Rheumatology News

President-elect Donald Trump’s vision for the nation’s top health agencies is coming into focus with three nominations announced Nov. 22 that drew both criticism and praise:

• Surgeon and health researcher Martin A. Makary, MD, MPH, to lead the US Food and Drug Administration (FDA).
• Former Republican congressman and physician David J. Weldon, MD, for director of the US Centers for Disease Control and Prevention (CDC).
• Fox News contributor Janette Nesheiwat, MD, for surgeon general.

Earlier in November, Trump nominated vaccine skeptic and former presidential candidate Robert F. Kennedy Jr. to lead the US Department of Health and Human Services (HHS). 

Here’s what to know about the latest nominees, who, like Kennedy, must be confirmed by the US Senate.

 

Martin A. Makary

Currently a professor at the Johns Hopkins School of Medicine and chief of islet transplant surgery at Johns Hopkins Hospital, Makary co-invented in 2006 a surgery checklist that became a widely-used patient safety tool. 

As a US FDA commissioner, Makary would preside over a $6.5 billion agency with more than 18,000 employees. The agency, part of HHS, oversees human and animal drugs and vaccines, medical devices, food, tobacco and other products. Some of Makary’s views align closely with those of HHS nominee Kennedy. 

Makary is also chief medical officer of telehealth platform Sesame.

Makary was primarily known as a health researcher and author of books about price transparency and the cost of health care until the COVID-19 pandemic, when he became an outspoken critic of the federal response, lambasting restrictions and mandates advocated by the CDC and other public health officials. 

In 2023, Makary told the House Select Subcommittee on the COVID Pandemic that federal officials had ignored what he called “natural immunity.” Studies have shown that natural immunity is “at least as effective as vaccinated immunity, and probably better,” testified Makary.

Makary called for an overhaul of the US FDA in a 2021 Fox News opinion, saying that its culture was “defined by counterproductive rigidity and a refusal to adapt.”

Blind Spots, his most recent book, takes on what he calls “medical dogma” and challenges conventional views on subjects ranging from the microbiome to marijuana to cancer prevention, hormone replacement therapy, antibiotics and peanut allergies.

In an interview he posted to X, Makary blames inappropriate use of antibiotics for a variety of childhood illnesses. He cites increases in obesity, learning disabilities, attention deficit disorder, asthma, celiac disease, ulcerative colitis and Crohn’s disease as all potentially causally related to antibiotics given in childhood.

Makary is an advisor to two conservative think tanks, the Foundation for Research on Equal Opportunity, and to Paragon Health Institute, begun in 2021 by two former top officials in the previous Trump administration.

Makary would “cut the bureaucratic red tape at the agency to make sure Americans get the medical cures and treatments they deserve,” Trump said on his social media platform, Truth Social, and in a press release.

While Los Angeles Times owner and physician-entrepreneur Patrick Soon-Shiong, MBBCh, MSc, praised the nomination of Makary (and the two other nominees) as “inspired,” other physicians criticized Makary for his anti-COVID mandate views and “fear-mongering” over COVID vaccine side effects.

 

Janette Nesheiwat

As surgeon general, Nesheiwat would serve as the top “health communicator in chief” and oversee the 6000 member US Public Health Service Commissioned Corps.

She is a frequent medical contributor to Fox News and serves as a medical director for a group of urgent care clinics in New York. She received her medical degree from the American University of the Caribbean School of Medicine and completed a family medicine residency at the University of Arkansas for Medical Sciences. She is board-certified in family medicine.

Nesheiwat sells vitamin supplements on her website and in December will publish a book on “miracles in medicine” and her Christian faith. 

Trump said in a statement that Nesheiwat “is a fierce advocate and strong communicator for preventive medicine and public health. She is committed to ensuring that Americans have access to affordable, quality healthcare, and believes in empowering individuals to take charge of their health to live longer, healthier lives.”

While Nesheiwat was critical of COVID mandates, she voiced more support for COVID vaccines and mask-wearing during the pandemic than her fellow nominees, leading some Trump supporters to criticize her nomination. 

“A good appointment, happy about this: I got to know @DoctorJanette during the pandemic, exchanging information. She is very smart, thoughtful, interested in learning, and a compassionate doctor, and…a truly nice person,” noted vaccine researcher Peter Hotez, MD, PhD, said on X.

 

David J. Weldon

If confirmed, former congressman Weldon would oversee the sprawling CDC, an agency with a roughly $17 billion budget, 15,000 employees or contractors, and numerous centers covering everything from health statistics to vaccines to epidemiology.

After earning his medical degree from the University at Buffalo School of Medicine, Weldon served in the US Army and US Army reserve. The Republican later served for 14 years in Congress representing Florida’s 15th district, which covers the Tampa region.

He now practices as an internist in Brevard County, Florida.

In Congress, Weldon raised concerns about the safety of some vaccines and promoted the false narrative that a former vaccine ingredient, thimerosal, caused autism, the Washington Post reported. Thimerosal has not been used in child vaccines for more than two decades. He also introduced a bill to move vaccine safety oversight from the CDC to an independent agency within HHS.

Trump said in a statement that Weldon “will proudly restore the CDC to its true purpose, and will work to end the Chronic Disease Epidemic.” 

But some physicians criticized Weldon for what they called his anti-vaccine views.

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

President-elect Donald Trump’s vision for the nation’s top health agencies is coming into focus with three nominations announced Nov. 22 that drew both criticism and praise:

• Surgeon and health researcher Martin A. Makary, MD, MPH, to lead the US Food and Drug Administration (FDA).
• Former Republican congressman and physician David J. Weldon, MD, for director of the US Centers for Disease Control and Prevention (CDC).
• Fox News contributor Janette Nesheiwat, MD, for surgeon general.

Earlier in November, Trump nominated vaccine skeptic and former presidential candidate Robert F. Kennedy Jr. to lead the US Department of Health and Human Services (HHS). 

Here’s what to know about the latest nominees, who, like Kennedy, must be confirmed by the US Senate.

