Megan Brooks

The Food and Drug Administration has approved vonoprazan 10-mg and 20-mg tablets (Voquezna, Phathom Pharmaceuticals) for the healing and maintenance of all grades of erosive esophagitis, also known as erosive gastroesophageal reflux disease (GERD), as well as relief of associated heartburn, the company has announced.

Vonoprazan, an oral potassium-competitive acid blocker (PCAB), provides more potent inhibition of gastric acid than do proton pump inhibitors (PPIs) and is seen as a potential alternative.

Olivier Le Moal/Getty Images

The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study.

The randomized, double-blind, multicenter study enrolled 1,024 patients with erosive GERD in the United States and Europe and compared vonoprazan with the PPI lansoprazole (Prevacid) in the healing and maintenance of healing of erosive GERD and associated heartburn symptom relief.

Vonoprazan 20 mg was noninferior to lansoprazole 30 mg for complete healing by week 8 in patients with all grades of erosive GERD, with healing rates of 93% vs. 85% for lansoprazole.

In addition, vonoprazan showed superior rates of healing in patients with moderate to severe disease (LA Grade C/D) at week 2 (70% vs. 53% with lansoprazole). Vonoprazan was also noninferior to lansoprazole in terms of heartburn-free days over the healing period.

In the maintenance phase of the trial, vonoprazan 10 mg was superior to lansoprazole 15 mg in maintaining healing at 6 months in all patients who were randomly assigned (79% vs. 72%) and in the subset of patients with moderate to severe erosive GERD (75% vs. 61%).

Adverse event (AE) rates for vonoprazan were comparable to lansoprazole. The most common AEs in the healing phase (≥ 2% with vonoprazan) were gastritis, diarrhea, abdominal distention, abdominal pain, and nausea.

The most common AEs in the maintenance phase (≥ 3% with vonoprazan) were gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection.

“For many GERD patients with erosive esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms,” Colin W. Howden, MD, professor emeritus, University of Tennessee, Memphis, said in the news release.

Vonoprazan provides clinicians with a “new first-in-class therapeutic option that demonstrated faster healing in the more difficult-to-treat GERD patients with erosive esophagitis,” Dr. Howden added.

Vonoprazan is expected to be available in the United States in December.

The FDA also recently approved reformulated vonoprazan tablets for Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) for the treatment of Helicobacter pylori infection in adults, Phathom Pharmaceuticals announced.

In February, the FDA had put both the vonoprazan new drug application for erosive esophagitis and the postapproval supplement for H. pylori on hold until the company addressed concerns over the presence of nitrosamine impurities.

Dr. Howden is a former editor-in-chief of GI&Hepatology News. A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved vonoprazan 10-mg and 20-mg tablets (Voquezna, Phathom Pharmaceuticals) for the healing and maintenance of all grades of erosive esophagitis, also known as erosive gastroesophageal reflux disease (GERD), as well as relief of associated heartburn, the company has announced.

Vonoprazan, an oral potassium-competitive acid blocker (PCAB), provides more potent inhibition of gastric acid than do proton pump inhibitors (PPIs) and is seen as a potential alternative.

Olivier Le Moal/Getty Images

The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study.

The randomized, double-blind, multicenter study enrolled 1,024 patients with erosive GERD in the United States and Europe and compared vonoprazan with the PPI lansoprazole (Prevacid) in the healing and maintenance of healing of erosive GERD and associated heartburn symptom relief.

Vonoprazan 20 mg was noninferior to lansoprazole 30 mg for complete healing by week 8 in patients with all grades of erosive GERD, with healing rates of 93% vs. 85% for lansoprazole.

In addition, vonoprazan showed superior rates of healing in patients with moderate to severe disease (LA Grade C/D) at week 2 (70% vs. 53% with lansoprazole). Vonoprazan was also noninferior to lansoprazole in terms of heartburn-free days over the healing period.

In the maintenance phase of the trial, vonoprazan 10 mg was superior to lansoprazole 15 mg in maintaining healing at 6 months in all patients who were randomly assigned (79% vs. 72%) and in the subset of patients with moderate to severe erosive GERD (75% vs. 61%).

Adverse event (AE) rates for vonoprazan were comparable to lansoprazole. The most common AEs in the healing phase (≥ 2% with vonoprazan) were gastritis, diarrhea, abdominal distention, abdominal pain, and nausea.

The most common AEs in the maintenance phase (≥ 3% with vonoprazan) were gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection.

“For many GERD patients with erosive esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms,” Colin W. Howden, MD, professor emeritus, University of Tennessee, Memphis, said in the news release.

Vonoprazan provides clinicians with a “new first-in-class therapeutic option that demonstrated faster healing in the more difficult-to-treat GERD patients with erosive esophagitis,” Dr. Howden added.

Vonoprazan is expected to be available in the United States in December.

The FDA also recently approved reformulated vonoprazan tablets for Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) for the treatment of Helicobacter pylori infection in adults, Phathom Pharmaceuticals announced.

In February, the FDA had put both the vonoprazan new drug application for erosive esophagitis and the postapproval supplement for H. pylori on hold until the company addressed concerns over the presence of nitrosamine impurities.

Dr. Howden is a former editor-in-chief of GI&Hepatology News. A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved vonoprazan 10-mg and 20-mg tablets (Voquezna, Phathom Pharmaceuticals) for the healing and maintenance of all grades of erosive esophagitis, also known as erosive gastroesophageal reflux disease (GERD), as well as relief of associated heartburn, the company has announced.

Vonoprazan, an oral potassium-competitive acid blocker (PCAB), provides more potent inhibition of gastric acid than do proton pump inhibitors (PPIs) and is seen as a potential alternative.

Olivier Le Moal/Getty Images

The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study.

The randomized, double-blind, multicenter study enrolled 1,024 patients with erosive GERD in the United States and Europe and compared vonoprazan with the PPI lansoprazole (Prevacid) in the healing and maintenance of healing of erosive GERD and associated heartburn symptom relief.

Vonoprazan 20 mg was noninferior to lansoprazole 30 mg for complete healing by week 8 in patients with all grades of erosive GERD, with healing rates of 93% vs. 85% for lansoprazole.

In addition, vonoprazan showed superior rates of healing in patients with moderate to severe disease (LA Grade C/D) at week 2 (70% vs. 53% with lansoprazole). Vonoprazan was also noninferior to lansoprazole in terms of heartburn-free days over the healing period.

