Patients diagnosed with advanced hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2-) breast cancer have significantly improved outcomes with the combination of a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy compared with endocrine therapy alone.

Dr Sara Hurvitz, director of the Breast Cancer Clinical Trials Program at UCLA, discusses the efficacy, tolerability, and patient quality-of-life factors to consider when deciding which of the three available CDK4/6 inhibitors — palbociclib, ribociclib, or abemaciclib — is appropriate for your patient in the frontline setting.

Reporting on data from the ongoing MONALEESA, MONARCH, and PALOMA trials, Dr Hurvitz spotlights the differences and similarities between agents that may help steer treatment decisions for pre- or perimenopausal patients

--

Associate Professor, David Geffen School of Medicine at UCLA; Medical Director, Jonsson Comprehensive Cancer Center Clinical Research Unit; Co-director, Santa Monica-UCLA Outpatient Oncology Practices; Director, Breast Cancer Clinical Trials Program, UCLA, Los Angeles, California

Sara A. Hurvitz, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Ambrx; Amgen; Arvinas; Bayer; BioMarin; Cascadian Therapeutics; Daiichi Sankyo; Dignitana; Genentech/Roche; Gilead Sciences; GlaxoSmithKline; Immunomedics; Lilly; MacroGenics; Merrimack; Novartis; OBI Pharma; Pfizer; Phoenix Molecular Designs; Pieris; Puma Biotechnology; Radius; Samumed; Sanofi; Seattle Genetics; Zymeworks

Has been reimbursed for travel, accommodations, or other expenses by Lilly

Patients diagnosed with advanced hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2-) breast cancer have significantly improved outcomes with the combination of a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy compared with endocrine therapy alone.

Dr Sara Hurvitz, director of the Breast Cancer Clinical Trials Program at UCLA, discusses the efficacy, tolerability, and patient quality-of-life factors to consider when deciding which of the three available CDK4/6 inhibitors — palbociclib, ribociclib, or abemaciclib — is appropriate for your patient in the frontline setting.

Reporting on data from the ongoing MONALEESA, MONARCH, and PALOMA trials, Dr Hurvitz spotlights the differences and similarities between agents that may help steer treatment decisions for pre- or perimenopausal patients

--

Associate Professor, David Geffen School of Medicine at UCLA; Medical Director, Jonsson Comprehensive Cancer Center Clinical Research Unit; Co-director, Santa Monica-UCLA Outpatient Oncology Practices; Director, Breast Cancer Clinical Trials Program, UCLA, Los Angeles, California

Sara A. Hurvitz, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Ambrx; Amgen; Arvinas; Bayer; BioMarin; Cascadian Therapeutics; Daiichi Sankyo; Dignitana; Genentech/Roche; Gilead Sciences; GlaxoSmithKline; Immunomedics; Lilly; MacroGenics; Merrimack; Novartis; OBI Pharma; Pfizer; Phoenix Molecular Designs; Pieris; Puma Biotechnology; Radius; Samumed; Sanofi; Seattle Genetics; Zymeworks

Has been reimbursed for travel, accommodations, or other expenses by Lilly

Patients diagnosed with advanced hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2-) breast cancer have significantly improved outcomes with the combination of a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy compared with endocrine therapy alone.

Dr Sara Hurvitz, director of the Breast Cancer Clinical Trials Program at UCLA, discusses the efficacy, tolerability, and patient quality-of-life factors to consider when deciding which of the three available CDK4/6 inhibitors — palbociclib, ribociclib, or abemaciclib — is appropriate for your patient in the frontline setting.

Reporting on data from the ongoing MONALEESA, MONARCH, and PALOMA trials, Dr Hurvitz spotlights the differences and similarities between agents that may help steer treatment decisions for pre- or perimenopausal patients

--

Associate Professor, David Geffen School of Medicine at UCLA; Medical Director, Jonsson Comprehensive Cancer Center Clinical Research Unit; Co-director, Santa Monica-UCLA Outpatient Oncology Practices; Director, Breast Cancer Clinical Trials Program, UCLA, Los Angeles, California

Sara A. Hurvitz, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Ambrx; Amgen; Arvinas; Bayer; BioMarin; Cascadian Therapeutics; Daiichi Sankyo; Dignitana; Genentech/Roche; Gilead Sciences; GlaxoSmithKline; Immunomedics; Lilly; MacroGenics; Merrimack; Novartis; OBI Pharma; Pfizer; Phoenix Molecular Designs; Pieris; Puma Biotechnology; Radius; Samumed; Sanofi; Seattle Genetics; Zymeworks

Has been reimbursed for travel, accommodations, or other expenses by Lilly

What is your approach to differentiating EPI from other pancreatic conditions when making a diagnosis?

Dr. Kothari: Exocrine pancreatic insufficiency, or EPI, is a condition largely defined by malabsorption as the result of inadequate digestive enzymes. The resulting symptoms from maldigestion include bloating, malodorous gas, abdominal pain, changes in bowel habits, and weight change. EPI can be caused by intrinsic pancreatic disorders (such as chronic pancreatitis, acute pancreatitis, cystic fibrosis or pancreatic cancer) or from extra-pancreatic diseases (including the result of gastrointestinal surgery). Thus, EPI should be considered a consequence of an already existing gastrointestinal disorder.

Can you a speak a little bit more about the signs and symptoms or characteristics that are most common in patients with EPI?

Dr. Kothari: The symptoms of EPI can range from bloating and abdominal pain with mild to overt steatorrhea with greasy and oily stools that are difficult to flush with malodorous flatulence, weight loss, and symptoms of vitamin and micronutrient deficiency. The pathophysiology of these symptoms results from inadequate enzymes which are needed for digestion. Particularly, lipase is the major enzyme needed for fat digestion and thus when not present leads to fat maldigestion resulting in symptoms. Furthermore, undigested fats result in alterations in gut motility which can further exacerbate symptoms to include nausea, vomiting, early satiety and inadequate stool evacuation.

Patients who have fat malabsorption, particularly for pancreatic insufficiency, can also have malnutrition as a result of inadequate absorption of nutrients and micronutrients. Particularly, we think about fat-soluble vitamins-- vitamin A, vitamin E, vitamin D, and vitamin K and in the initial evaluation of patients with established EPI, one could consider evaluation of comorbid bone disease.

How crucial is having the correct interpretation of the clinical presentation to pinpointing the diagnosis?

Dr. Kothari: This is a great question because, with exocrine pancreatic insufficiency as there is growing publicity for the disorder and because symptoms can be rather non-specific when mild, it is important to be informed on how best to make this diagnosis. Thus, it is important to review the predisposing conditions that may lead to the diagnosis of EPI. These conditions include cystic fibrosis, chronic pancreatitis, acute pancreatitis, previous pancreatic surgery, history of pancreatic cancer (or suspicion for new pancreatic cancer), history of diabetes, celiac disease, history of luminal surgeries (including bariatric surgery), and inflammatory bowel disease. Further, since EPI can be a result of intrinsic pancreatic pathologies, it is critical to consider the risk factors for chronic pancreatitis which include alcohol and tobacco ingestion, prior episodes of recurrent acute pancreatitis, genetic conditions that may predispose patients to chronic pancreatitis, including cystic fibrosis, and hereditary conditions that also result in pancreatitis. As clinicians, it is our role to obtain an accurate history to best gauge the risk factors for EPI.

After reviewing risk factors, we then must review the clinical presentation to know if the symptoms could be from EPI which include bloating, gas, abdominal pain, weight changes, changes in bowel habits and consequences of vitamin deficiencies. Since the symptoms of mild EPI can be similar to other GI conditions such as SIBO, celiac disease, and functional bowel disorders, gauging whether a patient has risk factors for EPI will help the clinician understand how likely a diagnosis of EPI may be and if and what testing would be appropriate.

In my practice, I consider diagnostic testing in patients who may be at risk for EPI and have mild symptoms such malodorous gas, bloating and mild steatorrhea. For patient with clear evidence of steatorrhea (weight loss and vitamin deficiencies) and have strong risk factors for EPI (i.e. heavy alcohol and tobacco and/or a history of recurrent or severe acute pancreatitis), I might consider imaging and/or empiric therapies as to expedite care.

How difficult is it to diagnose EPI and what steps do you take to ensure that you prescribe patients with the proper therapy?

Dr. Kothari: The diagnosis of pancreatic insufficiency, in my mind, needs to start with assessing the pre-test probability of the patient having EPI, since testing could lead to a false positive.

The test of choice in most scenarios for diagnosing pancreatic insufficiency is a stool test known as the fecal elastase. It is a measurement of pancreatic elastase in the stool. The test itself is a concentration. For any condition that results in a dilute stool sample, that'll result in a falsely low value that can give a patient a false positive test. Now, this can be corrected  by the lab concentrating the stool sample before running the test, but that testing center needs to know how to do that.

