18 years and older, with an average age of 47.6 years. Approximately half of the participants were men, and the majority was non-Hispanic white. Serum Zn, Cu, and Se were identified at the Environmental Health Sciences Laboratory of the Centers for Disease Control and Prevention National Center for Environmental Health. The lower limits of detection for Zn, Cu, and Se were 2.9 mcg/dL, 2.5 mcg/dL, and 4.5 mcg/L, respectively. Sleep disorders were assessed based on self-reports of discussions with health professionals about sleep disorders, and via the Sleep Disorder Questionnaire.
After adjusting for sociodemographic, behavioral characteristics, and health characteristics, adults in the highest tertiles of serum Zn had a 30% reduced risk of sleep disorders, compared with those in the lowest tertiles of serum Zn (odds ratio, 0.70; P = .035). In measures of trace metals ratios, serum Zn/Cu and Zn/Se also were significantly associated with reduced risk of sleep disorders for individuals in the highest tertiles, compared with those in the lowest tertiles (OR, 0.62 and OR, 0.68, respectively).
However, serum Cu, Se and Cu/Se were not associated with sleep disorder risk.
Sociodemographic factors included age, sex, race, education level, family income level; behavioral characteristics included smoking, alcohol consumption, physical activity, and caffeine intake.
The researchers also used a restricted cubic spline model to examine the dose-response relationships between serum trace metals, serum trace metals ratios, and sleep disorders. In this analysis, higher levels of serum Zn, Zn/Cu, and Zn/Se were related to reduced risk of sleep disorders, while no significant association appeared between serum Cu, Se, or Cu/Se and sleep disorders risk.
The findings showing a lack of association between Se and sleep disorders were not consistent with previous studies, the researchers wrote in their discussion. Previous research has shown that a higher Se was less likely to be associated with trouble falling asleep, and has shown a potential treatment effect of Se on obstructive sleep apnea, they said.
“Although serum Cu and Se levels were not correlated to sleep disorders in our study, the Zn/Cu and Zn/Se may provide some novel insights,” they wrote. For example, Zn/Cu has been used as a predictor of several clinical complications related to an increased risk of sleep disorders including cardiovascular disease, cancer, and major depressive disorder, they noted.
The findings were limited by several factors including the cross-sectional design, use of self-reports, and the inability to examine relationships between trace metals and specific sleep disorder symptoms, such as restless legs syndrome, insomnia, and obstructive sleep apnea, the researchers noted.
However, the results were strengthened by the large national sample, and support data from previous studies, they said.
“The inverse associations of serum Zn, and Zn/Cu, Zn/Se with sleep disorders enlightened us that increasing Zn intake may be an excellent approach to prevent sleep disorders due to its benefits from these three aspects,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Sleep-disordered breathing promotes elevated arterial stiffness and preeclampsia
, based on data from 181 individuals.
The intermittent hypoxia resulting from sleep-disordered breathing (SDB) has been linked to cardiovascular disease and hypertension, wrote Kim Phan, PhD, of McGill University, Montreal, and colleagues.
SDB has been associated with increased preeclampsia risk, and women with preeclampsia show increased arterial stiffness, but an association between SDB and arterial stiffness in pregnancy has not been explored, they said.
In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 181 women with high-risk singleton pregnancies recruited from two tertiary obstetrics clinics in Montreal. High-risk pregnancy was defined as meeting at least one of the following criteria: age 35 years and older, body mass index 25 kg/m2 or higher, chronic hypertension, preexisting diabetes mellitus, preexisting renal disease, or personal or first-degree relative with a history of preeclampsia.
Participants were assessed at each trimester via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaire. Sleep-disordered breathing was defined as loud snoring or witnessed sleep apneas at least three times a week. Arterial stiffness was assessed via applanation tonometry every 4 weeks from baseline throughout pregnancy.