In the maintenance phase of the trial, vonoprazan 10 mg was superior to lansoprazole 15 mg in maintaining healing at 6 months in all patients who were randomly assigned (79% vs. 72%) and in the subset of patients with moderate to severe erosive GERD (75% vs. 61%).

Adverse event (AE) rates for vonoprazan were comparable to lansoprazole. The most common AEs in the healing phase (≥ 2% with vonoprazan) were gastritis, diarrhea, abdominal distention, abdominal pain, and nausea.

The most common AEs in the maintenance phase (≥ 3% with vonoprazan) were gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection.

“For many GERD patients with erosive esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms,” Colin W. Howden, MD, professor emeritus, University of Tennessee, Memphis, said in the news release.

Vonoprazan provides clinicians with a “new first-in-class therapeutic option that demonstrated faster healing in the more difficult-to-treat GERD patients with erosive esophagitis,” Dr. Howden added.

Vonoprazan is expected to be available in the United States in December.

The FDA also recently approved reformulated vonoprazan tablets for Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) for the treatment of Helicobacter pylori infection in adults, Phathom Pharmaceuticals announced.

In February, the FDA had put both the vonoprazan new drug application for erosive esophagitis and the postapproval supplement for H. pylori on hold until the company addressed concerns over the presence of nitrosamine impurities.

Dr. Howden is a former editor-in-chief of GI&Hepatology News. A version of this article appeared on Medscape.com.

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

A version of this article first appeared on Medscape.com .

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

A version of this article first appeared on Medscape.com .

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

A version of this article first appeared on Medscape.com .

A new global analysis highlights the substantial burden of premature deaths from cancer around the world – a burden that could potentially be averted through prevention, early detection, and timely treatment.

According to the analysis, in 2020, over half of all cancer deaths – 5.28 million of 9.96 million – occurred prematurely (before age 70), leading to a loss of roughly 183 million life-years from the disease worldwide.

More than two-thirds of premature cancer-related deaths – 3.6 million, or 68% – were potentially preventable through lifestyle changes or early detection efforts, such as cancer screening, dietary changes, or smoking cessation, and about one-third – 1.65 million, or 31% – may have been treatable.

But two biostatisticians not involved in the study who took a deep dive into it urged caution in interpreting the data.

Nilanjan Chatterjee, PhD, Bloomberg Distinguished Professor, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, said the study does a “great job in bringing a lot of diverse data together to show there is very high potential for preventing premature deaths due to cancer worldwide.”

However, for a variety of reasons, Dr. Chatterjee explained, one should not “overinterpret” the high percentage of potentially preventable cancer deaths.

Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong, in Australia, agreed.

“It’s likely many cancer deaths are, in theory, preventable, but the numbers around just how many are necessarily vague,” said Dr. Meyerowitz-Katz. “Also, ‘in theory preventable’ doesn’t necessarily mean that we can actually do it in practice.”
 

Invest in cancer prevention

The study, led by researchers from the World Health Organization’s International Agency for Research on Cancer and partners, provides estimates of premature deaths from 36 cancers across 185 countries.

The findings, published in The Lancet Global Health along with a new Lancet Commission report – “Women, Power, and Cancer” also highlighted the “underrecognized” cancer burden among women around the world.

Cancer ranks in the top three causes of premature mortality among women in almost all countries worldwide, but it is often “deprioritized,” the Lancet Commission report explained.

Of the nearly 5.3 million premature cancer deaths in 2020, 2.9 million occurred in men, and 2.3 million occurred in women, the investigators found. Of the premature deaths among women, 1.5 million could have potentially been avoided through prevention or detection efforts, while the remaining 800,000 might have been averted “if all women everywhere could access optimal cancer care,” the authors said.

Lung cancer was the leading contributor to preventable premature years of life lost in countries that have medium to very high scores on the Human Development Index (HDI), whereas cervical cancer was the leading contributor in low-HDI countries. HDI rankings are based on life expectancy, education, and gross national income.

Among women, as many as 72% of cancer death were premature in low-HDI countries, vs 36% in very high-HDI countries.

Overall, across all four tiers of HDI, colorectal and breast cancers represented the major treatable cancers.

Reducing exposure to four main risk factors – tobacco smoking, alcohol consumption, high body weight, and infections – would go a long way toward reducing potentially preventable premature cancer-related deaths, the authors said.

“Globally, there are marked inequalities between countries in reaching the target of reducing premature mortality from noncommunicable diseases, including cancer,” author Isabelle Soerjomataram, MD, PhD, deputy head of cancer surveillance at the International Agency for Research on Cancer, said in a press release.

“Greater investments in cancer prevention programs can reduce the prevalence of key risk factors for cancer, and increased coverage of vaccination alongside early diagnosis and screening linked to timely treatment can and must address the current cancer inequalities that are seen worldwide,” she added.
 

Caveats and cautionary notes

The authors acknowledge that the study has limitations related to its methodology and underlying assumptions. For instance, some premature cancer deaths that were classified as preventable may have been averted through curative therapy as well.

The findings also represent a snapshot of premature mortality in 2020 but do not necessarily predict progress in cancer control over time.

In Dr. Chatterjee’s view, this is “an excellent descriptive study that gives a good overall picture about the potential for saving a very large fraction of premature death due to cancer by implementing what is now known about primary and secondary interventions, and treatments.”

However, estimates for the effects of various risk factors and interventions are often derived from observational nonrandomized studies, which can have various types of biases, he said.

“Additionally, availability of data, observational or randomized, are often limited from many countries in Africa, Latin America, and Asia, where the cancer burdens are increasing,” Dr. Chatterjee told this news organization. “Therefore, extrapolating evidence generated mostly from North America and European countries to other understudied settings could be problematic due to difference in background in genetics, environment, socioeconomic, and cultural differences.”

Dr. Meyerowitz-Katz said the issue with this “very complex” article is that it includes “models built upon models, all of which include layers of assumptions that aren’t always obvious and may be wrong.”

On top of that, he said, “there are questions over whether the modifiable risk factors are really modifiable. Can we really get rid of 100% of ‘lack of physical exercise’? What would that even look like?”

Overall, Dr. Meyerowitz-Katz noted, “Yes, some proportion of these cancers could be prevented, and that percentage may be large, but the exact 70% estimate is very uncertain in my opinion.”

The study had no commercial funding. The authors, Dr. Chatterjee, and Dr. Meyerowitz-Katz have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new global analysis highlights the substantial burden of premature deaths from cancer around the world – a burden that could potentially be averted through prevention, early detection, and timely treatment.