 

Martin A. Makary

Currently a professor at the Johns Hopkins School of Medicine and chief of islet transplant surgery at Johns Hopkins Hospital, Makary co-invented in 2006 a surgery checklist that became a widely-used patient safety tool. 

As a US FDA commissioner, Makary would preside over a $6.5 billion agency with more than 18,000 employees. The agency, part of HHS, oversees human and animal drugs and vaccines, medical devices, food, tobacco and other products. Some of Makary’s views align closely with those of HHS nominee Kennedy. 

Makary is also chief medical officer of telehealth platform Sesame.

Makary was primarily known as a health researcher and author of books about price transparency and the cost of health care until the COVID-19 pandemic, when he became an outspoken critic of the federal response, lambasting restrictions and mandates advocated by the CDC and other public health officials. 

In 2023, Makary told the House Select Subcommittee on the COVID Pandemic that federal officials had ignored what he called “natural immunity.” Studies have shown that natural immunity is “at least as effective as vaccinated immunity, and probably better,” testified Makary.

Makary called for an overhaul of the US FDA in a 2021 Fox News opinion, saying that its culture was “defined by counterproductive rigidity and a refusal to adapt.”

Blind Spots, his most recent book, takes on what he calls “medical dogma” and challenges conventional views on subjects ranging from the microbiome to marijuana to cancer prevention, hormone replacement therapy, antibiotics and peanut allergies.

In an interview he posted to X, Makary blames inappropriate use of antibiotics for a variety of childhood illnesses. He cites increases in obesity, learning disabilities, attention deficit disorder, asthma, celiac disease, ulcerative colitis and Crohn’s disease as all potentially causally related to antibiotics given in childhood.

Makary is an advisor to two conservative think tanks, the Foundation for Research on Equal Opportunity, and to Paragon Health Institute, begun in 2021 by two former top officials in the previous Trump administration.

Makary would “cut the bureaucratic red tape at the agency to make sure Americans get the medical cures and treatments they deserve,” Trump said on his social media platform, Truth Social, and in a press release.

While Los Angeles Times owner and physician-entrepreneur Patrick Soon-Shiong, MBBCh, MSc, praised the nomination of Makary (and the two other nominees) as “inspired,” other physicians criticized Makary for his anti-COVID mandate views and “fear-mongering” over COVID vaccine side effects.

 

Janette Nesheiwat

As surgeon general, Nesheiwat would serve as the top “health communicator in chief” and oversee the 6000 member US Public Health Service Commissioned Corps.

She is a frequent medical contributor to Fox News and serves as a medical director for a group of urgent care clinics in New York. She received her medical degree from the American University of the Caribbean School of Medicine and completed a family medicine residency at the University of Arkansas for Medical Sciences. She is board-certified in family medicine.

Nesheiwat sells vitamin supplements on her website and in December will publish a book on “miracles in medicine” and her Christian faith. 

Trump said in a statement that Nesheiwat “is a fierce advocate and strong communicator for preventive medicine and public health. She is committed to ensuring that Americans have access to affordable, quality healthcare, and believes in empowering individuals to take charge of their health to live longer, healthier lives.”

While Nesheiwat was critical of COVID mandates, she voiced more support for COVID vaccines and mask-wearing during the pandemic than her fellow nominees, leading some Trump supporters to criticize her nomination. 

“A good appointment, happy about this: I got to know @DoctorJanette during the pandemic, exchanging information. She is very smart, thoughtful, interested in learning, and a compassionate doctor, and…a truly nice person,” noted vaccine researcher Peter Hotez, MD, PhD, said on X.

 

David J. Weldon

If confirmed, former congressman Weldon would oversee the sprawling CDC, an agency with a roughly $17 billion budget, 15,000 employees or contractors, and numerous centers covering everything from health statistics to vaccines to epidemiology.

After earning his medical degree from the University at Buffalo School of Medicine, Weldon served in the US Army and US Army reserve. The Republican later served for 14 years in Congress representing Florida’s 15th district, which covers the Tampa region.

He now practices as an internist in Brevard County, Florida.

In Congress, Weldon raised concerns about the safety of some vaccines and promoted the false narrative that a former vaccine ingredient, thimerosal, caused autism, the Washington Post reported. Thimerosal has not been used in child vaccines for more than two decades. He also introduced a bill to move vaccine safety oversight from the CDC to an independent agency within HHS.

Trump said in a statement that Weldon “will proudly restore the CDC to its true purpose, and will work to end the Chronic Disease Epidemic.” 

But some physicians criticized Weldon for what they called his anti-vaccine views.

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

President-elect Donald Trump’s vision for the nation’s top health agencies is coming into focus with three nominations announced Nov. 22 that drew both criticism and praise:

• Surgeon and health researcher Martin A. Makary, MD, MPH, to lead the US Food and Drug Administration (FDA).
• Former Republican congressman and physician David J. Weldon, MD, for director of the US Centers for Disease Control and Prevention (CDC).
• Fox News contributor Janette Nesheiwat, MD, for surgeon general.

Earlier in November, Trump nominated vaccine skeptic and former presidential candidate Robert F. Kennedy Jr. to lead the US Department of Health and Human Services (HHS). 

Here’s what to know about the latest nominees, who, like Kennedy, must be confirmed by the US Senate.

 

Martin A. Makary

Currently a professor at the Johns Hopkins School of Medicine and chief of islet transplant surgery at Johns Hopkins Hospital, Makary co-invented in 2006 a surgery checklist that became a widely-used patient safety tool. 

As a US FDA commissioner, Makary would preside over a $6.5 billion agency with more than 18,000 employees. The agency, part of HHS, oversees human and animal drugs and vaccines, medical devices, food, tobacco and other products. Some of Makary’s views align closely with those of HHS nominee Kennedy. 

Makary is also chief medical officer of telehealth platform Sesame.

