Mixed Topics

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

The U.S. Senate voted mostly along party lines Wednesday to confirm Vice Adm. Vivek H. Murthy, MD, MBA, to serve as the 21st Surgeon General of the United States.

Seven Republicans – Bill Cassidy (La.), Susan Collins (Maine), Roger Marshall (Kan.), Susan Murkowski (Alaska), Rob Portman (Ohio), Mitt Romney (Utah), and Dan Sullivan (Alaska) – joined all the Democrats and independents in the 57-43 vote approving Dr. Murthy’s nomination.

Dr. Murthy, 43, previously served as the 19th Surgeon General, from December 2014 to April 2017, when he was asked to step down by President Donald J. Trump.

Surgeons General serve 4-year terms.

During his first tenure, Dr. Murthy issued the first-ever Surgeon General’s report on the crisis of addiction and issued a call to action to doctors to help battle the opioid crisis.

When Dr. Murthy was nominated by President-elect Joseph R. Biden Jr. in December, he was acting as cochair of the incoming administration’s COVID-19 transition advisory board.

Early in 2020, before the COVID-19 pandemic hit, Dr. Murthy published a timely book: “Together: The Healing Power of Human Connection in a Sometimes Lonely World”.

He earned his bachelor’s degree from Harvard and his MD and MBA degrees from Yale. He completed his internal medicine residency at Brigham and Women’s Hospital in Boston, where he also served as a hospitalist, and later joined Harvard Medical School as a faculty member in internal medicine.

He is married to Alice Chen, MD. The couple have two children.
 

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

The U.S. Senate voted mostly along party lines Wednesday to confirm Vice Adm. Vivek H. Murthy, MD, MBA, to serve as the 21st Surgeon General of the United States.

Seven Republicans – Bill Cassidy (La.), Susan Collins (Maine), Roger Marshall (Kan.), Susan Murkowski (Alaska), Rob Portman (Ohio), Mitt Romney (Utah), and Dan Sullivan (Alaska) – joined all the Democrats and independents in the 57-43 vote approving Dr. Murthy’s nomination.

Dr. Murthy, 43, previously served as the 19th Surgeon General, from December 2014 to April 2017, when he was asked to step down by President Donald J. Trump.

Surgeons General serve 4-year terms.

During his first tenure, Dr. Murthy issued the first-ever Surgeon General’s report on the crisis of addiction and issued a call to action to doctors to help battle the opioid crisis.

When Dr. Murthy was nominated by President-elect Joseph R. Biden Jr. in December, he was acting as cochair of the incoming administration’s COVID-19 transition advisory board.

Early in 2020, before the COVID-19 pandemic hit, Dr. Murthy published a timely book: “Together: The Healing Power of Human Connection in a Sometimes Lonely World”.

He earned his bachelor’s degree from Harvard and his MD and MBA degrees from Yale. He completed his internal medicine residency at Brigham and Women’s Hospital in Boston, where he also served as a hospitalist, and later joined Harvard Medical School as a faculty member in internal medicine.

He is married to Alice Chen, MD. The couple have two children.
 

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

The U.S. Senate voted mostly along party lines Wednesday to confirm Vice Adm. Vivek H. Murthy, MD, MBA, to serve as the 21st Surgeon General of the United States.

Seven Republicans – Bill Cassidy (La.), Susan Collins (Maine), Roger Marshall (Kan.), Susan Murkowski (Alaska), Rob Portman (Ohio), Mitt Romney (Utah), and Dan Sullivan (Alaska) – joined all the Democrats and independents in the 57-43 vote approving Dr. Murthy’s nomination.

Dr. Murthy, 43, previously served as the 19th Surgeon General, from December 2014 to April 2017, when he was asked to step down by President Donald J. Trump.

Surgeons General serve 4-year terms.

During his first tenure, Dr. Murthy issued the first-ever Surgeon General’s report on the crisis of addiction and issued a call to action to doctors to help battle the opioid crisis.

When Dr. Murthy was nominated by President-elect Joseph R. Biden Jr. in December, he was acting as cochair of the incoming administration’s COVID-19 transition advisory board.

Early in 2020, before the COVID-19 pandemic hit, Dr. Murthy published a timely book: “Together: The Healing Power of Human Connection in a Sometimes Lonely World”.

He earned his bachelor’s degree from Harvard and his MD and MBA degrees from Yale. He completed his internal medicine residency at Brigham and Women’s Hospital in Boston, where he also served as a hospitalist, and later joined Harvard Medical School as a faculty member in internal medicine.

He is married to Alice Chen, MD. The couple have two children.
 

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

Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.

ogichobanov/iStock/Getty Images Plus

In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.

“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.

For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.

Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.

The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
 

Oncologic indications one of two tracked cohorts

In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.

When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.

The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.

Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.

In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.

When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
 

Denosumab use greater in privately insured

In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .

In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.

Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.

In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.

Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.

There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”

Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.

Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.

Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.

ogichobanov/iStock/Getty Images Plus

In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.

“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.

For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.

Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.

The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
 

Oncologic indications one of two tracked cohorts

In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.

When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.

The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.

Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.

In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.

When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
 

Denosumab use greater in privately insured

In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .

In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.

Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.

In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.

Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.

There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”

Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.

Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.

Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.

ogichobanov/iStock/Getty Images Plus

In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.

“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.

For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.

Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.

The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
 

Oncologic indications one of two tracked cohorts

In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.

When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.

The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.

Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.

In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.

When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
 

Denosumab use greater in privately insured

In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .

In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.

Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.

In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.

Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.

There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”

Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.

Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.

One of the top research journals in the United States has placed its editor-in-chief on administrative leave pending the outcome of an investigation into a controversial podcast episode that critics labeled as racist.

The American Medical Association’s Joint Oversight Committee announced that Howard Bauchner, MD, is on leave beginning at the end of the day on March 25. Dr. Bauchner is the top editor at JAMA, the journal of the AMA.

“The decision to place the editor-in-chief on administrative leave neither implicates nor exonerates individuals and is standard operating procedure for such investigations,” the committee said in a statement.

More than 2,000 people signed a petition on Change.org calling for an investigation at JAMA over the February podcast episode, called “Structural Racism for Doctors: What Is It?”

Already, Edward H. Livingston, MD, the host of the podcast, has resigned as deputy editor of the journal.

During the podcast, Dr. Livingston, who is White, said, “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released in the week prior to his being on leave, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

This story will be updated.

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

One of the top research journals in the United States has placed its editor-in-chief on administrative leave pending the outcome of an investigation into a controversial podcast episode that critics labeled as racist.

The American Medical Association’s Joint Oversight Committee announced that Howard Bauchner, MD, is on leave beginning at the end of the day on March 25. Dr. Bauchner is the top editor at JAMA, the journal of the AMA.

“The decision to place the editor-in-chief on administrative leave neither implicates nor exonerates individuals and is standard operating procedure for such investigations,” the committee said in a statement.

More than 2,000 people signed a petition on Change.org calling for an investigation at JAMA over the February podcast episode, called “Structural Racism for Doctors: What Is It?”

Already, Edward H. Livingston, MD, the host of the podcast, has resigned as deputy editor of the journal.

During the podcast, Dr. Livingston, who is White, said, “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released in the week prior to his being on leave, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

This story will be updated.

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

One of the top research journals in the United States has placed its editor-in-chief on administrative leave pending the outcome of an investigation into a controversial podcast episode that critics labeled as racist.

The American Medical Association’s Joint Oversight Committee announced that Howard Bauchner, MD, is on leave beginning at the end of the day on March 25. Dr. Bauchner is the top editor at JAMA, the journal of the AMA.

“The decision to place the editor-in-chief on administrative leave neither implicates nor exonerates individuals and is standard operating procedure for such investigations,” the committee said in a statement.

More than 2,000 people signed a petition on Change.org calling for an investigation at JAMA over the February podcast episode, called “Structural Racism for Doctors: What Is It?”

Already, Edward H. Livingston, MD, the host of the podcast, has resigned as deputy editor of the journal.

During the podcast, Dr. Livingston, who is White, said, “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released in the week prior to his being on leave, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

This story will be updated.

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

I recently was contacted by my nurse to schedule follow-up for a patient of mine whose routine labs sent by his cardiologist showed a blood glucose of 48 and a potassium of 5.8. He did not have diabetes, was not on any medications that could cause hyperkalemia, and most importantly he was asymptomatic when the labs were drawn.

If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.

This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.

Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.¹ Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.²

Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.³ They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.

Low blood sugars caused by elevated WBCs in blood samples has been well described.⁴ It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.⁵ The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.

Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.⁶ This same issue has been seen in patients with extreme thrombocytosis.⁷Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.

2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.

3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.

4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.

5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.

6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.

7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.

I recently was contacted by my nurse to schedule follow-up for a patient of mine whose routine labs sent by his cardiologist showed a blood glucose of 48 and a potassium of 5.8. He did not have diabetes, was not on any medications that could cause hyperkalemia, and most importantly he was asymptomatic when the labs were drawn.

If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.

This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.

Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.¹ Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.²

Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.³ They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.

Low blood sugars caused by elevated WBCs in blood samples has been well described.⁴ It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.⁵ The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.

Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.⁶ This same issue has been seen in patients with extreme thrombocytosis.⁷Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.

2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.

3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.

4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.

5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.

6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.

7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.

I recently was contacted by my nurse to schedule follow-up for a patient of mine whose routine labs sent by his cardiologist showed a blood glucose of 48 and a potassium of 5.8. He did not have diabetes, was not on any medications that could cause hyperkalemia, and most importantly he was asymptomatic when the labs were drawn.