Overall, 23% of the study population met the criteria for SDB; SDB in the first or second trimester was associated with a significantly increased risk of preeclampsia (odds ratio 3.4). The effect of SDB on preeclampsia was increased in women who reported excessive daytime sleepiness, defined as scores higher than 10 on the Epworth Sleepiness Scale. The odds ratio for preeclampsia in the first or second trimester increased to 5.7 in women with hypersomnolence in addition to SDB. The risk of preeclampsia was even higher (OR 8.2) in the third trimester.
Self-reported total sleep time decreased in the second and third trimesters compared with the first, but reports of excessive daytime sleepiness remained consistent throughout the pregnancies, the researchers noted.
The results highlight the need to screen pregnant women for SDB in all three trimesters; however, “future studies will need to assess the incremental benefit of integrating SDB into risk assessment calculators in pregnancy,” the researchers wrote in their discussion. Randomized trials are needed to determine the value of interventions such as continuous positive airway pressure to reduce arterial stiffness and the risks of hypertensive disorders of pregnancy, they said. More data also are needed to examine the role of excessive daytime sleepiness as a modifier of arterial stiffness and preeclampsia risk, they noted.
The findings were limited by the prospective design, which prevents conclusions of causality, the researchers noted. Other limitations included the focus on high-risk pregnancy, which may limit generalizability, and the use of symptoms, not sleep recordings, to identify SDB, they said.
However, the results show an independent association between SDB and arterial stiffness during pregnancy, and offer potentially useful insights into the mechanisms of SDB-associated cardiovascular conditions, they noted.
“This work may inform future studies exploring the value of using arterial stiffness, as an early noninvasive indicator of subclinical vascular dysfunction in pregnant women with SDB,” they concluded.
The study was supported by the Fonds de recherche du Quebec – Sante (FRQS), Heart and Stroke Foundation of Canada, McGill University’s academic enrichment fund, and the Canadian Foundation for Women’s Health. The researchers had no financial conflicts to disclose.
, based on data from 181 individuals.
The intermittent hypoxia resulting from sleep-disordered breathing (SDB) has been linked to cardiovascular disease and hypertension, wrote Kim Phan, PhD, of McGill University, Montreal, and colleagues.
SDB has been associated with increased preeclampsia risk, and women with preeclampsia show increased arterial stiffness, but an association between SDB and arterial stiffness in pregnancy has not been explored, they said.
In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 181 women with high-risk singleton pregnancies recruited from two tertiary obstetrics clinics in Montreal. High-risk pregnancy was defined as meeting at least one of the following criteria: age 35 years and older, body mass index 25 kg/m2 or higher, chronic hypertension, preexisting diabetes mellitus, preexisting renal disease, or personal or first-degree relative with a history of preeclampsia.
Participants were assessed at each trimester via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaire. Sleep-disordered breathing was defined as loud snoring or witnessed sleep apneas at least three times a week. Arterial stiffness was assessed via applanation tonometry every 4 weeks from baseline throughout pregnancy.
Overall, 23% of the study population met the criteria for SDB; SDB in the first or second trimester was associated with a significantly increased risk of preeclampsia (odds ratio 3.4). The effect of SDB on preeclampsia was increased in women who reported excessive daytime sleepiness, defined as scores higher than 10 on the Epworth Sleepiness Scale. The odds ratio for preeclampsia in the first or second trimester increased to 5.7 in women with hypersomnolence in addition to SDB. The risk of preeclampsia was even higher (OR 8.2) in the third trimester.
Self-reported total sleep time decreased in the second and third trimesters compared with the first, but reports of excessive daytime sleepiness remained consistent throughout the pregnancies, the researchers noted.
The results highlight the need to screen pregnant women for SDB in all three trimesters; however, “future studies will need to assess the incremental benefit of integrating SDB into risk assessment calculators in pregnancy,” the researchers wrote in their discussion. Randomized trials are needed to determine the value of interventions such as continuous positive airway pressure to reduce arterial stiffness and the risks of hypertensive disorders of pregnancy, they said. More data also are needed to examine the role of excessive daytime sleepiness as a modifier of arterial stiffness and preeclampsia risk, they noted.