Makary was primarily known as a health researcher and author of books about price transparency and the cost of health care until the COVID-19 pandemic, when he became an outspoken critic of the federal response, lambasting restrictions and mandates advocated by the CDC and other public health officials. 

In 2023, Makary told the House Select Subcommittee on the COVID Pandemic that federal officials had ignored what he called “natural immunity.” Studies have shown that natural immunity is “at least as effective as vaccinated immunity, and probably better,” testified Makary.

Makary called for an overhaul of the US FDA in a 2021 Fox News opinion, saying that its culture was “defined by counterproductive rigidity and a refusal to adapt.”

Blind Spots, his most recent book, takes on what he calls “medical dogma” and challenges conventional views on subjects ranging from the microbiome to marijuana to cancer prevention, hormone replacement therapy, antibiotics and peanut allergies.

In an interview he posted to X, Makary blames inappropriate use of antibiotics for a variety of childhood illnesses. He cites increases in obesity, learning disabilities, attention deficit disorder, asthma, celiac disease, ulcerative colitis and Crohn’s disease as all potentially causally related to antibiotics given in childhood.

Makary is an advisor to two conservative think tanks, the Foundation for Research on Equal Opportunity, and to Paragon Health Institute, begun in 2021 by two former top officials in the previous Trump administration.

Makary would “cut the bureaucratic red tape at the agency to make sure Americans get the medical cures and treatments they deserve,” Trump said on his social media platform, Truth Social, and in a press release.

While Los Angeles Times owner and physician-entrepreneur Patrick Soon-Shiong, MBBCh, MSc, praised the nomination of Makary (and the two other nominees) as “inspired,” other physicians criticized Makary for his anti-COVID mandate views and “fear-mongering” over COVID vaccine side effects.

 

Janette Nesheiwat

As surgeon general, Nesheiwat would serve as the top “health communicator in chief” and oversee the 6000 member US Public Health Service Commissioned Corps.

She is a frequent medical contributor to Fox News and serves as a medical director for a group of urgent care clinics in New York. She received her medical degree from the American University of the Caribbean School of Medicine and completed a family medicine residency at the University of Arkansas for Medical Sciences. She is board-certified in family medicine.

Nesheiwat sells vitamin supplements on her website and in December will publish a book on “miracles in medicine” and her Christian faith. 

Trump said in a statement that Nesheiwat “is a fierce advocate and strong communicator for preventive medicine and public health. She is committed to ensuring that Americans have access to affordable, quality healthcare, and believes in empowering individuals to take charge of their health to live longer, healthier lives.”

While Nesheiwat was critical of COVID mandates, she voiced more support for COVID vaccines and mask-wearing during the pandemic than her fellow nominees, leading some Trump supporters to criticize her nomination. 

“A good appointment, happy about this: I got to know @DoctorJanette during the pandemic, exchanging information. She is very smart, thoughtful, interested in learning, and a compassionate doctor, and…a truly nice person,” noted vaccine researcher Peter Hotez, MD, PhD, said on X.

 

David J. Weldon

If confirmed, former congressman Weldon would oversee the sprawling CDC, an agency with a roughly $17 billion budget, 15,000 employees or contractors, and numerous centers covering everything from health statistics to vaccines to epidemiology.

After earning his medical degree from the University at Buffalo School of Medicine, Weldon served in the US Army and US Army reserve. The Republican later served for 14 years in Congress representing Florida’s 15th district, which covers the Tampa region.

He now practices as an internist in Brevard County, Florida.

In Congress, Weldon raised concerns about the safety of some vaccines and promoted the false narrative that a former vaccine ingredient, thimerosal, caused autism, the Washington Post reported. Thimerosal has not been used in child vaccines for more than two decades. He also introduced a bill to move vaccine safety oversight from the CDC to an independent agency within HHS.

Trump said in a statement that Weldon “will proudly restore the CDC to its true purpose, and will work to end the Chronic Disease Epidemic.” 

But some physicians criticized Weldon for what they called his anti-vaccine views.

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

WASHINGTON — A fully automated ultrasound scanning system combined with artificial intelligence–based disease activity scoring performed as well as expert rheumatologists in hand joint assessment of patients with rheumatoid arthritis (RA), new research found.

The system, made by a Danish company called ROPCA, comprises an ultrasound scanner called ARTHUR (RA Ultrasound Robot) that interacts directly with the patient and scans 11 joints per hand and a neural network–based software system, DIANA (Diagnosis Aid Network for RA), that evaluates the images and monitors RA activity.

 

The combined system classifies the degree of RA according to the joint European Alliance of Associations for Rheumatology (EULAR)–Outcome Measures in Rheumatology (OMERACT) standards for RA diagnosis. It received a CE Mark in Europe in 2022 and is currently in use in six rheumatology clinics in Denmark, Germany, Switzerland, and Austria, with more to come, ROPCA Co-founder and Chief Medical Officer Søren A. Just, MD, said in an interview.

“Automated systems could help rheumatologists in the early detection and monitoring of arthritis diseases. Systems can be placed or move in areas with insufficient rheumatological expertise,” Just said during a special late-breaker session presentation at the annual meeting of the American College of Rheumatology (ACR).

He said in an interview: “Currently, there are so many people referred and few and fewer rheumatologists. So we need to think differently. We need good automated assistants.” As a screening tool, the system can determine whether a person with hand pain has RA or just osteoarthritis “and also can give the patient an immediate answer, instead of waiting sometimes up to 6 months to get the information.”

Just, who is also a senior physician in the Department of Internal Medicine at Odense University Hospital in Denmark, said that his department is also using the system to assess flares in patients with established RA. “They can have a blood sample taken. They’re scanned by the robot, and you can see if there is any disease activity. But I think that screening of patients with joint pain is the beginning.”

Asked to comment, session moderator Gregory C. Gardner, MD, Emeritus Professor in the Division of Rheumatology at the University of Washington, Seattle, and a member of the ACR conference program committee, said in an interview “one of the reasons we chose to feature this abstract is because we’re interested in science at the convergence. We really thought this was a potential way to move the field forward for rheumatologists.”

