New documentary highlights human toll of high insulin cost

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A new documentary premiering at the 2023 South by Southwest (SXSW) Festival illustrates the human consequences of insulin’s high cost in the United States. Its creators hope that it will help spur action toward overall prescription pricing reform.

Pay or Die: A Documentary is scheduled to premiere March 11. It will be shown twice more during the festival, which runs from March 10 to 19 in Austin, Texas. The documentary was co-created and directed by filmmaker and cinematographer Scott Alexander Ruderman, who has type 1 diabetes, and his partner, producer and journalist Rachael Dyer. One of the executive producers is Sarah Silverman, a comic, actor, producer, and health care reform advocate.

The 90-minute film follows three human stories: A mother and young daughter who both have type 1 diabetes and become homeless after spending their rent money on insulin, a young adult diagnosed during the COVID-19 pandemic, and a mother whose 26-year-old son died from diabetic ketoacidosis (DKA) after his insulin was rationed.

“As an Australian now living in the U.S. and seeing how the health care system works here, especially for people with type 1 diabetes like Scott, and how access to insulin is a life-or-death situation, has been very eye-opening for me. I’m also half Canadian, and both are countries where access to health care is a human right, not a business,” Ms. Dyer said in an interview.

In response to the March 1 announcement from Eli Lilly about its insulin price cut, the film’s team told this news organization: “While we commend Eli Lilly in taking this first step and hope that Novo Nordisk and Sanofi [the two other major insulin manufacturers] follow suit, it is important to remember that the key issue is not about these companies voluntarily slashing prices; it’s about changing laws so the insulin manufacturers do not have the ability to raise the prices again.

“This is the life-or-death issue that we focus on in our documentary Pay or Die. It’s also important to note that insulin is just one of the many expensive prescription drugs in the U.S., which is why we need to call for reform. Affordable medication needs to be a basic human right within reach for all Americans.”
 

Physician perspective: Good news on insulin, but broader issues

The film features four physicians. One, Mayo Clinic oncologist/hematologist S. Vincent Rajkumar, MD, has spoken and published widely on insulin prices specifically and U.S. drug costs more broadly.

The other three are Joslin Clinic endocrinologist Elizabeth Halprin, MD, Massachusetts General Hospital internist Leigh Simmons, MD, and New York University physician and essayist Danielle Ofri, MD, PhD.

In an interview after the Lilly announcement, Dr. Rajkumar said, “I think this is very, very good news for patients. ... The fact that they’re doing it means they’re listening to us and listening to patients, which is good. And I do hope that other insulin manufacturers do the same shortly.”

However, he added, “for prescription drug prices and particularly cancer drug prices, there’s more reform that’s needed, and that’s at the policy level. ... The goal of the film was to use insulin to highlight the prescription drug price problem in the U.S.”
 

 

 

‘Then life changed’

The filmmaker, Mr. Ruderman, was diagnosed at age 19, during his freshman year in college. He spent several days hospitalized with DKA, and “then life changed,” he said in an interview. He went into photography first and later filmmaking, always with the uneasy knowledge that he could lose access to insulin at any time.

The impetus for the film came after he and Ms. Dyer walked into a pharmacy while visiting Canada in 2018 and discovered how much cheaper insulin was compared to the United States – roughly $20 per vial, compared to $300 in the U.S.

“When Rachael [Dyer] and I came back to the U.S., we were actually quite shocked about how many people are struggling to afford their medication ... the uninsured, those aging off their parents’ health insurance. So that was really the kickoff to us going into the field for the last 4 years making this documentary.”

As a freelancer, Mr. Ruderman has been personally paying for expensive “premium” health insurance that covers the pump and glucose monitors he uses. He buys insulin overseas as often as possible.

“Fortunately, I haven’t been in a situation where I’ve had to ration my insulin, but the fear is instilled in me. What if there’s a month when I can’t afford it? What am I going to do?” (Note: The writer of this article is in the same situation, which could be alleviated by Lilly’s action.)
 

Timing is everything

To be sure, even before Lilly’s announcement, some progress had been made since work on the film began.

The issue of insulin pricing has received wide media attention. More than 20 states have passed copay caps on insulin, and a new law capping the cost of insulin for Medicare beneficiaries at $35/month went into effect in January 2023. President Biden mentioned insulin during his State of the Union address, and Georgia Senator Raphael Warnock made the issue a centerpiece of his campaign.

But there have also been losses, including the failure thus far to pass a nationwide copay cap.

These recent developments make this a good time for the film’s debut, producer Yael Melamede said in an interview. “There’s a lot happening in the space, but also a lot of incredible disappointments along the way, so we are really interested in getting this film out now.”

Ms. Melamede, who owns a film production company, said, “I’ve done a lot of films that have some issue advocacy side to them. I love this film because it’s grounded in the stories of real people. ... We feel this is a perfect catalyst to keep the energy going and for people to say this is super-important and not get distracted.”

While the film doesn’t advocate for specific policies, there is a “call to action” at the end that points viewers to resources on the website for writing to their members of Congress along with additional ways to become personally involved.

Ms. Dyer told this news organization, “This film is not only focusing on type 1 diabetes. That is obviously the crux of the issue, but it is a broader health care message for everyone wanting to make a change for health care in this country, the richest country in the world.”

At SXSW, Pay or Die will be competing with seven other films in the documentary feature competition, and it is eligible to win other awards.

Several other activities at the festival will address the topics of diabetes and U.S. health care costs, including a panel discussion titled Crushing: The Burden of Diabetes on Patients, featuring musician and actor Nick Jonas, who has type 1 diabetes, and a representative from the continuous glucose monitor manufacturer Dexcom.