If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.

This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.

Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.¹ Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.²

Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.³ They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.

Low blood sugars caused by elevated WBCs in blood samples has been well described.⁴ It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.⁵ The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.

Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.⁶ This same issue has been seen in patients with extreme thrombocytosis.⁷Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.

2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.

3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.

4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.

5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.

6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.

7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.

Patients with hypothyroidism treated with the three most common pharmacologic strategies of levothyroxine (LT4) alone, LT4 in combination with triiodothyronine (T3), or desiccated thyroid extract showed no differences in thyroid symptoms or secondary outcomes in a double-blind, randomized study.

Sebastian Kaulitzki/Fotolia

“There are now proven good treatment options for the more than 1 in 10 patients with hypothyroidism who continue to experience symptoms of fatigue, mental fogginess, weight gain, and other symptoms despite taking levothyroxine,” first author Thanh Duc Hoang, DO, an endocrinologist at the Walter Reed National Military Medical Center, in Bethesda, Md., said in a press statement.

The findings were presented at the annual meeting of the Endocrine Society.

Commenting on the study, Alan P. Farwell, MD, said these new results are a valuable contribution to the understanding of treatment effects. “I think this is an interesting and important study and further studies are needed to clarify the optimal way to treat hypothyroidism,” said Dr. Farwell, who is director of endocrine clinics at Boston University.

Importantly, “the findings are different than studies where the patients are aware of what medication they are receiving,” he stressed in an interview, underscoring the importance of the double-blind design of the trial.

But Anne Cappola, MD, of the University of Pennsylvania, Philadelphia, pointed out that “the study was small and unlikely to have the statistical power to detect differences that could have been clinically important.”

Nevertheless, she too agreed that the double-blind study design is key: “My experience with patients is [the effects] are affected by patients’ perceptions about their thyroid medication. That is why studies designed so that patients do not know which treatment they are receiving are so important in this area.”
 

Randomized, double-blind comparison

Prior to the widespread availability of the current gold standard hypothyroidism treatment of LT4, the condition was typically treated with desiccated (animal) thyroid extract. And with many patients continuing to have a preference for this therapeutic approach, it is still commonly used.

Additionally, some patients treated with LT4 alone report greater improvements in symptoms with the addition of T3 – despite studies showing no benefits from the two together – leading to many clinicians commonly trying the combination approach.

To compare the efficacy of the three approaches in a prospective, double-blind, cross-over fashion, 75 patients received three therapeutic approaches each for 3 months: desiccated thyroid extract, an LT4/T3 combination, or LT4 alone.

After each 3-month treatment, patients completed a 36-point thyroid symptom questionnaire.

There was no significant differences in symptom relief, the primary outcome, between the three treatments (P = .32).

Overall, 45% of patients indicated they preferred desiccated thyroid as their first choice of treatment, 32% preferred LT4/T3 as their first choice, and 23% preferred LT4 alone.

For the secondary endpoints of weight, general health, depression (assessed using the Beck Depression Inventory), memory (Wechsler Memory Scale), lipids, and thyroid function, again, there were no significant differences between groups in any of the measures.
 

When switched to desiccated thyroid, many felt ‘much better’

A further exploratory analysis revealed that those who experienced symptoms while taking LT4 alone reported greater alleviation of symptoms with the other two treatments.

“As a whole group, there was no significant difference between the three treatment arms,” Dr. Hoang explained in an interview.

“However, with the subgroup analysis based on the scores of symptom questionnaires, we found that symptomatic patients on LT4 improved while being treated with LT4/T3 or desiccated thyroid,” he said.

Reports of improvements in switching to desiccated thyroid were notable, Dr. Hoang added. “Many patients when switched from LT4 to desiccated thyroid extract said they felt much better, [with] more energy, less mental fogginess, a better outlook, less flair of lupus symptoms, easier to lose weight, etc.”

The study also showed more patients with Hashimoto’s disease preferred desiccated thyroid extract and LT4/T3, compared with LT4 alone, however, the differences were not significant.
 

Treatment adjustments a helpful first step

Dr. Farwell noted that his approach when patients are still reporting symptoms despite LT4 treatment is to first try tweaking the dose.

“In my own practice, I prefer to adjust LT4 dosing first, and on occasion add T3, with a goal of getting both hormone levels in the upper half of the normal range,” he said. “I find that to be a better approach than desiccated thyroid extract. T3 should be taken twice a day due to its half-life.”

The approach is generally successful, he added. “Even those that come in asking for desiccated thyroid extract whom I am able to convince to try LT4/T3 end up being happy with their treatment in the end.

“The key is that you need to spend time discussing the options with patients and come to a consensus as to the therapy that will best resolve their symptoms and that they are most comfortable with,” he concluded.

In response to mounting evidence of different hypothyroidism treatment responses according to various subgroups of patients, experts recently called for the initiation of more thorough clinical trials on the issue of combination therapy, as recently reported by this news organization.

Dr. Hoang reported being a speaker for Acella Pharmaceuticals. Dr. Farwell and Dr. Cappola reported no relevant financial relationships.

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

Patients with hypothyroidism treated with the three most common pharmacologic strategies of levothyroxine (LT4) alone, LT4 in combination with triiodothyronine (T3), or desiccated thyroid extract showed no differences in thyroid symptoms or secondary outcomes in a double-blind, randomized study.

Sebastian Kaulitzki/Fotolia

“There are now proven good treatment options for the more than 1 in 10 patients with hypothyroidism who continue to experience symptoms of fatigue, mental fogginess, weight gain, and other symptoms despite taking levothyroxine,” first author Thanh Duc Hoang, DO, an endocrinologist at the Walter Reed National Military Medical Center, in Bethesda, Md., said in a press statement.

The findings were presented at the annual meeting of the Endocrine Society.

Commenting on the study, Alan P. Farwell, MD, said these new results are a valuable contribution to the understanding of treatment effects. “I think this is an interesting and important study and further studies are needed to clarify the optimal way to treat hypothyroidism,” said Dr. Farwell, who is director of endocrine clinics at Boston University.

Importantly, “the findings are different than studies where the patients are aware of what medication they are receiving,” he stressed in an interview, underscoring the importance of the double-blind design of the trial.

But Anne Cappola, MD, of the University of Pennsylvania, Philadelphia, pointed out that “the study was small and unlikely to have the statistical power to detect differences that could have been clinically important.”

Nevertheless, she too agreed that the double-blind study design is key: “My experience with patients is [the effects] are affected by patients’ perceptions about their thyroid medication. That is why studies designed so that patients do not know which treatment they are receiving are so important in this area.”
 

Randomized, double-blind comparison

Prior to the widespread availability of the current gold standard hypothyroidism treatment of LT4, the condition was typically treated with desiccated (animal) thyroid extract. And with many patients continuing to have a preference for this therapeutic approach, it is still commonly used.

Additionally, some patients treated with LT4 alone report greater improvements in symptoms with the addition of T3 – despite studies showing no benefits from the two together – leading to many clinicians commonly trying the combination approach.

To compare the efficacy of the three approaches in a prospective, double-blind, cross-over fashion, 75 patients received three therapeutic approaches each for 3 months: desiccated thyroid extract, an LT4/T3 combination, or LT4 alone.

After each 3-month treatment, patients completed a 36-point thyroid symptom questionnaire.

There was no significant differences in symptom relief, the primary outcome, between the three treatments (P = .32).

Overall, 45% of patients indicated they preferred desiccated thyroid as their first choice of treatment, 32% preferred LT4/T3 as their first choice, and 23% preferred LT4 alone.

For the secondary endpoints of weight, general health, depression (assessed using the Beck Depression Inventory), memory (Wechsler Memory Scale), lipids, and thyroid function, again, there were no significant differences between groups in any of the measures.
 

When switched to desiccated thyroid, many felt ‘much better’

A further exploratory analysis revealed that those who experienced symptoms while taking LT4 alone reported greater alleviation of symptoms with the other two treatments.

“As a whole group, there was no significant difference between the three treatment arms,” Dr. Hoang explained in an interview.

“However, with the subgroup analysis based on the scores of symptom questionnaires, we found that symptomatic patients on LT4 improved while being treated with LT4/T3 or desiccated thyroid,” he said.

Reports of improvements in switching to desiccated thyroid were notable, Dr. Hoang added. “Many patients when switched from LT4 to desiccated thyroid extract said they felt much better, [with] more energy, less mental fogginess, a better outlook, less flair of lupus symptoms, easier to lose weight, etc.”

The study also showed more patients with Hashimoto’s disease preferred desiccated thyroid extract and LT4/T3, compared with LT4 alone, however, the differences were not significant.
 

Treatment adjustments a helpful first step

Dr. Farwell noted that his approach when patients are still reporting symptoms despite LT4 treatment is to first try tweaking the dose.

“In my own practice, I prefer to adjust LT4 dosing first, and on occasion add T3, with a goal of getting both hormone levels in the upper half of the normal range,” he said. “I find that to be a better approach than desiccated thyroid extract. T3 should be taken twice a day due to its half-life.”

The approach is generally successful, he added. “Even those that come in asking for desiccated thyroid extract whom I am able to convince to try LT4/T3 end up being happy with their treatment in the end.

“The key is that you need to spend time discussing the options with patients and come to a consensus as to the therapy that will best resolve their symptoms and that they are most comfortable with,” he concluded.

