Feature

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

Arisa E. Ortiz, MD, began her term as president of the American Society for Laser Medicine and Surgery (ASLMS) during the organization’s annual meeting in April 2024.

After earning her medical degree from Albany Medical College, Albany, New York, Dr. Ortiz, a native of Los Angeles, completed her dermatology residency training at the University of California, Irvine, and the university’s Beckman Laser Institute. Next, she completed a laser and cosmetic dermatology fellowship at Massachusetts General Hospital, Harvard Medical School, and the Wellman Center for Photomedicine, all in Boston, and acquired additional fellowship training in Mohs micrographic surgery at the University of California, San Diego (UCSD). Dr. Ortiz is currently director of laser and cosmetic dermatology and a clinical professor of dermatology at UCSD.

Dr. Arisa E. Ortiz

She has authored more than 60 publications on new innovations in cutaneous surgery and is a frequent speaker at meetings of the American Academy of Dermatology, the American Society for Dermatologic Surgery (ASDS), and ASLMS, and she cochairs the annual Masters of Aesthetics Symposium in San Diego. Dr. Ortiz has received several awards, including the 2024 Castle Connolly Top Doctor Award and the Exceptional Women in Medicine Award; Newsweek America’s Best Dermatologists; the ASLMS Dr. Horace Furumoto Young Investigator Award, the ASLMS Best of Session Award for Cutaneous Applications, and the ASDS President’s Outstanding Service Award. Her primary research focuses on the laser treatment of nonmelanoma skin cancer.

In an interview, Dr. Ortiz spoke about her goals as ASLMS president and other topics related to dermatology.

Who inspired you most to become a doctor?

I’ve wanted to become a doctor for as long as I can remember. My fascination with science and the idea of helping people improve their health were driving forces. However, my biggest influence early on was my uncle, who was a pediatrician. His dedication and passion for medicine deeply inspired me and solidified my desire to pursue a career in healthcare.


I understand that a bout with chickenpox as a teenager influenced your decision to specialize in dermatology.

It’s an interesting and somewhat humorous story. When I was 18, I contracted chickenpox and ended up with scars on my face. It was a tough experience as a teenager, but it’s fascinating how such events can shape your life. In my quest for help, I opened the Yellow Pages and randomly chose a dermatologist nearby, who turned out to be Gary Lask, MD, director of lasers at UCLA [University of California, Los Angeles]. During our visit, I mentioned that I was premed, and he encouraged me to consider dermatology. About 6 years later, as a second-year medical student, I realized my passion for dermatology. I reached out to Dr. Lask and told him: “You were right. I want to be a dermatologist. Now, you have to help me get in!” Today, he remains my mentor, and I am deeply grateful for his guidance and support on this journey.



One of the initiatives for your term as ASLMS president includes a focus on safety standards for lasers and energy-based devices. Why is this important now?

courtesy Dr. Arisa E. Ortiz

Working at the university, I frequently encounter severe complications arising from the improper use of lasers and energy-based devices. As these procedures gain popularity, more providers are offering them, yet often without adequate training. As the world’s premier laser society, it is our duty to ensure patient safety. In the ever-evolving field of laser medicine, it is crucial that we continually strive to enhance the regulation of laser usage, ensuring that patients receive the highest standard of care with minimal risk.



One of the suggestions you have for the safety initiative is to offer a rigorous laser safety certification course with continuing education opportunities as a way foster a culture of heightened safety standards. Please explain what would be included in such a course and how it would align with current efforts to report adverse events such as the ASDS-Northwestern University Cutaneous Procedures Adverse Events Reporting (CAPER) registry and the Food and Drug Administration’s MedWatch Program.

A laser safety certification task force has been established to determine the best approach for developing a comprehensive course. The task force aims to assess the necessity of a formal safety certification in our industry, identify the resources needed to support such a certification, establish general safety protocols to form the content foundation, address potential legal concerns, and outline the process for formal certification program recognition. This exploratory work is expected to conclude by the end of the year. The proposed course may include modules on the fundamentals of laser physics, safe operation techniques, patient selection and management, and emergency protocols. Continuing education opportunities would be considered to keep practitioners updated on the latest advancements and safety protocols in laser medicine, thereby fostering a culture of heightened safety standards.



Another initiative for your term is the rollout of a tattoo removal program for former gang members based on the UCSD Clean Slate Tattoo Removal Program. Please tell us more about your vision for this national program.