Another panel, Young and Uninsured: Pay or Die, will include Dr. Rajkumar, Mr. Ruderman, Texas Representative James Talarico, who is advancing an insulin cap bill in that state, and Nicole Smith-Holt, the Minnesota mother of the young man who died because he couldn’t afford his insulin.

Mr. Ruderman, Ms. Dyer, Ms. Melamede, and Dr. Rajkumar have disclosed no relevant financial relationships.

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

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A new documentary premiering at the 2023 South by Southwest (SXSW) Festival illustrates the human consequences of insulin’s high cost in the United States. Its creators hope that it will help spur action toward overall prescription pricing reform.

Pay or Die: A Documentary is scheduled to premiere March 11. It will be shown twice more during the festival, which runs from March 10 to 19 in Austin, Texas. The documentary was co-created and directed by filmmaker and cinematographer Scott Alexander Ruderman, who has type 1 diabetes, and his partner, producer and journalist Rachael Dyer. One of the executive producers is Sarah Silverman, a comic, actor, producer, and health care reform advocate.

The 90-minute film follows three human stories: A mother and young daughter who both have type 1 diabetes and become homeless after spending their rent money on insulin, a young adult diagnosed during the COVID-19 pandemic, and a mother whose 26-year-old son died from diabetic ketoacidosis (DKA) after his insulin was rationed.

“As an Australian now living in the U.S. and seeing how the health care system works here, especially for people with type 1 diabetes like Scott, and how access to insulin is a life-or-death situation, has been very eye-opening for me. I’m also half Canadian, and both are countries where access to health care is a human right, not a business,” Ms. Dyer said in an interview.

In response to the March 1 announcement from Eli Lilly about its insulin price cut, the film’s team told this news organization: “While we commend Eli Lilly in taking this first step and hope that Novo Nordisk and Sanofi [the two other major insulin manufacturers] follow suit, it is important to remember that the key issue is not about these companies voluntarily slashing prices; it’s about changing laws so the insulin manufacturers do not have the ability to raise the prices again.

“This is the life-or-death issue that we focus on in our documentary Pay or Die. It’s also important to note that insulin is just one of the many expensive prescription drugs in the U.S., which is why we need to call for reform. Affordable medication needs to be a basic human right within reach for all Americans.”
 

Physician perspective: Good news on insulin, but broader issues

The film features four physicians. One, Mayo Clinic oncologist/hematologist S. Vincent Rajkumar, MD, has spoken and published widely on insulin prices specifically and U.S. drug costs more broadly.

The other three are Joslin Clinic endocrinologist Elizabeth Halprin, MD, Massachusetts General Hospital internist Leigh Simmons, MD, and New York University physician and essayist Danielle Ofri, MD, PhD.

In an interview after the Lilly announcement, Dr. Rajkumar said, “I think this is very, very good news for patients. ... The fact that they’re doing it means they’re listening to us and listening to patients, which is good. And I do hope that other insulin manufacturers do the same shortly.”

However, he added, “for prescription drug prices and particularly cancer drug prices, there’s more reform that’s needed, and that’s at the policy level. ... The goal of the film was to use insulin to highlight the prescription drug price problem in the U.S.”
 

 

 

‘Then life changed’

The filmmaker, Mr. Ruderman, was diagnosed at age 19, during his freshman year in college. He spent several days hospitalized with DKA, and “then life changed,” he said in an interview. He went into photography first and later filmmaking, always with the uneasy knowledge that he could lose access to insulin at any time.

The impetus for the film came after he and Ms. Dyer walked into a pharmacy while visiting Canada in 2018 and discovered how much cheaper insulin was compared to the United States – roughly $20 per vial, compared to $300 in the U.S.

“When Rachael [Dyer] and I came back to the U.S., we were actually quite shocked about how many people are struggling to afford their medication ... the uninsured, those aging off their parents’ health insurance. So that was really the kickoff to us going into the field for the last 4 years making this documentary.”

As a freelancer, Mr. Ruderman has been personally paying for expensive “premium” health insurance that covers the pump and glucose monitors he uses. He buys insulin overseas as often as possible.

“Fortunately, I haven’t been in a situation where I’ve had to ration my insulin, but the fear is instilled in me. What if there’s a month when I can’t afford it? What am I going to do?” (Note: The writer of this article is in the same situation, which could be alleviated by Lilly’s action.)
 

Timing is everything

To be sure, even before Lilly’s announcement, some progress had been made since work on the film began.

The issue of insulin pricing has received wide media attention. More than 20 states have passed copay caps on insulin, and a new law capping the cost of insulin for Medicare beneficiaries at $35/month went into effect in January 2023. President Biden mentioned insulin during his State of the Union address, and Georgia Senator Raphael Warnock made the issue a centerpiece of his campaign.

But there have also been losses, including the failure thus far to pass a nationwide copay cap.

These recent developments make this a good time for the film’s debut, producer Yael Melamede said in an interview. “There’s a lot happening in the space, but also a lot of incredible disappointments along the way, so we are really interested in getting this film out now.”

Ms. Melamede, who owns a film production company, said, “I’ve done a lot of films that have some issue advocacy side to them. I love this film because it’s grounded in the stories of real people. ... We feel this is a perfect catalyst to keep the energy going and for people to say this is super-important and not get distracted.”

While the film doesn’t advocate for specific policies, there is a “call to action” at the end that points viewers to resources on the website for writing to their members of Congress along with additional ways to become personally involved.

Ms. Dyer told this news organization, “This film is not only focusing on type 1 diabetes. That is obviously the crux of the issue, but it is a broader health care message for everyone wanting to make a change for health care in this country, the richest country in the world.”

At SXSW, Pay or Die will be competing with seven other films in the documentary feature competition, and it is eligible to win other awards.