The findings were limited by the prospective design, which prevents conclusions of causality, the researchers noted. Other limitations included the focus on high-risk pregnancy, which may limit generalizability, and the use of symptoms, not sleep recordings, to identify SDB, they said.
However, the results show an independent association between SDB and arterial stiffness during pregnancy, and offer potentially useful insights into the mechanisms of SDB-associated cardiovascular conditions, they noted.
“This work may inform future studies exploring the value of using arterial stiffness, as an early noninvasive indicator of subclinical vascular dysfunction in pregnant women with SDB,” they concluded.
The study was supported by the Fonds de recherche du Quebec – Sante (FRQS), Heart and Stroke Foundation of Canada, McGill University’s academic enrichment fund, and the Canadian Foundation for Women’s Health. The researchers had no financial conflicts to disclose.
, based on data from 181 individuals.
The intermittent hypoxia resulting from sleep-disordered breathing (SDB) has been linked to cardiovascular disease and hypertension, wrote Kim Phan, PhD, of McGill University, Montreal, and colleagues.
SDB has been associated with increased preeclampsia risk, and women with preeclampsia show increased arterial stiffness, but an association between SDB and arterial stiffness in pregnancy has not been explored, they said.
In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 181 women with high-risk singleton pregnancies recruited from two tertiary obstetrics clinics in Montreal. High-risk pregnancy was defined as meeting at least one of the following criteria: age 35 years and older, body mass index 25 kg/m2 or higher, chronic hypertension, preexisting diabetes mellitus, preexisting renal disease, or personal or first-degree relative with a history of preeclampsia.
Participants were assessed at each trimester via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaire. Sleep-disordered breathing was defined as loud snoring or witnessed sleep apneas at least three times a week. Arterial stiffness was assessed via applanation tonometry every 4 weeks from baseline throughout pregnancy.
Overall, 23% of the study population met the criteria for SDB; SDB in the first or second trimester was associated with a significantly increased risk of preeclampsia (odds ratio 3.4). The effect of SDB on preeclampsia was increased in women who reported excessive daytime sleepiness, defined as scores higher than 10 on the Epworth Sleepiness Scale. The odds ratio for preeclampsia in the first or second trimester increased to 5.7 in women with hypersomnolence in addition to SDB. The risk of preeclampsia was even higher (OR 8.2) in the third trimester.
Self-reported total sleep time decreased in the second and third trimesters compared with the first, but reports of excessive daytime sleepiness remained consistent throughout the pregnancies, the researchers noted.
The results highlight the need to screen pregnant women for SDB in all three trimesters; however, “future studies will need to assess the incremental benefit of integrating SDB into risk assessment calculators in pregnancy,” the researchers wrote in their discussion. Randomized trials are needed to determine the value of interventions such as continuous positive airway pressure to reduce arterial stiffness and the risks of hypertensive disorders of pregnancy, they said. More data also are needed to examine the role of excessive daytime sleepiness as a modifier of arterial stiffness and preeclampsia risk, they noted.
The findings were limited by the prospective design, which prevents conclusions of causality, the researchers noted. Other limitations included the focus on high-risk pregnancy, which may limit generalizability, and the use of symptoms, not sleep recordings, to identify SDB, they said.
However, the results show an independent association between SDB and arterial stiffness during pregnancy, and offer potentially useful insights into the mechanisms of SDB-associated cardiovascular conditions, they noted.
“This work may inform future studies exploring the value of using arterial stiffness, as an early noninvasive indicator of subclinical vascular dysfunction in pregnant women with SDB,” they concluded.
The study was supported by the Fonds de recherche du Quebec – Sante (FRQS), Heart and Stroke Foundation of Canada, McGill University’s academic enrichment fund, and the Canadian Foundation for Women’s Health. The researchers had no financial conflicts to disclose.
FROM THE AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY
FDA will review pediatric indication for roflumilast cream
, according to a press release from the manufacturer.
The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.
The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.
Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.
, according to a press release from the manufacturer.
The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.
The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.
Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.
, according to a press release from the manufacturer.
The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.
The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.
Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.