Gardner said it’s an advantage that the patient could potentially have an ARTHUR scan with a DIANA report and get blood tests done prior to a visit with the rheumatologist. “It’s really time-consuming for a human to do these studies, so if you automate it, that’s a step forward in terms of having the data available for the rheumatologist to view and use sequentially to follow how patients are doing.”

When introducing Just’s presentation, Gardner called it “the coolest abstract of the meeting.”

 

Both DIANA and ARTHUR Performed At Least as Well as Human Rheumatologists

In the study, 30 patients with RA underwent two scans by ARTHUR, followed by a scan from a rheumatologist specialist in musculoskeletal ultrasound. The scans were sent to DIANA, who graded the images according to the Global OMERACT-EULAR Synovitis Score, as did the human rheumatologist.

A “ground truth” was established by another human expert who evaluated both ARTHUR’s and the other rheumatologist’s images, blinded to the scanning method. The image with the highest disease activity was deemed “ground truth,” and agreement with that was assessed for the two individual methods.

 

Just showed a video of a patient being scanned by ARTHUR. The machine verbally guided her through removing her jewelry, applying the gel, and placing her hand on the screen under the scanner. ARTHUR’s arm moved around on the patient’s hand, locating the best angles to take grayscale images and Doppler images and Doppler video. The scan takes 15-20 minutes, and the images are stored, Just said.

The study patients had a mean age of 65 years, and 23 of the 30 were men. Their average disease duration was 11 years, and mean Disease Activity Score in 28 joints using C-reactive protein was 3.86, indicating moderate disease. A majority (73%) of patients were taking disease-modifying antirheumatic drugs, and about one third were taking biologics. ARTHUR scanned a total of 660 joints, and 564 scans were successful.

For repeatability between the two ARTHUR scans, percent exact agreement was 63% for synovial hypertrophy, 75% for Doppler activity, and 60% combined. Percent close (within a point) agreements were 93%, 94%, and 92%, respectively. Binary agreements as to whether the joint was healthy vs diseased were 88%, 91%, and 85%, respectively.

At the joint level, ARTHUR and DIANA’s percent exact agreement with ground truth was 49% for synovial hypertrophy, 63% for Doppler activity, and 48% combined. Binary agreements with disease vs healthy were 80%, 88%, and 78%, respectively.

The human rheumatologists scored very similarly. Percent exact agreement with ground truth was 51% for synovial hypertrophy, 64% for Doppler activity, and 50% combined. Percent close agreements were 94%, 94%, and 92%, respectively. And binary agreements with diseased vs healthy were 83%, 91%, and 80%, respectively.

At the patient level (all joints combined), ARTHUR and DIANA’s binary disease assessment of healthy vs disease showed agreement with the ground truth of 87% for synovial hypertrophy, 83% for Doppler activity, and 87% combined. Here, the rheumatologists scored lower, at 53%, 67%, and 60%, respectively.

“In this study, we think the precision of ARTHUR and DIANA was comparable to that of an experienced rheumatologist, at both the joint and patient level,” Just said.

Gardner pointed out another advantage of the system. “DIANA doesn’t get fatigued. ... With human reading, the precision may change based on the time of day or stress level. ... But with DIANA, you’re going to get consistent information.”

Just said that the Arthritis Foundation in Germany recently put ARTHUR and DIANA on a bus and took it to cities that lacked a rheumatologist. Patients lined up, answered a questionnaire, had blood drawn, and received their scans. A rheumatologist on the bus then interpreted the data and consulted with the individuals about their RA risk. “In the last trip, we screened 800 patients in 6 days. So there are definitely possibilities here.”

Just is co-owner of ROPCA. Gardner had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — A fully automated ultrasound scanning system combined with artificial intelligence–based disease activity scoring performed as well as expert rheumatologists in hand joint assessment of patients with rheumatoid arthritis (RA), new research found.

The system, made by a Danish company called ROPCA, comprises an ultrasound scanner called ARTHUR (RA Ultrasound Robot) that interacts directly with the patient and scans 11 joints per hand and a neural network–based software system, DIANA (Diagnosis Aid Network for RA), that evaluates the images and monitors RA activity.

 

The combined system classifies the degree of RA according to the joint European Alliance of Associations for Rheumatology (EULAR)–Outcome Measures in Rheumatology (OMERACT) standards for RA diagnosis. It received a CE Mark in Europe in 2022 and is currently in use in six rheumatology clinics in Denmark, Germany, Switzerland, and Austria, with more to come, ROPCA Co-founder and Chief Medical Officer Søren A. Just, MD, said in an interview.

“Automated systems could help rheumatologists in the early detection and monitoring of arthritis diseases. Systems can be placed or move in areas with insufficient rheumatological expertise,” Just said during a special late-breaker session presentation at the annual meeting of the American College of Rheumatology (ACR).

He said in an interview: “Currently, there are so many people referred and few and fewer rheumatologists. So we need to think differently. We need good automated assistants.” As a screening tool, the system can determine whether a person with hand pain has RA or just osteoarthritis “and also can give the patient an immediate answer, instead of waiting sometimes up to 6 months to get the information.”

Just, who is also a senior physician in the Department of Internal Medicine at Odense University Hospital in Denmark, said that his department is also using the system to assess flares in patients with established RA. “They can have a blood sample taken. They’re scanned by the robot, and you can see if there is any disease activity. But I think that screening of patients with joint pain is the beginning.”

Asked to comment, session moderator Gregory C. Gardner, MD, Emeritus Professor in the Division of Rheumatology at the University of Washington, Seattle, and a member of the ACR conference program committee, said in an interview “one of the reasons we chose to feature this abstract is because we’re interested in science at the convergence. We really thought this was a potential way to move the field forward for rheumatologists.”