Several other activities at the festival will address the topics of diabetes and U.S. health care costs, including a panel discussion titled Crushing: The Burden of Diabetes on Patients, featuring musician and actor Nick Jonas, who has type 1 diabetes, and a representative from the continuous glucose monitor manufacturer Dexcom.

Another panel, Young and Uninsured: Pay or Die, will include Dr. Rajkumar, Mr. Ruderman, Texas Representative James Talarico, who is advancing an insulin cap bill in that state, and Nicole Smith-Holt, the Minnesota mother of the young man who died because he couldn’t afford his insulin.

Mr. Ruderman, Ms. Dyer, Ms. Melamede, and Dr. Rajkumar have disclosed no relevant financial relationships.

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

A new documentary premiering at the 2023 South by Southwest (SXSW) Festival illustrates the human consequences of insulin’s high cost in the United States. Its creators hope that it will help spur action toward overall prescription pricing reform.

Pay or Die: A Documentary is scheduled to premiere March 11. It will be shown twice more during the festival, which runs from March 10 to 19 in Austin, Texas. The documentary was co-created and directed by filmmaker and cinematographer Scott Alexander Ruderman, who has type 1 diabetes, and his partner, producer and journalist Rachael Dyer. One of the executive producers is Sarah Silverman, a comic, actor, producer, and health care reform advocate.

The 90-minute film follows three human stories: A mother and young daughter who both have type 1 diabetes and become homeless after spending their rent money on insulin, a young adult diagnosed during the COVID-19 pandemic, and a mother whose 26-year-old son died from diabetic ketoacidosis (DKA) after his insulin was rationed.

“As an Australian now living in the U.S. and seeing how the health care system works here, especially for people with type 1 diabetes like Scott, and how access to insulin is a life-or-death situation, has been very eye-opening for me. I’m also half Canadian, and both are countries where access to health care is a human right, not a business,” Ms. Dyer said in an interview.

In response to the March 1 announcement from Eli Lilly about its insulin price cut, the film’s team told this news organization: “While we commend Eli Lilly in taking this first step and hope that Novo Nordisk and Sanofi [the two other major insulin manufacturers] follow suit, it is important to remember that the key issue is not about these companies voluntarily slashing prices; it’s about changing laws so the insulin manufacturers do not have the ability to raise the prices again.

“This is the life-or-death issue that we focus on in our documentary Pay or Die. It’s also important to note that insulin is just one of the many expensive prescription drugs in the U.S., which is why we need to call for reform. Affordable medication needs to be a basic human right within reach for all Americans.”
 

Physician perspective: Good news on insulin, but broader issues

The film features four physicians. One, Mayo Clinic oncologist/hematologist S. Vincent Rajkumar, MD, has spoken and published widely on insulin prices specifically and U.S. drug costs more broadly.

The other three are Joslin Clinic endocrinologist Elizabeth Halprin, MD, Massachusetts General Hospital internist Leigh Simmons, MD, and New York University physician and essayist Danielle Ofri, MD, PhD.

In an interview after the Lilly announcement, Dr. Rajkumar said, “I think this is very, very good news for patients. ... The fact that they’re doing it means they’re listening to us and listening to patients, which is good. And I do hope that other insulin manufacturers do the same shortly.”

However, he added, “for prescription drug prices and particularly cancer drug prices, there’s more reform that’s needed, and that’s at the policy level. ... The goal of the film was to use insulin to highlight the prescription drug price problem in the U.S.”
 

 

 

‘Then life changed’

The filmmaker, Mr. Ruderman, was diagnosed at age 19, during his freshman year in college. He spent several days hospitalized with DKA, and “then life changed,” he said in an interview. He went into photography first and later filmmaking, always with the uneasy knowledge that he could lose access to insulin at any time.

The impetus for the film came after he and Ms. Dyer walked into a pharmacy while visiting Canada in 2018 and discovered how much cheaper insulin was compared to the United States – roughly $20 per vial, compared to $300 in the U.S.

“When Rachael [Dyer] and I came back to the U.S., we were actually quite shocked about how many people are struggling to afford their medication ... the uninsured, those aging off their parents’ health insurance. So that was really the kickoff to us going into the field for the last 4 years making this documentary.”

As a freelancer, Mr. Ruderman has been personally paying for expensive “premium” health insurance that covers the pump and glucose monitors he uses. He buys insulin overseas as often as possible.

“Fortunately, I haven’t been in a situation where I’ve had to ration my insulin, but the fear is instilled in me. What if there’s a month when I can’t afford it? What am I going to do?” (Note: The writer of this article is in the same situation, which could be alleviated by Lilly’s action.)
 

Timing is everything

To be sure, even before Lilly’s announcement, some progress had been made since work on the film began.

The issue of insulin pricing has received wide media attention. More than 20 states have passed copay caps on insulin, and a new law capping the cost of insulin for Medicare beneficiaries at $35/month went into effect in January 2023. President Biden mentioned insulin during his State of the Union address, and Georgia Senator Raphael Warnock made the issue a centerpiece of his campaign.

But there have also been losses, including the failure thus far to pass a nationwide copay cap.

These recent developments make this a good time for the film’s debut, producer Yael Melamede said in an interview. “There’s a lot happening in the space, but also a lot of incredible disappointments along the way, so we are really interested in getting this film out now.”

Ms. Melamede, who owns a film production company, said, “I’ve done a lot of films that have some issue advocacy side to them. I love this film because it’s grounded in the stories of real people. ... We feel this is a perfect catalyst to keep the energy going and for people to say this is super-important and not get distracted.”

While the film doesn’t advocate for specific policies, there is a “call to action” at the end that points viewers to resources on the website for writing to their members of Congress along with additional ways to become personally involved.