UCSD Dermatology, in collaboration with UCSD Global Health, has been involved in the Clean Slate Tattoo Removal Program for the past decade. This initiative supports and rehabilitates former gang members by offering laser tattoo removal, helping them reintegrate into society. My vision is to equip our members with the necessary protocols to implement this outreach initiative in their own communities. By providing opportunities for reform and growth, we aim to foster safer and more inclusive communities nationwide.



You were one of the first clinicians to use a laser to treat basal cell carcinoma (BCC). Who are the ideal candidates for this procedure? Is the technique ready for wide clinical adoption? If not, what kind of studies are needed to make it so?

My research passion lies in optimizing laser treatments for BCC. During my fellowship with R. Rox Anderson, MD, and Mathew Avram, MD, at the MGH Wellman Center for Photomedicine, we conducted a pilot study using the 1064-nm Nd:YAG laser, achieving a 92% clearance rate after one treatment. Inspired by these results, we conducted a larger multicenter study, which demonstrated a 90% clearance rate after a single treatment. I now incorporate this technique into my daily practice. The ideal candidates for this procedure are patients with BCC that do not meet the Mohs Appropriate Use Criteria, such as those with nodular or superficial BCC subtypes on the body, individuals who are poor surgical candidates, or those who are surgically exhausted. However, I do not recommend this treatment for patients who are primarily concerned about facial scarring, particularly younger individuals; in such cases, Mohs surgery still remains the preferred option. While I believe this technique is ready for broader clinical adoption, it requires an understanding of laser endpoints. We are also exploring antibody-targeted gold nanorods to enhance the selectivity and standardization of the treatment.



Who inspires you most in your work today?

My patients are my greatest inspiration. Their trust and dedication motivate me to stay at the forefront of dermatologic advancements, ensuring I provide the most cutting-edge and safe treatments possible. Their commitment drives my relentless pursuit of continuous learning and innovation in the field.

What’s the best advice you can give to female dermatologists seeking leadership positions at the local, state, or national level?

My best advice is to have the courage to ask for what you seek. Societies are always looking for members who are eager to participate and contribute. If you express your interest in becoming more involved, there is likely a position available for you. The more you are willing to contribute to a society, the more likely you will be noticed and excel into higher leadership positions. Take initiative, show your commitment, and don’t hesitate to step forward when opportunities arise.



What’s the one tried-and-true laser- or energy-based procedure that you consider a “must” for your dermatology practice? And why?

Determining a single “must-have” laser- or energy-based procedure is a challenging question as it greatly depends on the specific needs of your patient population. However, one of the most common concerns among patients involves issues like redness and pigmentation. Therefore, having a versatile laser or an intense pulsed light device that effectively targets both red and brown pigmentation is indispensable for most practices.



In your view, what are the top three trends in aesthetic dermatology?

Over the years, I have observed several key trends in aesthetic dermatology:

• Minimally invasive procedures. There is a growing preference for less invasive treatments. Patients increasingly desire minimal downtime while still achieving significant results.
• Advancements in laser and energy-based devices for darker skin. There have been substantial advancements in technologies that are safer and more effective for darker skin tones. These developments play a crucial role in addressing diverse patient needs and providing inclusive dermatologic care.
• Natural aesthetic. I am hopeful that the trend toward an overdone appearance is fading. There seems to be a shift back towards a more natural and conservative aesthetic, emphasizing subtle enhancements over dramatic changes.

What development in dermatology are you most excited about in the next 5 years?

I am most excited to see how artificial intelligence and robotics play a role in energy-based devices.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.

Arisa E. Ortiz, MD, began her term as president of the American Society for Laser Medicine and Surgery (ASLMS) during the organization’s annual meeting in April 2024.

After earning her medical degree from Albany Medical College, Albany, New York, Dr. Ortiz, a native of Los Angeles, completed her dermatology residency training at the University of California, Irvine, and the university’s Beckman Laser Institute. Next, she completed a laser and cosmetic dermatology fellowship at Massachusetts General Hospital, Harvard Medical School, and the Wellman Center for Photomedicine, all in Boston, and acquired additional fellowship training in Mohs micrographic surgery at the University of California, San Diego (UCSD). Dr. Ortiz is currently director of laser and cosmetic dermatology and a clinical professor of dermatology at UCSD.