Gardner said it’s an advantage that the patient could potentially have an ARTHUR scan with a DIANA report and get blood tests done prior to a visit with the rheumatologist. “It’s really time-consuming for a human to do these studies, so if you automate it, that’s a step forward in terms of having the data available for the rheumatologist to view and use sequentially to follow how patients are doing.”

When introducing Just’s presentation, Gardner called it “the coolest abstract of the meeting.”

 

Both DIANA and ARTHUR Performed At Least as Well as Human Rheumatologists

In the study, 30 patients with RA underwent two scans by ARTHUR, followed by a scan from a rheumatologist specialist in musculoskeletal ultrasound. The scans were sent to DIANA, who graded the images according to the Global OMERACT-EULAR Synovitis Score, as did the human rheumatologist.

A “ground truth” was established by another human expert who evaluated both ARTHUR’s and the other rheumatologist’s images, blinded to the scanning method. The image with the highest disease activity was deemed “ground truth,” and agreement with that was assessed for the two individual methods.

 

Just showed a video of a patient being scanned by ARTHUR. The machine verbally guided her through removing her jewelry, applying the gel, and placing her hand on the screen under the scanner. ARTHUR’s arm moved around on the patient’s hand, locating the best angles to take grayscale images and Doppler images and Doppler video. The scan takes 15-20 minutes, and the images are stored, Just said.

The study patients had a mean age of 65 years, and 23 of the 30 were men. Their average disease duration was 11 years, and mean Disease Activity Score in 28 joints using C-reactive protein was 3.86, indicating moderate disease. A majority (73%) of patients were taking disease-modifying antirheumatic drugs, and about one third were taking biologics. ARTHUR scanned a total of 660 joints, and 564 scans were successful.

For repeatability between the two ARTHUR scans, percent exact agreement was 63% for synovial hypertrophy, 75% for Doppler activity, and 60% combined. Percent close (within a point) agreements were 93%, 94%, and 92%, respectively. Binary agreements as to whether the joint was healthy vs diseased were 88%, 91%, and 85%, respectively.

At the joint level, ARTHUR and DIANA’s percent exact agreement with ground truth was 49% for synovial hypertrophy, 63% for Doppler activity, and 48% combined. Binary agreements with disease vs healthy were 80%, 88%, and 78%, respectively.

The human rheumatologists scored very similarly. Percent exact agreement with ground truth was 51% for synovial hypertrophy, 64% for Doppler activity, and 50% combined. Percent close agreements were 94%, 94%, and 92%, respectively. And binary agreements with diseased vs healthy were 83%, 91%, and 80%, respectively.

At the patient level (all joints combined), ARTHUR and DIANA’s binary disease assessment of healthy vs disease showed agreement with the ground truth of 87% for synovial hypertrophy, 83% for Doppler activity, and 87% combined. Here, the rheumatologists scored lower, at 53%, 67%, and 60%, respectively.

“In this study, we think the precision of ARTHUR and DIANA was comparable to that of an experienced rheumatologist, at both the joint and patient level,” Just said.

Gardner pointed out another advantage of the system. “DIANA doesn’t get fatigued. ... With human reading, the precision may change based on the time of day or stress level. ... But with DIANA, you’re going to get consistent information.”

Just said that the Arthritis Foundation in Germany recently put ARTHUR and DIANA on a bus and took it to cities that lacked a rheumatologist. Patients lined up, answered a questionnaire, had blood drawn, and received their scans. A rheumatologist on the bus then interpreted the data and consulted with the individuals about their RA risk. “In the last trip, we screened 800 patients in 6 days. So there are definitely possibilities here.”

Just is co-owner of ROPCA. Gardner had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — A fully automated ultrasound scanning system combined with artificial intelligence–based disease activity scoring performed as well as expert rheumatologists in hand joint assessment of patients with rheumatoid arthritis (RA), new research found.

The system, made by a Danish company called ROPCA, comprises an ultrasound scanner called ARTHUR (RA Ultrasound Robot) that interacts directly with the patient and scans 11 joints per hand and a neural network–based software system, DIANA (Diagnosis Aid Network for RA), that evaluates the images and monitors RA activity.

 

The combined system classifies the degree of RA according to the joint European Alliance of Associations for Rheumatology (EULAR)–Outcome Measures in Rheumatology (OMERACT) standards for RA diagnosis. It received a CE Mark in Europe in 2022 and is currently in use in six rheumatology clinics in Denmark, Germany, Switzerland, and Austria, with more to come, ROPCA Co-founder and Chief Medical Officer Søren A. Just, MD, said in an interview.

“Automated systems could help rheumatologists in the early detection and monitoring of arthritis diseases. Systems can be placed or move in areas with insufficient rheumatological expertise,” Just said during a special late-breaker session presentation at the annual meeting of the American College of Rheumatology (ACR).

He said in an interview: “Currently, there are so many people referred and few and fewer rheumatologists. So we need to think differently. We need good automated assistants.” As a screening tool, the system can determine whether a person with hand pain has RA or just osteoarthritis “and also can give the patient an immediate answer, instead of waiting sometimes up to 6 months to get the information.”

Just, who is also a senior physician in the Department of Internal Medicine at Odense University Hospital in Denmark, said that his department is also using the system to assess flares in patients with established RA. “They can have a blood sample taken. They’re scanned by the robot, and you can see if there is any disease activity. But I think that screening of patients with joint pain is the beginning.”

Asked to comment, session moderator Gregory C. Gardner, MD, Emeritus Professor in the Division of Rheumatology at the University of Washington, Seattle, and a member of the ACR conference program committee, said in an interview “one of the reasons we chose to feature this abstract is because we’re interested in science at the convergence. We really thought this was a potential way to move the field forward for rheumatologists.”

Gardner said it’s an advantage that the patient could potentially have an ARTHUR scan with a DIANA report and get blood tests done prior to a visit with the rheumatologist. “It’s really time-consuming for a human to do these studies, so if you automate it, that’s a step forward in terms of having the data available for the rheumatologist to view and use sequentially to follow how patients are doing.”

When introducing Just’s presentation, Gardner called it “the coolest abstract of the meeting.”