In response to mounting evidence of different hypothyroidism treatment responses according to various subgroups of patients, experts recently called for the initiation of more thorough clinical trials on the issue of combination therapy, as recently reported by this news organization.

Dr. Hoang reported being a speaker for Acella Pharmaceuticals. Dr. Farwell and Dr. Cappola reported no relevant financial relationships.

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

Patients with hypothyroidism treated with the three most common pharmacologic strategies of levothyroxine (LT4) alone, LT4 in combination with triiodothyronine (T3), or desiccated thyroid extract showed no differences in thyroid symptoms or secondary outcomes in a double-blind, randomized study.

Sebastian Kaulitzki/Fotolia

“There are now proven good treatment options for the more than 1 in 10 patients with hypothyroidism who continue to experience symptoms of fatigue, mental fogginess, weight gain, and other symptoms despite taking levothyroxine,” first author Thanh Duc Hoang, DO, an endocrinologist at the Walter Reed National Military Medical Center, in Bethesda, Md., said in a press statement.

The findings were presented at the annual meeting of the Endocrine Society.

Commenting on the study, Alan P. Farwell, MD, said these new results are a valuable contribution to the understanding of treatment effects. “I think this is an interesting and important study and further studies are needed to clarify the optimal way to treat hypothyroidism,” said Dr. Farwell, who is director of endocrine clinics at Boston University.

Importantly, “the findings are different than studies where the patients are aware of what medication they are receiving,” he stressed in an interview, underscoring the importance of the double-blind design of the trial.

But Anne Cappola, MD, of the University of Pennsylvania, Philadelphia, pointed out that “the study was small and unlikely to have the statistical power to detect differences that could have been clinically important.”

Nevertheless, she too agreed that the double-blind study design is key: “My experience with patients is [the effects] are affected by patients’ perceptions about their thyroid medication. That is why studies designed so that patients do not know which treatment they are receiving are so important in this area.”
 

Randomized, double-blind comparison

Prior to the widespread availability of the current gold standard hypothyroidism treatment of LT4, the condition was typically treated with desiccated (animal) thyroid extract. And with many patients continuing to have a preference for this therapeutic approach, it is still commonly used.

Additionally, some patients treated with LT4 alone report greater improvements in symptoms with the addition of T3 – despite studies showing no benefits from the two together – leading to many clinicians commonly trying the combination approach.

To compare the efficacy of the three approaches in a prospective, double-blind, cross-over fashion, 75 patients received three therapeutic approaches each for 3 months: desiccated thyroid extract, an LT4/T3 combination, or LT4 alone.

After each 3-month treatment, patients completed a 36-point thyroid symptom questionnaire.

There was no significant differences in symptom relief, the primary outcome, between the three treatments (P = .32).

Overall, 45% of patients indicated they preferred desiccated thyroid as their first choice of treatment, 32% preferred LT4/T3 as their first choice, and 23% preferred LT4 alone.

For the secondary endpoints of weight, general health, depression (assessed using the Beck Depression Inventory), memory (Wechsler Memory Scale), lipids, and thyroid function, again, there were no significant differences between groups in any of the measures.
 

When switched to desiccated thyroid, many felt ‘much better’

A further exploratory analysis revealed that those who experienced symptoms while taking LT4 alone reported greater alleviation of symptoms with the other two treatments.

“As a whole group, there was no significant difference between the three treatment arms,” Dr. Hoang explained in an interview.

“However, with the subgroup analysis based on the scores of symptom questionnaires, we found that symptomatic patients on LT4 improved while being treated with LT4/T3 or desiccated thyroid,” he said.

Reports of improvements in switching to desiccated thyroid were notable, Dr. Hoang added. “Many patients when switched from LT4 to desiccated thyroid extract said they felt much better, [with] more energy, less mental fogginess, a better outlook, less flair of lupus symptoms, easier to lose weight, etc.”

The study also showed more patients with Hashimoto’s disease preferred desiccated thyroid extract and LT4/T3, compared with LT4 alone, however, the differences were not significant.
 

Treatment adjustments a helpful first step

Dr. Farwell noted that his approach when patients are still reporting symptoms despite LT4 treatment is to first try tweaking the dose.

“In my own practice, I prefer to adjust LT4 dosing first, and on occasion add T3, with a goal of getting both hormone levels in the upper half of the normal range,” he said. “I find that to be a better approach than desiccated thyroid extract. T3 should be taken twice a day due to its half-life.”

The approach is generally successful, he added. “Even those that come in asking for desiccated thyroid extract whom I am able to convince to try LT4/T3 end up being happy with their treatment in the end.

“The key is that you need to spend time discussing the options with patients and come to a consensus as to the therapy that will best resolve their symptoms and that they are most comfortable with,” he concluded.

In response to mounting evidence of different hypothyroidism treatment responses according to various subgroups of patients, experts recently called for the initiation of more thorough clinical trials on the issue of combination therapy, as recently reported by this news organization.

Dr. Hoang reported being a speaker for Acella Pharmaceuticals. Dr. Farwell and Dr. Cappola reported no relevant financial relationships.

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

Metyrapone, an inhibitor of endogenous adrenal corticosteroid synthesis currently used in U.S. practice to test adrenocorticotropic hormone (ACTH) function, was safe and effective for treating endogenous Cushing’s syndrome in a multicenter, open-label, single-arm study of 50 patients, the first prospective test of metyrapone (Metopirone) as a therapeutic agent.

Treatment with metyrapone for 12 weeks normalized mean levels of urinary free cortisol (UFC) in 23 of the 49 patients (47%) in the efficacy analysis, and cut pretreatment mean UFC levels by at least 50% in another 16 patients (33%). Treatment also improved clinical signs of hypercortisolism, associated comorbidities, and quality of life, and was well tolerated, Lynnette K. Nieman, MD, said at the annual meeting of the Endocrine Society.

“This prospective study confirms that metyrapone is effective, has a rapid onset of action, and is a safe medical treatment for endogenous Cushing’s syndrome,” declared Dr. Nieman, chief of the endocrinology consultation service of the National Institutes of Health Clinical Center in Bethesda, Md.

The study included a 24-week extension phase of continued metyrapone treatment in patients whose mean UFC level fell to less than two times the upper limit of normal (ULN), but Dr. Nieman did not report results from this extension.
 

Confirmation of off-label and European experience

“This was the first prospective study of metyrapone, albeit a small study and with only short-term data presented. It confirms what we have known from its off label use in the U.S. and retrospective studies in the U.K. and Europe: Metyrapone normalizes mean UFC in approximately half of patients. Probably with more aggressive up titration efficacy will have been even higher, but of course with the trade-off of adrenal insufficiency,” said Maria Fleseriu, MD, professor and director of the pituitary center at Oregon Health & Science University in Portland, who was not involved with the study.

“Longer-term data from this prospective study is clearly needed to evaluate for possible loss of response, as well as adverse events related to precursors accumulation. We also need data on tumor size with long-term use in patients with Cushing’s disease, “Dr. Fleseriu added in an interview.

“Metyrapone, an 11-hydroxylase inhibitor, is not [Food and Drug Administration–approved for therapy] and thus it will be hard for it to become a first-line medical therapy,” she continued. “Furthermore, multiple times a day administration is not ideal for most patients; however if metyrapone is readily available and cheaper than other drugs, its use might increase over time. Hirsutism in women (though not all women develop this) and hypertension could be issues with long-term use,” she cautioned.

“We have used metyrapone off label for many years. It has a rapid onset of action, and we also have experience using it in combination therapy with ketoconazole, especially in patients with severe Cushing’s, although ketoconazole is not [FDA] approved for Cushing’s syndrome, and all combination therapies are off-label, too,” Dr. Fleseriu noted.

Metyrapone is approved by the European Medicines Agency for treating Cushing’s syndrome based “on observational, retrospective studies published over more than 50 years,” according to Dr. Nieman. The drug has FDA approval only for diagnostic purposes.

The PROMPT (Effects of Metyrapone in Patients With Endogenous Cushing’s Syndrome) study enrolled patients in eight European countries who were newly diagnosed with endogenous Cushing’s syndrome of any etiology. The study excluded patients with an advanced adrenal carcinoma, as well as patients with recurrent or persistent Cushing’s disease following transsphenoidal surgery. Patients also needed three 24-hour measures of UFC that were at least 50% above the ULN (165 nmol/24 hours).

The average age of the patients was 46 years; 69% were women, 90% had Cushing’s disease, and 8% had ectopic ACTH secretion. The average time from initial symptom onset was 4 years. Sixty-one percent had a history of pituitary surgery, 69% were hypertensive, 43% had diabetes or glucose intolerance, and 41% had osteoporosis. The median mean UFC at entry was 570 nmol/24 hours, which is 3.5 times the ULN, and ranged from 291 to 8,476 nmol/24 hours.

Patients began on a metyrapone dosage of 750 mg/day unless their mean UFC exceeded 5 times the ULN, in which case the dosage doubled to 1,500 mg/day. During the 12-week period, clinicians up- or down-titrated the dosage to ideally achieve a UFC less than the ULN while maintaining serum cortisol levels of 7-12 mcg/dL to preclude adrenal insufficiency effects. The median dosage at the end of 12 weeks was 1,500 mg/day, and ranged from 250 to 5,500 mg/day. One of the 50 patients dropped out because of an unrelated acute medical condition, and two patients underwent pituitary surgery despite a response to metyrapone and were included in the efficacy analysis.