Dr. Arisa E. Ortiz

She has authored more than 60 publications on new innovations in cutaneous surgery and is a frequent speaker at meetings of the American Academy of Dermatology, the American Society for Dermatologic Surgery (ASDS), and ASLMS, and she cochairs the annual Masters of Aesthetics Symposium in San Diego. Dr. Ortiz has received several awards, including the 2024 Castle Connolly Top Doctor Award and the Exceptional Women in Medicine Award; Newsweek America’s Best Dermatologists; the ASLMS Dr. Horace Furumoto Young Investigator Award, the ASLMS Best of Session Award for Cutaneous Applications, and the ASDS President’s Outstanding Service Award. Her primary research focuses on the laser treatment of nonmelanoma skin cancer.

In an interview, Dr. Ortiz spoke about her goals as ASLMS president and other topics related to dermatology.

Who inspired you most to become a doctor?

I’ve wanted to become a doctor for as long as I can remember. My fascination with science and the idea of helping people improve their health were driving forces. However, my biggest influence early on was my uncle, who was a pediatrician. His dedication and passion for medicine deeply inspired me and solidified my desire to pursue a career in healthcare.


I understand that a bout with chickenpox as a teenager influenced your decision to specialize in dermatology.

It’s an interesting and somewhat humorous story. When I was 18, I contracted chickenpox and ended up with scars on my face. It was a tough experience as a teenager, but it’s fascinating how such events can shape your life. In my quest for help, I opened the Yellow Pages and randomly chose a dermatologist nearby, who turned out to be Gary Lask, MD, director of lasers at UCLA [University of California, Los Angeles]. During our visit, I mentioned that I was premed, and he encouraged me to consider dermatology. About 6 years later, as a second-year medical student, I realized my passion for dermatology. I reached out to Dr. Lask and told him: “You were right. I want to be a dermatologist. Now, you have to help me get in!” Today, he remains my mentor, and I am deeply grateful for his guidance and support on this journey.



One of the initiatives for your term as ASLMS president includes a focus on safety standards for lasers and energy-based devices. Why is this important now?

courtesy Dr. Arisa E. Ortiz

Working at the university, I frequently encounter severe complications arising from the improper use of lasers and energy-based devices. As these procedures gain popularity, more providers are offering them, yet often without adequate training. As the world’s premier laser society, it is our duty to ensure patient safety. In the ever-evolving field of laser medicine, it is crucial that we continually strive to enhance the regulation of laser usage, ensuring that patients receive the highest standard of care with minimal risk.



One of the suggestions you have for the safety initiative is to offer a rigorous laser safety certification course with continuing education opportunities as a way foster a culture of heightened safety standards. Please explain what would be included in such a course and how it would align with current efforts to report adverse events such as the ASDS-Northwestern University Cutaneous Procedures Adverse Events Reporting (CAPER) registry and the Food and Drug Administration’s MedWatch Program.

A laser safety certification task force has been established to determine the best approach for developing a comprehensive course. The task force aims to assess the necessity of a formal safety certification in our industry, identify the resources needed to support such a certification, establish general safety protocols to form the content foundation, address potential legal concerns, and outline the process for formal certification program recognition. This exploratory work is expected to conclude by the end of the year. The proposed course may include modules on the fundamentals of laser physics, safe operation techniques, patient selection and management, and emergency protocols. Continuing education opportunities would be considered to keep practitioners updated on the latest advancements and safety protocols in laser medicine, thereby fostering a culture of heightened safety standards.



Another initiative for your term is the rollout of a tattoo removal program for former gang members based on the UCSD Clean Slate Tattoo Removal Program. Please tell us more about your vision for this national program.

UCSD Dermatology, in collaboration with UCSD Global Health, has been involved in the Clean Slate Tattoo Removal Program for the past decade. This initiative supports and rehabilitates former gang members by offering laser tattoo removal, helping them reintegrate into society. My vision is to equip our members with the necessary protocols to implement this outreach initiative in their own communities. By providing opportunities for reform and growth, we aim to foster safer and more inclusive communities nationwide.



You were one of the first clinicians to use a laser to treat basal cell carcinoma (BCC). Who are the ideal candidates for this procedure? Is the technique ready for wide clinical adoption? If not, what kind of studies are needed to make it so?

My research passion lies in optimizing laser treatments for BCC. During my fellowship with R. Rox Anderson, MD, and Mathew Avram, MD, at the MGH Wellman Center for Photomedicine, we conducted a pilot study using the 1064-nm Nd:YAG laser, achieving a 92% clearance rate after one treatment. Inspired by these results, we conducted a larger multicenter study, which demonstrated a 90% clearance rate after a single treatment. I now incorporate this technique into my daily practice. The ideal candidates for this procedure are patients with BCC that do not meet the Mohs Appropriate Use Criteria, such as those with nodular or superficial BCC subtypes on the body, individuals who are poor surgical candidates, or those who are surgically exhausted. However, I do not recommend this treatment for patients who are primarily concerned about facial scarring, particularly younger individuals; in such cases, Mohs surgery still remains the preferred option. While I believe this technique is ready for broader clinical adoption, it requires an understanding of laser endpoints. We are also exploring antibody-targeted gold nanorods to enhance the selectivity and standardization of the treatment.