Ms. Dyer told this news organization, “This film is not only focusing on type 1 diabetes. That is obviously the crux of the issue, but it is a broader health care message for everyone wanting to make a change for health care in this country, the richest country in the world.”

At SXSW, Pay or Die will be competing with seven other films in the documentary feature competition, and it is eligible to win other awards.

Several other activities at the festival will address the topics of diabetes and U.S. health care costs, including a panel discussion titled Crushing: The Burden of Diabetes on Patients, featuring musician and actor Nick Jonas, who has type 1 diabetes, and a representative from the continuous glucose monitor manufacturer Dexcom.

Another panel, Young and Uninsured: Pay or Die, will include Dr. Rajkumar, Mr. Ruderman, Texas Representative James Talarico, who is advancing an insulin cap bill in that state, and Nicole Smith-Holt, the Minnesota mother of the young man who died because he couldn’t afford his insulin.

Mr. Ruderman, Ms. Dyer, Ms. Melamede, and Dr. Rajkumar have disclosed no relevant financial relationships.

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

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What do high BUN/Cr ratios mean?

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A 43-year-old man presents to the emergency department with dizziness and a 6-hour history of passing maroon stool. He has been in good health with the only medical problem in his history being depression.

He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.

Dr. Paauw

What is the most likely source of his bleeding?

A. Gastric ulcer

B. Meckel’s diverticulum

C. Arteriovenous malformation

D. Diverticulosis

E. Hemorrhoids

What makes the most sense

The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.

We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.

Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1

Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).

Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.

Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.

Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).

High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
 

Pearl

Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am J Emerg Med. 2006 May;24(3):280-5.

2. JAMA. 2012;307(10):1072-9.

3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.

4. Cardiorenal Med. 2020;10:415-28.

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A 43-year-old man presents to the emergency department with dizziness and a 6-hour history of passing maroon stool. He has been in good health with the only medical problem in his history being depression.

He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.

Dr. Paauw

What is the most likely source of his bleeding?

A. Gastric ulcer

B. Meckel’s diverticulum

C. Arteriovenous malformation

D. Diverticulosis

E. Hemorrhoids

What makes the most sense

The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.

We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.

Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1

Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).

Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.

Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.

Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).

High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
 

Pearl

Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am J Emerg Med. 2006 May;24(3):280-5.

2. JAMA. 2012;307(10):1072-9.

3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.

4. Cardiorenal Med. 2020;10:415-28.

A 43-year-old man presents to the emergency department with dizziness and a 6-hour history of passing maroon stool. He has been in good health with the only medical problem in his history being depression.

He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.

Dr. Paauw

What is the most likely source of his bleeding?

A. Gastric ulcer

B. Meckel’s diverticulum

C. Arteriovenous malformation

D. Diverticulosis

E. Hemorrhoids

What makes the most sense

The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.

We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.

Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1

Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).

Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.

Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.

Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).

High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
 

Pearl

Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am J Emerg Med. 2006 May;24(3):280-5.

2. JAMA. 2012;307(10):1072-9.

3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.

4. Cardiorenal Med. 2020;10:415-28.

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Commentary: Concerning PsA treatments and comorbidities, March 2023

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Dr. Chandran scans the journals, so you don't have to!

Vinod Chandran, MBBS, MD, DM, PhD
Psoriatic arthritis (PsA) is a heterogeneous disease with clinical manifestations affecting the skin, joints, spine, and periarticular structures, such as the entheses and tendons. The impact of these manifestations individually on health-related quality of life (QOL) and physical function is less studied. Using data from a cross-sectional observational study including 2222 patients with a physician-confirmed diagnosis of PsA, Walsh and colleagues report that the presence of enthesitis, dactylitis, inflammatory back pain, and peripheral joint involvement was significantly associated with worse QOL and self-rated health when compared with patients without these manifestations. Moreover, an increasing number of affected joints and greater body surface area with psoriasis were significantly correlated with poorer functional state and greater work productivity impairment. This study provides further insights into the effect of the different domains of PsA on the patient. Clinicians managing PsA should therefore evaluate these domains and aim to reduce disease activity in each domain to improve QOL and function.

 

With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.

 

In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.

 

Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.

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Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

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Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

Author and Disclosure Information

Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

Dr. Chandran scans the journals, so you don't have to!
Dr. Chandran scans the journals, so you don't have to!

Vinod Chandran, MBBS, MD, DM, PhD
Psoriatic arthritis (PsA) is a heterogeneous disease with clinical manifestations affecting the skin, joints, spine, and periarticular structures, such as the entheses and tendons. The impact of these manifestations individually on health-related quality of life (QOL) and physical function is less studied. Using data from a cross-sectional observational study including 2222 patients with a physician-confirmed diagnosis of PsA, Walsh and colleagues report that the presence of enthesitis, dactylitis, inflammatory back pain, and peripheral joint involvement was significantly associated with worse QOL and self-rated health when compared with patients without these manifestations. Moreover, an increasing number of affected joints and greater body surface area with psoriasis were significantly correlated with poorer functional state and greater work productivity impairment. This study provides further insights into the effect of the different domains of PsA on the patient. Clinicians managing PsA should therefore evaluate these domains and aim to reduce disease activity in each domain to improve QOL and function.

 

With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.

 

In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.

 

Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.

Vinod Chandran, MBBS, MD, DM, PhD
Psoriatic arthritis (PsA) is a heterogeneous disease with clinical manifestations affecting the skin, joints, spine, and periarticular structures, such as the entheses and tendons. The impact of these manifestations individually on health-related quality of life (QOL) and physical function is less studied. Using data from a cross-sectional observational study including 2222 patients with a physician-confirmed diagnosis of PsA, Walsh and colleagues report that the presence of enthesitis, dactylitis, inflammatory back pain, and peripheral joint involvement was significantly associated with worse QOL and self-rated health when compared with patients without these manifestations. Moreover, an increasing number of affected joints and greater body surface area with psoriasis were significantly correlated with poorer functional state and greater work productivity impairment. This study provides further insights into the effect of the different domains of PsA on the patient. Clinicians managing PsA should therefore evaluate these domains and aim to reduce disease activity in each domain to improve QOL and function.