The other assumption that we make with this stool test is that we assume that the elastase is a stable molecule that can traverse all the gut and be collected adequately. And for any reason, if that enzyme is degraded for any reason, it's also going to provide a low test, a low result, resulting in a false positive.

If they have risk factors for chronic pancreatitis or pancreatic disease and they're presenting with symptoms of EPI, then the usual test that I'll choose is dedicated pancreatic imaging such as an MRI or dedicated CT pancreatic imaging, or endoscopic ultrasound. If we clinch a diagnosis of chronic pancreatitis and they have symptoms of pancreatic insufficiency, I think that’s enough to presume a diagnosis of exocrine pancreatic insufficiency and start treatment.

On the other hand, in patients who do not have risk factors for pancreatic disease but there remains some clinical suspicion for exocrine pancreatic insufficiency, then it may be reasonable to check a fecal elastase to rule out pancreatic insufficiency. If the test results are low, then follow-up dedicated pancreas imaging would be the next step in delineating intrinsic pancreatic conditions form extra-pancreatic causes.  If pancreas imaging effectively rules out pancreatic disease then I consider checking for celiac disease, ruling out small intestinal bacterial overgrowth and considering assessment of luminal motility (either with a capsule or small bowel follow through). Although functional neuroendocrine tumors have been previously considered a cause of EPI, these tumors tend to present with secretory diarrhea which typically present differently (and often more dramatically) than other causes of EPI. Thus, I do not routinely check vasoactive hormone levels.

I think the American Gastroenterological Association has great patient education documents for our patients. Thus, I would encourage our colleagues to use the AGA for their resources for our patients on EPI.

What is your approach to differentiating EPI from other pancreatic conditions when making a diagnosis?

Dr. Kothari: Exocrine pancreatic insufficiency, or EPI, is a condition largely defined by malabsorption as the result of inadequate digestive enzymes. The resulting symptoms from maldigestion include bloating, malodorous gas, abdominal pain, changes in bowel habits, and weight change. EPI can be caused by intrinsic pancreatic disorders (such as chronic pancreatitis, acute pancreatitis, cystic fibrosis or pancreatic cancer) or from extra-pancreatic diseases (including the result of gastrointestinal surgery). Thus, EPI should be considered a consequence of an already existing gastrointestinal disorder.

Can you a speak a little bit more about the signs and symptoms or characteristics that are most common in patients with EPI?

Dr. Kothari: The symptoms of EPI can range from bloating and abdominal pain with mild to overt steatorrhea with greasy and oily stools that are difficult to flush with malodorous flatulence, weight loss, and symptoms of vitamin and micronutrient deficiency. The pathophysiology of these symptoms results from inadequate enzymes which are needed for digestion. Particularly, lipase is the major enzyme needed for fat digestion and thus when not present leads to fat maldigestion resulting in symptoms. Furthermore, undigested fats result in alterations in gut motility which can further exacerbate symptoms to include nausea, vomiting, early satiety and inadequate stool evacuation.

Patients who have fat malabsorption, particularly for pancreatic insufficiency, can also have malnutrition as a result of inadequate absorption of nutrients and micronutrients. Particularly, we think about fat-soluble vitamins-- vitamin A, vitamin E, vitamin D, and vitamin K and in the initial evaluation of patients with established EPI, one could consider evaluation of comorbid bone disease.

How crucial is having the correct interpretation of the clinical presentation to pinpointing the diagnosis?

Dr. Kothari: This is a great question because, with exocrine pancreatic insufficiency as there is growing publicity for the disorder and because symptoms can be rather non-specific when mild, it is important to be informed on how best to make this diagnosis. Thus, it is important to review the predisposing conditions that may lead to the diagnosis of EPI. These conditions include cystic fibrosis, chronic pancreatitis, acute pancreatitis, previous pancreatic surgery, history of pancreatic cancer (or suspicion for new pancreatic cancer), history of diabetes, celiac disease, history of luminal surgeries (including bariatric surgery), and inflammatory bowel disease. Further, since EPI can be a result of intrinsic pancreatic pathologies, it is critical to consider the risk factors for chronic pancreatitis which include alcohol and tobacco ingestion, prior episodes of recurrent acute pancreatitis, genetic conditions that may predispose patients to chronic pancreatitis, including cystic fibrosis, and hereditary conditions that also result in pancreatitis. As clinicians, it is our role to obtain an accurate history to best gauge the risk factors for EPI.

After reviewing risk factors, we then must review the clinical presentation to know if the symptoms could be from EPI which include bloating, gas, abdominal pain, weight changes, changes in bowel habits and consequences of vitamin deficiencies. Since the symptoms of mild EPI can be similar to other GI conditions such as SIBO, celiac disease, and functional bowel disorders, gauging whether a patient has risk factors for EPI will help the clinician understand how likely a diagnosis of EPI may be and if and what testing would be appropriate.

In my practice, I consider diagnostic testing in patients who may be at risk for EPI and have mild symptoms such malodorous gas, bloating and mild steatorrhea. For patient with clear evidence of steatorrhea (weight loss and vitamin deficiencies) and have strong risk factors for EPI (i.e. heavy alcohol and tobacco and/or a history of recurrent or severe acute pancreatitis), I might consider imaging and/or empiric therapies as to expedite care.

How difficult is it to diagnose EPI and what steps do you take to ensure that you prescribe patients with the proper therapy?

Dr. Kothari: The diagnosis of pancreatic insufficiency, in my mind, needs to start with assessing the pre-test probability of the patient having EPI, since testing could lead to a false positive.

The test of choice in most scenarios for diagnosing pancreatic insufficiency is a stool test known as the fecal elastase. It is a measurement of pancreatic elastase in the stool. The test itself is a concentration. For any condition that results in a dilute stool sample, that'll result in a falsely low value that can give a patient a false positive test. Now, this can be corrected  by the lab concentrating the stool sample before running the test, but that testing center needs to know how to do that.

The other assumption that we make with this stool test is that we assume that the elastase is a stable molecule that can traverse all the gut and be collected adequately. And for any reason, if that enzyme is degraded for any reason, it's also going to provide a low test, a low result, resulting in a false positive.

If they have risk factors for chronic pancreatitis or pancreatic disease and they're presenting with symptoms of EPI, then the usual test that I'll choose is dedicated pancreatic imaging such as an MRI or dedicated CT pancreatic imaging, or endoscopic ultrasound. If we clinch a diagnosis of chronic pancreatitis and they have symptoms of pancreatic insufficiency, I think that’s enough to presume a diagnosis of exocrine pancreatic insufficiency and start treatment.

On the other hand, in patients who do not have risk factors for pancreatic disease but there remains some clinical suspicion for exocrine pancreatic insufficiency, then it may be reasonable to check a fecal elastase to rule out pancreatic insufficiency. If the test results are low, then follow-up dedicated pancreas imaging would be the next step in delineating intrinsic pancreatic conditions form extra-pancreatic causes.  If pancreas imaging effectively rules out pancreatic disease then I consider checking for celiac disease, ruling out small intestinal bacterial overgrowth and considering assessment of luminal motility (either with a capsule or small bowel follow through). Although functional neuroendocrine tumors have been previously considered a cause of EPI, these tumors tend to present with secretory diarrhea which typically present differently (and often more dramatically) than other causes of EPI. Thus, I do not routinely check vasoactive hormone levels.

I think the American Gastroenterological Association has great patient education documents for our patients. Thus, I would encourage our colleagues to use the AGA for their resources for our patients on EPI.

What is your approach to differentiating EPI from other pancreatic conditions when making a diagnosis?

Dr. Kothari: Exocrine pancreatic insufficiency, or EPI, is a condition largely defined by malabsorption as the result of inadequate digestive enzymes. The resulting symptoms from maldigestion include bloating, malodorous gas, abdominal pain, changes in bowel habits, and weight change. EPI can be caused by intrinsic pancreatic disorders (such as chronic pancreatitis, acute pancreatitis, cystic fibrosis or pancreatic cancer) or from extra-pancreatic diseases (including the result of gastrointestinal surgery). Thus, EPI should be considered a consequence of an already existing gastrointestinal disorder.

Can you a speak a little bit more about the signs and symptoms or characteristics that are most common in patients with EPI?