Who inspires you most in your work today?

My patients are my greatest inspiration. Their trust and dedication motivate me to stay at the forefront of dermatologic advancements, ensuring I provide the most cutting-edge and safe treatments possible. Their commitment drives my relentless pursuit of continuous learning and innovation in the field.

What’s the best advice you can give to female dermatologists seeking leadership positions at the local, state, or national level?

My best advice is to have the courage to ask for what you seek. Societies are always looking for members who are eager to participate and contribute. If you express your interest in becoming more involved, there is likely a position available for you. The more you are willing to contribute to a society, the more likely you will be noticed and excel into higher leadership positions. Take initiative, show your commitment, and don’t hesitate to step forward when opportunities arise.



What’s the one tried-and-true laser- or energy-based procedure that you consider a “must” for your dermatology practice? And why?

Determining a single “must-have” laser- or energy-based procedure is a challenging question as it greatly depends on the specific needs of your patient population. However, one of the most common concerns among patients involves issues like redness and pigmentation. Therefore, having a versatile laser or an intense pulsed light device that effectively targets both red and brown pigmentation is indispensable for most practices.



In your view, what are the top three trends in aesthetic dermatology?

Over the years, I have observed several key trends in aesthetic dermatology:

• Minimally invasive procedures. There is a growing preference for less invasive treatments. Patients increasingly desire minimal downtime while still achieving significant results.
• Advancements in laser and energy-based devices for darker skin. There have been substantial advancements in technologies that are safer and more effective for darker skin tones. These developments play a crucial role in addressing diverse patient needs and providing inclusive dermatologic care.
• Natural aesthetic. I am hopeful that the trend toward an overdone appearance is fading. There seems to be a shift back towards a more natural and conservative aesthetic, emphasizing subtle enhancements over dramatic changes.

What development in dermatology are you most excited about in the next 5 years?

I am most excited to see how artificial intelligence and robotics play a role in energy-based devices.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.

Arisa E. Ortiz, MD, began her term as president of the American Society for Laser Medicine and Surgery (ASLMS) during the organization’s annual meeting in April 2024.

After earning her medical degree from Albany Medical College, Albany, New York, Dr. Ortiz, a native of Los Angeles, completed her dermatology residency training at the University of California, Irvine, and the university’s Beckman Laser Institute. Next, she completed a laser and cosmetic dermatology fellowship at Massachusetts General Hospital, Harvard Medical School, and the Wellman Center for Photomedicine, all in Boston, and acquired additional fellowship training in Mohs micrographic surgery at the University of California, San Diego (UCSD). Dr. Ortiz is currently director of laser and cosmetic dermatology and a clinical professor of dermatology at UCSD.

Dr. Arisa E. Ortiz

She has authored more than 60 publications on new innovations in cutaneous surgery and is a frequent speaker at meetings of the American Academy of Dermatology, the American Society for Dermatologic Surgery (ASDS), and ASLMS, and she cochairs the annual Masters of Aesthetics Symposium in San Diego. Dr. Ortiz has received several awards, including the 2024 Castle Connolly Top Doctor Award and the Exceptional Women in Medicine Award; Newsweek America’s Best Dermatologists; the ASLMS Dr. Horace Furumoto Young Investigator Award, the ASLMS Best of Session Award for Cutaneous Applications, and the ASDS President’s Outstanding Service Award. Her primary research focuses on the laser treatment of nonmelanoma skin cancer.

In an interview, Dr. Ortiz spoke about her goals as ASLMS president and other topics related to dermatology.

Who inspired you most to become a doctor?

I’ve wanted to become a doctor for as long as I can remember. My fascination with science and the idea of helping people improve their health were driving forces. However, my biggest influence early on was my uncle, who was a pediatrician. His dedication and passion for medicine deeply inspired me and solidified my desire to pursue a career in healthcare.


I understand that a bout with chickenpox as a teenager influenced your decision to specialize in dermatology.