According to the analysis, in 2020, over half of all cancer deaths – 5.28 million of 9.96 million – occurred prematurely (before age 70), leading to a loss of roughly 183 million life-years from the disease worldwide.

More than two-thirds of premature cancer-related deaths – 3.6 million, or 68% – were potentially preventable through lifestyle changes or early detection efforts, such as cancer screening, dietary changes, or smoking cessation, and about one-third – 1.65 million, or 31% – may have been treatable.

But two biostatisticians not involved in the study who took a deep dive into it urged caution in interpreting the data.

Nilanjan Chatterjee, PhD, Bloomberg Distinguished Professor, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, said the study does a “great job in bringing a lot of diverse data together to show there is very high potential for preventing premature deaths due to cancer worldwide.”

However, for a variety of reasons, Dr. Chatterjee explained, one should not “overinterpret” the high percentage of potentially preventable cancer deaths.

Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong, in Australia, agreed.

“It’s likely many cancer deaths are, in theory, preventable, but the numbers around just how many are necessarily vague,” said Dr. Meyerowitz-Katz. “Also, ‘in theory preventable’ doesn’t necessarily mean that we can actually do it in practice.”
 

Invest in cancer prevention

The study, led by researchers from the World Health Organization’s International Agency for Research on Cancer and partners, provides estimates of premature deaths from 36 cancers across 185 countries.

The findings, published in The Lancet Global Health along with a new Lancet Commission report – “Women, Power, and Cancer” also highlighted the “underrecognized” cancer burden among women around the world.

Cancer ranks in the top three causes of premature mortality among women in almost all countries worldwide, but it is often “deprioritized,” the Lancet Commission report explained.

Of the nearly 5.3 million premature cancer deaths in 2020, 2.9 million occurred in men, and 2.3 million occurred in women, the investigators found. Of the premature deaths among women, 1.5 million could have potentially been avoided through prevention or detection efforts, while the remaining 800,000 might have been averted “if all women everywhere could access optimal cancer care,” the authors said.

Lung cancer was the leading contributor to preventable premature years of life lost in countries that have medium to very high scores on the Human Development Index (HDI), whereas cervical cancer was the leading contributor in low-HDI countries. HDI rankings are based on life expectancy, education, and gross national income.

Among women, as many as 72% of cancer death were premature in low-HDI countries, vs 36% in very high-HDI countries.

Overall, across all four tiers of HDI, colorectal and breast cancers represented the major treatable cancers.

Reducing exposure to four main risk factors – tobacco smoking, alcohol consumption, high body weight, and infections – would go a long way toward reducing potentially preventable premature cancer-related deaths, the authors said.

“Globally, there are marked inequalities between countries in reaching the target of reducing premature mortality from noncommunicable diseases, including cancer,” author Isabelle Soerjomataram, MD, PhD, deputy head of cancer surveillance at the International Agency for Research on Cancer, said in a press release.

“Greater investments in cancer prevention programs can reduce the prevalence of key risk factors for cancer, and increased coverage of vaccination alongside early diagnosis and screening linked to timely treatment can and must address the current cancer inequalities that are seen worldwide,” she added.
 

Caveats and cautionary notes

The authors acknowledge that the study has limitations related to its methodology and underlying assumptions. For instance, some premature cancer deaths that were classified as preventable may have been averted through curative therapy as well.

The findings also represent a snapshot of premature mortality in 2020 but do not necessarily predict progress in cancer control over time.

In Dr. Chatterjee’s view, this is “an excellent descriptive study that gives a good overall picture about the potential for saving a very large fraction of premature death due to cancer by implementing what is now known about primary and secondary interventions, and treatments.”

However, estimates for the effects of various risk factors and interventions are often derived from observational nonrandomized studies, which can have various types of biases, he said.

“Additionally, availability of data, observational or randomized, are often limited from many countries in Africa, Latin America, and Asia, where the cancer burdens are increasing,” Dr. Chatterjee told this news organization. “Therefore, extrapolating evidence generated mostly from North America and European countries to other understudied settings could be problematic due to difference in background in genetics, environment, socioeconomic, and cultural differences.”

Dr. Meyerowitz-Katz said the issue with this “very complex” article is that it includes “models built upon models, all of which include layers of assumptions that aren’t always obvious and may be wrong.”

On top of that, he said, “there are questions over whether the modifiable risk factors are really modifiable. Can we really get rid of 100% of ‘lack of physical exercise’? What would that even look like?”

Overall, Dr. Meyerowitz-Katz noted, “Yes, some proportion of these cancers could be prevented, and that percentage may be large, but the exact 70% estimate is very uncertain in my opinion.”

The study had no commercial funding. The authors, Dr. Chatterjee, and Dr. Meyerowitz-Katz have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new global analysis highlights the substantial burden of premature deaths from cancer around the world – a burden that could potentially be averted through prevention, early detection, and timely treatment.

According to the analysis, in 2020, over half of all cancer deaths – 5.28 million of 9.96 million – occurred prematurely (before age 70), leading to a loss of roughly 183 million life-years from the disease worldwide.

More than two-thirds of premature cancer-related deaths – 3.6 million, or 68% – were potentially preventable through lifestyle changes or early detection efforts, such as cancer screening, dietary changes, or smoking cessation, and about one-third – 1.65 million, or 31% – may have been treatable.

But two biostatisticians not involved in the study who took a deep dive into it urged caution in interpreting the data.

Nilanjan Chatterjee, PhD, Bloomberg Distinguished Professor, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, said the study does a “great job in bringing a lot of diverse data together to show there is very high potential for preventing premature deaths due to cancer worldwide.”

However, for a variety of reasons, Dr. Chatterjee explained, one should not “overinterpret” the high percentage of potentially preventable cancer deaths.

Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong, in Australia, agreed.

“It’s likely many cancer deaths are, in theory, preventable, but the numbers around just how many are necessarily vague,” said Dr. Meyerowitz-Katz. “Also, ‘in theory preventable’ doesn’t necessarily mean that we can actually do it in practice.”
 

Invest in cancer prevention

The study, led by researchers from the World Health Organization’s International Agency for Research on Cancer and partners, provides estimates of premature deaths from 36 cancers across 185 countries.

The findings, published in The Lancet Global Health along with a new Lancet Commission report – “Women, Power, and Cancer” also highlighted the “underrecognized” cancer burden among women around the world.

Cancer ranks in the top three causes of premature mortality among women in almost all countries worldwide, but it is often “deprioritized,” the Lancet Commission report explained.