Dr. Kothari: The symptoms of EPI can range from bloating and abdominal pain with mild to overt steatorrhea with greasy and oily stools that are difficult to flush with malodorous flatulence, weight loss, and symptoms of vitamin and micronutrient deficiency. The pathophysiology of these symptoms results from inadequate enzymes which are needed for digestion. Particularly, lipase is the major enzyme needed for fat digestion and thus when not present leads to fat maldigestion resulting in symptoms. Furthermore, undigested fats result in alterations in gut motility which can further exacerbate symptoms to include nausea, vomiting, early satiety and inadequate stool evacuation.

Patients who have fat malabsorption, particularly for pancreatic insufficiency, can also have malnutrition as a result of inadequate absorption of nutrients and micronutrients. Particularly, we think about fat-soluble vitamins-- vitamin A, vitamin E, vitamin D, and vitamin K and in the initial evaluation of patients with established EPI, one could consider evaluation of comorbid bone disease.

How crucial is having the correct interpretation of the clinical presentation to pinpointing the diagnosis?

Dr. Kothari: This is a great question because, with exocrine pancreatic insufficiency as there is growing publicity for the disorder and because symptoms can be rather non-specific when mild, it is important to be informed on how best to make this diagnosis. Thus, it is important to review the predisposing conditions that may lead to the diagnosis of EPI. These conditions include cystic fibrosis, chronic pancreatitis, acute pancreatitis, previous pancreatic surgery, history of pancreatic cancer (or suspicion for new pancreatic cancer), history of diabetes, celiac disease, history of luminal surgeries (including bariatric surgery), and inflammatory bowel disease. Further, since EPI can be a result of intrinsic pancreatic pathologies, it is critical to consider the risk factors for chronic pancreatitis which include alcohol and tobacco ingestion, prior episodes of recurrent acute pancreatitis, genetic conditions that may predispose patients to chronic pancreatitis, including cystic fibrosis, and hereditary conditions that also result in pancreatitis. As clinicians, it is our role to obtain an accurate history to best gauge the risk factors for EPI.

After reviewing risk factors, we then must review the clinical presentation to know if the symptoms could be from EPI which include bloating, gas, abdominal pain, weight changes, changes in bowel habits and consequences of vitamin deficiencies. Since the symptoms of mild EPI can be similar to other GI conditions such as SIBO, celiac disease, and functional bowel disorders, gauging whether a patient has risk factors for EPI will help the clinician understand how likely a diagnosis of EPI may be and if and what testing would be appropriate.

In my practice, I consider diagnostic testing in patients who may be at risk for EPI and have mild symptoms such malodorous gas, bloating and mild steatorrhea. For patient with clear evidence of steatorrhea (weight loss and vitamin deficiencies) and have strong risk factors for EPI (i.e. heavy alcohol and tobacco and/or a history of recurrent or severe acute pancreatitis), I might consider imaging and/or empiric therapies as to expedite care.

How difficult is it to diagnose EPI and what steps do you take to ensure that you prescribe patients with the proper therapy?

Dr. Kothari: The diagnosis of pancreatic insufficiency, in my mind, needs to start with assessing the pre-test probability of the patient having EPI, since testing could lead to a false positive.

The test of choice in most scenarios for diagnosing pancreatic insufficiency is a stool test known as the fecal elastase. It is a measurement of pancreatic elastase in the stool. The test itself is a concentration. For any condition that results in a dilute stool sample, that'll result in a falsely low value that can give a patient a false positive test. Now, this can be corrected  by the lab concentrating the stool sample before running the test, but that testing center needs to know how to do that.

The other assumption that we make with this stool test is that we assume that the elastase is a stable molecule that can traverse all the gut and be collected adequately. And for any reason, if that enzyme is degraded for any reason, it's also going to provide a low test, a low result, resulting in a false positive.

If they have risk factors for chronic pancreatitis or pancreatic disease and they're presenting with symptoms of EPI, then the usual test that I'll choose is dedicated pancreatic imaging such as an MRI or dedicated CT pancreatic imaging, or endoscopic ultrasound. If we clinch a diagnosis of chronic pancreatitis and they have symptoms of pancreatic insufficiency, I think that’s enough to presume a diagnosis of exocrine pancreatic insufficiency and start treatment.

On the other hand, in patients who do not have risk factors for pancreatic disease but there remains some clinical suspicion for exocrine pancreatic insufficiency, then it may be reasonable to check a fecal elastase to rule out pancreatic insufficiency. If the test results are low, then follow-up dedicated pancreas imaging would be the next step in delineating intrinsic pancreatic conditions form extra-pancreatic causes.  If pancreas imaging effectively rules out pancreatic disease then I consider checking for celiac disease, ruling out small intestinal bacterial overgrowth and considering assessment of luminal motility (either with a capsule or small bowel follow through). Although functional neuroendocrine tumors have been previously considered a cause of EPI, these tumors tend to present with secretory diarrhea which typically present differently (and often more dramatically) than other causes of EPI. Thus, I do not routinely check vasoactive hormone levels.

I think the American Gastroenterological Association has great patient education documents for our patients. Thus, I would encourage our colleagues to use the AGA for their resources for our patients on EPI.

The United States has never achieved a single high standard of medical care equity for all of its people, and the trend line does not appear favorable. The closest we have reached is basic Medicare (Parts A and B), military medicine, the Veterans Health Administration, and large nonprofit groups like Kaiser Permanente. It seems that the nature of we individualistic Americans is to always try to seek an advantage.

But even achieving equity in medical care would not ensure equity in health. The social determinants of health (income level, education, politics, government, geography, neighborhood, country of origin, language spoken, literacy, gender, and yes – race and ethnicity) have far more influence on health equity than does medical care.

Narratives can both reflect and influence culture. Considering the harmful effects of the current political divisiveness in the United States, the timing is ideal for our three leading medical and health education organizations – the American Medical Association, the Association of American Medical Colleges (AAMC), and the Centers for Disease Control and Prevention – to publish a definitive position paper called “Advancing Health Equity: A Guide to Language, Narrative and Concepts.”
 

What’s in a word?

According to William Shakespeare, “A rose by any other name would smell as sweet” (Romeo and Juliet). Maybe. But if the word used were “thorn” or “thistle,” it just would not be the same.

Words comprise language and wield enormous power with human beings. Wars are fought over geographic boundaries often defined by the language spoken by the people: think 2022, Russian-speaking Ukrainians. Think Winston Churchill’s massive 1,500-page “A History of the English-Speaking Peoples.” Think about the political power of French in Quebec, Canada.

Thus, it should be no surprise that words, acronyms, and abbreviations become rallying cries for political activists of all stripes: PC, January 6, Woke, 1619, BLM, Critical Race Theory, 1776, Remember Pearl Harbor, Remember the Alamo, the Civil War or the War Between the States, the War for Southern Independence, the War of Northern Aggression, the War of the Rebellion, or simply “The Lost Cause.” How about Realpolitik?

Is “medical language” the language of the people or of the profession? Physicians must understand each other, and physicians also must communicate clearly with patients using words that convey neutral meanings and don’t interfere with objective understanding. Medical editors prefer the brevity of one or a few words to clearly convey meaning.

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

The United States has never achieved a single high standard of medical care equity for all of its people, and the trend line does not appear favorable. The closest we have reached is basic Medicare (Parts A and B), military medicine, the Veterans Health Administration, and large nonprofit groups like Kaiser Permanente. It seems that the nature of we individualistic Americans is to always try to seek an advantage.

But even achieving equity in medical care would not ensure equity in health. The social determinants of health (income level, education, politics, government, geography, neighborhood, country of origin, language spoken, literacy, gender, and yes – race and ethnicity) have far more influence on health equity than does medical care.

Narratives can both reflect and influence culture. Considering the harmful effects of the current political divisiveness in the United States, the timing is ideal for our three leading medical and health education organizations – the American Medical Association, the Association of American Medical Colleges (AAMC), and the Centers for Disease Control and Prevention – to publish a definitive position paper called “Advancing Health Equity: A Guide to Language, Narrative and Concepts.”
 

What’s in a word?

According to William Shakespeare, “A rose by any other name would smell as sweet” (Romeo and Juliet). Maybe. But if the word used were “thorn” or “thistle,” it just would not be the same.

Words comprise language and wield enormous power with human beings. Wars are fought over geographic boundaries often defined by the language spoken by the people: think 2022, Russian-speaking Ukrainians. Think Winston Churchill’s massive 1,500-page “A History of the English-Speaking Peoples.” Think about the political power of French in Quebec, Canada.

Thus, it should be no surprise that words, acronyms, and abbreviations become rallying cries for political activists of all stripes: PC, January 6, Woke, 1619, BLM, Critical Race Theory, 1776, Remember Pearl Harbor, Remember the Alamo, the Civil War or the War Between the States, the War for Southern Independence, the War of Northern Aggression, the War of the Rebellion, or simply “The Lost Cause.” How about Realpolitik?

Is “medical language” the language of the people or of the profession? Physicians must understand each other, and physicians also must communicate clearly with patients using words that convey neutral meanings and don’t interfere with objective understanding. Medical editors prefer the brevity of one or a few words to clearly convey meaning.

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

The United States has never achieved a single high standard of medical care equity for all of its people, and the trend line does not appear favorable. The closest we have reached is basic Medicare (Parts A and B), military medicine, the Veterans Health Administration, and large nonprofit groups like Kaiser Permanente. It seems that the nature of we individualistic Americans is to always try to seek an advantage.

But even achieving equity in medical care would not ensure equity in health. The social determinants of health (income level, education, politics, government, geography, neighborhood, country of origin, language spoken, literacy, gender, and yes – race and ethnicity) have far more influence on health equity than does medical care.

Narratives can both reflect and influence culture. Considering the harmful effects of the current political divisiveness in the United States, the timing is ideal for our three leading medical and health education organizations – the American Medical Association, the Association of American Medical Colleges (AAMC), and the Centers for Disease Control and Prevention – to publish a definitive position paper called “Advancing Health Equity: A Guide to Language, Narrative and Concepts.”
 

What’s in a word?

According to William Shakespeare, “A rose by any other name would smell as sweet” (Romeo and Juliet). Maybe. But if the word used were “thorn” or “thistle,” it just would not be the same.

Words comprise language and wield enormous power with human beings. Wars are fought over geographic boundaries often defined by the language spoken by the people: think 2022, Russian-speaking Ukrainians. Think Winston Churchill’s massive 1,500-page “A History of the English-Speaking Peoples.” Think about the political power of French in Quebec, Canada.

Thus, it should be no surprise that words, acronyms, and abbreviations become rallying cries for political activists of all stripes: PC, January 6, Woke, 1619, BLM, Critical Race Theory, 1776, Remember Pearl Harbor, Remember the Alamo, the Civil War or the War Between the States, the War for Southern Independence, the War of Northern Aggression, the War of the Rebellion, or simply “The Lost Cause.” How about Realpolitik?

Is “medical language” the language of the people or of the profession? Physicians must understand each other, and physicians also must communicate clearly with patients using words that convey neutral meanings and don’t interfere with objective understanding. Medical editors prefer the brevity of one or a few words to clearly convey meaning.

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

Correct answer: B. Absence of ganglion cells on rectal biopsy. 
 
Rationale  
Hirschsprung's disease occurs in approximately 1 out of 5,000 live births and is caused by absence of ganglion cells in the myenteric plexus of the intestine. The condition arises from failure of the neural crest cells to fully migrate caudally along the intestine during early gestation, resulting in a distal portion of the intestine being aganglionic. Rectal and distal sigmoid involvement is seen in around 85% of cases, with the other 15 percent involving more proximal intestine. It can rarely involve the entire colon and small intestine. Ganglion cells inhibit local smooth muscles, resulting in the characteristic inability for aganglionic bowel to relax. This lack of inhibition gives rise to the absence of rectoanal inhibitory reflex (RAIRs) during anorectal manometry. The lack of inhibition also produces a transition zone on contrast enema, with the distal aganglionic bowel being narrow and the more proximal bowel containing ganglia being dilated. Lack of meconium passage in the first 48 hours of life raises concern for Hirschsprung's disease. Other causes for possible failure to pass meconium include cystic fibrosis, anorectal malformation, small left colon syndrome, meconium plug syndrome and megacystis-microcolon-intestinal hypoperistalsis syndrome.  
 
References 
Kenny, S et al. Semin Pediatr Surg. 2010 Aug;19(3):194-200. 
Wyllie R et al. Pediatric Gastrointestinal and Liver Disease. 4th edition. Elsevier Saunders, Philadelphia, 2011.

Correct answer: B. Absence of ganglion cells on rectal biopsy. 
 
Rationale  
Hirschsprung's disease occurs in approximately 1 out of 5,000 live births and is caused by absence of ganglion cells in the myenteric plexus of the intestine. The condition arises from failure of the neural crest cells to fully migrate caudally along the intestine during early gestation, resulting in a distal portion of the intestine being aganglionic. Rectal and distal sigmoid involvement is seen in around 85% of cases, with the other 15 percent involving more proximal intestine. It can rarely involve the entire colon and small intestine. Ganglion cells inhibit local smooth muscles, resulting in the characteristic inability for aganglionic bowel to relax. This lack of inhibition gives rise to the absence of rectoanal inhibitory reflex (RAIRs) during anorectal manometry. The lack of inhibition also produces a transition zone on contrast enema, with the distal aganglionic bowel being narrow and the more proximal bowel containing ganglia being dilated. Lack of meconium passage in the first 48 hours of life raises concern for Hirschsprung's disease. Other causes for possible failure to pass meconium include cystic fibrosis, anorectal malformation, small left colon syndrome, meconium plug syndrome and megacystis-microcolon-intestinal hypoperistalsis syndrome.  
 
References 
Kenny, S et al. Semin Pediatr Surg. 2010 Aug;19(3):194-200. 
Wyllie R et al. Pediatric Gastrointestinal and Liver Disease. 4th edition. Elsevier Saunders, Philadelphia, 2011.

Correct answer: B. Absence of ganglion cells on rectal biopsy. 
 
Rationale  
Hirschsprung's disease occurs in approximately 1 out of 5,000 live births and is caused by absence of ganglion cells in the myenteric plexus of the intestine. The condition arises from failure of the neural crest cells to fully migrate caudally along the intestine during early gestation, resulting in a distal portion of the intestine being aganglionic. Rectal and distal sigmoid involvement is seen in around 85% of cases, with the other 15 percent involving more proximal intestine. It can rarely involve the entire colon and small intestine. Ganglion cells inhibit local smooth muscles, resulting in the characteristic inability for aganglionic bowel to relax. This lack of inhibition gives rise to the absence of rectoanal inhibitory reflex (RAIRs) during anorectal manometry. The lack of inhibition also produces a transition zone on contrast enema, with the distal aganglionic bowel being narrow and the more proximal bowel containing ganglia being dilated. Lack of meconium passage in the first 48 hours of life raises concern for Hirschsprung's disease. Other causes for possible failure to pass meconium include cystic fibrosis, anorectal malformation, small left colon syndrome, meconium plug syndrome and megacystis-microcolon-intestinal hypoperistalsis syndrome.  
 
References 
Kenny, S et al. Semin Pediatr Surg. 2010 Aug;19(3):194-200. 
Wyllie R et al. Pediatric Gastrointestinal and Liver Disease. 4th edition. Elsevier Saunders, Philadelphia, 2011.

Correct answer: A. Amyloidosis involving the small intestine 
 
Rationale  
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.

Correct answer: A. Amyloidosis involving the small intestine 
 
Rationale  
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.

Correct answer: A. Amyloidosis involving the small intestine 
 
Rationale  
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.

In her month-long memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life (Knopf, 2017), author Ayelet Waldman turns herself into a one-woman experiment.

Over a single month she takes one-tenth of a recreational dose of LSD every third day. She plots her emotions, her productivity, and her pain along the way. Ms. Waldman obtains the LSD in a single vial, enough for 10 doses, from a researcher, who is retiring. What she’s looking for, she tells the reader, is a really good day – something that has been elusive in her turbulent life.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

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

In her month-long memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life (Knopf, 2017), author Ayelet Waldman turns herself into a one-woman experiment.

Over a single month she takes one-tenth of a recreational dose of LSD every third day. She plots her emotions, her productivity, and her pain along the way. Ms. Waldman obtains the LSD in a single vial, enough for 10 doses, from a researcher, who is retiring. What she’s looking for, she tells the reader, is a really good day – something that has been elusive in her turbulent life.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

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

In her month-long memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life (Knopf, 2017), author Ayelet Waldman turns herself into a one-woman experiment.

Over a single month she takes one-tenth of a recreational dose of LSD every third day. She plots her emotions, her productivity, and her pain along the way. Ms. Waldman obtains the LSD in a single vial, enough for 10 doses, from a researcher, who is retiring. What she’s looking for, she tells the reader, is a really good day – something that has been elusive in her turbulent life.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

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

A panel of experts that advises the FDA narrowly voted to reject a new drug intended to treat amyotrophic lateral scelrosis (ALS). Six of 10 members of the FDA Peripheral and Central Nervous System Drugs Advisory Committee decided there is not enough evidence to support approval of the drug from Amylyx Pharmaceuticals. The evidence from a single phase 2 trial is insufficient, the panel said.

The fate of the drug, known as AMX0035, and the panel’s vote, has been closely watched as new treatments for this devastating disease are greatly needed. Committee members said they were moved by passionate testimony from patients, caregivers, and others. But, they believe the evidence does not meet the required standard for FDA approval.

“We were asked to look for substantial evidence of persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar and was problematic,” said Kenneth Fischbeck, MD, investigator with the National Institute of Neurological Disorders and Stroke. “It would be a disservice to patients and their families to move ahead and approve a treatment that is of uncertain benefit,” said Dr. Fischbeck.

The committee’s vote is not binding. While the FDA often follows its advisors’ decisions, the agency last year approved a controversial new drug for Alzheimer’s disease after a similar advisory committee voted against it.
 

Phase 3 study in the works

This new ALS drug was shown to slow the decline caused by ALS, sometimes known as Lou Gehrig’s disease, Jamie Timmons, MD, head of scientific communications at Amylyx Pharmaceuticals, said. The study found the drug slowed decline by 25%, compared with patients taking a placebo. That change is considered clinically meaningful.

This is the first time a treatment has shown a benefit on both function and survival in ALS, the two key measures in a relentlessly progressive, fatal disease, said Joshua Cohen, co-CEO and co-founder of Amylyx.

During the meeting, patients with ALS said they were willing to accept greater risk for the possibility of having even a little more time with their loved ones and argued that the drug contains two compounds that are already available. They pleaded for the FDA to exercise its regulatory flexibility in approving this experimental drug.

However, the FDA panel raised a number of issues with the trial. These concerns included the study’s small sample size and no survival benefit at 24 weeks.

Many panel members said they hope an ongoing phase III trial will be more definitive because it’s so much larger. The results of that trial are expected by early 2024.

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

A panel of experts that advises the FDA narrowly voted to reject a new drug intended to treat amyotrophic lateral scelrosis (ALS). Six of 10 members of the FDA Peripheral and Central Nervous System Drugs Advisory Committee decided there is not enough evidence to support approval of the drug from Amylyx Pharmaceuticals. The evidence from a single phase 2 trial is insufficient, the panel said.

The fate of the drug, known as AMX0035, and the panel’s vote, has been closely watched as new treatments for this devastating disease are greatly needed. Committee members said they were moved by passionate testimony from patients, caregivers, and others. But, they believe the evidence does not meet the required standard for FDA approval.

“We were asked to look for substantial evidence of persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar and was problematic,” said Kenneth Fischbeck, MD, investigator with the National Institute of Neurological Disorders and Stroke. “It would be a disservice to patients and their families to move ahead and approve a treatment that is of uncertain benefit,” said Dr. Fischbeck.

The committee’s vote is not binding. While the FDA often follows its advisors’ decisions, the agency last year approved a controversial new drug for Alzheimer’s disease after a similar advisory committee voted against it.
 

Phase 3 study in the works

This new ALS drug was shown to slow the decline caused by ALS, sometimes known as Lou Gehrig’s disease, Jamie Timmons, MD, head of scientific communications at Amylyx Pharmaceuticals, said. The study found the drug slowed decline by 25%, compared with patients taking a placebo. That change is considered clinically meaningful.

This is the first time a treatment has shown a benefit on both function and survival in ALS, the two key measures in a relentlessly progressive, fatal disease, said Joshua Cohen, co-CEO and co-founder of Amylyx.

During the meeting, patients with ALS said they were willing to accept greater risk for the possibility of having even a little more time with their loved ones and argued that the drug contains two compounds that are already available. They pleaded for the FDA to exercise its regulatory flexibility in approving this experimental drug.

However, the FDA panel raised a number of issues with the trial. These concerns included the study’s small sample size and no survival benefit at 24 weeks.

Many panel members said they hope an ongoing phase III trial will be more definitive because it’s so much larger. The results of that trial are expected by early 2024.

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

A panel of experts that advises the FDA narrowly voted to reject a new drug intended to treat amyotrophic lateral scelrosis (ALS). Six of 10 members of the FDA Peripheral and Central Nervous System Drugs Advisory Committee decided there is not enough evidence to support approval of the drug from Amylyx Pharmaceuticals. The evidence from a single phase 2 trial is insufficient, the panel said.

The fate of the drug, known as AMX0035, and the panel’s vote, has been closely watched as new treatments for this devastating disease are greatly needed. Committee members said they were moved by passionate testimony from patients, caregivers, and others. But, they believe the evidence does not meet the required standard for FDA approval.

“We were asked to look for substantial evidence of persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar and was problematic,” said Kenneth Fischbeck, MD, investigator with the National Institute of Neurological Disorders and Stroke. “It would be a disservice to patients and their families to move ahead and approve a treatment that is of uncertain benefit,” said Dr. Fischbeck.

The committee’s vote is not binding. While the FDA often follows its advisors’ decisions, the agency last year approved a controversial new drug for Alzheimer’s disease after a similar advisory committee voted against it.
 

Phase 3 study in the works

This new ALS drug was shown to slow the decline caused by ALS, sometimes known as Lou Gehrig’s disease, Jamie Timmons, MD, head of scientific communications at Amylyx Pharmaceuticals, said. The study found the drug slowed decline by 25%, compared with patients taking a placebo. That change is considered clinically meaningful.

This is the first time a treatment has shown a benefit on both function and survival in ALS, the two key measures in a relentlessly progressive, fatal disease, said Joshua Cohen, co-CEO and co-founder of Amylyx.

During the meeting, patients with ALS said they were willing to accept greater risk for the possibility of having even a little more time with their loved ones and argued that the drug contains two compounds that are already available. They pleaded for the FDA to exercise its regulatory flexibility in approving this experimental drug.

However, the FDA panel raised a number of issues with the trial. These concerns included the study’s small sample size and no survival benefit at 24 weeks.

Many panel members said they hope an ongoing phase III trial will be more definitive because it’s so much larger. The results of that trial are expected by early 2024.

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

Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies. 

While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders. 

Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.

Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology. 

Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways. 

These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation. 

Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.

Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy. 

During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management. 

As awareness of vascular anomalies grows and research on effective treatments continues, a new focus on this natural offshoot of hematology and oncology offers adult and pediatric specialists in our field a fertile area for career development.

Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.

Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies. 

While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders. 

Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.

Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology. 

Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways. 

These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation. 

Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.

Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy. 

During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management. 

As awareness of vascular anomalies grows and research on effective treatments continues, a new focus on this natural offshoot of hematology and oncology offers adult and pediatric specialists in our field a fertile area for career development.

Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.

Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies. 

While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders. 

Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.

Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology. 

Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways. 

These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation. 

Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.

Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy. 

During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management. 

As awareness of vascular anomalies grows and research on effective treatments continues, a new focus on this natural offshoot of hematology and oncology offers adult and pediatric specialists in our field a fertile area for career development.

Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.

Over the last several years, payer policies that dictate and restrict treatments for patients with inflammatory bowel diseases (IBD) have proliferated. The implementation of new coverage restrictions, expansion of services and procedures requiring prior authorization (PA), and dosing and access restriction to covered drugs, and the requirement of repeated treatment reviews including nonmedical switching for stable patients are widespread. The AGA administered a member needs assessment survey in December 2021 to determine the extent to which these policies harm patients and overburden gastroenterologists and their staff.

Survey findings

Most of the 100 surveyed members reported facing administrative burdens that prevented timely access to patient care. Utilization management practices such as PA, step therapy, and nonmedical switching and dosing restrictions create critical barriers to high quality GI care for patients with chronic conditions and jeopardize the physician-patient relationship. At a time when physicians have faced unprecedented challenges because of the public health emergency from the COVID-19 pandemic, these burdens also contribute to increasing physician burnout.

Prior authorization: Among AGA members, 96% of members said that PA is burdensome, with 61% indicating that it is significantly burdensome. Almost 99% of members indicated that PA has a negative impact on patients’ access to clinically appropriate treatments; 89% reported that the burden associated with PA has increased over the last 5 years in their practice.

Step therapy: Among members, 87% described the impact step therapy has on their practice as burdensome. Almost 90% of members said step therapy negatively impacted patients’ access to clinically appropriate treatments. Almost 90% of members felt that there was an overall negative impact on patient clinical outcomes for those patients who were required to follow a step therapy protocol.

An increasing number of insurance companies are restricting effective biologic therapy to Food and Drug Administration–labeled doses, in direct conflict with current established best practices. It is most concerning that many patients who had been stable on optimized dosing are suddenly notified that they will no longer be able to receive the dose or treatment frequency prescribed by their physician. The concept of optimizing drug therapy based on disease activity and therapeutic drug monitoring is well established, and artificial restrictions to FDA-labeled doses force unnecessary drug deescalation. This transparent effort to reduce costs lacks evidence for safety. Our sickest patients often require higher doses for induction in order to respond, given drug losses, yet some payers refuse to cover the doses these patients require. This new payer-centered effort prioritizes cost containment over the judgment of the treating physician. It causes direct patient harm risking efficacy or loss of response, and subsequent irreversible disease-related complications.
 

Medicare drug costs

Medicare patients receiving self-injectable or oral medications are not eligible for co-pay assistance programs through pharmaceutical companies because of federal rules. For non-Medicare patients, these programs reduce the co-pay costs to as low as $5 per month. Medicare patients are able to receive infusions like infliximab and vedolizumab at no cost. However, any self-injectable or oral agent can carry a co-pay of over $1,000. Other than for patients meeting income-based eligibility requirements (e.g., below the poverty line), these treatments become prohibitively expensive. Thousands of patients have had to discontinue their self-injectable and/or oral medications because of this cost or have been denied access to the therapy altogether because of cost.

Need for change

These recent changes in insurance policies have resulted in increased harm to our patients with IBD rather than improving the safety or quality of their care. These changes create barriers to disease treatment and have not improved quality of care, patient outcomes, or quality of life. The AGA and other societies have published multiple guidelines and literature on the management of patients with IBD that should serve as the foundation for insurers’ medication coverage policies. Additionally, insurance companies should seek input from panels of IBD experts when developing their medication coverage policies to ensure they are patient oriented and facilitate high-quality IBD care.

The following are opportunities for insurers to improve the IBD drug approval process:

• Simplify the appeal process.
• Guarantee rapid response/turnaround to appeal processes to avoid additional delays in care.
• Incorporate experienced expert review by a gastroenterologist.
• Ensure coverage of drug and disease monitoring.
• Integrate expert input in policy development.

Conclusion

Effective patient care in IBD, as well as in other chronic gastrointestinal diseases, requires a collaborative approach to maximize clinical outcomes. It is an exciting time in our field, with rapidly expanding therapeutic options to treat IBD that have the potential to modify the disease course and prevent long-term complications for patients. However, optimizing the use of these treatments to achieve disease remission is challenging and requires the ability to individualize the timely choice of medications at the right dose for each patient to capture and monitor response. The ability to provide individualized, data driven care is essential to improving the quality of life of our patients, as well as to reducing health care spending over time.

Achieving high-value care is a goal that benefits everyone involved in the health care system. Policies that interfere with the timely treatment of sick patients with the right therapies, optimized to achieve disease remission, hurt the very patients that our health care system exists to serve. We cannot stand by while impediments to treatment result in harm to our patients and worsen clinical outcomes. Collaboratively developing aligned incentives can lead us to patient-centered policies that fulfill a shared purpose to optimize the health of people with chronic digestive diseases.

The authors reported having no relevant conflicts of interest.

Dr. Feuerstein is with the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center and is an associate professor of medicine Harvard Medical School, both in Boston. Dr. Sofia is an assistant professor of medicine with the division of gastroenterology and hepatology at Oregon Health and Science University, Portland. Dr. Guha is a professor of medicine at the division of gastroenterology, hepatology and nutrition and is codirector of the Center for Interventional Gastroenterology at UTHealth (iGUT) at UT Health Science Center, Houston. Dr. Streett is a clinical professor of medicine, gastroenterology, and hepatology and director of the IBD Education and Advanced IBD Fellowship at Stanford (Calif.) Medicine.

Over the last several years, payer policies that dictate and restrict treatments for patients with inflammatory bowel diseases (IBD) have proliferated. The implementation of new coverage restrictions, expansion of services and procedures requiring prior authorization (PA), and dosing and access restriction to covered drugs, and the requirement of repeated treatment reviews including nonmedical switching for stable patients are widespread. The AGA administered a member needs assessment survey in December 2021 to determine the extent to which these policies harm patients and overburden gastroenterologists and their staff.

Survey findings

Most of the 100 surveyed members reported facing administrative burdens that prevented timely access to patient care. Utilization management practices such as PA, step therapy, and nonmedical switching and dosing restrictions create critical barriers to high quality GI care for patients with chronic conditions and jeopardize the physician-patient relationship. At a time when physicians have faced unprecedented challenges because of the public health emergency from the COVID-19 pandemic, these burdens also contribute to increasing physician burnout.

Prior authorization: Among AGA members, 96% of members said that PA is burdensome, with 61% indicating that it is significantly burdensome. Almost 99% of members indicated that PA has a negative impact on patients’ access to clinically appropriate treatments; 89% reported that the burden associated with PA has increased over the last 5 years in their practice.

Step therapy: Among members, 87% described the impact step therapy has on their practice as burdensome. Almost 90% of members said step therapy negatively impacted patients’ access to clinically appropriate treatments. Almost 90% of members felt that there was an overall negative impact on patient clinical outcomes for those patients who were required to follow a step therapy protocol.

An increasing number of insurance companies are restricting effective biologic therapy to Food and Drug Administration–labeled doses, in direct conflict with current established best practices. It is most concerning that many patients who had been stable on optimized dosing are suddenly notified that they will no longer be able to receive the dose or treatment frequency prescribed by their physician. The concept of optimizing drug therapy based on disease activity and therapeutic drug monitoring is well established, and artificial restrictions to FDA-labeled doses force unnecessary drug deescalation. This transparent effort to reduce costs lacks evidence for safety. Our sickest patients often require higher doses for induction in order to respond, given drug losses, yet some payers refuse to cover the doses these patients require. This new payer-centered effort prioritizes cost containment over the judgment of the treating physician. It causes direct patient harm risking efficacy or loss of response, and subsequent irreversible disease-related complications.
 

Medicare drug costs

Medicare patients receiving self-injectable or oral medications are not eligible for co-pay assistance programs through pharmaceutical companies because of federal rules. For non-Medicare patients, these programs reduce the co-pay costs to as low as $5 per month. Medicare patients are able to receive infusions like infliximab and vedolizumab at no cost. However, any self-injectable or oral agent can carry a co-pay of over $1,000. Other than for patients meeting income-based eligibility requirements (e.g., below the poverty line), these treatments become prohibitively expensive. Thousands of patients have had to discontinue their self-injectable and/or oral medications because of this cost or have been denied access to the therapy altogether because of cost.

Need for change

These recent changes in insurance policies have resulted in increased harm to our patients with IBD rather than improving the safety or quality of their care. These changes create barriers to disease treatment and have not improved quality of care, patient outcomes, or quality of life. The AGA and other societies have published multiple guidelines and literature on the management of patients with IBD that should serve as the foundation for insurers’ medication coverage policies. Additionally, insurance companies should seek input from panels of IBD experts when developing their medication coverage policies to ensure they are patient oriented and facilitate high-quality IBD care.

The following are opportunities for insurers to improve the IBD drug approval process:

• Simplify the appeal process.
• Guarantee rapid response/turnaround to appeal processes to avoid additional delays in care.
• Incorporate experienced expert review by a gastroenterologist.
• Ensure coverage of drug and disease monitoring.
• Integrate expert input in policy development.

Conclusion

Effective patient care in IBD, as well as in other chronic gastrointestinal diseases, requires a collaborative approach to maximize clinical outcomes. It is an exciting time in our field, with rapidly expanding therapeutic options to treat IBD that have the potential to modify the disease course and prevent long-term complications for patients. However, optimizing the use of these treatments to achieve disease remission is challenging and requires the ability to individualize the timely choice of medications at the right dose for each patient to capture and monitor response. The ability to provide individualized, data driven care is essential to improving the quality of life of our patients, as well as to reducing health care spending over time.

Achieving high-value care is a goal that benefits everyone involved in the health care system. Policies that interfere with the timely treatment of sick patients with the right therapies, optimized to achieve disease remission, hurt the very patients that our health care system exists to serve. We cannot stand by while impediments to treatment result in harm to our patients and worsen clinical outcomes. Collaboratively developing aligned incentives can lead us to patient-centered policies that fulfill a shared purpose to optimize the health of people with chronic digestive diseases.

The authors reported having no relevant conflicts of interest.

Dr. Feuerstein is with the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center and is an associate professor of medicine Harvard Medical School, both in Boston. Dr. Sofia is an assistant professor of medicine with the division of gastroenterology and hepatology at Oregon Health and Science University, Portland. Dr. Guha is a professor of medicine at the division of gastroenterology, hepatology and nutrition and is codirector of the Center for Interventional Gastroenterology at UTHealth (iGUT) at UT Health Science Center, Houston. Dr. Streett is a clinical professor of medicine, gastroenterology, and hepatology and director of the IBD Education and Advanced IBD Fellowship at Stanford (Calif.) Medicine.

Over the last several years, payer policies that dictate and restrict treatments for patients with inflammatory bowel diseases (IBD) have proliferated. The implementation of new coverage restrictions, expansion of services and procedures requiring prior authorization (PA), and dosing and access restriction to covered drugs, and the requirement of repeated treatment reviews including nonmedical switching for stable patients are widespread. The AGA administered a member needs assessment survey in December 2021 to determine the extent to which these policies harm patients and overburden gastroenterologists and their staff.

Survey findings

Most of the 100 surveyed members reported facing administrative burdens that prevented timely access to patient care. Utilization management practices such as PA, step therapy, and nonmedical switching and dosing restrictions create critical barriers to high quality GI care for patients with chronic conditions and jeopardize the physician-patient relationship. At a time when physicians have faced unprecedented challenges because of the public health emergency from the COVID-19 pandemic, these burdens also contribute to increasing physician burnout.

Prior authorization: Among AGA members, 96% of members said that PA is burdensome, with 61% indicating that it is significantly burdensome. Almost 99% of members indicated that PA has a negative impact on patients’ access to clinically appropriate treatments; 89% reported that the burden associated with PA has increased over the last 5 years in their practice.

Step therapy: Among members, 87% described the impact step therapy has on their practice as burdensome. Almost 90% of members said step therapy negatively impacted patients’ access to clinically appropriate treatments. Almost 90% of members felt that there was an overall negative impact on patient clinical outcomes for those patients who were required to follow a step therapy protocol.

An increasing number of insurance companies are restricting effective biologic therapy to Food and Drug Administration–labeled doses, in direct conflict with current established best practices. It is most concerning that many patients who had been stable on optimized dosing are suddenly notified that they will no longer be able to receive the dose or treatment frequency prescribed by their physician. The concept of optimizing drug therapy based on disease activity and therapeutic drug monitoring is well established, and artificial restrictions to FDA-labeled doses force unnecessary drug deescalation. This transparent effort to reduce costs lacks evidence for safety. Our sickest patients often require higher doses for induction in order to respond, given drug losses, yet some payers refuse to cover the doses these patients require. This new payer-centered effort prioritizes cost containment over the judgment of the treating physician. It causes direct patient harm risking efficacy or loss of response, and subsequent irreversible disease-related complications.
 

Medicare drug costs

Medicare patients receiving self-injectable or oral medications are not eligible for co-pay assistance programs through pharmaceutical companies because of federal rules. For non-Medicare patients, these programs reduce the co-pay costs to as low as $5 per month. Medicare patients are able to receive infusions like infliximab and vedolizumab at no cost. However, any self-injectable or oral agent can carry a co-pay of over $1,000. Other than for patients meeting income-based eligibility requirements (e.g., below the poverty line), these treatments become prohibitively expensive. Thousands of patients have had to discontinue their self-injectable and/or oral medications because of this cost or have been denied access to the therapy altogether because of cost.

Need for change

These recent changes in insurance policies have resulted in increased harm to our patients with IBD rather than improving the safety or quality of their care. These changes create barriers to disease treatment and have not improved quality of care, patient outcomes, or quality of life. The AGA and other societies have published multiple guidelines and literature on the management of patients with IBD that should serve as the foundation for insurers’ medication coverage policies. Additionally, insurance companies should seek input from panels of IBD experts when developing their medication coverage policies to ensure they are patient oriented and facilitate high-quality IBD care.

The following are opportunities for insurers to improve the IBD drug approval process:

• Simplify the appeal process.
• Guarantee rapid response/turnaround to appeal processes to avoid additional delays in care.
• Incorporate experienced expert review by a gastroenterologist.
• Ensure coverage of drug and disease monitoring.
• Integrate expert input in policy development.

Conclusion

Effective patient care in IBD, as well as in other chronic gastrointestinal diseases, requires a collaborative approach to maximize clinical outcomes. It is an exciting time in our field, with rapidly expanding therapeutic options to treat IBD that have the potential to modify the disease course and prevent long-term complications for patients. However, optimizing the use of these treatments to achieve disease remission is challenging and requires the ability to individualize the timely choice of medications at the right dose for each patient to capture and monitor response. The ability to provide individualized, data driven care is essential to improving the quality of life of our patients, as well as to reducing health care spending over time.

Achieving high-value care is a goal that benefits everyone involved in the health care system. Policies that interfere with the timely treatment of sick patients with the right therapies, optimized to achieve disease remission, hurt the very patients that our health care system exists to serve. We cannot stand by while impediments to treatment result in harm to our patients and worsen clinical outcomes. Collaboratively developing aligned incentives can lead us to patient-centered policies that fulfill a shared purpose to optimize the health of people with chronic digestive diseases.

The authors reported having no relevant conflicts of interest.

Dr. Feuerstein is with the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center and is an associate professor of medicine Harvard Medical School, both in Boston. Dr. Sofia is an assistant professor of medicine with the division of gastroenterology and hepatology at Oregon Health and Science University, Portland. Dr. Guha is a professor of medicine at the division of gastroenterology, hepatology and nutrition and is codirector of the Center for Interventional Gastroenterology at UTHealth (iGUT) at UT Health Science Center, Houston. Dr. Streett is a clinical professor of medicine, gastroenterology, and hepatology and director of the IBD Education and Advanced IBD Fellowship at Stanford (Calif.) Medicine.

BOSTON – Dupilumab, a human monoclonal IgG4 antibody, was an effective treatment for prurigo nodularis (PN), improving itching and skin lesions after 12 and 24 weeks of treatment, in a phase 3 trial presented at the American Academy of Dermatology 2022 Annual Meeting.

There are currently no Food and Drug Administration–approved systemic therapies for PN. Although several treatments for the disease are used off label for the condition, such as ultraviolet light therapy and immunosuppressive agents, moderate to severe PN is usually difficult to control, noted Gil Yosipovitch, MD, director of the Miami Itch Center at the University of Miami Miller School of Medicine, Florida. He led the research and presented the findings at the conference.

“Many dermatologists feel very uncomfortable dealing with these patients because they suffer from chronicity, they are miserable, and previously, the drugs didn’t work well,” Dr. Yosipovitch told this news organization. The results from this trial “are very promising,” he said. “It opens a new field of treatment for itchy conditions.”

The trial, named LIBERTY-PN PRIME2, enrolled patients aged 18-80 who had been living with PN for at least 3 months. Patients had at least 20 lesions at baseline as well as severe itch, defined as a score of 7 or greater on the Worst Itch Numerical Rating Scale (WI-NRS). The scale ranges from 0 (no itch) to 10 (worst itch imaginable). Participants also had a history of treatment failure with medium to super-potent topical corticosteroids (TCSs), or treatment with TCSs was not medically advisable for them.

The randomized, double-blinded study enrolled 160 adults with PN. Of those, 78 were assigned to the treatment arm and received a 600-mg loading dose of dupilumab, administered subcutaneously, followed by 300-mg doses every 2 weeks for 24 weeks; 82 patients were allocated to receive placebo.

During the study, 25 patients in the placebo arm discontinued treatment. In the treatment arm, one patient was not treated and two discontinued treatment due to lack of efficacy.

The primary endpoint of the study was a reduction of at least 4 points on the WI-NRS at 12 weeks. Secondary endpoints included at least a 4-point WI-NRS reduction at 24 weeks and clear to nearly clear skin, defined as having a score of 0 or 1 on the Investigator’s Global Assessment PN-Stage (IGN PN-S). The scale ranges from 0 (clear) to 4 (severe).

At 12 weeks, 37.2% of patients given dupilumab reported a reduction of at least 4 points in WI-NRS, compared with 22.0% of patients given placebo (P = .0216). By 24 weeks, 57.7% of adults who received dupilumab achieved a greater than or equal to 4-point reduction in WI-NRS, compared with 19.5% of those who received placebo (P < .0001). Additionally, 44.9% of participants in the treatment arm achieved a score of 0 or 1 on the IGA PN-S, compared with 15.9% of those in the placebo arm (P < .0001).

Forty-four participants who received dupilumab (57.1%) and 42 participants who received placebo (51.2%) reported at least one treatment-emergent adverse event (TEAE) during the study, though none of these events were serious. The most common TEAE in the study was headache, occurring in five patients taking placebo and four patients receiving dupilumab. In the dupilumab group, there were five cases of herpes virus infection, four non-herpes skin infections, and three cases of conjunctivitis. In the placebo group, seven non-herpes skin infections were reported.

Sanofi and Regeneron, who jointly developed dupilumab, plan to file for regulatory approval for dupilumab for PN “around the world” in the first half of this year, according to a press release.

“It’s great news and a step in the right direction,” Sarina Elmariah, MD, PhD, a dermatologist at Massachusetts General Hospital and instructor of dermatology at Harvard Medical School, both in Boston, told this news organization. She was not involved with the research.

“We’re finally starting to shed light on this condition and its pathogenesis,” she said. She noted that other potential therapeutics for PN are also in development. “It’s reflective of the fact that we are making strides in this area.”

Sanofi and Regeneron Pharmaceuticals sponsored the LIBERTY-PN PRIME2 trial. Dr. Yosipovitch has reported financial relationships with Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, and Trevi Therapeutics. Dr. Elmariah is on the advisory boards of Sanofi, Galderma, and Trevi Therapeutics.

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

BOSTON – Dupilumab, a human monoclonal IgG4 antibody, was an effective treatment for prurigo nodularis (PN), improving itching and skin lesions after 12 and 24 weeks of treatment, in a phase 3 trial presented at the American Academy of Dermatology 2022 Annual Meeting.

There are currently no Food and Drug Administration–approved systemic therapies for PN. Although several treatments for the disease are used off label for the condition, such as ultraviolet light therapy and immunosuppressive agents, moderate to severe PN is usually difficult to control, noted Gil Yosipovitch, MD, director of the Miami Itch Center at the University of Miami Miller School of Medicine, Florida. He led the research and presented the findings at the conference.

“Many dermatologists feel very uncomfortable dealing with these patients because they suffer from chronicity, they are miserable, and previously, the drugs didn’t work well,” Dr. Yosipovitch told this news organization. The results from this trial “are very promising,” he said. “It opens a new field of treatment for itchy conditions.”

The trial, named LIBERTY-PN PRIME2, enrolled patients aged 18-80 who had been living with PN for at least 3 months. Patients had at least 20 lesions at baseline as well as severe itch, defined as a score of 7 or greater on the Worst Itch Numerical Rating Scale (WI-NRS). The scale ranges from 0 (no itch) to 10 (worst itch imaginable). Participants also had a history of treatment failure with medium to super-potent topical corticosteroids (TCSs), or treatment with TCSs was not medically advisable for them.

The randomized, double-blinded study enrolled 160 adults with PN. Of those, 78 were assigned to the treatment arm and received a 600-mg loading dose of dupilumab, administered subcutaneously, followed by 300-mg doses every 2 weeks for 24 weeks; 82 patients were allocated to receive placebo.

During the study, 25 patients in the placebo arm discontinued treatment. In the treatment arm, one patient was not treated and two discontinued treatment due to lack of efficacy.

The primary endpoint of the study was a reduction of at least 4 points on the WI-NRS at 12 weeks. Secondary endpoints included at least a 4-point WI-NRS reduction at 24 weeks and clear to nearly clear skin, defined as having a score of 0 or 1 on the Investigator’s Global Assessment PN-Stage (IGN PN-S). The scale ranges from 0 (clear) to 4 (severe).

At 12 weeks, 37.2% of patients given dupilumab reported a reduction of at least 4 points in WI-NRS, compared with 22.0% of patients given placebo (P = .0216). By 24 weeks, 57.7% of adults who received dupilumab achieved a greater than or equal to 4-point reduction in WI-NRS, compared with 19.5% of those who received placebo (P < .0001). Additionally, 44.9% of participants in the treatment arm achieved a score of 0 or 1 on the IGA PN-S, compared with 15.9% of those in the placebo arm (P < .0001).

Forty-four participants who received dupilumab (57.1%) and 42 participants who received placebo (51.2%) reported at least one treatment-emergent adverse event (TEAE) during the study, though none of these events were serious. The most common TEAE in the study was headache, occurring in five patients taking placebo and four patients receiving dupilumab. In the dupilumab group, there were five cases of herpes virus infection, four non-herpes skin infections, and three cases of conjunctivitis. In the placebo group, seven non-herpes skin infections were reported.

Sanofi and Regeneron, who jointly developed dupilumab, plan to file for regulatory approval for dupilumab for PN “around the world” in the first half of this year, according to a press release.

“It’s great news and a step in the right direction,” Sarina Elmariah, MD, PhD, a dermatologist at Massachusetts General Hospital and instructor of dermatology at Harvard Medical School, both in Boston, told this news organization. She was not involved with the research.

“We’re finally starting to shed light on this condition and its pathogenesis,” she said. She noted that other potential therapeutics for PN are also in development. “It’s reflective of the fact that we are making strides in this area.”

Sanofi and Regeneron Pharmaceuticals sponsored the LIBERTY-PN PRIME2 trial. Dr. Yosipovitch has reported financial relationships with Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, and Trevi Therapeutics. Dr. Elmariah is on the advisory boards of Sanofi, Galderma, and Trevi Therapeutics.

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

BOSTON – Dupilumab, a human monoclonal IgG4 antibody, was an effective treatment for prurigo nodularis (PN), improving itching and skin lesions after 12 and 24 weeks of treatment, in a phase 3 trial presented at the American Academy of Dermatology 2022 Annual Meeting.

There are currently no Food and Drug Administration–approved systemic therapies for PN. Although several treatments for the disease are used off label for the condition, such as ultraviolet light therapy and immunosuppressive agents, moderate to severe PN is usually difficult to control, noted Gil Yosipovitch, MD, director of the Miami Itch Center at the University of Miami Miller School of Medicine, Florida. He led the research and presented the findings at the conference.

“Many dermatologists feel very uncomfortable dealing with these patients because they suffer from chronicity, they are miserable, and previously, the drugs didn’t work well,” Dr. Yosipovitch told this news organization. The results from this trial “are very promising,” he said. “It opens a new field of treatment for itchy conditions.”

The trial, named LIBERTY-PN PRIME2, enrolled patients aged 18-80 who had been living with PN for at least 3 months. Patients had at least 20 lesions at baseline as well as severe itch, defined as a score of 7 or greater on the Worst Itch Numerical Rating Scale (WI-NRS). The scale ranges from 0 (no itch) to 10 (worst itch imaginable). Participants also had a history of treatment failure with medium to super-potent topical corticosteroids (TCSs), or treatment with TCSs was not medically advisable for them.

The randomized, double-blinded study enrolled 160 adults with PN. Of those, 78 were assigned to the treatment arm and received a 600-mg loading dose of dupilumab, administered subcutaneously, followed by 300-mg doses every 2 weeks for 24 weeks; 82 patients were allocated to receive placebo.

During the study, 25 patients in the placebo arm discontinued treatment. In the treatment arm, one patient was not treated and two discontinued treatment due to lack of efficacy.

The primary endpoint of the study was a reduction of at least 4 points on the WI-NRS at 12 weeks. Secondary endpoints included at least a 4-point WI-NRS reduction at 24 weeks and clear to nearly clear skin, defined as having a score of 0 or 1 on the Investigator’s Global Assessment PN-Stage (IGN PN-S). The scale ranges from 0 (clear) to 4 (severe).

At 12 weeks, 37.2% of patients given dupilumab reported a reduction of at least 4 points in WI-NRS, compared with 22.0% of patients given placebo (P = .0216). By 24 weeks, 57.7% of adults who received dupilumab achieved a greater than or equal to 4-point reduction in WI-NRS, compared with 19.5% of those who received placebo (P < .0001). Additionally, 44.9% of participants in the treatment arm achieved a score of 0 or 1 on the IGA PN-S, compared with 15.9% of those in the placebo arm (P < .0001).

Forty-four participants who received dupilumab (57.1%) and 42 participants who received placebo (51.2%) reported at least one treatment-emergent adverse event (TEAE) during the study, though none of these events were serious. The most common TEAE in the study was headache, occurring in five patients taking placebo and four patients receiving dupilumab. In the dupilumab group, there were five cases of herpes virus infection, four non-herpes skin infections, and three cases of conjunctivitis. In the placebo group, seven non-herpes skin infections were reported.

Sanofi and Regeneron, who jointly developed dupilumab, plan to file for regulatory approval for dupilumab for PN “around the world” in the first half of this year, according to a press release.

“It’s great news and a step in the right direction,” Sarina Elmariah, MD, PhD, a dermatologist at Massachusetts General Hospital and instructor of dermatology at Harvard Medical School, both in Boston, told this news organization. She was not involved with the research.

“We’re finally starting to shed light on this condition and its pathogenesis,” she said. She noted that other potential therapeutics for PN are also in development. “It’s reflective of the fact that we are making strides in this area.”

Sanofi and Regeneron Pharmaceuticals sponsored the LIBERTY-PN PRIME2 trial. Dr. Yosipovitch has reported financial relationships with Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, and Trevi Therapeutics. Dr. Elmariah is on the advisory boards of Sanofi, Galderma, and Trevi Therapeutics.

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