It’s an interesting and somewhat humorous story. When I was 18, I contracted chickenpox and ended up with scars on my face. It was a tough experience as a teenager, but it’s fascinating how such events can shape your life. In my quest for help, I opened the Yellow Pages and randomly chose a dermatologist nearby, who turned out to be Gary Lask, MD, director of lasers at UCLA [University of California, Los Angeles]. During our visit, I mentioned that I was premed, and he encouraged me to consider dermatology. About 6 years later, as a second-year medical student, I realized my passion for dermatology. I reached out to Dr. Lask and told him: “You were right. I want to be a dermatologist. Now, you have to help me get in!” Today, he remains my mentor, and I am deeply grateful for his guidance and support on this journey.



One of the initiatives for your term as ASLMS president includes a focus on safety standards for lasers and energy-based devices. Why is this important now?

courtesy Dr. Arisa E. Ortiz

Working at the university, I frequently encounter severe complications arising from the improper use of lasers and energy-based devices. As these procedures gain popularity, more providers are offering them, yet often without adequate training. As the world’s premier laser society, it is our duty to ensure patient safety. In the ever-evolving field of laser medicine, it is crucial that we continually strive to enhance the regulation of laser usage, ensuring that patients receive the highest standard of care with minimal risk.



One of the suggestions you have for the safety initiative is to offer a rigorous laser safety certification course with continuing education opportunities as a way foster a culture of heightened safety standards. Please explain what would be included in such a course and how it would align with current efforts to report adverse events such as the ASDS-Northwestern University Cutaneous Procedures Adverse Events Reporting (CAPER) registry and the Food and Drug Administration’s MedWatch Program.

A laser safety certification task force has been established to determine the best approach for developing a comprehensive course. The task force aims to assess the necessity of a formal safety certification in our industry, identify the resources needed to support such a certification, establish general safety protocols to form the content foundation, address potential legal concerns, and outline the process for formal certification program recognition. This exploratory work is expected to conclude by the end of the year. The proposed course may include modules on the fundamentals of laser physics, safe operation techniques, patient selection and management, and emergency protocols. Continuing education opportunities would be considered to keep practitioners updated on the latest advancements and safety protocols in laser medicine, thereby fostering a culture of heightened safety standards.



Another initiative for your term is the rollout of a tattoo removal program for former gang members based on the UCSD Clean Slate Tattoo Removal Program. Please tell us more about your vision for this national program.

UCSD Dermatology, in collaboration with UCSD Global Health, has been involved in the Clean Slate Tattoo Removal Program for the past decade. This initiative supports and rehabilitates former gang members by offering laser tattoo removal, helping them reintegrate into society. My vision is to equip our members with the necessary protocols to implement this outreach initiative in their own communities. By providing opportunities for reform and growth, we aim to foster safer and more inclusive communities nationwide.



You were one of the first clinicians to use a laser to treat basal cell carcinoma (BCC). Who are the ideal candidates for this procedure? Is the technique ready for wide clinical adoption? If not, what kind of studies are needed to make it so?

My research passion lies in optimizing laser treatments for BCC. During my fellowship with R. Rox Anderson, MD, and Mathew Avram, MD, at the MGH Wellman Center for Photomedicine, we conducted a pilot study using the 1064-nm Nd:YAG laser, achieving a 92% clearance rate after one treatment. Inspired by these results, we conducted a larger multicenter study, which demonstrated a 90% clearance rate after a single treatment. I now incorporate this technique into my daily practice. The ideal candidates for this procedure are patients with BCC that do not meet the Mohs Appropriate Use Criteria, such as those with nodular or superficial BCC subtypes on the body, individuals who are poor surgical candidates, or those who are surgically exhausted. However, I do not recommend this treatment for patients who are primarily concerned about facial scarring, particularly younger individuals; in such cases, Mohs surgery still remains the preferred option. While I believe this technique is ready for broader clinical adoption, it requires an understanding of laser endpoints. We are also exploring antibody-targeted gold nanorods to enhance the selectivity and standardization of the treatment.



Who inspires you most in your work today?

My patients are my greatest inspiration. Their trust and dedication motivate me to stay at the forefront of dermatologic advancements, ensuring I provide the most cutting-edge and safe treatments possible. Their commitment drives my relentless pursuit of continuous learning and innovation in the field.

What’s the best advice you can give to female dermatologists seeking leadership positions at the local, state, or national level?

My best advice is to have the courage to ask for what you seek. Societies are always looking for members who are eager to participate and contribute. If you express your interest in becoming more involved, there is likely a position available for you. The more you are willing to contribute to a society, the more likely you will be noticed and excel into higher leadership positions. Take initiative, show your commitment, and don’t hesitate to step forward when opportunities arise.