After the first week on treatment, patients had a median 49% cut from their baseline UFC level, and after 12 weeks this rose to a median 74% cut from baseline. The study’s primary endpoint was normalization of UFC after 12 weeks, which occurred in 47% of patients, while 22% had a normal level in a late-night salivary cortisol measurement.

Two-thirds of patients had an improvement or resolution of their signs and symptoms, on average quality of life scores improved, median systolic and diastolic blood pressures decreased by 4-5 mm Hg, and average A1c levels were stable, but the mean cholesterol level decreased significantly, and testosterone levels rose significantly in women.

Proper dose titration makes a difference

Adverse events occurred in 26 of the 50 patients (52%) who received any treatment; 1 patient had a serious adverse event, 7 patients required a dosage adjustment because of adverse events, and 6 patients stopped treatment. The most common adverse events were gastrointestinal – nausea in 24% and decreased appetite in 18% – as well as mild symptoms consistent with adrenal insufficiency such as fatigue and headache. Six patients (12%) were identified with reversible adrenal insufficiency, and no patients complained of worsening acne or hirsutism.

“I think the adverse events are a function of [less than optimal] dose titration and variability in UFC levels,” said Dr. Nieman.

This test of metyrapone’s efficacy comes a year after the FDA approved osilodrostat (Isturisa) for treating Cushing’s disease (but not Cushing’s syndrome). Like metyrapone, osilodrostat controls cortisol overproduction by blocking the enzyme 11-beta-hydroxylase and preventing cortisol synthesis, and osilodrostat was the first agent with these properties to receive an FDA label for therapy.

Osilodrostat “is the only adrenal steroidogenesis inhibitor assessed in randomized controlled long-term trials – over 200 patients with Cushing’s disease – and it has been shown to be highly effective at maintaining normal urinary free cortisol in large majority of patients with Cushing’s disease, as well as Cushing’s syndrome in a study in Japan. Adrenal insufficiency was high [with osilodrostat], especially with the high dose in the trial with forced uptitration. In my clinical practice I have noticed less adrenal insufficiency, but I use much slower drug titration,” said Dr. Fleseriu.

“I think these drugs [metyrapone and osilodrostat] are relatively equivalent,” Dr. Nieman said during discussion of her report. “One nonmedical judgment will be cost,” she added. “Everyone is looking forward to what the pricing structure will be for the new drugs.”

Dr. Fleseriu noted that “for most patients, surgery is first-line therapy, and rarely medication is an alternative first option, especially for Cushing’s disease. However, medical therapy is essential in the management of patients with Cushing’s syndrome when curative surgery fails, surgery is not feasible, when a patient is awaiting radiation’s effect, and for recurrent cases of Cushing’s syndrome.”

PROMPT was sponsored by HRA Pharma, the company that markets metyrapone. Dr. Nieman had no disclosures, but several of her associates on the study are HRA employees. Dr. Fleseriu has been a consultant to Novartis, Recordati, Sparrow, and Strongbridge.

[email protected]

Metyrapone, an inhibitor of endogenous adrenal corticosteroid synthesis currently used in U.S. practice to test adrenocorticotropic hormone (ACTH) function, was safe and effective for treating endogenous Cushing’s syndrome in a multicenter, open-label, single-arm study of 50 patients, the first prospective test of metyrapone (Metopirone) as a therapeutic agent.

Treatment with metyrapone for 12 weeks normalized mean levels of urinary free cortisol (UFC) in 23 of the 49 patients (47%) in the efficacy analysis, and cut pretreatment mean UFC levels by at least 50% in another 16 patients (33%). Treatment also improved clinical signs of hypercortisolism, associated comorbidities, and quality of life, and was well tolerated, Lynnette K. Nieman, MD, said at the annual meeting of the Endocrine Society.

“This prospective study confirms that metyrapone is effective, has a rapid onset of action, and is a safe medical treatment for endogenous Cushing’s syndrome,” declared Dr. Nieman, chief of the endocrinology consultation service of the National Institutes of Health Clinical Center in Bethesda, Md.

The study included a 24-week extension phase of continued metyrapone treatment in patients whose mean UFC level fell to less than two times the upper limit of normal (ULN), but Dr. Nieman did not report results from this extension.
 

Confirmation of off-label and European experience

“This was the first prospective study of metyrapone, albeit a small study and with only short-term data presented. It confirms what we have known from its off label use in the U.S. and retrospective studies in the U.K. and Europe: Metyrapone normalizes mean UFC in approximately half of patients. Probably with more aggressive up titration efficacy will have been even higher, but of course with the trade-off of adrenal insufficiency,” said Maria Fleseriu, MD, professor and director of the pituitary center at Oregon Health & Science University in Portland, who was not involved with the study.

“Longer-term data from this prospective study is clearly needed to evaluate for possible loss of response, as well as adverse events related to precursors accumulation. We also need data on tumor size with long-term use in patients with Cushing’s disease, “Dr. Fleseriu added in an interview.

“Metyrapone, an 11-hydroxylase inhibitor, is not [Food and Drug Administration–approved for therapy] and thus it will be hard for it to become a first-line medical therapy,” she continued. “Furthermore, multiple times a day administration is not ideal for most patients; however if metyrapone is readily available and cheaper than other drugs, its use might increase over time. Hirsutism in women (though not all women develop this) and hypertension could be issues with long-term use,” she cautioned.

“We have used metyrapone off label for many years. It has a rapid onset of action, and we also have experience using it in combination therapy with ketoconazole, especially in patients with severe Cushing’s, although ketoconazole is not [FDA] approved for Cushing’s syndrome, and all combination therapies are off-label, too,” Dr. Fleseriu noted.

Metyrapone is approved by the European Medicines Agency for treating Cushing’s syndrome based “on observational, retrospective studies published over more than 50 years,” according to Dr. Nieman. The drug has FDA approval only for diagnostic purposes.

The PROMPT (Effects of Metyrapone in Patients With Endogenous Cushing’s Syndrome) study enrolled patients in eight European countries who were newly diagnosed with endogenous Cushing’s syndrome of any etiology. The study excluded patients with an advanced adrenal carcinoma, as well as patients with recurrent or persistent Cushing’s disease following transsphenoidal surgery. Patients also needed three 24-hour measures of UFC that were at least 50% above the ULN (165 nmol/24 hours).

The average age of the patients was 46 years; 69% were women, 90% had Cushing’s disease, and 8% had ectopic ACTH secretion. The average time from initial symptom onset was 4 years. Sixty-one percent had a history of pituitary surgery, 69% were hypertensive, 43% had diabetes or glucose intolerance, and 41% had osteoporosis. The median mean UFC at entry was 570 nmol/24 hours, which is 3.5 times the ULN, and ranged from 291 to 8,476 nmol/24 hours.

Patients began on a metyrapone dosage of 750 mg/day unless their mean UFC exceeded 5 times the ULN, in which case the dosage doubled to 1,500 mg/day. During the 12-week period, clinicians up- or down-titrated the dosage to ideally achieve a UFC less than the ULN while maintaining serum cortisol levels of 7-12 mcg/dL to preclude adrenal insufficiency effects. The median dosage at the end of 12 weeks was 1,500 mg/day, and ranged from 250 to 5,500 mg/day. One of the 50 patients dropped out because of an unrelated acute medical condition, and two patients underwent pituitary surgery despite a response to metyrapone and were included in the efficacy analysis.

After the first week on treatment, patients had a median 49% cut from their baseline UFC level, and after 12 weeks this rose to a median 74% cut from baseline. The study’s primary endpoint was normalization of UFC after 12 weeks, which occurred in 47% of patients, while 22% had a normal level in a late-night salivary cortisol measurement.

Two-thirds of patients had an improvement or resolution of their signs and symptoms, on average quality of life scores improved, median systolic and diastolic blood pressures decreased by 4-5 mm Hg, and average A1c levels were stable, but the mean cholesterol level decreased significantly, and testosterone levels rose significantly in women.

Proper dose titration makes a difference

Adverse events occurred in 26 of the 50 patients (52%) who received any treatment; 1 patient had a serious adverse event, 7 patients required a dosage adjustment because of adverse events, and 6 patients stopped treatment. The most common adverse events were gastrointestinal – nausea in 24% and decreased appetite in 18% – as well as mild symptoms consistent with adrenal insufficiency such as fatigue and headache. Six patients (12%) were identified with reversible adrenal insufficiency, and no patients complained of worsening acne or hirsutism.

“I think the adverse events are a function of [less than optimal] dose titration and variability in UFC levels,” said Dr. Nieman.

This test of metyrapone’s efficacy comes a year after the FDA approved osilodrostat (Isturisa) for treating Cushing’s disease (but not Cushing’s syndrome). Like metyrapone, osilodrostat controls cortisol overproduction by blocking the enzyme 11-beta-hydroxylase and preventing cortisol synthesis, and osilodrostat was the first agent with these properties to receive an FDA label for therapy.

Osilodrostat “is the only adrenal steroidogenesis inhibitor assessed in randomized controlled long-term trials – over 200 patients with Cushing’s disease – and it has been shown to be highly effective at maintaining normal urinary free cortisol in large majority of patients with Cushing’s disease, as well as Cushing’s syndrome in a study in Japan. Adrenal insufficiency was high [with osilodrostat], especially with the high dose in the trial with forced uptitration. In my clinical practice I have noticed less adrenal insufficiency, but I use much slower drug titration,” said Dr. Fleseriu.

“I think these drugs [metyrapone and osilodrostat] are relatively equivalent,” Dr. Nieman said during discussion of her report. “One nonmedical judgment will be cost,” she added. “Everyone is looking forward to what the pricing structure will be for the new drugs.”

Dr. Fleseriu noted that “for most patients, surgery is first-line therapy, and rarely medication is an alternative first option, especially for Cushing’s disease. However, medical therapy is essential in the management of patients with Cushing’s syndrome when curative surgery fails, surgery is not feasible, when a patient is awaiting radiation’s effect, and for recurrent cases of Cushing’s syndrome.”

PROMPT was sponsored by HRA Pharma, the company that markets metyrapone. Dr. Nieman had no disclosures, but several of her associates on the study are HRA employees. Dr. Fleseriu has been a consultant to Novartis, Recordati, Sparrow, and Strongbridge.

[email protected]

Metyrapone, an inhibitor of endogenous adrenal corticosteroid synthesis currently used in U.S. practice to test adrenocorticotropic hormone (ACTH) function, was safe and effective for treating endogenous Cushing’s syndrome in a multicenter, open-label, single-arm study of 50 patients, the first prospective test of metyrapone (Metopirone) as a therapeutic agent.

Treatment with metyrapone for 12 weeks normalized mean levels of urinary free cortisol (UFC) in 23 of the 49 patients (47%) in the efficacy analysis, and cut pretreatment mean UFC levels by at least 50% in another 16 patients (33%). Treatment also improved clinical signs of hypercortisolism, associated comorbidities, and quality of life, and was well tolerated, Lynnette K. Nieman, MD, said at the annual meeting of the Endocrine Society.

“This prospective study confirms that metyrapone is effective, has a rapid onset of action, and is a safe medical treatment for endogenous Cushing’s syndrome,” declared Dr. Nieman, chief of the endocrinology consultation service of the National Institutes of Health Clinical Center in Bethesda, Md.

The study included a 24-week extension phase of continued metyrapone treatment in patients whose mean UFC level fell to less than two times the upper limit of normal (ULN), but Dr. Nieman did not report results from this extension.
 

Confirmation of off-label and European experience

“This was the first prospective study of metyrapone, albeit a small study and with only short-term data presented. It confirms what we have known from its off label use in the U.S. and retrospective studies in the U.K. and Europe: Metyrapone normalizes mean UFC in approximately half of patients. Probably with more aggressive up titration efficacy will have been even higher, but of course with the trade-off of adrenal insufficiency,” said Maria Fleseriu, MD, professor and director of the pituitary center at Oregon Health & Science University in Portland, who was not involved with the study.

“Longer-term data from this prospective study is clearly needed to evaluate for possible loss of response, as well as adverse events related to precursors accumulation. We also need data on tumor size with long-term use in patients with Cushing’s disease, “Dr. Fleseriu added in an interview.

“Metyrapone, an 11-hydroxylase inhibitor, is not [Food and Drug Administration–approved for therapy] and thus it will be hard for it to become a first-line medical therapy,” she continued. “Furthermore, multiple times a day administration is not ideal for most patients; however if metyrapone is readily available and cheaper than other drugs, its use might increase over time. Hirsutism in women (though not all women develop this) and hypertension could be issues with long-term use,” she cautioned.

“We have used metyrapone off label for many years. It has a rapid onset of action, and we also have experience using it in combination therapy with ketoconazole, especially in patients with severe Cushing’s, although ketoconazole is not [FDA] approved for Cushing’s syndrome, and all combination therapies are off-label, too,” Dr. Fleseriu noted.

Metyrapone is approved by the European Medicines Agency for treating Cushing’s syndrome based “on observational, retrospective studies published over more than 50 years,” according to Dr. Nieman. The drug has FDA approval only for diagnostic purposes.

The PROMPT (Effects of Metyrapone in Patients With Endogenous Cushing’s Syndrome) study enrolled patients in eight European countries who were newly diagnosed with endogenous Cushing’s syndrome of any etiology. The study excluded patients with an advanced adrenal carcinoma, as well as patients with recurrent or persistent Cushing’s disease following transsphenoidal surgery. Patients also needed three 24-hour measures of UFC that were at least 50% above the ULN (165 nmol/24 hours).

The average age of the patients was 46 years; 69% were women, 90% had Cushing’s disease, and 8% had ectopic ACTH secretion. The average time from initial symptom onset was 4 years. Sixty-one percent had a history of pituitary surgery, 69% were hypertensive, 43% had diabetes or glucose intolerance, and 41% had osteoporosis. The median mean UFC at entry was 570 nmol/24 hours, which is 3.5 times the ULN, and ranged from 291 to 8,476 nmol/24 hours.

Patients began on a metyrapone dosage of 750 mg/day unless their mean UFC exceeded 5 times the ULN, in which case the dosage doubled to 1,500 mg/day. During the 12-week period, clinicians up- or down-titrated the dosage to ideally achieve a UFC less than the ULN while maintaining serum cortisol levels of 7-12 mcg/dL to preclude adrenal insufficiency effects. The median dosage at the end of 12 weeks was 1,500 mg/day, and ranged from 250 to 5,500 mg/day. One of the 50 patients dropped out because of an unrelated acute medical condition, and two patients underwent pituitary surgery despite a response to metyrapone and were included in the efficacy analysis.

After the first week on treatment, patients had a median 49% cut from their baseline UFC level, and after 12 weeks this rose to a median 74% cut from baseline. The study’s primary endpoint was normalization of UFC after 12 weeks, which occurred in 47% of patients, while 22% had a normal level in a late-night salivary cortisol measurement.

Two-thirds of patients had an improvement or resolution of their signs and symptoms, on average quality of life scores improved, median systolic and diastolic blood pressures decreased by 4-5 mm Hg, and average A1c levels were stable, but the mean cholesterol level decreased significantly, and testosterone levels rose significantly in women.

Proper dose titration makes a difference

Adverse events occurred in 26 of the 50 patients (52%) who received any treatment; 1 patient had a serious adverse event, 7 patients required a dosage adjustment because of adverse events, and 6 patients stopped treatment. The most common adverse events were gastrointestinal – nausea in 24% and decreased appetite in 18% – as well as mild symptoms consistent with adrenal insufficiency such as fatigue and headache. Six patients (12%) were identified with reversible adrenal insufficiency, and no patients complained of worsening acne or hirsutism.

“I think the adverse events are a function of [less than optimal] dose titration and variability in UFC levels,” said Dr. Nieman.

This test of metyrapone’s efficacy comes a year after the FDA approved osilodrostat (Isturisa) for treating Cushing’s disease (but not Cushing’s syndrome). Like metyrapone, osilodrostat controls cortisol overproduction by blocking the enzyme 11-beta-hydroxylase and preventing cortisol synthesis, and osilodrostat was the first agent with these properties to receive an FDA label for therapy.

Osilodrostat “is the only adrenal steroidogenesis inhibitor assessed in randomized controlled long-term trials – over 200 patients with Cushing’s disease – and it has been shown to be highly effective at maintaining normal urinary free cortisol in large majority of patients with Cushing’s disease, as well as Cushing’s syndrome in a study in Japan. Adrenal insufficiency was high [with osilodrostat], especially with the high dose in the trial with forced uptitration. In my clinical practice I have noticed less adrenal insufficiency, but I use much slower drug titration,” said Dr. Fleseriu.

“I think these drugs [metyrapone and osilodrostat] are relatively equivalent,” Dr. Nieman said during discussion of her report. “One nonmedical judgment will be cost,” she added. “Everyone is looking forward to what the pricing structure will be for the new drugs.”

Dr. Fleseriu noted that “for most patients, surgery is first-line therapy, and rarely medication is an alternative first option, especially for Cushing’s disease. However, medical therapy is essential in the management of patients with Cushing’s syndrome when curative surgery fails, surgery is not feasible, when a patient is awaiting radiation’s effect, and for recurrent cases of Cushing’s syndrome.”

PROMPT was sponsored by HRA Pharma, the company that markets metyrapone. Dr. Nieman had no disclosures, but several of her associates on the study are HRA employees. Dr. Fleseriu has been a consultant to Novartis, Recordati, Sparrow, and Strongbridge.

[email protected]

Each year in the month of March, advocates, physicians, and health care educators come together to promote the importance of colorectal cancer screening during Colorectal Cancer Awareness Month. As independent GI physicians, we work within our communities to promote colorectal screening year-round.

We also understand that our education efforts do not end with the people in our community who need to be screened. Independent GI practices also engage with primary care physicians who often initiate conversations about available screening tests and when people should be screened.

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States.¹ It is expected to kill more than 50,000 Americans this year alone.² This is why screening for colorectal cancer is so important. The American Cancer Society recommends screening for all average-risk patients aged 45-75 years.³

The good news? If caught early, the survival rate is very high. In fact, when caught early, the five-year survival rate is 90 percent. Unfortunately, one in three Americans who are eligible for screenings do not get screened. For certain groups, there are larger numbers of people who are not getting screened. And there are groups for whom the death rates from colorectal cancer are much higher.
 

Disparities in colorectal cancer screenings

According to the American Cancer Society, Blacks and Hispanics are less likely to receive prompt follow up after an abnormal CRC screening result and are more likely to be diagnosed with late-stage cancer.⁴ African Americans have the highest death rate when compared with all other racial groups in the United States. American Indians and Alaska Natives are the only groups for which CRC death rates are not declining.