Of the nearly 5.3 million premature cancer deaths in 2020, 2.9 million occurred in men, and 2.3 million occurred in women, the investigators found. Of the premature deaths among women, 1.5 million could have potentially been avoided through prevention or detection efforts, while the remaining 800,000 might have been averted “if all women everywhere could access optimal cancer care,” the authors said.

Lung cancer was the leading contributor to preventable premature years of life lost in countries that have medium to very high scores on the Human Development Index (HDI), whereas cervical cancer was the leading contributor in low-HDI countries. HDI rankings are based on life expectancy, education, and gross national income.

Among women, as many as 72% of cancer death were premature in low-HDI countries, vs 36% in very high-HDI countries.

Overall, across all four tiers of HDI, colorectal and breast cancers represented the major treatable cancers.

Reducing exposure to four main risk factors – tobacco smoking, alcohol consumption, high body weight, and infections – would go a long way toward reducing potentially preventable premature cancer-related deaths, the authors said.

“Globally, there are marked inequalities between countries in reaching the target of reducing premature mortality from noncommunicable diseases, including cancer,” author Isabelle Soerjomataram, MD, PhD, deputy head of cancer surveillance at the International Agency for Research on Cancer, said in a press release.

“Greater investments in cancer prevention programs can reduce the prevalence of key risk factors for cancer, and increased coverage of vaccination alongside early diagnosis and screening linked to timely treatment can and must address the current cancer inequalities that are seen worldwide,” she added.
 

Caveats and cautionary notes

The authors acknowledge that the study has limitations related to its methodology and underlying assumptions. For instance, some premature cancer deaths that were classified as preventable may have been averted through curative therapy as well.

The findings also represent a snapshot of premature mortality in 2020 but do not necessarily predict progress in cancer control over time.

In Dr. Chatterjee’s view, this is “an excellent descriptive study that gives a good overall picture about the potential for saving a very large fraction of premature death due to cancer by implementing what is now known about primary and secondary interventions, and treatments.”

However, estimates for the effects of various risk factors and interventions are often derived from observational nonrandomized studies, which can have various types of biases, he said.

“Additionally, availability of data, observational or randomized, are often limited from many countries in Africa, Latin America, and Asia, where the cancer burdens are increasing,” Dr. Chatterjee told this news organization. “Therefore, extrapolating evidence generated mostly from North America and European countries to other understudied settings could be problematic due to difference in background in genetics, environment, socioeconomic, and cultural differences.”

Dr. Meyerowitz-Katz said the issue with this “very complex” article is that it includes “models built upon models, all of which include layers of assumptions that aren’t always obvious and may be wrong.”

On top of that, he said, “there are questions over whether the modifiable risk factors are really modifiable. Can we really get rid of 100% of ‘lack of physical exercise’? What would that even look like?”

Overall, Dr. Meyerowitz-Katz noted, “Yes, some proportion of these cancers could be prevented, and that percentage may be large, but the exact 70% estimate is very uncertain in my opinion.”

The study had no commercial funding. The authors, Dr. Chatterjee, and Dr. Meyerowitz-Katz have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

T3D-959, an oral dual delta/gamma peroxisome proliferator-activated nuclear receptor (PPAR) agonist, has shown promise in a phase 2 randomized, placebo-controlled study of adults with mild to moderate Alzheimer’s disease (AD).

Topline results provide “clinical evidence of a modification of multiple AD pathologies associated with amyloid plaque burden,” said John Didsbury, PhD, chief executive officer of T3D Therapeutics Inc., the company developing the drug.

While the primary cognitive endpoints were not met in the overall study population, the data suggest that a “high plasma pTau-217/non–pTau-217 ratio, a marker of AD pathology, likely defines an AD population responsive to T3D-959 therapy,” Dr. Didsbury said.

He said it’s important to note that no PET imaging (amyloid/tau) or biomarkers were used as entry criteria and, in hindsight, some participants likely did not have AD, which likely played a role in the negative primary outcome.

The findings from the PIONEER study were presented at the annual Clinical Trials on Alzheimer’s Disease conference.
 

‘Surprised and shocked’

The PPAR family of proteins helps regulate blood sugar and triglyceride levels. The rationale for evaluating PPAR agonists in AD is based on the hypothesis that sporadic AD is fundamentally an age-related metabolic disease.

T3D-959 is the first PPAR delta-activating compound to be developed for the treatment of AD. Uniquely, this drug also activates PPAR gamma, which may provide potential additive or synergistic effects in regulating dysfunctional brain glucose energy and lipid metabolism in AD.

The PIONEER tested three doses of T3D-959 (15 mg, 30 mg, and 45 mg) vs. placebo in 250 adults with mild to moderate AD (Mini-Mental State Examination [MMSE] 14-26, Clinical Dementia Rating (CDR)-Global 0.5-2.0, and Sum of Boxes [CDR-SB] ≥ 3.0). T3D-959 or placebo was taken once daily for 24 weeks.

In the overall population, the primary endpoints – Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) and Clinical Global Impression of Change (CGIC) – were not met.

“Plain and simple, when we saw this data, we were surprised and shocked,” said Dr. Didsbury, and wondered, “How can placebo be doing so well on a 6-month AD trial?”

“We suspect the presence of non-AD subjects in the trial based on the lower-than-typical number of ApoE4 positive subjects, increased cognitive performance and learning effects observed, and only 45% of trial subjects having a low pTau-217 ratio, a biomarker indicating that they would have no AD pathology plasma,” he explained.

Plasma baseline pTau-217 ratio correlates with AD risk and severity and is a marker of AD pathology; in the subgroup with high pTau-217 ratio, the ADAS-Cog11 endpoint was met in the 30-mg T3D-959 group vs. the placebo group (–0.74 vs. 1.27; P = .112), “consistent with clinical benefit,” Dr. Didsbury noted.

The secondary endpoint of change in plasma amyloid-beta (Ab)42/40 ratio was also met in the 30-mg T3D-959 group – increasing at week 24 with T3D-959 vs. decreasing with placebo (P = .0206), with even greater improvement in the high pTau-217 ratio group. In this group, improvement of Ab42/40 ratio was nearly twofold greater than the overall group.

T3D-959 had a similar magnitude of effect on Ab42/40 as lecanemab (Leqembi) at 6 months, the researchers point out in their late-breaking abstract.

Biomarkers of all three AD diagnostic criteria (amyloid/tau/neurodegeneration) were improved, as well as markers of inflammation, insulin resistance, and dysfunctional lipid metabolism – results that demonstrate “peripheral targeted engagement,” Dr. Didsbury said.

“Along with the strong safety profile of T3D-959, the evidence supports a larger study evaluating T3D-959 30 mg/day in patients with mild to moderate AD and a baseline plasma p-Tau-217/non–pTau-217 ratio of ≥ 0.015,” the researchers conclude in their abstract.
 

Lessons learned

Commenting on the research for this article, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, noted that “the idea behind this treatment is that impaired glucose metabolism in the brain leads to toxic misfolded proteins, including amyloid and tau in people with Alzheimer’s disease.”

“The treatment focuses on improving regulation of glucose and lipid metabolism in the brain. This is one of more than 140 approaches that are being tested today to target the biological drivers and contributors to Alzheimer’s disease,” Dr. Edelmayer said.

Because biomarkers were not used to enroll participants, “there was a high population of people in the trial who did not have Alzheimer’s. This very likely contributed to the negative result,” she noted.

However, the results also suggest that those taking the drug who had a high pTau217 ratio – and are likely to have brain amyloid plaques – had less cognitive decline, she noted.

Lessons learned from this negative trial include “the proper dose to balance efficacy and safety, and how to screen participants for their next study,” Dr. Edelmayer said.

Funding for the study was provided by the National Institute on Aging/National Institutes of Health and the Alzheimer’s Association. Dr. Didsbury and Dr. Edelmayer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

T3D-959, an oral dual delta/gamma peroxisome proliferator-activated nuclear receptor (PPAR) agonist, has shown promise in a phase 2 randomized, placebo-controlled study of adults with mild to moderate Alzheimer’s disease (AD).

Topline results provide “clinical evidence of a modification of multiple AD pathologies associated with amyloid plaque burden,” said John Didsbury, PhD, chief executive officer of T3D Therapeutics Inc., the company developing the drug.

While the primary cognitive endpoints were not met in the overall study population, the data suggest that a “high plasma pTau-217/non–pTau-217 ratio, a marker of AD pathology, likely defines an AD population responsive to T3D-959 therapy,” Dr. Didsbury said.

He said it’s important to note that no PET imaging (amyloid/tau) or biomarkers were used as entry criteria and, in hindsight, some participants likely did not have AD, which likely played a role in the negative primary outcome.

The findings from the PIONEER study were presented at the annual Clinical Trials on Alzheimer’s Disease conference.
 

‘Surprised and shocked’

The PPAR family of proteins helps regulate blood sugar and triglyceride levels. The rationale for evaluating PPAR agonists in AD is based on the hypothesis that sporadic AD is fundamentally an age-related metabolic disease.

T3D-959 is the first PPAR delta-activating compound to be developed for the treatment of AD. Uniquely, this drug also activates PPAR gamma, which may provide potential additive or synergistic effects in regulating dysfunctional brain glucose energy and lipid metabolism in AD.

The PIONEER tested three doses of T3D-959 (15 mg, 30 mg, and 45 mg) vs. placebo in 250 adults with mild to moderate AD (Mini-Mental State Examination [MMSE] 14-26, Clinical Dementia Rating (CDR)-Global 0.5-2.0, and Sum of Boxes [CDR-SB] ≥ 3.0). T3D-959 or placebo was taken once daily for 24 weeks.

In the overall population, the primary endpoints – Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) and Clinical Global Impression of Change (CGIC) – were not met.

“Plain and simple, when we saw this data, we were surprised and shocked,” said Dr. Didsbury, and wondered, “How can placebo be doing so well on a 6-month AD trial?”

“We suspect the presence of non-AD subjects in the trial based on the lower-than-typical number of ApoE4 positive subjects, increased cognitive performance and learning effects observed, and only 45% of trial subjects having a low pTau-217 ratio, a biomarker indicating that they would have no AD pathology plasma,” he explained.

Plasma baseline pTau-217 ratio correlates with AD risk and severity and is a marker of AD pathology; in the subgroup with high pTau-217 ratio, the ADAS-Cog11 endpoint was met in the 30-mg T3D-959 group vs. the placebo group (–0.74 vs. 1.27; P = .112), “consistent with clinical benefit,” Dr. Didsbury noted.

The secondary endpoint of change in plasma amyloid-beta (Ab)42/40 ratio was also met in the 30-mg T3D-959 group – increasing at week 24 with T3D-959 vs. decreasing with placebo (P = .0206), with even greater improvement in the high pTau-217 ratio group. In this group, improvement of Ab42/40 ratio was nearly twofold greater than the overall group.

T3D-959 had a similar magnitude of effect on Ab42/40 as lecanemab (Leqembi) at 6 months, the researchers point out in their late-breaking abstract.

Biomarkers of all three AD diagnostic criteria (amyloid/tau/neurodegeneration) were improved, as well as markers of inflammation, insulin resistance, and dysfunctional lipid metabolism – results that demonstrate “peripheral targeted engagement,” Dr. Didsbury said.

“Along with the strong safety profile of T3D-959, the evidence supports a larger study evaluating T3D-959 30 mg/day in patients with mild to moderate AD and a baseline plasma p-Tau-217/non–pTau-217 ratio of ≥ 0.015,” the researchers conclude in their abstract.
 

Lessons learned

Commenting on the research for this article, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, noted that “the idea behind this treatment is that impaired glucose metabolism in the brain leads to toxic misfolded proteins, including amyloid and tau in people with Alzheimer’s disease.”

“The treatment focuses on improving regulation of glucose and lipid metabolism in the brain. This is one of more than 140 approaches that are being tested today to target the biological drivers and contributors to Alzheimer’s disease,” Dr. Edelmayer said.

Because biomarkers were not used to enroll participants, “there was a high population of people in the trial who did not have Alzheimer’s. This very likely contributed to the negative result,” she noted.

However, the results also suggest that those taking the drug who had a high pTau217 ratio – and are likely to have brain amyloid plaques – had less cognitive decline, she noted.

Lessons learned from this negative trial include “the proper dose to balance efficacy and safety, and how to screen participants for their next study,” Dr. Edelmayer said.

Funding for the study was provided by the National Institute on Aging/National Institutes of Health and the Alzheimer’s Association. Dr. Didsbury and Dr. Edelmayer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

T3D-959, an oral dual delta/gamma peroxisome proliferator-activated nuclear receptor (PPAR) agonist, has shown promise in a phase 2 randomized, placebo-controlled study of adults with mild to moderate Alzheimer’s disease (AD).

Topline results provide “clinical evidence of a modification of multiple AD pathologies associated with amyloid plaque burden,” said John Didsbury, PhD, chief executive officer of T3D Therapeutics Inc., the company developing the drug.

While the primary cognitive endpoints were not met in the overall study population, the data suggest that a “high plasma pTau-217/non–pTau-217 ratio, a marker of AD pathology, likely defines an AD population responsive to T3D-959 therapy,” Dr. Didsbury said.

He said it’s important to note that no PET imaging (amyloid/tau) or biomarkers were used as entry criteria and, in hindsight, some participants likely did not have AD, which likely played a role in the negative primary outcome.

The findings from the PIONEER study were presented at the annual Clinical Trials on Alzheimer’s Disease conference.
 

‘Surprised and shocked’

The PPAR family of proteins helps regulate blood sugar and triglyceride levels. The rationale for evaluating PPAR agonists in AD is based on the hypothesis that sporadic AD is fundamentally an age-related metabolic disease.

T3D-959 is the first PPAR delta-activating compound to be developed for the treatment of AD. Uniquely, this drug also activates PPAR gamma, which may provide potential additive or synergistic effects in regulating dysfunctional brain glucose energy and lipid metabolism in AD.

The PIONEER tested three doses of T3D-959 (15 mg, 30 mg, and 45 mg) vs. placebo in 250 adults with mild to moderate AD (Mini-Mental State Examination [MMSE] 14-26, Clinical Dementia Rating (CDR)-Global 0.5-2.0, and Sum of Boxes [CDR-SB] ≥ 3.0). T3D-959 or placebo was taken once daily for 24 weeks.

In the overall population, the primary endpoints – Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) and Clinical Global Impression of Change (CGIC) – were not met.

“Plain and simple, when we saw this data, we were surprised and shocked,” said Dr. Didsbury, and wondered, “How can placebo be doing so well on a 6-month AD trial?”

“We suspect the presence of non-AD subjects in the trial based on the lower-than-typical number of ApoE4 positive subjects, increased cognitive performance and learning effects observed, and only 45% of trial subjects having a low pTau-217 ratio, a biomarker indicating that they would have no AD pathology plasma,” he explained.

Plasma baseline pTau-217 ratio correlates with AD risk and severity and is a marker of AD pathology; in the subgroup with high pTau-217 ratio, the ADAS-Cog11 endpoint was met in the 30-mg T3D-959 group vs. the placebo group (–0.74 vs. 1.27; P = .112), “consistent with clinical benefit,” Dr. Didsbury noted.

The secondary endpoint of change in plasma amyloid-beta (Ab)42/40 ratio was also met in the 30-mg T3D-959 group – increasing at week 24 with T3D-959 vs. decreasing with placebo (P = .0206), with even greater improvement in the high pTau-217 ratio group. In this group, improvement of Ab42/40 ratio was nearly twofold greater than the overall group.

T3D-959 had a similar magnitude of effect on Ab42/40 as lecanemab (Leqembi) at 6 months, the researchers point out in their late-breaking abstract.

Biomarkers of all three AD diagnostic criteria (amyloid/tau/neurodegeneration) were improved, as well as markers of inflammation, insulin resistance, and dysfunctional lipid metabolism – results that demonstrate “peripheral targeted engagement,” Dr. Didsbury said.

“Along with the strong safety profile of T3D-959, the evidence supports a larger study evaluating T3D-959 30 mg/day in patients with mild to moderate AD and a baseline plasma p-Tau-217/non–pTau-217 ratio of ≥ 0.015,” the researchers conclude in their abstract.
 

Lessons learned

Commenting on the research for this article, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, noted that “the idea behind this treatment is that impaired glucose metabolism in the brain leads to toxic misfolded proteins, including amyloid and tau in people with Alzheimer’s disease.”

“The treatment focuses on improving regulation of glucose and lipid metabolism in the brain. This is one of more than 140 approaches that are being tested today to target the biological drivers and contributors to Alzheimer’s disease,” Dr. Edelmayer said.

Because biomarkers were not used to enroll participants, “there was a high population of people in the trial who did not have Alzheimer’s. This very likely contributed to the negative result,” she noted.

However, the results also suggest that those taking the drug who had a high pTau217 ratio – and are likely to have brain amyloid plaques – had less cognitive decline, she noted.

Lessons learned from this negative trial include “the proper dose to balance efficacy and safety, and how to screen participants for their next study,” Dr. Edelmayer said.

Funding for the study was provided by the National Institute on Aging/National Institutes of Health and the Alzheimer’s Association. Dr. Didsbury and Dr. Edelmayer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Starting treatment with buprenorphine for opioid use disorder (OUD) via telehealth is associated with longer retention in treatment, compared with starting treatment in-person, new research suggests.

METHODOLOGY:

• Researchers analyzed Medicaid claims data from November 2019 through the end of 2020 in Kentucky and Ohio to investigate the impact of a policy change implemented during the COVID-19 pandemic that allowed the use of telehealth to prescribe buprenorphine for OUD.
• The two main outcomes of interest were retention in treatment after initiation (telehealth vs. traditional) and opioid-related nonfatal overdose after initiation.

TAKEAWAY:

• For both states combined, nearly 92,000 adults had a buprenorphine prescription in at least one quarter in 2020, with nearly 43,000 of those individuals starting treatment in 2020. 
• Sharp increases in telehealth delivery of buprenorphine were noted at the beginning of 2020 at the pandemic outset, and this was associated with greater retention in treatment (Kentucky adjusted odds ratio, 1.13; 95% confidence interval, 1.01-1.27 and Ohio aOR, 1.19; 95% CI, 1.06-1.32).
• Furthermore, 90-day retention rates were higher among those who started treatment via telehealth versus those who started treatment in nontelehealth settings in Kentucky (48% vs. 44%, respectively) and in Ohio (32% vs. 28%, respectively).
• There was no increased risk of nonfatal overdose with telehealth treatment, providing added evidence to suggest that patients were not harmed by having increased access to buprenorphine treatment via telehealth.

IN PRACTICE:

“These results offer important insights for states with a high burden of OUD looking to policies and methods to reduce barriers to treatment,” the authors write.

SOURCE:

The study, with first author Lindsey Hammerslag, PhD, with University of Kentucky College of Medicine, Lexington, was published online  in JAMA Network Open, with an invited commentary by Lindsey Allen, PhD, Northwestern University, Chicago, on navigating the path to effective, equitable, and evidence-based telehealth for OUD treatment.

LIMITATIONS:

The analysis was limited to Medicaid patients in two states over 1 year and there may have been unmeasured confounders, such as perceived patient stability, that influenced the findings. Because Medicaid data were not linked to emergency services or death records, this study considered only medically treated overdose.

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse and carried out in partnership with the Substance Abuse and Mental Health Services Administration. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Starting treatment with buprenorphine for opioid use disorder (OUD) via telehealth is associated with longer retention in treatment, compared with starting treatment in-person, new research suggests.

METHODOLOGY:

• Researchers analyzed Medicaid claims data from November 2019 through the end of 2020 in Kentucky and Ohio to investigate the impact of a policy change implemented during the COVID-19 pandemic that allowed the use of telehealth to prescribe buprenorphine for OUD.
• The two main outcomes of interest were retention in treatment after initiation (telehealth vs. traditional) and opioid-related nonfatal overdose after initiation.

TAKEAWAY:

• For both states combined, nearly 92,000 adults had a buprenorphine prescription in at least one quarter in 2020, with nearly 43,000 of those individuals starting treatment in 2020. 
• Sharp increases in telehealth delivery of buprenorphine were noted at the beginning of 2020 at the pandemic outset, and this was associated with greater retention in treatment (Kentucky adjusted odds ratio, 1.13; 95% confidence interval, 1.01-1.27 and Ohio aOR, 1.19; 95% CI, 1.06-1.32).
• Furthermore, 90-day retention rates were higher among those who started treatment via telehealth versus those who started treatment in nontelehealth settings in Kentucky (48% vs. 44%, respectively) and in Ohio (32% vs. 28%, respectively).
• There was no increased risk of nonfatal overdose with telehealth treatment, providing added evidence to suggest that patients were not harmed by having increased access to buprenorphine treatment via telehealth.

IN PRACTICE:

“These results offer important insights for states with a high burden of OUD looking to policies and methods to reduce barriers to treatment,” the authors write.

SOURCE:

The study, with first author Lindsey Hammerslag, PhD, with University of Kentucky College of Medicine, Lexington, was published online  in JAMA Network Open, with an invited commentary by Lindsey Allen, PhD, Northwestern University, Chicago, on navigating the path to effective, equitable, and evidence-based telehealth for OUD treatment.

LIMITATIONS:

The analysis was limited to Medicaid patients in two states over 1 year and there may have been unmeasured confounders, such as perceived patient stability, that influenced the findings. Because Medicaid data were not linked to emergency services or death records, this study considered only medically treated overdose.

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse and carried out in partnership with the Substance Abuse and Mental Health Services Administration. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Starting treatment with buprenorphine for opioid use disorder (OUD) via telehealth is associated with longer retention in treatment, compared with starting treatment in-person, new research suggests.

METHODOLOGY:

• Researchers analyzed Medicaid claims data from November 2019 through the end of 2020 in Kentucky and Ohio to investigate the impact of a policy change implemented during the COVID-19 pandemic that allowed the use of telehealth to prescribe buprenorphine for OUD.
• The two main outcomes of interest were retention in treatment after initiation (telehealth vs. traditional) and opioid-related nonfatal overdose after initiation.

TAKEAWAY:

• For both states combined, nearly 92,000 adults had a buprenorphine prescription in at least one quarter in 2020, with nearly 43,000 of those individuals starting treatment in 2020. 
• Sharp increases in telehealth delivery of buprenorphine were noted at the beginning of 2020 at the pandemic outset, and this was associated with greater retention in treatment (Kentucky adjusted odds ratio, 1.13; 95% confidence interval, 1.01-1.27 and Ohio aOR, 1.19; 95% CI, 1.06-1.32).
• Furthermore, 90-day retention rates were higher among those who started treatment via telehealth versus those who started treatment in nontelehealth settings in Kentucky (48% vs. 44%, respectively) and in Ohio (32% vs. 28%, respectively).
• There was no increased risk of nonfatal overdose with telehealth treatment, providing added evidence to suggest that patients were not harmed by having increased access to buprenorphine treatment via telehealth.

IN PRACTICE:

“These results offer important insights for states with a high burden of OUD looking to policies and methods to reduce barriers to treatment,” the authors write.

SOURCE:

The study, with first author Lindsey Hammerslag, PhD, with University of Kentucky College of Medicine, Lexington, was published online  in JAMA Network Open, with an invited commentary by Lindsey Allen, PhD, Northwestern University, Chicago, on navigating the path to effective, equitable, and evidence-based telehealth for OUD treatment.

LIMITATIONS:

The analysis was limited to Medicaid patients in two states over 1 year and there may have been unmeasured confounders, such as perceived patient stability, that influenced the findings. Because Medicaid data were not linked to emergency services or death records, this study considered only medically treated overdose.

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse and carried out in partnership with the Substance Abuse and Mental Health Services Administration. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Intensive antihypertensive treatment provides the same benefit with regard to cardiovascular disease (CVD) and all-cause mortality regardless of the presence or absence of orthostatic or standing hypotension, new research shows.

METHODOLOGY:

• In response to ongoing concern about the benefits of intensive versus standard blood pressure treatment for adults with orthostatic hypotension (OH), researchers conducted a meta-analysis of individual patient data from nine randomized clinical trials to see whether the benefit of antihypertensive treatment was diminished for patients who had OH at baseline. Benefit was defined as a reduction in nonfatal CVD events and all-cause mortality.
• The included trials assessed BP pharmacologic treatment (more intensive BP goal or active agent) and had data on OH.

TAKEAWAY:

• The nine trials included 29,235 participants (mean age, 69 years; 48% women) who were followed for a median of 4 years; 9% had OH and 5% had standing hypotension at baseline.
• Having OH at baseline was significantly associated with the composite of CVD or all-cause mortality (hazard ratio, 1.14; 95% confidence interval, 1.04-1.26) and with all-cause mortality (HR, 1.24; 95% CI, 1.09-1.41). The same was true for baseline standing hypotension (composite outcome: HR, 1.39; 95% CI, 1.24-1.57; all-cause mortality: HR, 1.38; 95% CI, 1.14-1.66).
• More intensive BP treatment or active therapy significantly and similarly lowered risk of CVD or all-cause mortality among adults who did not have OH at baseline (HR, 0.81; 95% CI, 0.76-0.86) as well as those with OH at baseline (HR, 0.83; 95% CI, 0.70-1.00).
• More intensive BP treatment or active therapy also significantly lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85) and nonsignificantly lowered the risk among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18).

IN PRACTICE:

“These findings suggest that orthostatic hypotension alone (that is, without symptoms) and standing hypotension measured prior to intensification of BP treatment should not deter adoption of more intensive BP treatment in adults with hypertension,” the authors conclude.

The findings should “reassure clinicians that patients with OH (and perhaps standing hypotension) will derive the full expected benefits from antihypertensive therapy,” add the authors of an accompanying editorial. “This also applies to patients treated to lower BP goals, albeit with less certainty.”

SOURCE:

The study, with first author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, and the accompanying editorial were published online in JAMA.

LIMITATIONS:

In the hypertension trials that were included in the analysis, the study populations differed, as did BP measurement procedures, interventions, duration, and CVD outcome ascertainment processes and definitions. Some trials excluded adults with low standing systolic BP, limiting the number of participants with standing hypotension. OH was determined on the basis of a seated-to-standing protocol; supine-to-standing protocols are more sensitive and may not be interchangeable. Medications used in the trials may not reflect current medicine practice, or the trials may not have included agents thought to be more likely to affect OH and falls.

DISCLOSURES:

The study had no specific funding. Dr. Juraschek has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Intensive antihypertensive treatment provides the same benefit with regard to cardiovascular disease (CVD) and all-cause mortality regardless of the presence or absence of orthostatic or standing hypotension, new research shows.

METHODOLOGY:

• In response to ongoing concern about the benefits of intensive versus standard blood pressure treatment for adults with orthostatic hypotension (OH), researchers conducted a meta-analysis of individual patient data from nine randomized clinical trials to see whether the benefit of antihypertensive treatment was diminished for patients who had OH at baseline. Benefit was defined as a reduction in nonfatal CVD events and all-cause mortality.
• The included trials assessed BP pharmacologic treatment (more intensive BP goal or active agent) and had data on OH.

TAKEAWAY:

• The nine trials included 29,235 participants (mean age, 69 years; 48% women) who were followed for a median of 4 years; 9% had OH and 5% had standing hypotension at baseline.
• Having OH at baseline was significantly associated with the composite of CVD or all-cause mortality (hazard ratio, 1.14; 95% confidence interval, 1.04-1.26) and with all-cause mortality (HR, 1.24; 95% CI, 1.09-1.41). The same was true for baseline standing hypotension (composite outcome: HR, 1.39; 95% CI, 1.24-1.57; all-cause mortality: HR, 1.38; 95% CI, 1.14-1.66).
• More intensive BP treatment or active therapy significantly and similarly lowered risk of CVD or all-cause mortality among adults who did not have OH at baseline (HR, 0.81; 95% CI, 0.76-0.86) as well as those with OH at baseline (HR, 0.83; 95% CI, 0.70-1.00).
• More intensive BP treatment or active therapy also significantly lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85) and nonsignificantly lowered the risk among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18).

IN PRACTICE:

“These findings suggest that orthostatic hypotension alone (that is, without symptoms) and standing hypotension measured prior to intensification of BP treatment should not deter adoption of more intensive BP treatment in adults with hypertension,” the authors conclude.

The findings should “reassure clinicians that patients with OH (and perhaps standing hypotension) will derive the full expected benefits from antihypertensive therapy,” add the authors of an accompanying editorial. “This also applies to patients treated to lower BP goals, albeit with less certainty.”

SOURCE:

The study, with first author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, and the accompanying editorial were published online in JAMA.

LIMITATIONS:

In the hypertension trials that were included in the analysis, the study populations differed, as did BP measurement procedures, interventions, duration, and CVD outcome ascertainment processes and definitions. Some trials excluded adults with low standing systolic BP, limiting the number of participants with standing hypotension. OH was determined on the basis of a seated-to-standing protocol; supine-to-standing protocols are more sensitive and may not be interchangeable. Medications used in the trials may not reflect current medicine practice, or the trials may not have included agents thought to be more likely to affect OH and falls.

DISCLOSURES:

The study had no specific funding. Dr. Juraschek has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Intensive antihypertensive treatment provides the same benefit with regard to cardiovascular disease (CVD) and all-cause mortality regardless of the presence or absence of orthostatic or standing hypotension, new research shows.

METHODOLOGY:

• In response to ongoing concern about the benefits of intensive versus standard blood pressure treatment for adults with orthostatic hypotension (OH), researchers conducted a meta-analysis of individual patient data from nine randomized clinical trials to see whether the benefit of antihypertensive treatment was diminished for patients who had OH at baseline. Benefit was defined as a reduction in nonfatal CVD events and all-cause mortality.
• The included trials assessed BP pharmacologic treatment (more intensive BP goal or active agent) and had data on OH.

TAKEAWAY:

• The nine trials included 29,235 participants (mean age, 69 years; 48% women) who were followed for a median of 4 years; 9% had OH and 5% had standing hypotension at baseline.
• Having OH at baseline was significantly associated with the composite of CVD or all-cause mortality (hazard ratio, 1.14; 95% confidence interval, 1.04-1.26) and with all-cause mortality (HR, 1.24; 95% CI, 1.09-1.41). The same was true for baseline standing hypotension (composite outcome: HR, 1.39; 95% CI, 1.24-1.57; all-cause mortality: HR, 1.38; 95% CI, 1.14-1.66).
• More intensive BP treatment or active therapy significantly and similarly lowered risk of CVD or all-cause mortality among adults who did not have OH at baseline (HR, 0.81; 95% CI, 0.76-0.86) as well as those with OH at baseline (HR, 0.83; 95% CI, 0.70-1.00).
• More intensive BP treatment or active therapy also significantly lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85) and nonsignificantly lowered the risk among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18).

IN PRACTICE:

“These findings suggest that orthostatic hypotension alone (that is, without symptoms) and standing hypotension measured prior to intensification of BP treatment should not deter adoption of more intensive BP treatment in adults with hypertension,” the authors conclude.

The findings should “reassure clinicians that patients with OH (and perhaps standing hypotension) will derive the full expected benefits from antihypertensive therapy,” add the authors of an accompanying editorial. “This also applies to patients treated to lower BP goals, albeit with less certainty.”

SOURCE:

The study, with first author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, and the accompanying editorial were published online in JAMA.

LIMITATIONS:

In the hypertension trials that were included in the analysis, the study populations differed, as did BP measurement procedures, interventions, duration, and CVD outcome ascertainment processes and definitions. Some trials excluded adults with low standing systolic BP, limiting the number of participants with standing hypotension. OH was determined on the basis of a seated-to-standing protocol; supine-to-standing protocols are more sensitive and may not be interchangeable. Medications used in the trials may not reflect current medicine practice, or the trials may not have included agents thought to be more likely to affect OH and falls.

DISCLOSURES:

The study had no specific funding. Dr. Juraschek has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.