 

Both DIANA and ARTHUR Performed At Least as Well as Human Rheumatologists

In the study, 30 patients with RA underwent two scans by ARTHUR, followed by a scan from a rheumatologist specialist in musculoskeletal ultrasound. The scans were sent to DIANA, who graded the images according to the Global OMERACT-EULAR Synovitis Score, as did the human rheumatologist.

A “ground truth” was established by another human expert who evaluated both ARTHUR’s and the other rheumatologist’s images, blinded to the scanning method. The image with the highest disease activity was deemed “ground truth,” and agreement with that was assessed for the two individual methods.

 

Just showed a video of a patient being scanned by ARTHUR. The machine verbally guided her through removing her jewelry, applying the gel, and placing her hand on the screen under the scanner. ARTHUR’s arm moved around on the patient’s hand, locating the best angles to take grayscale images and Doppler images and Doppler video. The scan takes 15-20 minutes, and the images are stored, Just said.

The study patients had a mean age of 65 years, and 23 of the 30 were men. Their average disease duration was 11 years, and mean Disease Activity Score in 28 joints using C-reactive protein was 3.86, indicating moderate disease. A majority (73%) of patients were taking disease-modifying antirheumatic drugs, and about one third were taking biologics. ARTHUR scanned a total of 660 joints, and 564 scans were successful.

For repeatability between the two ARTHUR scans, percent exact agreement was 63% for synovial hypertrophy, 75% for Doppler activity, and 60% combined. Percent close (within a point) agreements were 93%, 94%, and 92%, respectively. Binary agreements as to whether the joint was healthy vs diseased were 88%, 91%, and 85%, respectively.

At the joint level, ARTHUR and DIANA’s percent exact agreement with ground truth was 49% for synovial hypertrophy, 63% for Doppler activity, and 48% combined. Binary agreements with disease vs healthy were 80%, 88%, and 78%, respectively.

The human rheumatologists scored very similarly. Percent exact agreement with ground truth was 51% for synovial hypertrophy, 64% for Doppler activity, and 50% combined. Percent close agreements were 94%, 94%, and 92%, respectively. And binary agreements with diseased vs healthy were 83%, 91%, and 80%, respectively.

At the patient level (all joints combined), ARTHUR and DIANA’s binary disease assessment of healthy vs disease showed agreement with the ground truth of 87% for synovial hypertrophy, 83% for Doppler activity, and 87% combined. Here, the rheumatologists scored lower, at 53%, 67%, and 60%, respectively.

“In this study, we think the precision of ARTHUR and DIANA was comparable to that of an experienced rheumatologist, at both the joint and patient level,” Just said.

Gardner pointed out another advantage of the system. “DIANA doesn’t get fatigued. ... With human reading, the precision may change based on the time of day or stress level. ... But with DIANA, you’re going to get consistent information.”

Just said that the Arthritis Foundation in Germany recently put ARTHUR and DIANA on a bus and took it to cities that lacked a rheumatologist. Patients lined up, answered a questionnaire, had blood drawn, and received their scans. A rheumatologist on the bus then interpreted the data and consulted with the individuals about their RA risk. “In the last trip, we screened 800 patients in 6 days. So there are definitely possibilities here.”

Just is co-owner of ROPCA. Gardner had no disclosures.

A version of this article appeared on Medscape.com.

A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found. 

There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet. 

Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands. 

Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy. 

The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).

Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).

At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said. 

She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said. 

The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.

During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.

She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.

Kretova reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found. 

There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet. 

Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands. 

Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy. 

The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).

Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).

At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said. 

She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said. 

The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.

During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.

She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.

Kretova reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found. 

There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet. 

Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands. 

Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy. 

The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).

Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).

At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said. 

She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said. 

The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.

During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.

She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.

Kretova reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

WASHINGTON — The investigational anti-CD40 ligand agent dapirolizumab pegol (DZP) outperformed placebo in improving disease activity and reducing high-dose corticosteroid use in patients with systemic lupus erythematosus (SLE) in the phase 3 PHOENYCS GO trial.

“We really think that dapirolizumab pegol may represent a novel treatment for lupus, particularly given its broad immune modulatory effects,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She presented the study in a late-breaking poster session at the American College of Rheumatology (ACR) 2024 Annual Meeting.

There is a “huge unmet need” for drugs for lupus, Clowse told this news organization. Patients with SLE continue to have high disease burden, including ongoing symptoms often driven by inflammation. Corticosteroids are often the best medications to control disease activity, she said, but they can result in long-term toxicity.

 

What Makes DZP Unique?

Through CD40 ligand signaling, DZP has been shown to reduce B- and T-cell activation and to downregulate interferon pathways. Previous antibodies targeting the CD40 ligand have been associated with an increased risk for thromboembolic events. However, DZP lacks the Fc portion of the antibody, which can bind to platelets and cause clotting. Data from phase 1, 2, and 3 trials thus far do not show an elevated risk for these events, Clowse explained. In fact, safety signals were strong enough that patients with antiphospholipid antibodies — a key driver for blood clots in patients with SLE — were included in the trial.

In PHOENYCS GO, investigators enrolled 321 patients with moderate to severe SLE with persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medications such as antimalarials, corticosteroids, and immunosuppressants.

Patients were randomized 2:1 to receive intravenous DZP (24 mg/kg) plus SOC or intravenous placebo plus SOC every 4 weeks, with patients and investigators blinded to treatment assignments.

Patients taking a corticosteroid dose > 7.5 mg/day began a mandatory steroid taper by week 8 of the trial, with the goal of reducing that to < 7.5 mg/day. The tapering regimen was at the discretion of providers and was adapted to each patient’s individual disease activity.

The primary endpoint was British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response at week 48.

Patients in the DZP and placebo groups were on average 43.5 and 41.5 years old, respectively. More than 90% of patients were women, all on concomitant SLE medications. About half of the participants took a daily corticosteroid dose > 7.5 mg.