What’s the one tried-and-true laser- or energy-based procedure that you consider a “must” for your dermatology practice? And why?

Determining a single “must-have” laser- or energy-based procedure is a challenging question as it greatly depends on the specific needs of your patient population. However, one of the most common concerns among patients involves issues like redness and pigmentation. Therefore, having a versatile laser or an intense pulsed light device that effectively targets both red and brown pigmentation is indispensable for most practices.



In your view, what are the top three trends in aesthetic dermatology?

Over the years, I have observed several key trends in aesthetic dermatology:

• Minimally invasive procedures. There is a growing preference for less invasive treatments. Patients increasingly desire minimal downtime while still achieving significant results.
• Advancements in laser and energy-based devices for darker skin. There have been substantial advancements in technologies that are safer and more effective for darker skin tones. These developments play a crucial role in addressing diverse patient needs and providing inclusive dermatologic care.
• Natural aesthetic. I am hopeful that the trend toward an overdone appearance is fading. There seems to be a shift back towards a more natural and conservative aesthetic, emphasizing subtle enhancements over dramatic changes.

What development in dermatology are you most excited about in the next 5 years?

I am most excited to see how artificial intelligence and robotics play a role in energy-based devices.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Lauren Opladen remembers the agonizing wait all too well.

At age 17, struggling with paralyzing depression after losing her brother to suicide and her father to amyotrophic lateral sclerosis, her teacher suggested she seek help.

So, she did. But she had to spend 3 days inside an emergency department at the University of Rochester Medical Center in Rochester, New York, where the Comprehensive Psychiatric Emergency Program (CPEP) provides immediate care for youth and adults experiencing psychiatric emergencies.

“We were sleeping on a couch just waiting for all these services, when that’s precious time wasted,” Ms. Opladen said.

Ms. Opladen made it through that dark period, and 5 years later, she is a registered nurse at the same hospital. Every day she walks past a new facility she wishes had existed during her troubled teenage years: An urgent care center for children and adolescents experiencing mental health crises.

Brighter Days Pediatric Mental Health Urgent Care Center, Rochester, New York, opened in July as a walk-in clinic offering rapid assessment, crisis intervention, and short-term stabilization, provides referrals to counseling or psychiatric care. Children and adolescents at immediate risk of harming themselves or others, or who need inpatient care, are sent to CPEP or another emergency department in the area.

Similar walk-in facilities linking youth to longer-term services are popping up in nearly a dozen states, including New York, Ohio, Massachusetts, and Wisconsin. The emerging model of care may offer a crucial bridge between traditional outpatient services and emergency room (ER) visits for some young people experiencing mental health crises.

“We’ve seen a significant increase in the number of children and adolescents presenting to emergency departments with mental health concerns,” said Michael A. Scharf, MD, chief of the Division of Child and Adolescent Psychiatry at the University of Rochester Medical Center, who oversees operations at Brighter Days. “These urgent care centers provide a more appropriate setting for many of these cases, offering specialized care without the often overwhelming environment of an ER.”

The urgency of addressing youth behavioral health has become increasingly apparent. The most recent data from the US Centers for Disease Control and Prevention showed that over a 6-month period in 2020, during the early months of the COVID-19 pandemic, visits to the emergency department for mental health problems spiked 24% among children aged 5-11 years and 31% among 12-17-year-olds compared with the same period in 2019. Between March 2021 and February 2022, such emergency visits rose by 22% for teen girls, while falling by 15% for boys ages 5-12 years and 9% for older boys. Most visits occur during the school year.

But staffing shortages and limited physical space are taxing the capacity of the healthcare system to screen, diagnose, and manage these patients, according to a 2023 report published in Pediatrics.
 

Urgent Care: A Misnomer?

Some in the mental health community said the label “urgent” in these centers’ titles is misleading. Brighter Days and similar facilities do not conduct involuntary holds, administer medication, or handle serious cases like psychotic episodes.

David Mathison, MD, senior vice president of clinic operations at PM Pediatrics, a chain of pediatric urgent care clinics in Maryland, said patients and their families may mistakenly believe the centers will address mental health problems quickly.

“It’s really not urgent behavioral health. It’s really just another access point to get behavioral health,” Dr. Mathison said. “Crises in pediatrics are so much more complex” than physical injuries or acute infections, which are the bread and butter of urgent care centers.