 

With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.

 

In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.

 

Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.

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PsA: Baseline disease activity predicts DAPSA response in patients treated with apremilast

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Key clinical point: Nearly half of the patients with psoriatic arthritis (PsA) treated with apremilast achieved disease activity index for psoriatic arthritis (DAPSA) low disease activity/remission at 6 or 12 months, with lower baseline disease activity being the only factor associated with the achievement of low disease activity or remission.

Major finding: Overall, 42.7% and 54.9% of patients achieved DAPSA low disease activity or remission at 6 and 12 months, respectively. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio [OR] 0.84) and 12 months (OR 0.91; both P < .01).

Study details: Findings are from a retrospective study including 293 patients with PsA who were treated with apremilast.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Becciolini A et al. Predictors of DAPSA response in psoriatic arthritis patients treated with apremilast in a retrospective observational multi-centric study. Biomedicines. 2023;11(2):433 (Feb 2). Doi: 10.3390/biomedicines11020433

 

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Key clinical point: Nearly half of the patients with psoriatic arthritis (PsA) treated with apremilast achieved disease activity index for psoriatic arthritis (DAPSA) low disease activity/remission at 6 or 12 months, with lower baseline disease activity being the only factor associated with the achievement of low disease activity or remission.

Major finding: Overall, 42.7% and 54.9% of patients achieved DAPSA low disease activity or remission at 6 and 12 months, respectively. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio [OR] 0.84) and 12 months (OR 0.91; both P < .01).

Study details: Findings are from a retrospective study including 293 patients with PsA who were treated with apremilast.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Becciolini A et al. Predictors of DAPSA response in psoriatic arthritis patients treated with apremilast in a retrospective observational multi-centric study. Biomedicines. 2023;11(2):433 (Feb 2). Doi: 10.3390/biomedicines11020433

 

Key clinical point: Nearly half of the patients with psoriatic arthritis (PsA) treated with apremilast achieved disease activity index for psoriatic arthritis (DAPSA) low disease activity/remission at 6 or 12 months, with lower baseline disease activity being the only factor associated with the achievement of low disease activity or remission.

Major finding: Overall, 42.7% and 54.9% of patients achieved DAPSA low disease activity or remission at 6 and 12 months, respectively. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio [OR] 0.84) and 12 months (OR 0.91; both P < .01).

Study details: Findings are from a retrospective study including 293 patients with PsA who were treated with apremilast.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Becciolini A et al. Predictors of DAPSA response in psoriatic arthritis patients treated with apremilast in a retrospective observational multi-centric study. Biomedicines. 2023;11(2):433 (Feb 2). Doi: 10.3390/biomedicines11020433

 

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Long-term safety and tolerability of upadacitinib in PsA

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Key clinical point: Upadacitinib demonstrated an acceptable long-term safety profile and was generally well tolerated with no new safety signals in patients with psoriatic arthritis (PsA).

 

Major finding: Overall, patients with PsA receiving 15 mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and deaths (0.8/100 PY).

 

Study details: This integrated safety analysis of 12 phase 3 trials included 6991 patients with PsA (n = 907), rheumatoid arthritis (n = 3,209), ankylosing spondylitis (n = 182), and atopic dermatitis (n = 2693) who received upadacitinib (15 or 30 mg once daily); 1008 patients with RA (n = 579) and PsA (n = 429) who received 40 mg adalimumab every other week; and 314 patients with RA who received methotrexate.

 

Disclosures: This study was funded by AbbVie. Five authors declared being full-time employees of AbbVie or Mount Sinai or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

 

Source: Burmester GR et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735;15(Feb 8). Doi: 10.1136/rmdopen-2022-002735

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Key clinical point: Upadacitinib demonstrated an acceptable long-term safety profile and was generally well tolerated with no new safety signals in patients with psoriatic arthritis (PsA).

 

Major finding: Overall, patients with PsA receiving 15 mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and deaths (0.8/100 PY).

 

Study details: This integrated safety analysis of 12 phase 3 trials included 6991 patients with PsA (n = 907), rheumatoid arthritis (n = 3,209), ankylosing spondylitis (n = 182), and atopic dermatitis (n = 2693) who received upadacitinib (15 or 30 mg once daily); 1008 patients with RA (n = 579) and PsA (n = 429) who received 40 mg adalimumab every other week; and 314 patients with RA who received methotrexate.

 

Disclosures: This study was funded by AbbVie. Five authors declared being full-time employees of AbbVie or Mount Sinai or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

 

Source: Burmester GR et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735;15(Feb 8). Doi: 10.1136/rmdopen-2022-002735

Key clinical point: Upadacitinib demonstrated an acceptable long-term safety profile and was generally well tolerated with no new safety signals in patients with psoriatic arthritis (PsA).

 

Major finding: Overall, patients with PsA receiving 15 mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and deaths (0.8/100 PY).

 

Study details: This integrated safety analysis of 12 phase 3 trials included 6991 patients with PsA (n = 907), rheumatoid arthritis (n = 3,209), ankylosing spondylitis (n = 182), and atopic dermatitis (n = 2693) who received upadacitinib (15 or 30 mg once daily); 1008 patients with RA (n = 579) and PsA (n = 429) who received 40 mg adalimumab every other week; and 314 patients with RA who received methotrexate.