At 48 weeks, half of the DZP group (49.5%) achieved BICLA response compared with 34.6% in the placebo group (P = .0110). A higher proportion of patients taking DZP achieved SLE Responder Index-4 response than those taking placebo (60.1% vs 41.1%, respectively; P = .0014), and the rate of severe British Isles Lupus Assessment Group flares in the DZP group was half that of the placebo group (11.6% vs 23.4%; P = .0257). In the subgroup of patients who underwent corticosteroid tapering, 72.4% receiving DZP and 52.9% taking placebo reduced their dose to < 7.5 mg/day by 48 weeks (P = .0404).

DZP was generally well tolerated. Over 48 weeks, 82.6% of the DZP group and 75% of the placebo group reported treatment-emergent adverse events, but serious occurrences were more common in the placebo group (14.8%) than in the DZP group (9.9%). Herpes viral infections were higher in the placebo group, although there were three ophthalmic herpes cases in the DZP group. There was one case of acute myocardial infarction and one death linked to gangrene-related sepsis in patients receiving DZP.

 

A ‘Mild to Moderate’ Response

Although these are definitely positive results, they show a “mild to moderate response” to DZP, commented Gregory Gardner, MD, an emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, and chair of the American College of Rheumatology’s annual meeting planning committee. He moderated the session where the research was presented. Although DZP showed efficacy among some patients, he noted, “there were still 51% patients that it didn’t work for.” 

The drug uses an alternative pathway to current lupus drugs, Gardner added, and more research is needed to understand how best to use this medication in practice.

Clowse noted that DZP could be particularly beneficial for patients with SLE who want to get pregnant. Many drugs used to treat the disease are teratogenic; however, “because of the lack of Fc portion on this drug, it very likely does not cross the placenta in any kind of significant amount,” she said. Although there are not yet any reproductive safety data on DZP, she added, “that is a great potential niche.”

Biogen and UCB, which are jointly developing DZP, aim to start a second phase 3 trial of DZP in patients with SLE, called PHOENYCS FLY, in 2024.

The trial was sponsored by UCB. Clowse is a consultant and has received grant/research support from GSK and UCB. Gardner had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

WASHINGTON — The investigational anti-CD40 ligand agent dapirolizumab pegol (DZP) outperformed placebo in improving disease activity and reducing high-dose corticosteroid use in patients with systemic lupus erythematosus (SLE) in the phase 3 PHOENYCS GO trial.

“We really think that dapirolizumab pegol may represent a novel treatment for lupus, particularly given its broad immune modulatory effects,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She presented the study in a late-breaking poster session at the American College of Rheumatology (ACR) 2024 Annual Meeting.

There is a “huge unmet need” for drugs for lupus, Clowse told this news organization. Patients with SLE continue to have high disease burden, including ongoing symptoms often driven by inflammation. Corticosteroids are often the best medications to control disease activity, she said, but they can result in long-term toxicity.

 

What Makes DZP Unique?

Through CD40 ligand signaling, DZP has been shown to reduce B- and T-cell activation and to downregulate interferon pathways. Previous antibodies targeting the CD40 ligand have been associated with an increased risk for thromboembolic events. However, DZP lacks the Fc portion of the antibody, which can bind to platelets and cause clotting. Data from phase 1, 2, and 3 trials thus far do not show an elevated risk for these events, Clowse explained. In fact, safety signals were strong enough that patients with antiphospholipid antibodies — a key driver for blood clots in patients with SLE — were included in the trial.

In PHOENYCS GO, investigators enrolled 321 patients with moderate to severe SLE with persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medications such as antimalarials, corticosteroids, and immunosuppressants.

Patients were randomized 2:1 to receive intravenous DZP (24 mg/kg) plus SOC or intravenous placebo plus SOC every 4 weeks, with patients and investigators blinded to treatment assignments.

Patients taking a corticosteroid dose > 7.5 mg/day began a mandatory steroid taper by week 8 of the trial, with the goal of reducing that to < 7.5 mg/day. The tapering regimen was at the discretion of providers and was adapted to each patient’s individual disease activity.

The primary endpoint was British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response at week 48.

Patients in the DZP and placebo groups were on average 43.5 and 41.5 years old, respectively. More than 90% of patients were women, all on concomitant SLE medications. About half of the participants took a daily corticosteroid dose > 7.5 mg.

At 48 weeks, half of the DZP group (49.5%) achieved BICLA response compared with 34.6% in the placebo group (P = .0110). A higher proportion of patients taking DZP achieved SLE Responder Index-4 response than those taking placebo (60.1% vs 41.1%, respectively; P = .0014), and the rate of severe British Isles Lupus Assessment Group flares in the DZP group was half that of the placebo group (11.6% vs 23.4%; P = .0257). In the subgroup of patients who underwent corticosteroid tapering, 72.4% receiving DZP and 52.9% taking placebo reduced their dose to < 7.5 mg/day by 48 weeks (P = .0404).

DZP was generally well tolerated. Over 48 weeks, 82.6% of the DZP group and 75% of the placebo group reported treatment-emergent adverse events, but serious occurrences were more common in the placebo group (14.8%) than in the DZP group (9.9%). Herpes viral infections were higher in the placebo group, although there were three ophthalmic herpes cases in the DZP group. There was one case of acute myocardial infarction and one death linked to gangrene-related sepsis in patients receiving DZP.

 

A ‘Mild to Moderate’ Response

Although these are definitely positive results, they show a “mild to moderate response” to DZP, commented Gregory Gardner, MD, an emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, and chair of the American College of Rheumatology’s annual meeting planning committee. He moderated the session where the research was presented. Although DZP showed efficacy among some patients, he noted, “there were still 51% patients that it didn’t work for.” 

The drug uses an alternative pathway to current lupus drugs, Gardner added, and more research is needed to understand how best to use this medication in practice.