“An urgent care center almost implies you’re going to come in for a solution to a simple problem, and it’s going to be done relatively quickly on demand, and it’s just not what the behavioral health centers do,” he said.

Dr. Mathison, who also serves on the executive committee for the section on urgent care at the American Academy of Pediatrics, likened the centers to in-person versions of crisis center hotlines, which offer virtual counseling and talk therapy and may refer individuals to specialists who can provide clinical care over the long term.

Instead, Brighter Days and other centers provide crisis de-escalation for individuals experiencing an exacerbation of a diagnosed mental illness, such a manic episode from bipolar disorder.

“Most places aren’t just going to change their therapy without either contacting their psychiatrist or having psychiatrists on staff,” Dr. Mathison said.

Other challenges at Brighter Days and similar centers include staffing with appropriately trained mental health professionals, given the nationwide shortage of child and adolescent psychiatrists, Dr. Scharf said.

The number of child and adolescent psychiatrists per 100,000 children varies significantly across states. Nationally, the average stands at 14 psychiatrists per 100,000 children, but ranges from as low as 4 to 65, according to the American Academy of Child & Adolescent Psychiatry.

For now, Dr. Scharf said, patients who visit Brighter Days are billed as if they are having a routine pediatric office visit as opposed to a pricier trip to the emergency department. And the center accepts all individuals, regardless of their insurance status.

Ms. Opladen said the urgent care center represents a significant improvement over her experience at the emergency department’s psychiatric triage.

“I saw how awful it was and just the environment,” she said. “The first thing I thought was, what do I need to do to get out of here?”

She said the pediatric mental health urgent care centers are “the complete opposite.” Like Brighter Days, these centers are designed to look more like a pediatrician’s office, with bright welcoming colors and games and toys.

“It’s separated from everything else. There’s a welcome, relaxed space,” she said. “The welcoming feel is just a whole different environment, and that’s really how it should be.”
 

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

Lauren Opladen remembers the agonizing wait all too well.

At age 17, struggling with paralyzing depression after losing her brother to suicide and her father to amyotrophic lateral sclerosis, her teacher suggested she seek help.

So, she did. But she had to spend 3 days inside an emergency department at the University of Rochester Medical Center in Rochester, New York, where the Comprehensive Psychiatric Emergency Program (CPEP) provides immediate care for youth and adults experiencing psychiatric emergencies.

“We were sleeping on a couch just waiting for all these services, when that’s precious time wasted,” Ms. Opladen said.

Ms. Opladen made it through that dark period, and 5 years later, she is a registered nurse at the same hospital. Every day she walks past a new facility she wishes had existed during her troubled teenage years: An urgent care center for children and adolescents experiencing mental health crises.

Brighter Days Pediatric Mental Health Urgent Care Center, Rochester, New York, opened in July as a walk-in clinic offering rapid assessment, crisis intervention, and short-term stabilization, provides referrals to counseling or psychiatric care. Children and adolescents at immediate risk of harming themselves or others, or who need inpatient care, are sent to CPEP or another emergency department in the area.

Similar walk-in facilities linking youth to longer-term services are popping up in nearly a dozen states, including New York, Ohio, Massachusetts, and Wisconsin. The emerging model of care may offer a crucial bridge between traditional outpatient services and emergency room (ER) visits for some young people experiencing mental health crises.

“We’ve seen a significant increase in the number of children and adolescents presenting to emergency departments with mental health concerns,” said Michael A. Scharf, MD, chief of the Division of Child and Adolescent Psychiatry at the University of Rochester Medical Center, who oversees operations at Brighter Days. “These urgent care centers provide a more appropriate setting for many of these cases, offering specialized care without the often overwhelming environment of an ER.”

The urgency of addressing youth behavioral health has become increasingly apparent. The most recent data from the US Centers for Disease Control and Prevention showed that over a 6-month period in 2020, during the early months of the COVID-19 pandemic, visits to the emergency department for mental health problems spiked 24% among children aged 5-11 years and 31% among 12-17-year-olds compared with the same period in 2019. Between March 2021 and February 2022, such emergency visits rose by 22% for teen girls, while falling by 15% for boys ages 5-12 years and 9% for older boys. Most visits occur during the school year.

But staffing shortages and limited physical space are taxing the capacity of the healthcare system to screen, diagnose, and manage these patients, according to a 2023 report published in Pediatrics.
 

Urgent Care: A Misnomer?

Some in the mental health community said the label “urgent” in these centers’ titles is misleading. Brighter Days and similar facilities do not conduct involuntary holds, administer medication, or handle serious cases like psychotic episodes.