There are many factors that drive disparities, but the main factors seem to be socioeconomic status and differences in access to early detection and treatment. While some of these issues are complex and difficult to change, increasing awareness and providing education can be easier than you might think.
 

Working with your community as a private GI practitioner

To address economic factors, Atlanta Gastroenterology Associates has a program that provides resources on a sliding fee scale to people in our community who do not have insurance and are concerned about having to pay for CRC screening out of pocket. This includes the costs for anesthesia, colonoscopy, and pathology services.

We also have a Direct Access Program, which allows people to self-schedule a screening and fill out a survey that assesses their candidacy for screening colonoscopy. This allows our patients to bypass an initial prescreening office visit and associated copays. Patients are provided instructions for colonoscopy prep and show up for the colonoscopy on the day of their procedure. When the colonoscopy is completed, we give them a patient education card on CRC screening to share with friends and family members who need to be screened.

Atlanta is a very diverse city, and representation is important. But, fortunately, the size of Atlanta Gastroenterology Associates allows us to have representation within many communities. We attend a significant number of health fairs and community events, many of which are sourced internally. Our physicians and staff are members of churches and social groups that we work with to provide screening materials and conduct informational events.

Word of mouth is the best advertising, and it works the same way with health education. There are a lot of myths that we must debunk. And in many of our communities, people are worrying about paying the bills to keep the lights on – they are not thinking about getting screened. But, if they hear from a friend or family member that their screening colonoscopy was a good experience and that resources were provided to help pay for the procedure, it really does make a difference.

You do not need to join a large practice to have an impact. All over the country, there are community groups working to increase screening rates, and engaging with those groups is a good start. During the COVID-19 pandemic, we are all using social media and other platforms to connect. You do not need a lot of resources to set up a Zoom meeting with people in your community to discuss CRC screening.
 

Engaging with referring physicians

As a private practice practitioner, part of growing your practice is engaging with the primary care physicians in your area to ensure that they are up to date on the latest research in CRC screening and that they are discussing available screening options with their patients.

Preventing cancer should always be our first goal. Most CRCs begin as a polyp. Finding, quantifying, localizing, and removing polyps through screening colonoscopy is the most effective strategy for preventing this cancer. That is why colonoscopy remains the preferred method for colon cancer screening.

The Multi-Society Task Force on Colorectal Cancer recommends that, in sequential approaches, physicians should offer colonoscopy first.⁵ For patients who decline to have a colonoscopy, the FIT test should be offered next, followed by second-tier tests such as Cologuard and CT colonography for patients who decline both first-tier options.

Beyond the science of colorectal screening, we want to make sure that our primary care partners are aware of the disparities that exist – and which patients are at higher risk – so that they can engage with their patients to encourage screening.

For example, in our practice, we work with local Asian American community groups to help make sure that the “model minority” myth – that Asian Americans are healthier, wealthier, and better educated than the average American – does not become a barrier to screening. While Asian Americans may have lower overall rates of some types of cancer, there are some cancers that disproportionately affect certain Asian American groups. Rates of CRC in Japanese men, for instance, are 23% higher than in non-Hispanic Whites.

Additionally, we work with our primary care colleagues to help them understand that patients may have insurance considerations when choosing a test. While insurance typically covers 100% of a preventive screening test, a follow-up colonoscopy for a positive stool test is considered a diagnostic or therapeutic service and may not be fully covered. Medicare patients may face a coinsurance bill after their follow-up colonoscopy for a positive stool test. Legislation was passed last year to remove this barrier, but Medicare beneficiaries may have some out-of-pocket costs until it is completely removed in 2030.
 

Are you joining a practice that supports CRC education? Just ask!

We all want to work for an organization that aligns with our core values, and for GI physicians like us, CRC screening is a core component of our everyday work.

If you are considering joining a private practice, ask how the practice is doing with their CRC awareness programs and if it leads to increases in screenings. Inquire about the groups that are being engaged with and why. Is the practice focused on communities that have disparities in screening and treatment, and is it able to complete the entire screening process for individuals in communities that are more adversely affected by colorectal cancer?

We have found that candidates who have the most success in our practice are people who want to work at Atlanta Gastroenterology Associates but are also active in their communities and have a sense of how they want to be of service in their community. It is a sign of leadership in people – the idea that they are really going to get out and network and build a practice that serves everyone in their community. These actions make a difference in getting more people screened and in decreasing the disparities that exist.

Dr. Aja McCutchen is the chair of the quality committee at Atlanta Gastroenterology Associates and serves as chair of the Digestive Health Physicians Association’s Diversity, Equity and Inclusion Committee. She reports having nothing to disclose.

References

1. Siegel RL et al. CA Cancer J Clin. 2018 Jan;68(1):7-30.

2. Key Statistics for Colorectal Cancer. Cancer.org.

3. Wolf AMD et al. CA Cancer J Clin. 2018 Jul;68(4):250-281.

4. American Cancer Society. Colorectal Cancer Facts & Figures 2020-2022.

5. Rex DK et al. Am J Gastroenterol. 2017;112(7):1016-30.

Each year in the month of March, advocates, physicians, and health care educators come together to promote the importance of colorectal cancer screening during Colorectal Cancer Awareness Month. As independent GI physicians, we work within our communities to promote colorectal screening year-round.

We also understand that our education efforts do not end with the people in our community who need to be screened. Independent GI practices also engage with primary care physicians who often initiate conversations about available screening tests and when people should be screened.

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States.¹ It is expected to kill more than 50,000 Americans this year alone.² This is why screening for colorectal cancer is so important. The American Cancer Society recommends screening for all average-risk patients aged 45-75 years.³

The good news? If caught early, the survival rate is very high. In fact, when caught early, the five-year survival rate is 90 percent. Unfortunately, one in three Americans who are eligible for screenings do not get screened. For certain groups, there are larger numbers of people who are not getting screened. And there are groups for whom the death rates from colorectal cancer are much higher.
 

Disparities in colorectal cancer screenings

According to the American Cancer Society, Blacks and Hispanics are less likely to receive prompt follow up after an abnormal CRC screening result and are more likely to be diagnosed with late-stage cancer.⁴ African Americans have the highest death rate when compared with all other racial groups in the United States. American Indians and Alaska Natives are the only groups for which CRC death rates are not declining.

There are many factors that drive disparities, but the main factors seem to be socioeconomic status and differences in access to early detection and treatment. While some of these issues are complex and difficult to change, increasing awareness and providing education can be easier than you might think.
 

Working with your community as a private GI practitioner

To address economic factors, Atlanta Gastroenterology Associates has a program that provides resources on a sliding fee scale to people in our community who do not have insurance and are concerned about having to pay for CRC screening out of pocket. This includes the costs for anesthesia, colonoscopy, and pathology services.

We also have a Direct Access Program, which allows people to self-schedule a screening and fill out a survey that assesses their candidacy for screening colonoscopy. This allows our patients to bypass an initial prescreening office visit and associated copays. Patients are provided instructions for colonoscopy prep and show up for the colonoscopy on the day of their procedure. When the colonoscopy is completed, we give them a patient education card on CRC screening to share with friends and family members who need to be screened.

Atlanta is a very diverse city, and representation is important. But, fortunately, the size of Atlanta Gastroenterology Associates allows us to have representation within many communities. We attend a significant number of health fairs and community events, many of which are sourced internally. Our physicians and staff are members of churches and social groups that we work with to provide screening materials and conduct informational events.

Word of mouth is the best advertising, and it works the same way with health education. There are a lot of myths that we must debunk. And in many of our communities, people are worrying about paying the bills to keep the lights on – they are not thinking about getting screened. But, if they hear from a friend or family member that their screening colonoscopy was a good experience and that resources were provided to help pay for the procedure, it really does make a difference.

You do not need to join a large practice to have an impact. All over the country, there are community groups working to increase screening rates, and engaging with those groups is a good start. During the COVID-19 pandemic, we are all using social media and other platforms to connect. You do not need a lot of resources to set up a Zoom meeting with people in your community to discuss CRC screening.
 

Engaging with referring physicians

As a private practice practitioner, part of growing your practice is engaging with the primary care physicians in your area to ensure that they are up to date on the latest research in CRC screening and that they are discussing available screening options with their patients.

Preventing cancer should always be our first goal. Most CRCs begin as a polyp. Finding, quantifying, localizing, and removing polyps through screening colonoscopy is the most effective strategy for preventing this cancer. That is why colonoscopy remains the preferred method for colon cancer screening.

The Multi-Society Task Force on Colorectal Cancer recommends that, in sequential approaches, physicians should offer colonoscopy first.⁵ For patients who decline to have a colonoscopy, the FIT test should be offered next, followed by second-tier tests such as Cologuard and CT colonography for patients who decline both first-tier options.

Beyond the science of colorectal screening, we want to make sure that our primary care partners are aware of the disparities that exist – and which patients are at higher risk – so that they can engage with their patients to encourage screening.

For example, in our practice, we work with local Asian American community groups to help make sure that the “model minority” myth – that Asian Americans are healthier, wealthier, and better educated than the average American – does not become a barrier to screening. While Asian Americans may have lower overall rates of some types of cancer, there are some cancers that disproportionately affect certain Asian American groups. Rates of CRC in Japanese men, for instance, are 23% higher than in non-Hispanic Whites.

Additionally, we work with our primary care colleagues to help them understand that patients may have insurance considerations when choosing a test. While insurance typically covers 100% of a preventive screening test, a follow-up colonoscopy for a positive stool test is considered a diagnostic or therapeutic service and may not be fully covered. Medicare patients may face a coinsurance bill after their follow-up colonoscopy for a positive stool test. Legislation was passed last year to remove this barrier, but Medicare beneficiaries may have some out-of-pocket costs until it is completely removed in 2030.
 

Are you joining a practice that supports CRC education? Just ask!

We all want to work for an organization that aligns with our core values, and for GI physicians like us, CRC screening is a core component of our everyday work.

If you are considering joining a private practice, ask how the practice is doing with their CRC awareness programs and if it leads to increases in screenings. Inquire about the groups that are being engaged with and why. Is the practice focused on communities that have disparities in screening and treatment, and is it able to complete the entire screening process for individuals in communities that are more adversely affected by colorectal cancer?

We have found that candidates who have the most success in our practice are people who want to work at Atlanta Gastroenterology Associates but are also active in their communities and have a sense of how they want to be of service in their community. It is a sign of leadership in people – the idea that they are really going to get out and network and build a practice that serves everyone in their community. These actions make a difference in getting more people screened and in decreasing the disparities that exist.

Dr. Aja McCutchen is the chair of the quality committee at Atlanta Gastroenterology Associates and serves as chair of the Digestive Health Physicians Association’s Diversity, Equity and Inclusion Committee. She reports having nothing to disclose.

References

1. Siegel RL et al. CA Cancer J Clin. 2018 Jan;68(1):7-30.

2. Key Statistics for Colorectal Cancer. Cancer.org.

3. Wolf AMD et al. CA Cancer J Clin. 2018 Jul;68(4):250-281.

4. American Cancer Society. Colorectal Cancer Facts & Figures 2020-2022.

5. Rex DK et al. Am J Gastroenterol. 2017;112(7):1016-30.

Each year in the month of March, advocates, physicians, and health care educators come together to promote the importance of colorectal cancer screening during Colorectal Cancer Awareness Month. As independent GI physicians, we work within our communities to promote colorectal screening year-round.

We also understand that our education efforts do not end with the people in our community who need to be screened. Independent GI practices also engage with primary care physicians who often initiate conversations about available screening tests and when people should be screened.

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States.¹ It is expected to kill more than 50,000 Americans this year alone.² This is why screening for colorectal cancer is so important. The American Cancer Society recommends screening for all average-risk patients aged 45-75 years.³

The good news? If caught early, the survival rate is very high. In fact, when caught early, the five-year survival rate is 90 percent. Unfortunately, one in three Americans who are eligible for screenings do not get screened. For certain groups, there are larger numbers of people who are not getting screened. And there are groups for whom the death rates from colorectal cancer are much higher.
 

Disparities in colorectal cancer screenings

According to the American Cancer Society, Blacks and Hispanics are less likely to receive prompt follow up after an abnormal CRC screening result and are more likely to be diagnosed with late-stage cancer.⁴ African Americans have the highest death rate when compared with all other racial groups in the United States. American Indians and Alaska Natives are the only groups for which CRC death rates are not declining.

There are many factors that drive disparities, but the main factors seem to be socioeconomic status and differences in access to early detection and treatment. While some of these issues are complex and difficult to change, increasing awareness and providing education can be easier than you might think.
 

Working with your community as a private GI practitioner

To address economic factors, Atlanta Gastroenterology Associates has a program that provides resources on a sliding fee scale to people in our community who do not have insurance and are concerned about having to pay for CRC screening out of pocket. This includes the costs for anesthesia, colonoscopy, and pathology services.

We also have a Direct Access Program, which allows people to self-schedule a screening and fill out a survey that assesses their candidacy for screening colonoscopy. This allows our patients to bypass an initial prescreening office visit and associated copays. Patients are provided instructions for colonoscopy prep and show up for the colonoscopy on the day of their procedure. When the colonoscopy is completed, we give them a patient education card on CRC screening to share with friends and family members who need to be screened.

Atlanta is a very diverse city, and representation is important. But, fortunately, the size of Atlanta Gastroenterology Associates allows us to have representation within many communities. We attend a significant number of health fairs and community events, many of which are sourced internally. Our physicians and staff are members of churches and social groups that we work with to provide screening materials and conduct informational events.

Word of mouth is the best advertising, and it works the same way with health education. There are a lot of myths that we must debunk. And in many of our communities, people are worrying about paying the bills to keep the lights on – they are not thinking about getting screened. But, if they hear from a friend or family member that their screening colonoscopy was a good experience and that resources were provided to help pay for the procedure, it really does make a difference.

You do not need to join a large practice to have an impact. All over the country, there are community groups working to increase screening rates, and engaging with those groups is a good start. During the COVID-19 pandemic, we are all using social media and other platforms to connect. You do not need a lot of resources to set up a Zoom meeting with people in your community to discuss CRC screening.
 

Engaging with referring physicians

As a private practice practitioner, part of growing your practice is engaging with the primary care physicians in your area to ensure that they are up to date on the latest research in CRC screening and that they are discussing available screening options with their patients.

Preventing cancer should always be our first goal. Most CRCs begin as a polyp. Finding, quantifying, localizing, and removing polyps through screening colonoscopy is the most effective strategy for preventing this cancer. That is why colonoscopy remains the preferred method for colon cancer screening.

The Multi-Society Task Force on Colorectal Cancer recommends that, in sequential approaches, physicians should offer colonoscopy first.⁵ For patients who decline to have a colonoscopy, the FIT test should be offered next, followed by second-tier tests such as Cologuard and CT colonography for patients who decline both first-tier options.

Beyond the science of colorectal screening, we want to make sure that our primary care partners are aware of the disparities that exist – and which patients are at higher risk – so that they can engage with their patients to encourage screening.

For example, in our practice, we work with local Asian American community groups to help make sure that the “model minority” myth – that Asian Americans are healthier, wealthier, and better educated than the average American – does not become a barrier to screening. While Asian Americans may have lower overall rates of some types of cancer, there are some cancers that disproportionately affect certain Asian American groups. Rates of CRC in Japanese men, for instance, are 23% higher than in non-Hispanic Whites.

Additionally, we work with our primary care colleagues to help them understand that patients may have insurance considerations when choosing a test. While insurance typically covers 100% of a preventive screening test, a follow-up colonoscopy for a positive stool test is considered a diagnostic or therapeutic service and may not be fully covered. Medicare patients may face a coinsurance bill after their follow-up colonoscopy for a positive stool test. Legislation was passed last year to remove this barrier, but Medicare beneficiaries may have some out-of-pocket costs until it is completely removed in 2030.
 

Are you joining a practice that supports CRC education? Just ask!

We all want to work for an organization that aligns with our core values, and for GI physicians like us, CRC screening is a core component of our everyday work.

If you are considering joining a private practice, ask how the practice is doing with their CRC awareness programs and if it leads to increases in screenings. Inquire about the groups that are being engaged with and why. Is the practice focused on communities that have disparities in screening and treatment, and is it able to complete the entire screening process for individuals in communities that are more adversely affected by colorectal cancer?

We have found that candidates who have the most success in our practice are people who want to work at Atlanta Gastroenterology Associates but are also active in their communities and have a sense of how they want to be of service in their community. It is a sign of leadership in people – the idea that they are really going to get out and network and build a practice that serves everyone in their community. These actions make a difference in getting more people screened and in decreasing the disparities that exist.

Dr. Aja McCutchen is the chair of the quality committee at Atlanta Gastroenterology Associates and serves as chair of the Digestive Health Physicians Association’s Diversity, Equity and Inclusion Committee. She reports having nothing to disclose.

References

1. Siegel RL et al. CA Cancer J Clin. 2018 Jan;68(1):7-30.

2. Key Statistics for Colorectal Cancer. Cancer.org.

3. Wolf AMD et al. CA Cancer J Clin. 2018 Jul;68(4):250-281.

4. American Cancer Society. Colorectal Cancer Facts & Figures 2020-2022.

5. Rex DK et al. Am J Gastroenterol. 2017;112(7):1016-30.

Among patients who undergo surgery for hidradenitis suppurativa (HS), wide excision and flap-based reconstruction are associated with lower postsurgical recurrence, yet these options should be balanced against potentially higher morbidity of extensive procedures.

Those are among the key findings of a systematic review and meta-analysis published online in Dermatologic Surgery.

“There is a major need to better understand the best surgical approaches to HS,” one of the study authors, Christopher Sayed, MD, associate professor of dermatology at the University of North Carolina at Chapel Hill, said in an interview. Previous studies have mostly reviewed outcomes for procedure types in individual cohorts, “but no recent reports have combined and analyzed data from recent studies.”

When Dr. Sayed and colleagues set out to summarize the literature on HS surgery regarding patient characteristics, surgical approaches, and study quality, as well as compare postsurgical recurrence rates, the most recent meta-analysis on postoperative recurrence rates of HS included studies published between 1990 and 2015. “In the past few years, surgical management of HS has become an increasingly popular area of study,” corresponding author Ashley Riddle, MD, MPH, who is currently an internal medicine resident at the Carolinas Medical Center, Charlotte, said in an interview. “We sought to provide an updated picture of the HS surgical landscape by analyzing studies published between 2004 to 2019. We also limited our analysis to studies with follow-up periods of greater than 1 year and included information on disease severity, adverse events, and patient satisfaction when available.”

Of 715 relevant studies identified in the medical literature, the researchers included 59 in the review and 33 in the meta-analysis. Of these 59 studies, 56 were case series, 2 were randomized, controlled trials, and one was a retrospective cohort study.

Of the 50 studies reporting gender and age at time of surgery, 61% of patients were female and their average age was 37 years. Of the 25 studies that reported Hurley scores, 73% had Hurley stage 3 HS. Of the 38 studies reporting the number of procedures per anatomic region, the most commonly operated on regions were the axilla (59%) and the inguinal region (20%).

The researchers found that 22 studies of wide excision had the lowest pooled recurrence rate at 8%, while local excision had the highest pooled recurrence rate at 34%. Meanwhile, among studies of wide/radical excision, flap repair had a pooled recurrence rate of 0%, while delayed primary closure had the highest pooled recurrence rate at 38%.

“Extensive excisions of HS seem to portend a lower risk of postoperative recurrence, but there are many approaches available that may be more appropriate for certain patients,” Dr. Riddle said. “The influence of patient factors such as comorbidities and disease severity on surgical outcomes is unclear and is a potential area of future study.”

Dr. Sayed, an author of the 2019 North American guidelines for the clinical management of HS, pointed out that most studies in the review and meta-analysis included patients who had diabetes, were on biologics or other therapy, were actively smoking, or had other comorbidities that sometimes influence surgeons to delay surgical treatment because they consider it elective. “Most studies indicated minimal or no risk of significant complications relating to these factors, so they should ideally not become obstacles for patients interested in surgical care,” he said.

Dr. Riddle said that she was surprised by how relatively few studies had been published on more conservative surgical approaches such as skin tissue–sparing excision with electrosurgical peeling, deroofing, local excision, and CO₂ laser–based evaporation.

The researchers acknowledged certain limitations of their work, including the high risk of bias for most included studies. “Almost all studies were retrospective with substantial methodological limitations, and there were no head-to-head comparisons of different surgical approaches,” Dr. Riddle said. “Patient comorbidities and postoperative complications were variably reported.”

Dr. Sayed disclosed that he is a speaker for AbbVie and Novartis; an investigator for AbbVie, Novartis, InflaRx, and UCB; and on the advisory board of AbbVie and InflaRx. The remaining authors reported having no financial disclosures.

[email protected]

Among patients who undergo surgery for hidradenitis suppurativa (HS), wide excision and flap-based reconstruction are associated with lower postsurgical recurrence, yet these options should be balanced against potentially higher morbidity of extensive procedures.

Those are among the key findings of a systematic review and meta-analysis published online in Dermatologic Surgery.

“There is a major need to better understand the best surgical approaches to HS,” one of the study authors, Christopher Sayed, MD, associate professor of dermatology at the University of North Carolina at Chapel Hill, said in an interview. Previous studies have mostly reviewed outcomes for procedure types in individual cohorts, “but no recent reports have combined and analyzed data from recent studies.”

When Dr. Sayed and colleagues set out to summarize the literature on HS surgery regarding patient characteristics, surgical approaches, and study quality, as well as compare postsurgical recurrence rates, the most recent meta-analysis on postoperative recurrence rates of HS included studies published between 1990 and 2015. “In the past few years, surgical management of HS has become an increasingly popular area of study,” corresponding author Ashley Riddle, MD, MPH, who is currently an internal medicine resident at the Carolinas Medical Center, Charlotte, said in an interview. “We sought to provide an updated picture of the HS surgical landscape by analyzing studies published between 2004 to 2019. We also limited our analysis to studies with follow-up periods of greater than 1 year and included information on disease severity, adverse events, and patient satisfaction when available.”

Of 715 relevant studies identified in the medical literature, the researchers included 59 in the review and 33 in the meta-analysis. Of these 59 studies, 56 were case series, 2 were randomized, controlled trials, and one was a retrospective cohort study.

Of the 50 studies reporting gender and age at time of surgery, 61% of patients were female and their average age was 37 years. Of the 25 studies that reported Hurley scores, 73% had Hurley stage 3 HS. Of the 38 studies reporting the number of procedures per anatomic region, the most commonly operated on regions were the axilla (59%) and the inguinal region (20%).

The researchers found that 22 studies of wide excision had the lowest pooled recurrence rate at 8%, while local excision had the highest pooled recurrence rate at 34%. Meanwhile, among studies of wide/radical excision, flap repair had a pooled recurrence rate of 0%, while delayed primary closure had the highest pooled recurrence rate at 38%.

“Extensive excisions of HS seem to portend a lower risk of postoperative recurrence, but there are many approaches available that may be more appropriate for certain patients,” Dr. Riddle said. “The influence of patient factors such as comorbidities and disease severity on surgical outcomes is unclear and is a potential area of future study.”

Dr. Sayed, an author of the 2019 North American guidelines for the clinical management of HS, pointed out that most studies in the review and meta-analysis included patients who had diabetes, were on biologics or other therapy, were actively smoking, or had other comorbidities that sometimes influence surgeons to delay surgical treatment because they consider it elective. “Most studies indicated minimal or no risk of significant complications relating to these factors, so they should ideally not become obstacles for patients interested in surgical care,” he said.

Dr. Riddle said that she was surprised by how relatively few studies had been published on more conservative surgical approaches such as skin tissue–sparing excision with electrosurgical peeling, deroofing, local excision, and CO₂ laser–based evaporation.

The researchers acknowledged certain limitations of their work, including the high risk of bias for most included studies. “Almost all studies were retrospective with substantial methodological limitations, and there were no head-to-head comparisons of different surgical approaches,” Dr. Riddle said. “Patient comorbidities and postoperative complications were variably reported.”

Dr. Sayed disclosed that he is a speaker for AbbVie and Novartis; an investigator for AbbVie, Novartis, InflaRx, and UCB; and on the advisory board of AbbVie and InflaRx. The remaining authors reported having no financial disclosures.

[email protected]

Among patients who undergo surgery for hidradenitis suppurativa (HS), wide excision and flap-based reconstruction are associated with lower postsurgical recurrence, yet these options should be balanced against potentially higher morbidity of extensive procedures.

Those are among the key findings of a systematic review and meta-analysis published online in Dermatologic Surgery.

“There is a major need to better understand the best surgical approaches to HS,” one of the study authors, Christopher Sayed, MD, associate professor of dermatology at the University of North Carolina at Chapel Hill, said in an interview. Previous studies have mostly reviewed outcomes for procedure types in individual cohorts, “but no recent reports have combined and analyzed data from recent studies.”

When Dr. Sayed and colleagues set out to summarize the literature on HS surgery regarding patient characteristics, surgical approaches, and study quality, as well as compare postsurgical recurrence rates, the most recent meta-analysis on postoperative recurrence rates of HS included studies published between 1990 and 2015. “In the past few years, surgical management of HS has become an increasingly popular area of study,” corresponding author Ashley Riddle, MD, MPH, who is currently an internal medicine resident at the Carolinas Medical Center, Charlotte, said in an interview. “We sought to provide an updated picture of the HS surgical landscape by analyzing studies published between 2004 to 2019. We also limited our analysis to studies with follow-up periods of greater than 1 year and included information on disease severity, adverse events, and patient satisfaction when available.”

Of 715 relevant studies identified in the medical literature, the researchers included 59 in the review and 33 in the meta-analysis. Of these 59 studies, 56 were case series, 2 were randomized, controlled trials, and one was a retrospective cohort study.

Of the 50 studies reporting gender and age at time of surgery, 61% of patients were female and their average age was 37 years. Of the 25 studies that reported Hurley scores, 73% had Hurley stage 3 HS. Of the 38 studies reporting the number of procedures per anatomic region, the most commonly operated on regions were the axilla (59%) and the inguinal region (20%).

The researchers found that 22 studies of wide excision had the lowest pooled recurrence rate at 8%, while local excision had the highest pooled recurrence rate at 34%. Meanwhile, among studies of wide/radical excision, flap repair had a pooled recurrence rate of 0%, while delayed primary closure had the highest pooled recurrence rate at 38%.

“Extensive excisions of HS seem to portend a lower risk of postoperative recurrence, but there are many approaches available that may be more appropriate for certain patients,” Dr. Riddle said. “The influence of patient factors such as comorbidities and disease severity on surgical outcomes is unclear and is a potential area of future study.”

Dr. Sayed, an author of the 2019 North American guidelines for the clinical management of HS, pointed out that most studies in the review and meta-analysis included patients who had diabetes, were on biologics or other therapy, were actively smoking, or had other comorbidities that sometimes influence surgeons to delay surgical treatment because they consider it elective. “Most studies indicated minimal or no risk of significant complications relating to these factors, so they should ideally not become obstacles for patients interested in surgical care,” he said.

Dr. Riddle said that she was surprised by how relatively few studies had been published on more conservative surgical approaches such as skin tissue–sparing excision with electrosurgical peeling, deroofing, local excision, and CO₂ laser–based evaporation.

The researchers acknowledged certain limitations of their work, including the high risk of bias for most included studies. “Almost all studies were retrospective with substantial methodological limitations, and there were no head-to-head comparisons of different surgical approaches,” Dr. Riddle said. “Patient comorbidities and postoperative complications were variably reported.”

Dr. Sayed disclosed that he is a speaker for AbbVie and Novartis; an investigator for AbbVie, Novartis, InflaRx, and UCB; and on the advisory board of AbbVie and InflaRx. The remaining authors reported having no financial disclosures.

[email protected]