 

Disclosures: This study was funded by AbbVie. Five authors declared being full-time employees of AbbVie or Mount Sinai or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

 

Source: Burmester GR et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735;15(Feb 8). Doi: 10.1136/rmdopen-2022-002735

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Baseline cardiovascular risk may influence MACE and malignancy incidences in tofacitinib-treated PsA patients

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Key clinical point: Preventive monitoring for cardiovascular risk is suggested in tofacitinib-treated patients with psoriatic arthritis (PsA) as higher atherosclerotic cardiovascular disease (ASCVD) risk appears to be associated with a higher incidence of major cardiovascular events (MACE) and malignancies.

Major finding: The risk for MACE appeared to be higher among patients with PsA and high vs low 10-year ASCVD risk (incidence rate [IR] 1.37 [95% CI 0.03-7.63] vs 0.08 [95% CI 0.0-0.42]), with the incidence of malignancies being the highest in patients with PsA and an intermediate 10-year ASCVD risk (IR 2.56, 95% CI 1.11-5.05).

Study details: Findings are from a post hoc analysis of 10 clinical trials including patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib.

Disclosures: This study was sponsored by Pfizer. Some authors declared receiving speaker fees or grant or research support or serving as consultants for various sources, including Pfizer. Some authors declared being employees and shareholders of Pfizer or Syneos Health, a paid contractor to Pfizer.

Source: Kristensen LE et al. Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib. Ther Adv Musculoskelet Dis. 2023 (Feb 7). Doi: 10.1177/1759720X221149965

 

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Key clinical point: Preventive monitoring for cardiovascular risk is suggested in tofacitinib-treated patients with psoriatic arthritis (PsA) as higher atherosclerotic cardiovascular disease (ASCVD) risk appears to be associated with a higher incidence of major cardiovascular events (MACE) and malignancies.

Major finding: The risk for MACE appeared to be higher among patients with PsA and high vs low 10-year ASCVD risk (incidence rate [IR] 1.37 [95% CI 0.03-7.63] vs 0.08 [95% CI 0.0-0.42]), with the incidence of malignancies being the highest in patients with PsA and an intermediate 10-year ASCVD risk (IR 2.56, 95% CI 1.11-5.05).

Study details: Findings are from a post hoc analysis of 10 clinical trials including patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib.

Disclosures: This study was sponsored by Pfizer. Some authors declared receiving speaker fees or grant or research support or serving as consultants for various sources, including Pfizer. Some authors declared being employees and shareholders of Pfizer or Syneos Health, a paid contractor to Pfizer.

Source: Kristensen LE et al. Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib. Ther Adv Musculoskelet Dis. 2023 (Feb 7). Doi: 10.1177/1759720X221149965

 

Key clinical point: Preventive monitoring for cardiovascular risk is suggested in tofacitinib-treated patients with psoriatic arthritis (PsA) as higher atherosclerotic cardiovascular disease (ASCVD) risk appears to be associated with a higher incidence of major cardiovascular events (MACE) and malignancies.

Major finding: The risk for MACE appeared to be higher among patients with PsA and high vs low 10-year ASCVD risk (incidence rate [IR] 1.37 [95% CI 0.03-7.63] vs 0.08 [95% CI 0.0-0.42]), with the incidence of malignancies being the highest in patients with PsA and an intermediate 10-year ASCVD risk (IR 2.56, 95% CI 1.11-5.05).

Study details: Findings are from a post hoc analysis of 10 clinical trials including patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib.

Disclosures: This study was sponsored by Pfizer. Some authors declared receiving speaker fees or grant or research support or serving as consultants for various sources, including Pfizer. Some authors declared being employees and shareholders of Pfizer or Syneos Health, a paid contractor to Pfizer.

Source: Kristensen LE et al. Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib. Ther Adv Musculoskelet Dis. 2023 (Feb 7). Doi: 10.1177/1759720X221149965

 

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Circulating microRNA can differentiate between psoriasis and psoriatic arthritis

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Key clinical point: Signatures of circulating microRNA in patients with psoriatic arthritis (PsA) and patients with psoriasis were significantly different from those in control individuals, with some even being differentially regulated between PsA and psoriasis.

 

Major finding: Overall, 9 microRNA best differentiated patients with PsA and psoriasis from control individuals (area under the curve [AUC] 0.70; all P < .05) and 4 microRNA best differentiated patients with PsA from patients with psoriasis (all P < .05). A combination of 4 microRNA (miR-19b-3p, miR-21-5p, miR-92a-3p, and let-7b-5p) vs miR-92a-3p alone could better differentiate between patients with PsA and psoriasis (AUC 0.92 vs 0.82).

 

Study details: This cross-sectional study included 51 patients with PsA, 40 patients with psoriasis, and 50 control individuals.

 

Disclosures: This study did not receive any specific funding. Two authors declared being employees or shareholders of TAmiRNA GmbH or holding intellectual property for the diagnostic use of microRNA in bone diseases.

 

Source: Haschka J et al. Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis. Rheumatology (Oxford). 2023 (Feb 3). Doi: 10.1093/rheumatology/kead059

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Key clinical point: Signatures of circulating microRNA in patients with psoriatic arthritis (PsA) and patients with psoriasis were significantly different from those in control individuals, with some even being differentially regulated between PsA and psoriasis.

 

Major finding: Overall, 9 microRNA best differentiated patients with PsA and psoriasis from control individuals (area under the curve [AUC] 0.70; all P < .05) and 4 microRNA best differentiated patients with PsA from patients with psoriasis (all P < .05). A combination of 4 microRNA (miR-19b-3p, miR-21-5p, miR-92a-3p, and let-7b-5p) vs miR-92a-3p alone could better differentiate between patients with PsA and psoriasis (AUC 0.92 vs 0.82).

 

Study details: This cross-sectional study included 51 patients with PsA, 40 patients with psoriasis, and 50 control individuals.

 

Disclosures: This study did not receive any specific funding. Two authors declared being employees or shareholders of TAmiRNA GmbH or holding intellectual property for the diagnostic use of microRNA in bone diseases.

 

Source: Haschka J et al. Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis. Rheumatology (Oxford). 2023 (Feb 3). Doi: 10.1093/rheumatology/kead059

Key clinical point: Signatures of circulating microRNA in patients with psoriatic arthritis (PsA) and patients with psoriasis were significantly different from those in control individuals, with some even being differentially regulated between PsA and psoriasis.

 

Major finding: Overall, 9 microRNA best differentiated patients with PsA and psoriasis from control individuals (area under the curve [AUC] 0.70; all P < .05) and 4 microRNA best differentiated patients with PsA from patients with psoriasis (all P < .05). A combination of 4 microRNA (miR-19b-3p, miR-21-5p, miR-92a-3p, and let-7b-5p) vs miR-92a-3p alone could better differentiate between patients with PsA and psoriasis (AUC 0.92 vs 0.82).

 

Study details: This cross-sectional study included 51 patients with PsA, 40 patients with psoriasis, and 50 control individuals.

 

Disclosures: This study did not receive any specific funding. Two authors declared being employees or shareholders of TAmiRNA GmbH or holding intellectual property for the diagnostic use of microRNA in bone diseases.

 

Source: Haschka J et al. Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis. Rheumatology (Oxford). 2023 (Feb 3). Doi: 10.1093/rheumatology/kead059

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Crude mortality rate doubled in PsA patients during COVID-19 pandemic

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Key clinical point: The crude mortality rate increased by two-fold in patients with psoriatic arthritis (PsA) during the COVID-19 pandemic compared with the pre-pandemic era, with pulmonary reasons being the major risk factors for mortality.

Major finding: Although standard mortality rates were similar between patients with PsA and the general population during the pre-pandemic period (0.95; 95% CI 0.61-1.49), the crude mortality rate, which was 5.07 before the pandemic, increased by 2.12-fold during the pandemic in the PsA population. Interestingly, deaths due to pulmonary reasons increased from 6% during the pre-pandemic era to 66% during the pandemic.

Study details: Findings are from an international multicenter registry study including 1216 patients with PsA who were followed up for 7500 patient-years.

Disclosures: This study did not report the source of funding. Some authors declared receiving honoraria or research grants from several sources.

Source: Erden A et al. Mortality in psoriatic arthritis patients, changes over time, and the impact of COVID-19: Results from a multicenter Psoriatic Arthritis Registry (PsART-ID). Clin Rheumatol. 2023;42(2):385-390(Jan 13). Doi: 10.1007/s10067-022-06492-6

 

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Key clinical point: The crude mortality rate increased by two-fold in patients with psoriatic arthritis (PsA) during the COVID-19 pandemic compared with the pre-pandemic era, with pulmonary reasons being the major risk factors for mortality.

Major finding: Although standard mortality rates were similar between patients with PsA and the general population during the pre-pandemic period (0.95; 95% CI 0.61-1.49), the crude mortality rate, which was 5.07 before the pandemic, increased by 2.12-fold during the pandemic in the PsA population. Interestingly, deaths due to pulmonary reasons increased from 6% during the pre-pandemic era to 66% during the pandemic.

Study details: Findings are from an international multicenter registry study including 1216 patients with PsA who were followed up for 7500 patient-years.

Disclosures: This study did not report the source of funding. Some authors declared receiving honoraria or research grants from several sources.

Source: Erden A et al. Mortality in psoriatic arthritis patients, changes over time, and the impact of COVID-19: Results from a multicenter Psoriatic Arthritis Registry (PsART-ID). Clin Rheumatol. 2023;42(2):385-390(Jan 13). Doi: 10.1007/s10067-022-06492-6

 

Key clinical point: The crude mortality rate increased by two-fold in patients with psoriatic arthritis (PsA) during the COVID-19 pandemic compared with the pre-pandemic era, with pulmonary reasons being the major risk factors for mortality.

Major finding: Although standard mortality rates were similar between patients with PsA and the general population during the pre-pandemic period (0.95; 95% CI 0.61-1.49), the crude mortality rate, which was 5.07 before the pandemic, increased by 2.12-fold during the pandemic in the PsA population. Interestingly, deaths due to pulmonary reasons increased from 6% during the pre-pandemic era to 66% during the pandemic.

Study details: Findings are from an international multicenter registry study including 1216 patients with PsA who were followed up for 7500 patient-years.

Disclosures: This study did not report the source of funding. Some authors declared receiving honoraria or research grants from several sources.

Source: Erden A et al. Mortality in psoriatic arthritis patients, changes over time, and the impact of COVID-19: Results from a multicenter Psoriatic Arthritis Registry (PsART-ID). Clin Rheumatol. 2023;42(2):385-390(Jan 13). Doi: 10.1007/s10067-022-06492-6

 

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Real-world evidence on impact of PsA manifestation on patient outcomes

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Key clinical point: All multiple manifestations of psoriatic arthritis (PsA) negatively affect quality of life (QoL), with dactylitis, peripheral joint disease, and psoriasis impairing functional status, whereas joint, skin, and periarticular symptoms independently impair work productivity.

Major finding: Presence vs absence of enthesitis, dactylitis, inflammatory back pain, and peripheral joint involvement was associated with worse QoL and self-rated health (all P < .05), whereas increasing number of affected joints and greater body surface area involvement significantly correlated with poorer functional state and greater work productivity impairment (all P < .05).

Study details: Findings are from a cross-sectional observational study including 2222 patients with physician-confirmed diagnosis of PsA.

Disclosures: This study did not receive any specific funding. Some authors declared receiving grants from, serving as a consultant for, being an employee of, or owning shares in different sources.

Source: Walsh JA et al. Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe. Joint Bone Spine. 2023;105534 (Jan 25). Doi: 10.1016/j.jbspin.2023.105534

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Key clinical point: All multiple manifestations of psoriatic arthritis (PsA) negatively affect quality of life (QoL), with dactylitis, peripheral joint disease, and psoriasis impairing functional status, whereas joint, skin, and periarticular symptoms independently impair work productivity.

Major finding: Presence vs absence of enthesitis, dactylitis, inflammatory back pain, and peripheral joint involvement was associated with worse QoL and self-rated health (all P < .05), whereas increasing number of affected joints and greater body surface area involvement significantly correlated with poorer functional state and greater work productivity impairment (all P < .05).

Study details: Findings are from a cross-sectional observational study including 2222 patients with physician-confirmed diagnosis of PsA.

Disclosures: This study did not receive any specific funding. Some authors declared receiving grants from, serving as a consultant for, being an employee of, or owning shares in different sources.

Source: Walsh JA et al. Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe. Joint Bone Spine. 2023;105534 (Jan 25). Doi: 10.1016/j.jbspin.2023.105534

Key clinical point: All multiple manifestations of psoriatic arthritis (PsA) negatively affect quality of life (QoL), with dactylitis, peripheral joint disease, and psoriasis impairing functional status, whereas joint, skin, and periarticular symptoms independently impair work productivity.

Major finding: Presence vs absence of enthesitis, dactylitis, inflammatory back pain, and peripheral joint involvement was associated with worse QoL and self-rated health (all P < .05), whereas increasing number of affected joints and greater body surface area involvement significantly correlated with poorer functional state and greater work productivity impairment (all P < .05).

Study details: Findings are from a cross-sectional observational study including 2222 patients with physician-confirmed diagnosis of PsA.

Disclosures: This study did not receive any specific funding. Some authors declared receiving grants from, serving as a consultant for, being an employee of, or owning shares in different sources.

Source: Walsh JA et al. Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe. Joint Bone Spine. 2023;105534 (Jan 25). Doi: 10.1016/j.jbspin.2023.105534

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Concomitant PsA tied with higher comorbidities and low treatment persistence in psoriasis

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Key clinical point:  Patients with psoriasis and concomitant psoriatic arthritis (PsA) had a greater comorbidity burden compared with those with psoriasis alone, which negatively impacted treatment persistence.

Major finding: Among patients receiving ustekinumab, those with concomitant PsA vs psoriasis alone had higher comorbidity burden, including diabetes (odds ratio [OR] 1.52; 95% CI 1.16-1.97), hypertension (OR 1.55; 95% CI 1.27-1.89), and obesity (OR 1.33; 95% CI 1.1-1.61), and a shorter time to ustekinumab discontinuation (hazard ratio 1.98; P < .0001).

Study details: This was a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs.

Disclosures: This study was funded by Janssen-Cilag Ltd. W Tillett and A Ogdie declared receiving fees and grants or research support from various sources, including Janssen. A Passey and P Gorecki declared being employees of Janssen-Cilag Ltd.

Source: Tillett W et al. Impact of psoriatic arthritis and comorbidities on ustekinumab outcomes in psoriasis: A retrospective, observational BADBIR cohort study. RMD Open. 2023;9(1):e002533 (Jan 17). Doi: 10.1136/rmdopen-2022-002533

 

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Key clinical point:  Patients with psoriasis and concomitant psoriatic arthritis (PsA) had a greater comorbidity burden compared with those with psoriasis alone, which negatively impacted treatment persistence.

Major finding: Among patients receiving ustekinumab, those with concomitant PsA vs psoriasis alone had higher comorbidity burden, including diabetes (odds ratio [OR] 1.52; 95% CI 1.16-1.97), hypertension (OR 1.55; 95% CI 1.27-1.89), and obesity (OR 1.33; 95% CI 1.1-1.61), and a shorter time to ustekinumab discontinuation (hazard ratio 1.98; P < .0001).

Study details: This was a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs.

Disclosures: This study was funded by Janssen-Cilag Ltd. W Tillett and A Ogdie declared receiving fees and grants or research support from various sources, including Janssen. A Passey and P Gorecki declared being employees of Janssen-Cilag Ltd.

Source: Tillett W et al. Impact of psoriatic arthritis and comorbidities on ustekinumab outcomes in psoriasis: A retrospective, observational BADBIR cohort study. RMD Open. 2023;9(1):e002533 (Jan 17). Doi: 10.1136/rmdopen-2022-002533

 

Key clinical point:  Patients with psoriasis and concomitant psoriatic arthritis (PsA) had a greater comorbidity burden compared with those with psoriasis alone, which negatively impacted treatment persistence.

Major finding: Among patients receiving ustekinumab, those with concomitant PsA vs psoriasis alone had higher comorbidity burden, including diabetes (odds ratio [OR] 1.52; 95% CI 1.16-1.97), hypertension (OR 1.55; 95% CI 1.27-1.89), and obesity (OR 1.33; 95% CI 1.1-1.61), and a shorter time to ustekinumab discontinuation (hazard ratio 1.98; P < .0001).

Study details: This was a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs.

Disclosures: This study was funded by Janssen-Cilag Ltd. W Tillett and A Ogdie declared receiving fees and grants or research support from various sources, including Janssen. A Passey and P Gorecki declared being employees of Janssen-Cilag Ltd.

Source: Tillett W et al. Impact of psoriatic arthritis and comorbidities on ustekinumab outcomes in psoriasis: A retrospective, observational BADBIR cohort study. RMD Open. 2023;9(1):e002533 (Jan 17). Doi: 10.1136/rmdopen-2022-002533

 

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