Clowse noted that DZP could be particularly beneficial for patients with SLE who want to get pregnant. Many drugs used to treat the disease are teratogenic; however, “because of the lack of Fc portion on this drug, it very likely does not cross the placenta in any kind of significant amount,” she said. Although there are not yet any reproductive safety data on DZP, she added, “that is a great potential niche.”

Biogen and UCB, which are jointly developing DZP, aim to start a second phase 3 trial of DZP in patients with SLE, called PHOENYCS FLY, in 2024.

The trial was sponsored by UCB. Clowse is a consultant and has received grant/research support from GSK and UCB. Gardner had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

WASHINGTON — The investigational anti-CD40 ligand agent dapirolizumab pegol (DZP) outperformed placebo in improving disease activity and reducing high-dose corticosteroid use in patients with systemic lupus erythematosus (SLE) in the phase 3 PHOENYCS GO trial.

“We really think that dapirolizumab pegol may represent a novel treatment for lupus, particularly given its broad immune modulatory effects,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She presented the study in a late-breaking poster session at the American College of Rheumatology (ACR) 2024 Annual Meeting.

There is a “huge unmet need” for drugs for lupus, Clowse told this news organization. Patients with SLE continue to have high disease burden, including ongoing symptoms often driven by inflammation. Corticosteroids are often the best medications to control disease activity, she said, but they can result in long-term toxicity.

 

What Makes DZP Unique?

Through CD40 ligand signaling, DZP has been shown to reduce B- and T-cell activation and to downregulate interferon pathways. Previous antibodies targeting the CD40 ligand have been associated with an increased risk for thromboembolic events. However, DZP lacks the Fc portion of the antibody, which can bind to platelets and cause clotting. Data from phase 1, 2, and 3 trials thus far do not show an elevated risk for these events, Clowse explained. In fact, safety signals were strong enough that patients with antiphospholipid antibodies — a key driver for blood clots in patients with SLE — were included in the trial.

In PHOENYCS GO, investigators enrolled 321 patients with moderate to severe SLE with persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medications such as antimalarials, corticosteroids, and immunosuppressants.

Patients were randomized 2:1 to receive intravenous DZP (24 mg/kg) plus SOC or intravenous placebo plus SOC every 4 weeks, with patients and investigators blinded to treatment assignments.

Patients taking a corticosteroid dose > 7.5 mg/day began a mandatory steroid taper by week 8 of the trial, with the goal of reducing that to < 7.5 mg/day. The tapering regimen was at the discretion of providers and was adapted to each patient’s individual disease activity.

The primary endpoint was British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response at week 48.

Patients in the DZP and placebo groups were on average 43.5 and 41.5 years old, respectively. More than 90% of patients were women, all on concomitant SLE medications. About half of the participants took a daily corticosteroid dose > 7.5 mg.

At 48 weeks, half of the DZP group (49.5%) achieved BICLA response compared with 34.6% in the placebo group (P = .0110). A higher proportion of patients taking DZP achieved SLE Responder Index-4 response than those taking placebo (60.1% vs 41.1%, respectively; P = .0014), and the rate of severe British Isles Lupus Assessment Group flares in the DZP group was half that of the placebo group (11.6% vs 23.4%; P = .0257). In the subgroup of patients who underwent corticosteroid tapering, 72.4% receiving DZP and 52.9% taking placebo reduced their dose to < 7.5 mg/day by 48 weeks (P = .0404).

DZP was generally well tolerated. Over 48 weeks, 82.6% of the DZP group and 75% of the placebo group reported treatment-emergent adverse events, but serious occurrences were more common in the placebo group (14.8%) than in the DZP group (9.9%). Herpes viral infections were higher in the placebo group, although there were three ophthalmic herpes cases in the DZP group. There was one case of acute myocardial infarction and one death linked to gangrene-related sepsis in patients receiving DZP.

 

A ‘Mild to Moderate’ Response

Although these are definitely positive results, they show a “mild to moderate response” to DZP, commented Gregory Gardner, MD, an emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, and chair of the American College of Rheumatology’s annual meeting planning committee. He moderated the session where the research was presented. Although DZP showed efficacy among some patients, he noted, “there were still 51% patients that it didn’t work for.” 

The drug uses an alternative pathway to current lupus drugs, Gardner added, and more research is needed to understand how best to use this medication in practice.

Clowse noted that DZP could be particularly beneficial for patients with SLE who want to get pregnant. Many drugs used to treat the disease are teratogenic; however, “because of the lack of Fc portion on this drug, it very likely does not cross the placenta in any kind of significant amount,” she said. Although there are not yet any reproductive safety data on DZP, she added, “that is a great potential niche.”

Biogen and UCB, which are jointly developing DZP, aim to start a second phase 3 trial of DZP in patients with SLE, called PHOENYCS FLY, in 2024.

The trial was sponsored by UCB. Clowse is a consultant and has received grant/research support from GSK and UCB. Gardner had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas. 

The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:

• Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
• No gout flares over 12 months
• No tophi
• Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
• Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.

Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.

Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”

“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.

 

Simplified Version Created With Only Three Criteria

In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.

To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).

Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.

Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah. 

Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.

Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.

During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked. 

Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said. 

During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.

Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said. 

Tabi-Amponsah and Dalbeth did not disclose any financial relationships. 

 

A version of this article appeared on Medscape.com.

In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas. 

The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:

• Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
• No gout flares over 12 months
• No tophi
• Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
• Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.

Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.

Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”

“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.

 

Simplified Version Created With Only Three Criteria

In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.

To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).

Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.

Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah. 

Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.

Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.

During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked. 

Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said. 

During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.

Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said. 

Tabi-Amponsah and Dalbeth did not disclose any financial relationships. 

 

A version of this article appeared on Medscape.com.

In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas. 

The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:

• Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
• No gout flares over 12 months
• No tophi
• Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
• Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.

Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.

Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”

“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.

 

Simplified Version Created With Only Three Criteria

In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.

To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).

Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.

Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah. 

Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.

Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.

During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked. 

Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said. 

During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.

Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said. 

Tabi-Amponsah and Dalbeth did not disclose any financial relationships. 

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures.