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Circulating Proteins Predict Crohn’s Disease Years in Advance
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
FROM GASTROENTEROLOGY
No Racial Disparities in CVD Outcomes For VA Patients with Prostate Cancer Receiving ADT
TOPLINE: Veterans treated in the Veterans Health Administration (VHA) who had preexisting cardiometabolic disease and received androgen deprivation therapy (ADT) with radiation therapy developed major adverse cardiovascular events (MACE) at 4 times the rate compared to those without cardiometabolic disease. Black and White veterans showed similar cardiovascular outcomes regardless of treatment type.
METHODOLOGY:
Researchers conducted a retrospective cohort study examining 39,580 veterans in the VHA system diagnosed with prostate cancer between 2000 and 2015, following them for a median of 9.6 years to assess time to MACE diagnosis.
- Analysis utilized a 1:1 propensity score matching process to compare outcomes between treatment types (ADT with radiation therapy vs radiation therapy alone) and racial groups (Black vs White men).
- Participants had a mean age of 65.9 years at diagnosis; 68% identified as White and 32% as Black, and 83% had stage 2 disease classified with 43.1% intermediate risk. Most lived in nonrural zip codes
- Primary outcome measure was time to MACE, defined as a composite of cardiovascular death, myocardial infarction, or ischemic stroke, with patients censored at non-cardiovascular death or study end.
TAKEAWAY:
Compared to those without CMD, the hazard ratio (HR) for MACE for men with preexisting CMD who received ADT was 4.2. Those receiving radiation alone had an HR of 2.5.
- Patients diagnosed between 2010 and 2015 showed significantly lower MACE rates compared to those diagnosed in 2000 to 2005: HR, 0.23; 95% CI, 0.08-0.71 for White patients; and HR, 0.23; 95% CI, 0.07-0.77 for Black patients.
- Multiple comorbidities were associated with doubled MACE risk (HR, 2.22; 95% CI, 1.08-4.59) compared to those without comorbidities.
- No significant differences in MACE rates were observed between Black and White veterans, regardless of treatment type.
IN PRACTICE: “Within the VHA, men treated with ADT + radiation therapy for prostate cancer do not appear to be at greater risk for MACE than those receiving radiation therapy alone. Black men have similar risk of MACE as White men, whether receiving radiation therapy alone or in combination with ADT," the authors wrote.
SOURCE: The study was led by Alexander R. Lucas, Virginia Commonwealth University School of Public Health in Richmond. It was published online on February 6 in Cardio-Oncology.
LIMITATIONS: According to the authors, the retrospective nature of the data may have limited their ability to detect MACE events occurring outside the VHA. Additionally, the study was limited to men who initiated ADT prior to radiation therapy, excluding those who had surgery or radiation before ADT. The researchers also note that the analysis did not compare outcomes between different types of ADT treatments, such as GnRH agonists vs antagonists, which may have different cardiovascular risk profiles.
DISCLOSURES: Alexander R. Lucas’s work was partly funded by grants 1KO1HL161419 and NRG FP00019789. Ashit K. Paul disclosed receiving honorarium for serving on scientific consultancy panels of SANOFI-Genzyme, Bayer, and Tempus & Cardinal Health. Additional disclosures are noted but not specified in the article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
TOPLINE: Veterans treated in the Veterans Health Administration (VHA) who had preexisting cardiometabolic disease and received androgen deprivation therapy (ADT) with radiation therapy developed major adverse cardiovascular events (MACE) at 4 times the rate compared to those without cardiometabolic disease. Black and White veterans showed similar cardiovascular outcomes regardless of treatment type.
METHODOLOGY:
Researchers conducted a retrospective cohort study examining 39,580 veterans in the VHA system diagnosed with prostate cancer between 2000 and 2015, following them for a median of 9.6 years to assess time to MACE diagnosis.
- Analysis utilized a 1:1 propensity score matching process to compare outcomes between treatment types (ADT with radiation therapy vs radiation therapy alone) and racial groups (Black vs White men).
- Participants had a mean age of 65.9 years at diagnosis; 68% identified as White and 32% as Black, and 83% had stage 2 disease classified with 43.1% intermediate risk. Most lived in nonrural zip codes
- Primary outcome measure was time to MACE, defined as a composite of cardiovascular death, myocardial infarction, or ischemic stroke, with patients censored at non-cardiovascular death or study end.
TAKEAWAY:
Compared to those without CMD, the hazard ratio (HR) for MACE for men with preexisting CMD who received ADT was 4.2. Those receiving radiation alone had an HR of 2.5.
- Patients diagnosed between 2010 and 2015 showed significantly lower MACE rates compared to those diagnosed in 2000 to 2005: HR, 0.23; 95% CI, 0.08-0.71 for White patients; and HR, 0.23; 95% CI, 0.07-0.77 for Black patients.
- Multiple comorbidities were associated with doubled MACE risk (HR, 2.22; 95% CI, 1.08-4.59) compared to those without comorbidities.
- No significant differences in MACE rates were observed between Black and White veterans, regardless of treatment type.
IN PRACTICE: “Within the VHA, men treated with ADT + radiation therapy for prostate cancer do not appear to be at greater risk for MACE than those receiving radiation therapy alone. Black men have similar risk of MACE as White men, whether receiving radiation therapy alone or in combination with ADT," the authors wrote.
SOURCE: The study was led by Alexander R. Lucas, Virginia Commonwealth University School of Public Health in Richmond. It was published online on February 6 in Cardio-Oncology.
LIMITATIONS: According to the authors, the retrospective nature of the data may have limited their ability to detect MACE events occurring outside the VHA. Additionally, the study was limited to men who initiated ADT prior to radiation therapy, excluding those who had surgery or radiation before ADT. The researchers also note that the analysis did not compare outcomes between different types of ADT treatments, such as GnRH agonists vs antagonists, which may have different cardiovascular risk profiles.
DISCLOSURES: Alexander R. Lucas’s work was partly funded by grants 1KO1HL161419 and NRG FP00019789. Ashit K. Paul disclosed receiving honorarium for serving on scientific consultancy panels of SANOFI-Genzyme, Bayer, and Tempus & Cardinal Health. Additional disclosures are noted but not specified in the article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
TOPLINE: Veterans treated in the Veterans Health Administration (VHA) who had preexisting cardiometabolic disease and received androgen deprivation therapy (ADT) with radiation therapy developed major adverse cardiovascular events (MACE) at 4 times the rate compared to those without cardiometabolic disease. Black and White veterans showed similar cardiovascular outcomes regardless of treatment type.
METHODOLOGY:
Researchers conducted a retrospective cohort study examining 39,580 veterans in the VHA system diagnosed with prostate cancer between 2000 and 2015, following them for a median of 9.6 years to assess time to MACE diagnosis.
- Analysis utilized a 1:1 propensity score matching process to compare outcomes between treatment types (ADT with radiation therapy vs radiation therapy alone) and racial groups (Black vs White men).
- Participants had a mean age of 65.9 years at diagnosis; 68% identified as White and 32% as Black, and 83% had stage 2 disease classified with 43.1% intermediate risk. Most lived in nonrural zip codes
- Primary outcome measure was time to MACE, defined as a composite of cardiovascular death, myocardial infarction, or ischemic stroke, with patients censored at non-cardiovascular death or study end.
TAKEAWAY:
Compared to those without CMD, the hazard ratio (HR) for MACE for men with preexisting CMD who received ADT was 4.2. Those receiving radiation alone had an HR of 2.5.
- Patients diagnosed between 2010 and 2015 showed significantly lower MACE rates compared to those diagnosed in 2000 to 2005: HR, 0.23; 95% CI, 0.08-0.71 for White patients; and HR, 0.23; 95% CI, 0.07-0.77 for Black patients.
- Multiple comorbidities were associated with doubled MACE risk (HR, 2.22; 95% CI, 1.08-4.59) compared to those without comorbidities.
- No significant differences in MACE rates were observed between Black and White veterans, regardless of treatment type.
IN PRACTICE: “Within the VHA, men treated with ADT + radiation therapy for prostate cancer do not appear to be at greater risk for MACE than those receiving radiation therapy alone. Black men have similar risk of MACE as White men, whether receiving radiation therapy alone or in combination with ADT," the authors wrote.
SOURCE: The study was led by Alexander R. Lucas, Virginia Commonwealth University School of Public Health in Richmond. It was published online on February 6 in Cardio-Oncology.
LIMITATIONS: According to the authors, the retrospective nature of the data may have limited their ability to detect MACE events occurring outside the VHA. Additionally, the study was limited to men who initiated ADT prior to radiation therapy, excluding those who had surgery or radiation before ADT. The researchers also note that the analysis did not compare outcomes between different types of ADT treatments, such as GnRH agonists vs antagonists, which may have different cardiovascular risk profiles.
DISCLOSURES: Alexander R. Lucas’s work was partly funded by grants 1KO1HL161419 and NRG FP00019789. Ashit K. Paul disclosed receiving honorarium for serving on scientific consultancy panels of SANOFI-Genzyme, Bayer, and Tempus & Cardinal Health. Additional disclosures are noted but not specified in the article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
Where Are All the Nurses? Data Show That Some States Have a Far Higher Number of Nurses Per Capita Than Others
During their 12-hour shifts, registered nurses (RNs) in Arizona and Arkansas perform many of the same tasks as RNs in Wisconsin and Wyoming: Assessing patients, monitoring vital signs, administering medications, and charting records to provide the best patient care. The work might be similar, but there are vast differences in the number of RNs in each state.
In states like Idaho, Utah, and Nevada, which have the lowest number of nurses per capita, there are as few as 7 nurses per 1000 residents, compared with South Dakota and the District of Columbia, which have double the number of nurses than underserved states — giving them the highest number of nurses per capita.
Even states with the largest number of nurses per capita are not immune to the nursing shortage. The National Bureau of Labor Statistics estimates that there will be 195,400 job openings for RNs from 2021 to 2031.
So, what makes it easier for some states to recruit and retain RNs than others?
States With the Highest Number of Nurses Per Capita
South Dakota
RNs per 1000 residents: 15.79
Average wage: $67,030 or $32.23 per hour
Average rent in Sioux Falls: $1192 per month
The Midwestern state has more miles of shoreline than Florida, herds of wild buffalo, the highest summit east of the Rockies, and more nurses per capita than all other states . Healthcare is one of the major industries in the Mount Rushmore State.
Haifa Abou Samra, dean and professor at the University of South Dakota School of Health Sciences, Vermillion, isn’t surprised that RNs want to call the state home.
“South Dakota is a nice place to live,” Samra said. “[The] schools are wonderful. If people are growing families, there is support; neighbors support their neighbors, and it’s a relatively safe community.”
South Dakota has 19 approved nursing education programs that graduated 878 RNs in 2022. Scholarships and student loan forgiveness programs have helped attract qualified RNs, and collaborations between education and industry have been instrumental in addressing the nursing shortage, Samra told this news organization.
Even though RNs earn less than the median wage ($87,070 per year/41.38 per hour), South Dakota has a low cost of living and no individual income tax, which helps stretch those earnings.
District of Columbia
RNs per 1000 residents: 15.39
Average wage: $105,220 or $50.59 per hour
Average rent in Washington, DC: $2485 per month
After a shift at some of the top-ranking hospitals in the nation, RNs working in the compact capital region can explore museums, monuments, and cultural sites; walk along the banks of the Potomac River; or grab a bite at award-winning restaurants.
Washington, a top-ranking metro area because of its growth, high wages, and access to economic opportunities, is also home to several top-tier hospitals and some of the best healthcare in the nation, and RNs who want to pursue continuing education have access to top-tier universities.
Nurses in Washington, DC, might make some of the highest wages in the nation, but the region also has the second-highest cost of living in the United States, with average rents topping $2400 per month and an average home price of $594,337.
North Dakota
RNs per 1000 residents: 12.99
Average wage: $74,930 or $36.03 per hour
Average rent in Fargo: $1051 per month
North Dakota projects a 10.4% increase in employment for RNs, which is higher than the national average, and the state has implemented several strategies to address chronic nursing shortages. The Nurse Staffing Clearinghouse connects nursing school graduates with local employers and created a statewide nursing staffing pool for in-state recruitment of travel nurses.
But it’s not just plentiful job opportunities and a low cost of living that attract nurses to the Peace Garden State. The state and its largest cities, Bismarck and Fargo, hold several “best of” accolades, including nods for the safest places to live and among the Best Places to Raise a Family, giving it high marks for quality of life.
Sure, the winters are cold, but the outdoor recreation can’t be beaten. RNs can bundle up and see the bighorn sheep in the Badlands at Theodore Roosevelt National Park or explore expansive terrain for skiing, snowboarding, and snowmobile trails.
States With the Lowest Number of Nurses Per Capita
Nevada
RNs per 1000 residents: 7.92
Average wage: $96,201 or $46.25 per hour
Average rent in Las Vegas: $1478 per month
Despite a projected 23% job growth for RNs between 2020 and 2030, the state has struggled to fill open positions. It might be the higher-than-average cost of living (9.7% higher than the US average) or higher-than-average crime rates that make RNs reluctant to gamble on a job in the Silver State. But there are some big wins for nurses in the state.
Salaries are higher than the national average, there is no state income tax, and some of the lowest property taxes in the nation. Thanks to new legislation, RNs with student loan debt won’t have to bet on black at the casino to make their payments. The Health Equity and Loan Assistance Program is a new initiative that offers up to $120,000 in loan repayment assistance to providers, including RNs, who commit to working in underserved and rural areas across the state for 5 years.
The state also has incredible attractions, from the neon lights and over-the-top architecture in Las Vegas to iconic red rock canyons, stunning state parks, and landmarks like Hoover Dam and Lake Tahoe.
Utah
RNs per 1000 residents: 7.05
Average wage: $79,790 or $38.36 per hour
Average rent in Salt Lake City: $1611 per month
Healthcare is one of the biggest employers in Utah, and nurses are the most in-demand healthcare workers in the state. But below-average wages and a cost of living that is a whopping 28% higher than the national average could be some reasons that the Beehive State is struggling to attract nurses.
A high number of job vacancies mean higher patient-to-nurse ratios, creating additional stress for a workforce prone to burnout. Much of the state is rural, public transportation is inadequate, and poor air quality causes frequent haze and smog.
The challenges are offset by some big benefits: Utah has been ranked as the “best state” thanks to the strong economy, infrastructure, and quality education — and it doesn’t hurt that Utah is home to myriad outdoor recreation opportunities and the stunning scenery at landmarks like Bryce Canyon and Arches National Park.
Moreover, Utah is hustling to boost its RN workforce. The University of Utah, Salt Lake City, has increased enrollment by 25% and hired additional faculty to help boost the nursing workforce — and those who work in hospitals and health clinics across the state benefit from a flat 4.55% individual income tax rate.
Idaho
RNs per 1000 residents: 7.02
Average wage: $80,130 or $38.53 per hour
Average rent in Boise: $1646 per month
Although the nursing workforce in Idaho has increased, it still ranks as the lowest in the nation. Teresa Stanfill, DNP, RN, executive director for the Idaho Center for Nursing, said that the number of new nurses is too low to replace the number of retiring nurses.
The state introduced loan repayment programs that award up to $25,000 to cover student loan debt, and hospitals and health systems often offer sign-on bonuses and relocation packages to attract RNs. But long winters, an isolated location, and limited cultural options can make it harder to attract nurses to the state.
It’s easier to recruit RNs to suburban areas like Boise, Meridian, and Nampa, but rural parts of the state struggle, Stanfill added. The nursing shortage is among the reasons that 11 hospitals and emergency departments closed in 2024, and healthcare organizations slashed services across the state.
Idaho has a lot to offer RNs, from small-town charm, reasonable cost of living, and gorgeous landscapes that make it one of the top 10 fastest-growing states in the nation. Collaboration between industry leaders and nursing programs is focused on finding creative solutions to boost the nursing workforce in Idaho.
A version of this article first appeared on Medscape.com.
During their 12-hour shifts, registered nurses (RNs) in Arizona and Arkansas perform many of the same tasks as RNs in Wisconsin and Wyoming: Assessing patients, monitoring vital signs, administering medications, and charting records to provide the best patient care. The work might be similar, but there are vast differences in the number of RNs in each state.
In states like Idaho, Utah, and Nevada, which have the lowest number of nurses per capita, there are as few as 7 nurses per 1000 residents, compared with South Dakota and the District of Columbia, which have double the number of nurses than underserved states — giving them the highest number of nurses per capita.
Even states with the largest number of nurses per capita are not immune to the nursing shortage. The National Bureau of Labor Statistics estimates that there will be 195,400 job openings for RNs from 2021 to 2031.
So, what makes it easier for some states to recruit and retain RNs than others?
States With the Highest Number of Nurses Per Capita
South Dakota
RNs per 1000 residents: 15.79
Average wage: $67,030 or $32.23 per hour
Average rent in Sioux Falls: $1192 per month
The Midwestern state has more miles of shoreline than Florida, herds of wild buffalo, the highest summit east of the Rockies, and more nurses per capita than all other states . Healthcare is one of the major industries in the Mount Rushmore State.
Haifa Abou Samra, dean and professor at the University of South Dakota School of Health Sciences, Vermillion, isn’t surprised that RNs want to call the state home.
“South Dakota is a nice place to live,” Samra said. “[The] schools are wonderful. If people are growing families, there is support; neighbors support their neighbors, and it’s a relatively safe community.”
South Dakota has 19 approved nursing education programs that graduated 878 RNs in 2022. Scholarships and student loan forgiveness programs have helped attract qualified RNs, and collaborations between education and industry have been instrumental in addressing the nursing shortage, Samra told this news organization.
Even though RNs earn less than the median wage ($87,070 per year/41.38 per hour), South Dakota has a low cost of living and no individual income tax, which helps stretch those earnings.
District of Columbia
RNs per 1000 residents: 15.39
Average wage: $105,220 or $50.59 per hour
Average rent in Washington, DC: $2485 per month
After a shift at some of the top-ranking hospitals in the nation, RNs working in the compact capital region can explore museums, monuments, and cultural sites; walk along the banks of the Potomac River; or grab a bite at award-winning restaurants.
Washington, a top-ranking metro area because of its growth, high wages, and access to economic opportunities, is also home to several top-tier hospitals and some of the best healthcare in the nation, and RNs who want to pursue continuing education have access to top-tier universities.
Nurses in Washington, DC, might make some of the highest wages in the nation, but the region also has the second-highest cost of living in the United States, with average rents topping $2400 per month and an average home price of $594,337.
North Dakota
RNs per 1000 residents: 12.99
Average wage: $74,930 or $36.03 per hour
Average rent in Fargo: $1051 per month
North Dakota projects a 10.4% increase in employment for RNs, which is higher than the national average, and the state has implemented several strategies to address chronic nursing shortages. The Nurse Staffing Clearinghouse connects nursing school graduates with local employers and created a statewide nursing staffing pool for in-state recruitment of travel nurses.
But it’s not just plentiful job opportunities and a low cost of living that attract nurses to the Peace Garden State. The state and its largest cities, Bismarck and Fargo, hold several “best of” accolades, including nods for the safest places to live and among the Best Places to Raise a Family, giving it high marks for quality of life.
Sure, the winters are cold, but the outdoor recreation can’t be beaten. RNs can bundle up and see the bighorn sheep in the Badlands at Theodore Roosevelt National Park or explore expansive terrain for skiing, snowboarding, and snowmobile trails.
States With the Lowest Number of Nurses Per Capita
Nevada
RNs per 1000 residents: 7.92
Average wage: $96,201 or $46.25 per hour
Average rent in Las Vegas: $1478 per month
Despite a projected 23% job growth for RNs between 2020 and 2030, the state has struggled to fill open positions. It might be the higher-than-average cost of living (9.7% higher than the US average) or higher-than-average crime rates that make RNs reluctant to gamble on a job in the Silver State. But there are some big wins for nurses in the state.
Salaries are higher than the national average, there is no state income tax, and some of the lowest property taxes in the nation. Thanks to new legislation, RNs with student loan debt won’t have to bet on black at the casino to make their payments. The Health Equity and Loan Assistance Program is a new initiative that offers up to $120,000 in loan repayment assistance to providers, including RNs, who commit to working in underserved and rural areas across the state for 5 years.
The state also has incredible attractions, from the neon lights and over-the-top architecture in Las Vegas to iconic red rock canyons, stunning state parks, and landmarks like Hoover Dam and Lake Tahoe.
Utah
RNs per 1000 residents: 7.05
Average wage: $79,790 or $38.36 per hour
Average rent in Salt Lake City: $1611 per month
Healthcare is one of the biggest employers in Utah, and nurses are the most in-demand healthcare workers in the state. But below-average wages and a cost of living that is a whopping 28% higher than the national average could be some reasons that the Beehive State is struggling to attract nurses.
A high number of job vacancies mean higher patient-to-nurse ratios, creating additional stress for a workforce prone to burnout. Much of the state is rural, public transportation is inadequate, and poor air quality causes frequent haze and smog.
The challenges are offset by some big benefits: Utah has been ranked as the “best state” thanks to the strong economy, infrastructure, and quality education — and it doesn’t hurt that Utah is home to myriad outdoor recreation opportunities and the stunning scenery at landmarks like Bryce Canyon and Arches National Park.
Moreover, Utah is hustling to boost its RN workforce. The University of Utah, Salt Lake City, has increased enrollment by 25% and hired additional faculty to help boost the nursing workforce — and those who work in hospitals and health clinics across the state benefit from a flat 4.55% individual income tax rate.
Idaho
RNs per 1000 residents: 7.02
Average wage: $80,130 or $38.53 per hour
Average rent in Boise: $1646 per month
Although the nursing workforce in Idaho has increased, it still ranks as the lowest in the nation. Teresa Stanfill, DNP, RN, executive director for the Idaho Center for Nursing, said that the number of new nurses is too low to replace the number of retiring nurses.
The state introduced loan repayment programs that award up to $25,000 to cover student loan debt, and hospitals and health systems often offer sign-on bonuses and relocation packages to attract RNs. But long winters, an isolated location, and limited cultural options can make it harder to attract nurses to the state.
It’s easier to recruit RNs to suburban areas like Boise, Meridian, and Nampa, but rural parts of the state struggle, Stanfill added. The nursing shortage is among the reasons that 11 hospitals and emergency departments closed in 2024, and healthcare organizations slashed services across the state.
Idaho has a lot to offer RNs, from small-town charm, reasonable cost of living, and gorgeous landscapes that make it one of the top 10 fastest-growing states in the nation. Collaboration between industry leaders and nursing programs is focused on finding creative solutions to boost the nursing workforce in Idaho.
A version of this article first appeared on Medscape.com.
During their 12-hour shifts, registered nurses (RNs) in Arizona and Arkansas perform many of the same tasks as RNs in Wisconsin and Wyoming: Assessing patients, monitoring vital signs, administering medications, and charting records to provide the best patient care. The work might be similar, but there are vast differences in the number of RNs in each state.
In states like Idaho, Utah, and Nevada, which have the lowest number of nurses per capita, there are as few as 7 nurses per 1000 residents, compared with South Dakota and the District of Columbia, which have double the number of nurses than underserved states — giving them the highest number of nurses per capita.
Even states with the largest number of nurses per capita are not immune to the nursing shortage. The National Bureau of Labor Statistics estimates that there will be 195,400 job openings for RNs from 2021 to 2031.
So, what makes it easier for some states to recruit and retain RNs than others?
States With the Highest Number of Nurses Per Capita
South Dakota
RNs per 1000 residents: 15.79
Average wage: $67,030 or $32.23 per hour
Average rent in Sioux Falls: $1192 per month
The Midwestern state has more miles of shoreline than Florida, herds of wild buffalo, the highest summit east of the Rockies, and more nurses per capita than all other states . Healthcare is one of the major industries in the Mount Rushmore State.
Haifa Abou Samra, dean and professor at the University of South Dakota School of Health Sciences, Vermillion, isn’t surprised that RNs want to call the state home.
“South Dakota is a nice place to live,” Samra said. “[The] schools are wonderful. If people are growing families, there is support; neighbors support their neighbors, and it’s a relatively safe community.”
South Dakota has 19 approved nursing education programs that graduated 878 RNs in 2022. Scholarships and student loan forgiveness programs have helped attract qualified RNs, and collaborations between education and industry have been instrumental in addressing the nursing shortage, Samra told this news organization.
Even though RNs earn less than the median wage ($87,070 per year/41.38 per hour), South Dakota has a low cost of living and no individual income tax, which helps stretch those earnings.
District of Columbia
RNs per 1000 residents: 15.39
Average wage: $105,220 or $50.59 per hour
Average rent in Washington, DC: $2485 per month
After a shift at some of the top-ranking hospitals in the nation, RNs working in the compact capital region can explore museums, monuments, and cultural sites; walk along the banks of the Potomac River; or grab a bite at award-winning restaurants.
Washington, a top-ranking metro area because of its growth, high wages, and access to economic opportunities, is also home to several top-tier hospitals and some of the best healthcare in the nation, and RNs who want to pursue continuing education have access to top-tier universities.
Nurses in Washington, DC, might make some of the highest wages in the nation, but the region also has the second-highest cost of living in the United States, with average rents topping $2400 per month and an average home price of $594,337.
North Dakota
RNs per 1000 residents: 12.99
Average wage: $74,930 or $36.03 per hour
Average rent in Fargo: $1051 per month
North Dakota projects a 10.4% increase in employment for RNs, which is higher than the national average, and the state has implemented several strategies to address chronic nursing shortages. The Nurse Staffing Clearinghouse connects nursing school graduates with local employers and created a statewide nursing staffing pool for in-state recruitment of travel nurses.
But it’s not just plentiful job opportunities and a low cost of living that attract nurses to the Peace Garden State. The state and its largest cities, Bismarck and Fargo, hold several “best of” accolades, including nods for the safest places to live and among the Best Places to Raise a Family, giving it high marks for quality of life.
Sure, the winters are cold, but the outdoor recreation can’t be beaten. RNs can bundle up and see the bighorn sheep in the Badlands at Theodore Roosevelt National Park or explore expansive terrain for skiing, snowboarding, and snowmobile trails.
States With the Lowest Number of Nurses Per Capita
Nevada
RNs per 1000 residents: 7.92
Average wage: $96,201 or $46.25 per hour
Average rent in Las Vegas: $1478 per month
Despite a projected 23% job growth for RNs between 2020 and 2030, the state has struggled to fill open positions. It might be the higher-than-average cost of living (9.7% higher than the US average) or higher-than-average crime rates that make RNs reluctant to gamble on a job in the Silver State. But there are some big wins for nurses in the state.
Salaries are higher than the national average, there is no state income tax, and some of the lowest property taxes in the nation. Thanks to new legislation, RNs with student loan debt won’t have to bet on black at the casino to make their payments. The Health Equity and Loan Assistance Program is a new initiative that offers up to $120,000 in loan repayment assistance to providers, including RNs, who commit to working in underserved and rural areas across the state for 5 years.
The state also has incredible attractions, from the neon lights and over-the-top architecture in Las Vegas to iconic red rock canyons, stunning state parks, and landmarks like Hoover Dam and Lake Tahoe.
Utah
RNs per 1000 residents: 7.05
Average wage: $79,790 or $38.36 per hour
Average rent in Salt Lake City: $1611 per month
Healthcare is one of the biggest employers in Utah, and nurses are the most in-demand healthcare workers in the state. But below-average wages and a cost of living that is a whopping 28% higher than the national average could be some reasons that the Beehive State is struggling to attract nurses.
A high number of job vacancies mean higher patient-to-nurse ratios, creating additional stress for a workforce prone to burnout. Much of the state is rural, public transportation is inadequate, and poor air quality causes frequent haze and smog.
The challenges are offset by some big benefits: Utah has been ranked as the “best state” thanks to the strong economy, infrastructure, and quality education — and it doesn’t hurt that Utah is home to myriad outdoor recreation opportunities and the stunning scenery at landmarks like Bryce Canyon and Arches National Park.
Moreover, Utah is hustling to boost its RN workforce. The University of Utah, Salt Lake City, has increased enrollment by 25% and hired additional faculty to help boost the nursing workforce — and those who work in hospitals and health clinics across the state benefit from a flat 4.55% individual income tax rate.
Idaho
RNs per 1000 residents: 7.02
Average wage: $80,130 or $38.53 per hour
Average rent in Boise: $1646 per month
Although the nursing workforce in Idaho has increased, it still ranks as the lowest in the nation. Teresa Stanfill, DNP, RN, executive director for the Idaho Center for Nursing, said that the number of new nurses is too low to replace the number of retiring nurses.
The state introduced loan repayment programs that award up to $25,000 to cover student loan debt, and hospitals and health systems often offer sign-on bonuses and relocation packages to attract RNs. But long winters, an isolated location, and limited cultural options can make it harder to attract nurses to the state.
It’s easier to recruit RNs to suburban areas like Boise, Meridian, and Nampa, but rural parts of the state struggle, Stanfill added. The nursing shortage is among the reasons that 11 hospitals and emergency departments closed in 2024, and healthcare organizations slashed services across the state.
Idaho has a lot to offer RNs, from small-town charm, reasonable cost of living, and gorgeous landscapes that make it one of the top 10 fastest-growing states in the nation. Collaboration between industry leaders and nursing programs is focused on finding creative solutions to boost the nursing workforce in Idaho.
A version of this article first appeared on Medscape.com.
Bariatric Surgery: Nutrition’s Role in Patient Outcomes
, according to an updated clinical practice statement from the Obesity Medicine Association (OMA).
The update offers guidance on how to manage metabolic and bariatric surgery patients’ nutrition, from preoperative nutritional assessments through identification and treatment of the most common nutritional problems associated with bariatric procedures.
“The main takeaway really is that obesity is a complex and chronic disease. It requires the same model of care as diabetes or other chronic conditions,” said Rutuja Patel, DO, senior author and an obesity medicine specialist at Northwestern Medicine Regional Medical Group in Winfield, Illinois.
The development of an interdisciplinary team of medical providers with evidence-based nutrition knowledge and consistent information improves the quality of nutrition care provided to bariatric surgery patients, the authors wrote.
“Collaborative multidisciplinary care that takes into consideration the whole patient in a biopsychosocial way and uses multiple modalities — including medical, behavioral, nutritional, and others — leads to the best outcomes in these complex patients,” Patel said.
The updated statement, published online in Obesity Pillars, offers a variety of tools and checklists to aid clinicians, especially those who may not have access to a multidisciplinary team or dietitian knowledgeable about bariatric nutrition.
It is a follow-up to the OMA’s 2022 clinical practice statement, which provided an overview of bariatric surgery, gastrointestinal hormones, and the microbiome in patients with obesity.
Presurgical Guidance
The new guidance lays out the various components of preoperative nutrition screenings, among which is a medication review to determine if the patient is taking drugs that may affect weight and calorie intake. These include antihypertensives, diabetes agents, hormonal contraceptives, antidepressants, migraine medications, and antipsychotics.
In taking a patient’s history, clinicians should ask about major events associated with weight changes, such as medication changes, illness, pregnancy, divorce, stressful employment, food insecurity, and periods of disordered eating.
The fundamental approach to conducting a nutrition assessment is an understanding of the role that various sections of the gastrointestinal tract play in micronutrient absorption, the authors wrote. As an educational tool, the update includes a diagram that indicates the areas of the stomach, duodenum, jejunum, and ileum that may be altered by bariatric surgery and how they factor into micronutrient absorption.
“It makes it easier to see why certain surgical procedures are more likely to cause certain deficiencies,” Patel said.
Postsurgery Patient Management
Post surgery, clinicians should monitor patients for other problems that could affect nutrient absorption, including food intolerances, drug-nutrient interactions, and increased gastrointestinal transit time.
Patel and coauthors discussed the pros and cons of multivitamin mineral supplement formulations as well as specific vitamin and mineral recommendations for patients undergoing certain metabolic or bariatric surgery procedures. They included three supplemental cases in the appendix to illustrate supplementation recommendations and long-term maintenance suggestions.
“It’s important to remember that most of these deficiencies present without many clinical symptoms, so it becomes essential to screen for them and repeat as needed,” Patel said.
The update also tackles postoperative nutritional assessments and diet progression. No evidence supports following one postsurgical diet progression protocol over another, but they generally proceed from a clear liquid diet to foods with normal textures, the authors noted. Clinicians should adapt them according to the procedure type, they added.
In addition, clinicians must troubleshoot any nutrition-related concerns, including constipation, dehydration, nausea, heartburn, and fatigue, for up to a year after surgery, they wrote.
Metabolic and bariatric surgery patients should be evaluated annually at a minimum, if not more frequently, to gauge nutritional health, the authors wrote. Treating obesity as a disease involves more than weight loss — instead, it’s about improving the quality of life of patients through procedures, medications, and lifestyle modifications, they added.
Track New Developments
With ongoing changes in the field of metabolic and bariatric surgery, it’s helpful for clinicians to remain updated about new approaches across various disciplines linked to obesity management and treatment, said Christina Poa-Li, MD, a surgeon at Huntington Health Medical Center, affiliated with Cedars-Sinai Health System, in Pasadena, California, who was not involved in developing the updated practice statement.
“For example, the rapidly growing prescription of anti-obesity medications and their use in both preoperative and postoperative surgical patients drastically affect their nutrition,” she said. “Providers of various backgrounds and specialties will benefit from the most updated guidance on evaluating patient nutrition.”
Clinicians should consider expanding their patient population to include those with metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease, Poa-Li said.
“These patient subpopulations may not have been considered for bariatric surgery or even referral to a bariatric surgeon for consultation previously,” she said. “It is important to increase awareness among clinicians of the potential benefits for metabolic and bariatric surgery for these patients.”
The report didn’t receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Patel and Poa-Li reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to an updated clinical practice statement from the Obesity Medicine Association (OMA).
The update offers guidance on how to manage metabolic and bariatric surgery patients’ nutrition, from preoperative nutritional assessments through identification and treatment of the most common nutritional problems associated with bariatric procedures.
“The main takeaway really is that obesity is a complex and chronic disease. It requires the same model of care as diabetes or other chronic conditions,” said Rutuja Patel, DO, senior author and an obesity medicine specialist at Northwestern Medicine Regional Medical Group in Winfield, Illinois.
The development of an interdisciplinary team of medical providers with evidence-based nutrition knowledge and consistent information improves the quality of nutrition care provided to bariatric surgery patients, the authors wrote.
“Collaborative multidisciplinary care that takes into consideration the whole patient in a biopsychosocial way and uses multiple modalities — including medical, behavioral, nutritional, and others — leads to the best outcomes in these complex patients,” Patel said.
The updated statement, published online in Obesity Pillars, offers a variety of tools and checklists to aid clinicians, especially those who may not have access to a multidisciplinary team or dietitian knowledgeable about bariatric nutrition.
It is a follow-up to the OMA’s 2022 clinical practice statement, which provided an overview of bariatric surgery, gastrointestinal hormones, and the microbiome in patients with obesity.
Presurgical Guidance
The new guidance lays out the various components of preoperative nutrition screenings, among which is a medication review to determine if the patient is taking drugs that may affect weight and calorie intake. These include antihypertensives, diabetes agents, hormonal contraceptives, antidepressants, migraine medications, and antipsychotics.
In taking a patient’s history, clinicians should ask about major events associated with weight changes, such as medication changes, illness, pregnancy, divorce, stressful employment, food insecurity, and periods of disordered eating.
The fundamental approach to conducting a nutrition assessment is an understanding of the role that various sections of the gastrointestinal tract play in micronutrient absorption, the authors wrote. As an educational tool, the update includes a diagram that indicates the areas of the stomach, duodenum, jejunum, and ileum that may be altered by bariatric surgery and how they factor into micronutrient absorption.
“It makes it easier to see why certain surgical procedures are more likely to cause certain deficiencies,” Patel said.
Postsurgery Patient Management
Post surgery, clinicians should monitor patients for other problems that could affect nutrient absorption, including food intolerances, drug-nutrient interactions, and increased gastrointestinal transit time.
Patel and coauthors discussed the pros and cons of multivitamin mineral supplement formulations as well as specific vitamin and mineral recommendations for patients undergoing certain metabolic or bariatric surgery procedures. They included three supplemental cases in the appendix to illustrate supplementation recommendations and long-term maintenance suggestions.
“It’s important to remember that most of these deficiencies present without many clinical symptoms, so it becomes essential to screen for them and repeat as needed,” Patel said.
The update also tackles postoperative nutritional assessments and diet progression. No evidence supports following one postsurgical diet progression protocol over another, but they generally proceed from a clear liquid diet to foods with normal textures, the authors noted. Clinicians should adapt them according to the procedure type, they added.
In addition, clinicians must troubleshoot any nutrition-related concerns, including constipation, dehydration, nausea, heartburn, and fatigue, for up to a year after surgery, they wrote.
Metabolic and bariatric surgery patients should be evaluated annually at a minimum, if not more frequently, to gauge nutritional health, the authors wrote. Treating obesity as a disease involves more than weight loss — instead, it’s about improving the quality of life of patients through procedures, medications, and lifestyle modifications, they added.
Track New Developments
With ongoing changes in the field of metabolic and bariatric surgery, it’s helpful for clinicians to remain updated about new approaches across various disciplines linked to obesity management and treatment, said Christina Poa-Li, MD, a surgeon at Huntington Health Medical Center, affiliated with Cedars-Sinai Health System, in Pasadena, California, who was not involved in developing the updated practice statement.
“For example, the rapidly growing prescription of anti-obesity medications and their use in both preoperative and postoperative surgical patients drastically affect their nutrition,” she said. “Providers of various backgrounds and specialties will benefit from the most updated guidance on evaluating patient nutrition.”
Clinicians should consider expanding their patient population to include those with metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease, Poa-Li said.
“These patient subpopulations may not have been considered for bariatric surgery or even referral to a bariatric surgeon for consultation previously,” she said. “It is important to increase awareness among clinicians of the potential benefits for metabolic and bariatric surgery for these patients.”
The report didn’t receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Patel and Poa-Li reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to an updated clinical practice statement from the Obesity Medicine Association (OMA).
The update offers guidance on how to manage metabolic and bariatric surgery patients’ nutrition, from preoperative nutritional assessments through identification and treatment of the most common nutritional problems associated with bariatric procedures.
“The main takeaway really is that obesity is a complex and chronic disease. It requires the same model of care as diabetes or other chronic conditions,” said Rutuja Patel, DO, senior author and an obesity medicine specialist at Northwestern Medicine Regional Medical Group in Winfield, Illinois.
The development of an interdisciplinary team of medical providers with evidence-based nutrition knowledge and consistent information improves the quality of nutrition care provided to bariatric surgery patients, the authors wrote.
“Collaborative multidisciplinary care that takes into consideration the whole patient in a biopsychosocial way and uses multiple modalities — including medical, behavioral, nutritional, and others — leads to the best outcomes in these complex patients,” Patel said.
The updated statement, published online in Obesity Pillars, offers a variety of tools and checklists to aid clinicians, especially those who may not have access to a multidisciplinary team or dietitian knowledgeable about bariatric nutrition.
It is a follow-up to the OMA’s 2022 clinical practice statement, which provided an overview of bariatric surgery, gastrointestinal hormones, and the microbiome in patients with obesity.
Presurgical Guidance
The new guidance lays out the various components of preoperative nutrition screenings, among which is a medication review to determine if the patient is taking drugs that may affect weight and calorie intake. These include antihypertensives, diabetes agents, hormonal contraceptives, antidepressants, migraine medications, and antipsychotics.
In taking a patient’s history, clinicians should ask about major events associated with weight changes, such as medication changes, illness, pregnancy, divorce, stressful employment, food insecurity, and periods of disordered eating.
The fundamental approach to conducting a nutrition assessment is an understanding of the role that various sections of the gastrointestinal tract play in micronutrient absorption, the authors wrote. As an educational tool, the update includes a diagram that indicates the areas of the stomach, duodenum, jejunum, and ileum that may be altered by bariatric surgery and how they factor into micronutrient absorption.
“It makes it easier to see why certain surgical procedures are more likely to cause certain deficiencies,” Patel said.
Postsurgery Patient Management
Post surgery, clinicians should monitor patients for other problems that could affect nutrient absorption, including food intolerances, drug-nutrient interactions, and increased gastrointestinal transit time.
Patel and coauthors discussed the pros and cons of multivitamin mineral supplement formulations as well as specific vitamin and mineral recommendations for patients undergoing certain metabolic or bariatric surgery procedures. They included three supplemental cases in the appendix to illustrate supplementation recommendations and long-term maintenance suggestions.
“It’s important to remember that most of these deficiencies present without many clinical symptoms, so it becomes essential to screen for them and repeat as needed,” Patel said.
The update also tackles postoperative nutritional assessments and diet progression. No evidence supports following one postsurgical diet progression protocol over another, but they generally proceed from a clear liquid diet to foods with normal textures, the authors noted. Clinicians should adapt them according to the procedure type, they added.
In addition, clinicians must troubleshoot any nutrition-related concerns, including constipation, dehydration, nausea, heartburn, and fatigue, for up to a year after surgery, they wrote.
Metabolic and bariatric surgery patients should be evaluated annually at a minimum, if not more frequently, to gauge nutritional health, the authors wrote. Treating obesity as a disease involves more than weight loss — instead, it’s about improving the quality of life of patients through procedures, medications, and lifestyle modifications, they added.
Track New Developments
With ongoing changes in the field of metabolic and bariatric surgery, it’s helpful for clinicians to remain updated about new approaches across various disciplines linked to obesity management and treatment, said Christina Poa-Li, MD, a surgeon at Huntington Health Medical Center, affiliated with Cedars-Sinai Health System, in Pasadena, California, who was not involved in developing the updated practice statement.
“For example, the rapidly growing prescription of anti-obesity medications and their use in both preoperative and postoperative surgical patients drastically affect their nutrition,” she said. “Providers of various backgrounds and specialties will benefit from the most updated guidance on evaluating patient nutrition.”
Clinicians should consider expanding their patient population to include those with metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease, Poa-Li said.
“These patient subpopulations may not have been considered for bariatric surgery or even referral to a bariatric surgeon for consultation previously,” she said. “It is important to increase awareness among clinicians of the potential benefits for metabolic and bariatric surgery for these patients.”
The report didn’t receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Patel and Poa-Li reported no relevant disclosures.
A version of this article appeared on Medscape.com.
How Many Patients in Early Cancer Trials Get Drugs Ultimately Approved by FDA?
TOPLINE:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Bariatric Surgery Lowers Risk for Long-Term Liver Complications in MASH-Related Cirrhosis
according to a recent study by Cleveland Clinic researchers.
Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.
The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.
“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.
“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”
The study was published online in Nature Medicine.
Significantly Reduced Risks
As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.
Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.
After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.
Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.
Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5.
The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.
In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.
At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.
Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.
Potential to Fill an Unmet Need
Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.
The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.
“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.
“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”
No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.
A version of this article appeared on Medscape.com.
according to a recent study by Cleveland Clinic researchers.
Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.
The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.
“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.
“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”
The study was published online in Nature Medicine.
Significantly Reduced Risks
As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.
Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.
After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.
Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.
Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5.
The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.
In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.
At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.
Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.
Potential to Fill an Unmet Need
Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.
The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.
“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.
“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”
No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.
A version of this article appeared on Medscape.com.
according to a recent study by Cleveland Clinic researchers.
Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.
The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.
“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.
“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”
The study was published online in Nature Medicine.
Significantly Reduced Risks
As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.
Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.
After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.
Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.
Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5.
The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.
In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.
At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.
Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.
Potential to Fill an Unmet Need
Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.
The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.
“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.
“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”
No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.
A version of this article appeared on Medscape.com.
FROM NATURE MEDICINE
Open Clinical Trials for Patients With Prostate Cancer
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
Preventing Hepatitis B Reactivation: Updated Clinical Guidance From AGA
The document was published in Gastroenterology and replaces a previous guideline on prophylaxis for immunosuppressed patients issued in 2014.
Since then, many novel classes of immunosuppressives have been approved for various conditions, and potentially immunosuppressive therapies such as transcatheter arterial chemoembolization have been recognized as relevant to potential HBVr.
With reactivation a risk after immune-modulating exposures, such as to multiple drug classes and disease states, the update provides frontline clinicians with evidence-based advice for the management of HBVr in vulnerable individuals. And while antiviral prophylaxis is recommended for many, in select cases careful clinical monitoring may suffice for risk management.
“The risk of HBV reactivation depends on patient-, drug-, and disease-specific factors — and so it can range from very rare to more frequent,” said guideline coauthor Tracey G. Simon, MD, MPH, a hepatologist in the division of gastroenterology at Massachusetts General Hospital and an instructor at Harvard Medical School, both in Boston. “Not every at-risk individual needs pharmacologic treatment, but some certainly do, and this guideline was designed to try to better identify who needs treatment, based on those important drug- and virus-specific factors.”
Simon stressed the importance of creating this guideline to include many new therapies that carry varying degrees of reactivation risk. As to the strength of the evidence, she added, “for some of the questions, the panel was satisfied with the level of certainty. However, for other questions, the data are still very sparse, and so we have tried to ensure that these areas of uncertainty are highlighted clearly for providers and patients.”
Main Recommendations
AGA based its clinical recommendations on balancing desirable and undesirable effects, patient values and preferences, costs, and health equity considerations. It also provided a clinical decision support tool for making pharmacologic management decisions.
The panelists reviewed data on multiple immunosuppressive therapies from older agents such as anthracycline derivatives, corticosteroids, and anti–tumor necrosis factor (anti-TNF) drugs to chimeric antigen receptor T cells and recent biologics and inhibitors.
1. For individuals at high risk for HBVr, AGA recommended antiviral prophylaxis over monitoring alone. Strong recommendation, moderate-certainty evidence.
Implementation considerations: Use antivirals with a high barrier to resistance. Prophylaxis should be started before initiating medications that carry a risk for HBVr and should be continued for at least 6 months after discontinuation of risk-imposing therapy (at least 12 months for B cell–depleting agents).
2. For individuals at moderate risk for HBVr, antiviral prophylaxis was recommended over monitoring alone. Conditional recommendation, moderate-certainty evidence.
Implementation considerations: Use antivirals with a high barrier to resistance. Patients who place a higher value on avoiding long-term antiviral therapy and its associated cost and place a lower value on avoiding the small risk of reactivation (particularly those who are hepatitis B surface antigen [HBsAg]–negative) may reasonably select active monitoring over antiviral prophylaxis.
Careful consideration should be given to the feasibility and likelihood of adherence to long-term monitoring performed at 1- to 3-month intervals and including assessment of hepatitis B viral load and alanine aminotransferase.
3. For low-risk individuals, the AGA said monitoring alone may be used. Conditional recommendation, moderate-certainty evidence.
Implementation considerations: This recommendation assumes regular and sufficient follow-up with continued monitoring. Patients who place a higher value on avoiding the small risk of reactivation (particularly those on more than one low-risk immunosuppressive) and a lower value on the burden and cost of antiviral therapy may reasonably select antiviral therapy.
4. For individuals at risk for HBVr, the guideline recommended testing for hepatitis B. Strong recommendation, moderate-certainty evidence.
Implementation considerations: Given the Centers for Disease Control and Prevention’s universal screening guidance on hepatitis B for everyone aged 18 years or older by testing for HBsAg, anti-HBs, and total anti-hepatitis B core (HBc), the guideline said that stratifying screening practices by magnitude of HBVr risk is no longer needed.
It is reasonable to test initially for serologic markers alone (at minimum for HBsAg or anti-HBc) followed by viral load testing (HBV-DNA) if HBsAg and/or anti-HBc is positive.
Hepatitis C Virus (HCV) Coinfection With Direct-Acting Antiviral (DAA) Treatment
The panel identified 11 studies that provided data for the computation of baseline risk for HBVr in the HCV coinfection cohort undergoing DAA therapy.
In patients who were HBsAg-positive, the pooled baseline risk for HBVr was 240 per 1000, categorizing them to be at high risk for HBVr. The panel stated it is therefore reasonable to extend antiviral prophylaxis beyond the 12-24 weeks of DAA therapy to 6-12 months after cessation of DAA therapy, tailored by clinician judgment and patient preference.
A ‘Useful Clinical Tool’
Commenting on the guideline but not involved in it, Saikiran Kilaru, MD, a hepatologist at NYU Langone Health in New York City, said the update is “absolutely a useful clinical tool. Since the prior guidance was published, there has been a deluge of new medications and medication classes. Prior to the guidance, I was making recommendations based on the limited data available for hepatitis B reactivation risk for these new medications, using the 1%-10% moderate-risk category as guidance.”
In addition, Kilaru said, this guidance is driven by a higher level of evidence certainty than the mostly retrospective evidence that was previously available.
She cautioned that few downgraded risk categories are likely to cause consternation among physicians who have been operating without the benefit of larger meta-analyses of HBVr in new medication categories. “For example, the prior guidance had put anti-TNF as of moderate risk for hepatitis B core–positive-only patients and is now downgraded to low risk.” And other medications such as immune checkpoint inhibitors, which seemed to pose at least moderate risk based on smaller, retrospective studies are now considered to be in the low-risk category.
“It may take some time for these recommendations to be adopted, especially for physicians in the community who have seen fatal or severe reactivations in the past few years,” Kilaru said.
Kilaru pointed out that the guidance update does not clearly cover some standard immunosuppressive therapies used in autoimmune, rheumatologic, and posttransplant regimens, such as mycophenolate, tacrolimus, and cyclosporine. Nor does it address HBVr risk in some liver cancer treatments such as yttrium-90, which have been associated with reports of HBV reactivation.
The Future
According to Simon, more data are needed to better estimate HBVr risk in several important settings, including treatment with the most recently approved immunosuppressive drugs for which data are still limited, as well as combination treatments.
Kilaru noted that guideline updates such as this become increasingly relevant as cancer diagnoses rise and hepatitis B exposure and detection increase as well.
The AGA panel acknowledged that uncertainty remains in some patient risk categorizations. “As the armamentarium of immunotherapeutics evolves, it will be crucial to search for, use, and maintain studies that provide baseline HBV serologies; include a clear definition of HBVr; and enroll a large, nonselective cohort that can guide categorization of risk of HBVr,” the panelists wrote.
AGA provided all financial support for the development of this guideline. No funding from industry was offered or accepted to support the writing effort.
The authors reported no relevant competing interests, but one coauthor is an adviser for Gilead Sciences, and other authors disclosed various relationships with multiple private sector companies. Kilaru had no competing interests to disclose.
A version of this article appeared on Medscape.com.
The document was published in Gastroenterology and replaces a previous guideline on prophylaxis for immunosuppressed patients issued in 2014.
Since then, many novel classes of immunosuppressives have been approved for various conditions, and potentially immunosuppressive therapies such as transcatheter arterial chemoembolization have been recognized as relevant to potential HBVr.
With reactivation a risk after immune-modulating exposures, such as to multiple drug classes and disease states, the update provides frontline clinicians with evidence-based advice for the management of HBVr in vulnerable individuals. And while antiviral prophylaxis is recommended for many, in select cases careful clinical monitoring may suffice for risk management.
“The risk of HBV reactivation depends on patient-, drug-, and disease-specific factors — and so it can range from very rare to more frequent,” said guideline coauthor Tracey G. Simon, MD, MPH, a hepatologist in the division of gastroenterology at Massachusetts General Hospital and an instructor at Harvard Medical School, both in Boston. “Not every at-risk individual needs pharmacologic treatment, but some certainly do, and this guideline was designed to try to better identify who needs treatment, based on those important drug- and virus-specific factors.”
Simon stressed the importance of creating this guideline to include many new therapies that carry varying degrees of reactivation risk. As to the strength of the evidence, she added, “for some of the questions, the panel was satisfied with the level of certainty. However, for other questions, the data are still very sparse, and so we have tried to ensure that these areas of uncertainty are highlighted clearly for providers and patients.”
Main Recommendations
AGA based its clinical recommendations on balancing desirable and undesirable effects, patient values and preferences, costs, and health equity considerations. It also provided a clinical decision support tool for making pharmacologic management decisions.
The panelists reviewed data on multiple immunosuppressive therapies from older agents such as anthracycline derivatives, corticosteroids, and anti–tumor necrosis factor (anti-TNF) drugs to chimeric antigen receptor T cells and recent biologics and inhibitors.
1. For individuals at high risk for HBVr, AGA recommended antiviral prophylaxis over monitoring alone. Strong recommendation, moderate-certainty evidence.
Implementation considerations: Use antivirals with a high barrier to resistance. Prophylaxis should be started before initiating medications that carry a risk for HBVr and should be continued for at least 6 months after discontinuation of risk-imposing therapy (at least 12 months for B cell–depleting agents).
2. For individuals at moderate risk for HBVr, antiviral prophylaxis was recommended over monitoring alone. Conditional recommendation, moderate-certainty evidence.
Implementation considerations: Use antivirals with a high barrier to resistance. Patients who place a higher value on avoiding long-term antiviral therapy and its associated cost and place a lower value on avoiding the small risk of reactivation (particularly those who are hepatitis B surface antigen [HBsAg]–negative) may reasonably select active monitoring over antiviral prophylaxis.
Careful consideration should be given to the feasibility and likelihood of adherence to long-term monitoring performed at 1- to 3-month intervals and including assessment of hepatitis B viral load and alanine aminotransferase.
3. For low-risk individuals, the AGA said monitoring alone may be used. Conditional recommendation, moderate-certainty evidence.
Implementation considerations: This recommendation assumes regular and sufficient follow-up with continued monitoring. Patients who place a higher value on avoiding the small risk of reactivation (particularly those on more than one low-risk immunosuppressive) and a lower value on the burden and cost of antiviral therapy may reasonably select antiviral therapy.
4. For individuals at risk for HBVr, the guideline recommended testing for hepatitis B. Strong recommendation, moderate-certainty evidence.
Implementation considerations: Given the Centers for Disease Control and Prevention’s universal screening guidance on hepatitis B for everyone aged 18 years or older by testing for HBsAg, anti-HBs, and total anti-hepatitis B core (HBc), the guideline said that stratifying screening practices by magnitude of HBVr risk is no longer needed.
It is reasonable to test initially for serologic markers alone (at minimum for HBsAg or anti-HBc) followed by viral load testing (HBV-DNA) if HBsAg and/or anti-HBc is positive.
Hepatitis C Virus (HCV) Coinfection With Direct-Acting Antiviral (DAA) Treatment
The panel identified 11 studies that provided data for the computation of baseline risk for HBVr in the HCV coinfection cohort undergoing DAA therapy.
In patients who were HBsAg-positive, the pooled baseline risk for HBVr was 240 per 1000, categorizing them to be at high risk for HBVr. The panel stated it is therefore reasonable to extend antiviral prophylaxis beyond the 12-24 weeks of DAA therapy to 6-12 months after cessation of DAA therapy, tailored by clinician judgment and patient preference.
A ‘Useful Clinical Tool’
Commenting on the guideline but not involved in it, Saikiran Kilaru, MD, a hepatologist at NYU Langone Health in New York City, said the update is “absolutely a useful clinical tool. Since the prior guidance was published, there has been a deluge of new medications and medication classes. Prior to the guidance, I was making recommendations based on the limited data available for hepatitis B reactivation risk for these new medications, using the 1%-10% moderate-risk category as guidance.”
In addition, Kilaru said, this guidance is driven by a higher level of evidence certainty than the mostly retrospective evidence that was previously available.
She cautioned that few downgraded risk categories are likely to cause consternation among physicians who have been operating without the benefit of larger meta-analyses of HBVr in new medication categories. “For example, the prior guidance had put anti-TNF as of moderate risk for hepatitis B core–positive-only patients and is now downgraded to low risk.” And other medications such as immune checkpoint inhibitors, which seemed to pose at least moderate risk based on smaller, retrospective studies are now considered to be in the low-risk category.
“It may take some time for these recommendations to be adopted, especially for physicians in the community who have seen fatal or severe reactivations in the past few years,” Kilaru said.
Kilaru pointed out that the guidance update does not clearly cover some standard immunosuppressive therapies used in autoimmune, rheumatologic, and posttransplant regimens, such as mycophenolate, tacrolimus, and cyclosporine. Nor does it address HBVr risk in some liver cancer treatments such as yttrium-90, which have been associated with reports of HBV reactivation.
The Future
According to Simon, more data are needed to better estimate HBVr risk in several important settings, including treatment with the most recently approved immunosuppressive drugs for which data are still limited, as well as combination treatments.
Kilaru noted that guideline updates such as this become increasingly relevant as cancer diagnoses rise and hepatitis B exposure and detection increase as well.
The AGA panel acknowledged that uncertainty remains in some patient risk categorizations. “As the armamentarium of immunotherapeutics evolves, it will be crucial to search for, use, and maintain studies that provide baseline HBV serologies; include a clear definition of HBVr; and enroll a large, nonselective cohort that can guide categorization of risk of HBVr,” the panelists wrote.
AGA provided all financial support for the development of this guideline. No funding from industry was offered or accepted to support the writing effort.
The authors reported no relevant competing interests, but one coauthor is an adviser for Gilead Sciences, and other authors disclosed various relationships with multiple private sector companies. Kilaru had no competing interests to disclose.
A version of this article appeared on Medscape.com.
The document was published in Gastroenterology and replaces a previous guideline on prophylaxis for immunosuppressed patients issued in 2014.
Since then, many novel classes of immunosuppressives have been approved for various conditions, and potentially immunosuppressive therapies such as transcatheter arterial chemoembolization have been recognized as relevant to potential HBVr.
With reactivation a risk after immune-modulating exposures, such as to multiple drug classes and disease states, the update provides frontline clinicians with evidence-based advice for the management of HBVr in vulnerable individuals. And while antiviral prophylaxis is recommended for many, in select cases careful clinical monitoring may suffice for risk management.
“The risk of HBV reactivation depends on patient-, drug-, and disease-specific factors — and so it can range from very rare to more frequent,” said guideline coauthor Tracey G. Simon, MD, MPH, a hepatologist in the division of gastroenterology at Massachusetts General Hospital and an instructor at Harvard Medical School, both in Boston. “Not every at-risk individual needs pharmacologic treatment, but some certainly do, and this guideline was designed to try to better identify who needs treatment, based on those important drug- and virus-specific factors.”
Simon stressed the importance of creating this guideline to include many new therapies that carry varying degrees of reactivation risk. As to the strength of the evidence, she added, “for some of the questions, the panel was satisfied with the level of certainty. However, for other questions, the data are still very sparse, and so we have tried to ensure that these areas of uncertainty are highlighted clearly for providers and patients.”
Main Recommendations
AGA based its clinical recommendations on balancing desirable and undesirable effects, patient values and preferences, costs, and health equity considerations. It also provided a clinical decision support tool for making pharmacologic management decisions.
The panelists reviewed data on multiple immunosuppressive therapies from older agents such as anthracycline derivatives, corticosteroids, and anti–tumor necrosis factor (anti-TNF) drugs to chimeric antigen receptor T cells and recent biologics and inhibitors.
1. For individuals at high risk for HBVr, AGA recommended antiviral prophylaxis over monitoring alone. Strong recommendation, moderate-certainty evidence.
Implementation considerations: Use antivirals with a high barrier to resistance. Prophylaxis should be started before initiating medications that carry a risk for HBVr and should be continued for at least 6 months after discontinuation of risk-imposing therapy (at least 12 months for B cell–depleting agents).
2. For individuals at moderate risk for HBVr, antiviral prophylaxis was recommended over monitoring alone. Conditional recommendation, moderate-certainty evidence.
Implementation considerations: Use antivirals with a high barrier to resistance. Patients who place a higher value on avoiding long-term antiviral therapy and its associated cost and place a lower value on avoiding the small risk of reactivation (particularly those who are hepatitis B surface antigen [HBsAg]–negative) may reasonably select active monitoring over antiviral prophylaxis.
Careful consideration should be given to the feasibility and likelihood of adherence to long-term monitoring performed at 1- to 3-month intervals and including assessment of hepatitis B viral load and alanine aminotransferase.
3. For low-risk individuals, the AGA said monitoring alone may be used. Conditional recommendation, moderate-certainty evidence.
Implementation considerations: This recommendation assumes regular and sufficient follow-up with continued monitoring. Patients who place a higher value on avoiding the small risk of reactivation (particularly those on more than one low-risk immunosuppressive) and a lower value on the burden and cost of antiviral therapy may reasonably select antiviral therapy.
4. For individuals at risk for HBVr, the guideline recommended testing for hepatitis B. Strong recommendation, moderate-certainty evidence.
Implementation considerations: Given the Centers for Disease Control and Prevention’s universal screening guidance on hepatitis B for everyone aged 18 years or older by testing for HBsAg, anti-HBs, and total anti-hepatitis B core (HBc), the guideline said that stratifying screening practices by magnitude of HBVr risk is no longer needed.
It is reasonable to test initially for serologic markers alone (at minimum for HBsAg or anti-HBc) followed by viral load testing (HBV-DNA) if HBsAg and/or anti-HBc is positive.
Hepatitis C Virus (HCV) Coinfection With Direct-Acting Antiviral (DAA) Treatment
The panel identified 11 studies that provided data for the computation of baseline risk for HBVr in the HCV coinfection cohort undergoing DAA therapy.
In patients who were HBsAg-positive, the pooled baseline risk for HBVr was 240 per 1000, categorizing them to be at high risk for HBVr. The panel stated it is therefore reasonable to extend antiviral prophylaxis beyond the 12-24 weeks of DAA therapy to 6-12 months after cessation of DAA therapy, tailored by clinician judgment and patient preference.
A ‘Useful Clinical Tool’
Commenting on the guideline but not involved in it, Saikiran Kilaru, MD, a hepatologist at NYU Langone Health in New York City, said the update is “absolutely a useful clinical tool. Since the prior guidance was published, there has been a deluge of new medications and medication classes. Prior to the guidance, I was making recommendations based on the limited data available for hepatitis B reactivation risk for these new medications, using the 1%-10% moderate-risk category as guidance.”
In addition, Kilaru said, this guidance is driven by a higher level of evidence certainty than the mostly retrospective evidence that was previously available.
She cautioned that few downgraded risk categories are likely to cause consternation among physicians who have been operating without the benefit of larger meta-analyses of HBVr in new medication categories. “For example, the prior guidance had put anti-TNF as of moderate risk for hepatitis B core–positive-only patients and is now downgraded to low risk.” And other medications such as immune checkpoint inhibitors, which seemed to pose at least moderate risk based on smaller, retrospective studies are now considered to be in the low-risk category.
“It may take some time for these recommendations to be adopted, especially for physicians in the community who have seen fatal or severe reactivations in the past few years,” Kilaru said.
Kilaru pointed out that the guidance update does not clearly cover some standard immunosuppressive therapies used in autoimmune, rheumatologic, and posttransplant regimens, such as mycophenolate, tacrolimus, and cyclosporine. Nor does it address HBVr risk in some liver cancer treatments such as yttrium-90, which have been associated with reports of HBV reactivation.
The Future
According to Simon, more data are needed to better estimate HBVr risk in several important settings, including treatment with the most recently approved immunosuppressive drugs for which data are still limited, as well as combination treatments.
Kilaru noted that guideline updates such as this become increasingly relevant as cancer diagnoses rise and hepatitis B exposure and detection increase as well.
The AGA panel acknowledged that uncertainty remains in some patient risk categorizations. “As the armamentarium of immunotherapeutics evolves, it will be crucial to search for, use, and maintain studies that provide baseline HBV serologies; include a clear definition of HBVr; and enroll a large, nonselective cohort that can guide categorization of risk of HBVr,” the panelists wrote.
AGA provided all financial support for the development of this guideline. No funding from industry was offered or accepted to support the writing effort.
The authors reported no relevant competing interests, but one coauthor is an adviser for Gilead Sciences, and other authors disclosed various relationships with multiple private sector companies. Kilaru had no competing interests to disclose.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Identifying Pancreatic Cancer Remains Elusive: Here’s Why
Now, a growing body of evidence indicates that this deadly cancer has been steadily on the rise, particularly in younger individuals who may not even realize they are at risk.
A recent survey, for instance, found that 33% of 1000 respondents younger than 50 years believe that only older adults are at risk for pancreatic cancer, and more than half said they wouldn’t even recognize the early signs and symptoms, which include unexplained weight loss, fatigue, jaundice, abdominal pain that radiates to the back, nausea, and vomiting.
These survey findings allude to a bigger challenge: Identifying the disease remains elusive against a backdrop of these increasing rates and nonspecific risks and symptoms.
Currently, only about 15% of pancreatic cancers are caught at a localized, resectable stage, when 5-year survival rates are highest at 44%. But most are found later, after symptoms arise, and at this point, the 5-year survival odds plummet —16% for regional disease, 3% for distant, and 1% for stage IV.
“This disease is too often a silent killer, with no symptoms until it has progressed to less treatable stages,” said survey coauthor Zobeida Cruz-Monserrate, PhD, in the division of gastroenterology, hepatology and nutrition at Ohio State University Medical Center, Columbus.
Rising Rates
Since 2001, rates of pancreatic cancer have steadily increased by about 1% annually, and this increase appears greater among younger individuals, especially women.
A recent study in Gastroenterology, for instance, found that, while overall rates of pancreatic cancer among people aged 15-34 years remained low (0.3% in women and 0.2% in men) between 2001 and 2018, the average annual percent change in this age group was considerably higher than that for older individuals — 6.45% for women and 2.97% for men compared with 1.11% for women aged 55 years and 1.17% for men aged 55 years. Another recent analysis, published in Annals of Internal Medicine, reported similar increased rates in men and women aged 15-39 years between 2011 and 2019.
Although more than 90% of cases do occur in those 55 years or older, “we’re now seeing this disease in people who are in their 40s much more regularly,” Cruz-Monserrate said. “This is a concerning trend — and more research is needed to learn why.”
But it’s early days. Studies so far indicate that early onset pancreatic cancer tends to be even more aggressive, but the “underlying reason is not yet clear,” researcher wrote in a 2025 review.
Some evidence indicates younger individuals may have distinct molecular characteristics, whereas other research shows younger and older patients have similar genetic profiles. Younger patients may also be more likely to smoke, drink more, and delay seeking medical attention as well as experience delays in being diagnosed by physicians, the authors explained.
Catching It Early
Given the rising rates, early detection is especially important.
There are some known genetic and medical risk factors for pancreatic cancer. About 10% of these cancers are linked to heredity risk or genetic markers, including BRCA1 and BRCA2 or Lynch syndrome. People with chronic pancreatitis, type 2 diabetes, obesity, or with a family history of pancreatic cancer face an elevated risk.
Lifestyle factors can play a role as well. Alcohol consumption, a poor diet that includes red or processed meat, and smoking increase people’s risk for pancreatic cancer. In fact, smoking leads to a twofold higher risk, compared with not smoking.
However, uncovering pancreatic cancer from these factors alone can be like “finding a needle in a haystack,” said Srinivas Gaddam, MD, head of the pancreatic cancer screening and early detection program at Cedars-Sinai Medical Center in Los Angeles.
One strategy to help detect the disease earlier would be to screen more.
The latest guidance from the American Cancer Society suggests that people with a genetic predisposition or a family history of pancreatic cancer could benefit from annual surveillance with endoscopic ultrasound or MRI.
But the US Preventive Services Task Force currently recommends against routine screening of average-risk asymptomatic adults (JAMA. 2019;322[5]:438-444). The task force found no evidence that screening for pancreatic cancer improves disease-specific morbidity or mortality or all-cause mortality.
“The absolute incidence in younger people is far too small to make screening beneficial,” explained The Lancet Gastroenterology & Hepatology editors in a 2023 editorial.
In fact, more screening could lead to overdiagnosis, a concern reinforced by the recent study in Annals of Internal Medicine. That analysis found that much of the observed increase in early-onset pancreatic cancer stemmed from the detection of more small, early-stage endocrine cancer, rather than pancreatic adenocarcinoma, whereas mortality from the disease remained stable over the study period.
Recent findings do “suggest the potential for overdiagnosis and overtreatment, particularly in cases of indolent pancreatic neuroendocrine tumors,” Gaddam said.
Gaddam has observed an increase in both adenocarcinoma and neuroendocrine tumors in the clinic and in his research, especially in women younger than 50 years, but he noted these early onset diagnoses do remain rare.
Staying Vigilant
As the understanding of pancreatic cancer risks and symptoms evolves, ensuring that patients, especially younger individuals, recognize the warning signs, without causing alarm, remains a challenge.
The disease “presents more advanced in younger patients, but symptoms are so nonspecific,” said Randall Brand, MD, AGAF, director of the gastrointestinal malignancy early detection, diagnosis, and prevention program at the University of Pittsburgh Medical Center, Pennsylvania. Given that, “I am not sure how to best highlight a communication approach that would not cause undue stress to the patient and our healthcare resources.”
Gaddam agreed that it’s tough to pinpoint or communicate straightforward risks or symptoms to the general public without potentially leading to unnecessary screening.
At a minimum, however, clinicians can share more general risk-mitigating strategies with their patients.
Communicating such strategies may be especially important for younger patients, given that the recent survey found almost 40% of younger adults believe there’s nothing they can do to change their risk for pancreatic cancer.
However, Cruz-Monserrate explained, adults of all ages can lower their risks through regular exercise, limited alcohol and tobacco use, and a healthy diet with less red meat or processed meat.
Ultimately, for clinicians, given how difficult it is now to identify pancreatic cancer early, we have to “follow their good clinical judgment when alarming features, such as weight loss or nuances of pancreatic pain arise, and then get good imaging,” Gaddam said.
Cruz-Monserrate, Brand, and Gaddam reported no relevant disclosures.
A version of this article appeared on Medscape.com.
Now, a growing body of evidence indicates that this deadly cancer has been steadily on the rise, particularly in younger individuals who may not even realize they are at risk.
A recent survey, for instance, found that 33% of 1000 respondents younger than 50 years believe that only older adults are at risk for pancreatic cancer, and more than half said they wouldn’t even recognize the early signs and symptoms, which include unexplained weight loss, fatigue, jaundice, abdominal pain that radiates to the back, nausea, and vomiting.
These survey findings allude to a bigger challenge: Identifying the disease remains elusive against a backdrop of these increasing rates and nonspecific risks and symptoms.
Currently, only about 15% of pancreatic cancers are caught at a localized, resectable stage, when 5-year survival rates are highest at 44%. But most are found later, after symptoms arise, and at this point, the 5-year survival odds plummet —16% for regional disease, 3% for distant, and 1% for stage IV.
“This disease is too often a silent killer, with no symptoms until it has progressed to less treatable stages,” said survey coauthor Zobeida Cruz-Monserrate, PhD, in the division of gastroenterology, hepatology and nutrition at Ohio State University Medical Center, Columbus.
Rising Rates
Since 2001, rates of pancreatic cancer have steadily increased by about 1% annually, and this increase appears greater among younger individuals, especially women.
A recent study in Gastroenterology, for instance, found that, while overall rates of pancreatic cancer among people aged 15-34 years remained low (0.3% in women and 0.2% in men) between 2001 and 2018, the average annual percent change in this age group was considerably higher than that for older individuals — 6.45% for women and 2.97% for men compared with 1.11% for women aged 55 years and 1.17% for men aged 55 years. Another recent analysis, published in Annals of Internal Medicine, reported similar increased rates in men and women aged 15-39 years between 2011 and 2019.
Although more than 90% of cases do occur in those 55 years or older, “we’re now seeing this disease in people who are in their 40s much more regularly,” Cruz-Monserrate said. “This is a concerning trend — and more research is needed to learn why.”
But it’s early days. Studies so far indicate that early onset pancreatic cancer tends to be even more aggressive, but the “underlying reason is not yet clear,” researcher wrote in a 2025 review.
Some evidence indicates younger individuals may have distinct molecular characteristics, whereas other research shows younger and older patients have similar genetic profiles. Younger patients may also be more likely to smoke, drink more, and delay seeking medical attention as well as experience delays in being diagnosed by physicians, the authors explained.
Catching It Early
Given the rising rates, early detection is especially important.
There are some known genetic and medical risk factors for pancreatic cancer. About 10% of these cancers are linked to heredity risk or genetic markers, including BRCA1 and BRCA2 or Lynch syndrome. People with chronic pancreatitis, type 2 diabetes, obesity, or with a family history of pancreatic cancer face an elevated risk.
Lifestyle factors can play a role as well. Alcohol consumption, a poor diet that includes red or processed meat, and smoking increase people’s risk for pancreatic cancer. In fact, smoking leads to a twofold higher risk, compared with not smoking.
However, uncovering pancreatic cancer from these factors alone can be like “finding a needle in a haystack,” said Srinivas Gaddam, MD, head of the pancreatic cancer screening and early detection program at Cedars-Sinai Medical Center in Los Angeles.
One strategy to help detect the disease earlier would be to screen more.
The latest guidance from the American Cancer Society suggests that people with a genetic predisposition or a family history of pancreatic cancer could benefit from annual surveillance with endoscopic ultrasound or MRI.
But the US Preventive Services Task Force currently recommends against routine screening of average-risk asymptomatic adults (JAMA. 2019;322[5]:438-444). The task force found no evidence that screening for pancreatic cancer improves disease-specific morbidity or mortality or all-cause mortality.
“The absolute incidence in younger people is far too small to make screening beneficial,” explained The Lancet Gastroenterology & Hepatology editors in a 2023 editorial.
In fact, more screening could lead to overdiagnosis, a concern reinforced by the recent study in Annals of Internal Medicine. That analysis found that much of the observed increase in early-onset pancreatic cancer stemmed from the detection of more small, early-stage endocrine cancer, rather than pancreatic adenocarcinoma, whereas mortality from the disease remained stable over the study period.
Recent findings do “suggest the potential for overdiagnosis and overtreatment, particularly in cases of indolent pancreatic neuroendocrine tumors,” Gaddam said.
Gaddam has observed an increase in both adenocarcinoma and neuroendocrine tumors in the clinic and in his research, especially in women younger than 50 years, but he noted these early onset diagnoses do remain rare.
Staying Vigilant
As the understanding of pancreatic cancer risks and symptoms evolves, ensuring that patients, especially younger individuals, recognize the warning signs, without causing alarm, remains a challenge.
The disease “presents more advanced in younger patients, but symptoms are so nonspecific,” said Randall Brand, MD, AGAF, director of the gastrointestinal malignancy early detection, diagnosis, and prevention program at the University of Pittsburgh Medical Center, Pennsylvania. Given that, “I am not sure how to best highlight a communication approach that would not cause undue stress to the patient and our healthcare resources.”
Gaddam agreed that it’s tough to pinpoint or communicate straightforward risks or symptoms to the general public without potentially leading to unnecessary screening.
At a minimum, however, clinicians can share more general risk-mitigating strategies with their patients.
Communicating such strategies may be especially important for younger patients, given that the recent survey found almost 40% of younger adults believe there’s nothing they can do to change their risk for pancreatic cancer.
However, Cruz-Monserrate explained, adults of all ages can lower their risks through regular exercise, limited alcohol and tobacco use, and a healthy diet with less red meat or processed meat.
Ultimately, for clinicians, given how difficult it is now to identify pancreatic cancer early, we have to “follow their good clinical judgment when alarming features, such as weight loss or nuances of pancreatic pain arise, and then get good imaging,” Gaddam said.
Cruz-Monserrate, Brand, and Gaddam reported no relevant disclosures.
A version of this article appeared on Medscape.com.
Now, a growing body of evidence indicates that this deadly cancer has been steadily on the rise, particularly in younger individuals who may not even realize they are at risk.
A recent survey, for instance, found that 33% of 1000 respondents younger than 50 years believe that only older adults are at risk for pancreatic cancer, and more than half said they wouldn’t even recognize the early signs and symptoms, which include unexplained weight loss, fatigue, jaundice, abdominal pain that radiates to the back, nausea, and vomiting.
These survey findings allude to a bigger challenge: Identifying the disease remains elusive against a backdrop of these increasing rates and nonspecific risks and symptoms.
Currently, only about 15% of pancreatic cancers are caught at a localized, resectable stage, when 5-year survival rates are highest at 44%. But most are found later, after symptoms arise, and at this point, the 5-year survival odds plummet —16% for regional disease, 3% for distant, and 1% for stage IV.
“This disease is too often a silent killer, with no symptoms until it has progressed to less treatable stages,” said survey coauthor Zobeida Cruz-Monserrate, PhD, in the division of gastroenterology, hepatology and nutrition at Ohio State University Medical Center, Columbus.
Rising Rates
Since 2001, rates of pancreatic cancer have steadily increased by about 1% annually, and this increase appears greater among younger individuals, especially women.
A recent study in Gastroenterology, for instance, found that, while overall rates of pancreatic cancer among people aged 15-34 years remained low (0.3% in women and 0.2% in men) between 2001 and 2018, the average annual percent change in this age group was considerably higher than that for older individuals — 6.45% for women and 2.97% for men compared with 1.11% for women aged 55 years and 1.17% for men aged 55 years. Another recent analysis, published in Annals of Internal Medicine, reported similar increased rates in men and women aged 15-39 years between 2011 and 2019.
Although more than 90% of cases do occur in those 55 years or older, “we’re now seeing this disease in people who are in their 40s much more regularly,” Cruz-Monserrate said. “This is a concerning trend — and more research is needed to learn why.”
But it’s early days. Studies so far indicate that early onset pancreatic cancer tends to be even more aggressive, but the “underlying reason is not yet clear,” researcher wrote in a 2025 review.
Some evidence indicates younger individuals may have distinct molecular characteristics, whereas other research shows younger and older patients have similar genetic profiles. Younger patients may also be more likely to smoke, drink more, and delay seeking medical attention as well as experience delays in being diagnosed by physicians, the authors explained.
Catching It Early
Given the rising rates, early detection is especially important.
There are some known genetic and medical risk factors for pancreatic cancer. About 10% of these cancers are linked to heredity risk or genetic markers, including BRCA1 and BRCA2 or Lynch syndrome. People with chronic pancreatitis, type 2 diabetes, obesity, or with a family history of pancreatic cancer face an elevated risk.
Lifestyle factors can play a role as well. Alcohol consumption, a poor diet that includes red or processed meat, and smoking increase people’s risk for pancreatic cancer. In fact, smoking leads to a twofold higher risk, compared with not smoking.
However, uncovering pancreatic cancer from these factors alone can be like “finding a needle in a haystack,” said Srinivas Gaddam, MD, head of the pancreatic cancer screening and early detection program at Cedars-Sinai Medical Center in Los Angeles.
One strategy to help detect the disease earlier would be to screen more.
The latest guidance from the American Cancer Society suggests that people with a genetic predisposition or a family history of pancreatic cancer could benefit from annual surveillance with endoscopic ultrasound or MRI.
But the US Preventive Services Task Force currently recommends against routine screening of average-risk asymptomatic adults (JAMA. 2019;322[5]:438-444). The task force found no evidence that screening for pancreatic cancer improves disease-specific morbidity or mortality or all-cause mortality.
“The absolute incidence in younger people is far too small to make screening beneficial,” explained The Lancet Gastroenterology & Hepatology editors in a 2023 editorial.
In fact, more screening could lead to overdiagnosis, a concern reinforced by the recent study in Annals of Internal Medicine. That analysis found that much of the observed increase in early-onset pancreatic cancer stemmed from the detection of more small, early-stage endocrine cancer, rather than pancreatic adenocarcinoma, whereas mortality from the disease remained stable over the study period.
Recent findings do “suggest the potential for overdiagnosis and overtreatment, particularly in cases of indolent pancreatic neuroendocrine tumors,” Gaddam said.
Gaddam has observed an increase in both adenocarcinoma and neuroendocrine tumors in the clinic and in his research, especially in women younger than 50 years, but he noted these early onset diagnoses do remain rare.
Staying Vigilant
As the understanding of pancreatic cancer risks and symptoms evolves, ensuring that patients, especially younger individuals, recognize the warning signs, without causing alarm, remains a challenge.
The disease “presents more advanced in younger patients, but symptoms are so nonspecific,” said Randall Brand, MD, AGAF, director of the gastrointestinal malignancy early detection, diagnosis, and prevention program at the University of Pittsburgh Medical Center, Pennsylvania. Given that, “I am not sure how to best highlight a communication approach that would not cause undue stress to the patient and our healthcare resources.”
Gaddam agreed that it’s tough to pinpoint or communicate straightforward risks or symptoms to the general public without potentially leading to unnecessary screening.
At a minimum, however, clinicians can share more general risk-mitigating strategies with their patients.
Communicating such strategies may be especially important for younger patients, given that the recent survey found almost 40% of younger adults believe there’s nothing they can do to change their risk for pancreatic cancer.
However, Cruz-Monserrate explained, adults of all ages can lower their risks through regular exercise, limited alcohol and tobacco use, and a healthy diet with less red meat or processed meat.
Ultimately, for clinicians, given how difficult it is now to identify pancreatic cancer early, we have to “follow their good clinical judgment when alarming features, such as weight loss or nuances of pancreatic pain arise, and then get good imaging,” Gaddam said.
Cruz-Monserrate, Brand, and Gaddam reported no relevant disclosures.
A version of this article appeared on Medscape.com.
Vedolizumab Beats Infliximab as Second-Line Therapy for Ulcerative Colitis
BERLIN — suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.
Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.
The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.
The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.
The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.
Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.
Head-to-Head Trial
Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.
No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.
They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.
Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.
Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.
The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.
Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).
Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).
There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.
Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.
The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.
Questions Remain
Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.
“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.
This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.
Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”
“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.
Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”
Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.
The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.
“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.
The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.
A version of this article appeared on Medscape.com.
BERLIN — suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.
Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.
The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.
The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.
The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.
Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.
Head-to-Head Trial
Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.
No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.
They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.
Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.
Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.
The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.
Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).
Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).
There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.
Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.
The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.
Questions Remain
Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.
“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.
This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.
Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”
“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.
Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”
Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.
The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.
“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.
The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.
A version of this article appeared on Medscape.com.
BERLIN — suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.
Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.
The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.
The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.
The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.
Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.
Head-to-Head Trial
Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.
No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.
They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.
Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.
Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.
The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.
Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).
Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).
There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.
Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.
The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.
Questions Remain
Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.
“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.
This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.
Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”
“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.
Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”
Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.
The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.
“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.
The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.
A version of this article appeared on Medscape.com.
FROM ECCO 2025