David Mathison, MD, senior vice president of clinic operations at PM Pediatrics, a chain of pediatric urgent care clinics in Maryland, said patients and their families may mistakenly believe the centers will address mental health problems quickly.

“It’s really not urgent behavioral health. It’s really just another access point to get behavioral health,” Dr. Mathison said. “Crises in pediatrics are so much more complex” than physical injuries or acute infections, which are the bread and butter of urgent care centers.

“An urgent care center almost implies you’re going to come in for a solution to a simple problem, and it’s going to be done relatively quickly on demand, and it’s just not what the behavioral health centers do,” he said.

Dr. Mathison, who also serves on the executive committee for the section on urgent care at the American Academy of Pediatrics, likened the centers to in-person versions of crisis center hotlines, which offer virtual counseling and talk therapy and may refer individuals to specialists who can provide clinical care over the long term.

Instead, Brighter Days and other centers provide crisis de-escalation for individuals experiencing an exacerbation of a diagnosed mental illness, such a manic episode from bipolar disorder.

“Most places aren’t just going to change their therapy without either contacting their psychiatrist or having psychiatrists on staff,” Dr. Mathison said.

Other challenges at Brighter Days and similar centers include staffing with appropriately trained mental health professionals, given the nationwide shortage of child and adolescent psychiatrists, Dr. Scharf said.

The number of child and adolescent psychiatrists per 100,000 children varies significantly across states. Nationally, the average stands at 14 psychiatrists per 100,000 children, but ranges from as low as 4 to 65, according to the American Academy of Child & Adolescent Psychiatry.

For now, Dr. Scharf said, patients who visit Brighter Days are billed as if they are having a routine pediatric office visit as opposed to a pricier trip to the emergency department. And the center accepts all individuals, regardless of their insurance status.

Ms. Opladen said the urgent care center represents a significant improvement over her experience at the emergency department’s psychiatric triage.

“I saw how awful it was and just the environment,” she said. “The first thing I thought was, what do I need to do to get out of here?”

She said the pediatric mental health urgent care centers are “the complete opposite.” Like Brighter Days, these centers are designed to look more like a pediatrician’s office, with bright welcoming colors and games and toys.

“It’s separated from everything else. There’s a welcome, relaxed space,” she said. “The welcoming feel is just a whole different environment, and that’s really how it should be.”
 

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

Lauren Opladen remembers the agonizing wait all too well.

At age 17, struggling with paralyzing depression after losing her brother to suicide and her father to amyotrophic lateral sclerosis, her teacher suggested she seek help.

So, she did. But she had to spend 3 days inside an emergency department at the University of Rochester Medical Center in Rochester, New York, where the Comprehensive Psychiatric Emergency Program (CPEP) provides immediate care for youth and adults experiencing psychiatric emergencies.

“We were sleeping on a couch just waiting for all these services, when that’s precious time wasted,” Ms. Opladen said.

Ms. Opladen made it through that dark period, and 5 years later, she is a registered nurse at the same hospital. Every day she walks past a new facility she wishes had existed during her troubled teenage years: An urgent care center for children and adolescents experiencing mental health crises.

Brighter Days Pediatric Mental Health Urgent Care Center, Rochester, New York, opened in July as a walk-in clinic offering rapid assessment, crisis intervention, and short-term stabilization, provides referrals to counseling or psychiatric care. Children and adolescents at immediate risk of harming themselves or others, or who need inpatient care, are sent to CPEP or another emergency department in the area.

Similar walk-in facilities linking youth to longer-term services are popping up in nearly a dozen states, including New York, Ohio, Massachusetts, and Wisconsin. The emerging model of care may offer a crucial bridge between traditional outpatient services and emergency room (ER) visits for some young people experiencing mental health crises.

“We’ve seen a significant increase in the number of children and adolescents presenting to emergency departments with mental health concerns,” said Michael A. Scharf, MD, chief of the Division of Child and Adolescent Psychiatry at the University of Rochester Medical Center, who oversees operations at Brighter Days. “These urgent care centers provide a more appropriate setting for many of these cases, offering specialized care without the often overwhelming environment of an ER.”

The urgency of addressing youth behavioral health has become increasingly apparent. The most recent data from the US Centers for Disease Control and Prevention showed that over a 6-month period in 2020, during the early months of the COVID-19 pandemic, visits to the emergency department for mental health problems spiked 24% among children aged 5-11 years and 31% among 12-17-year-olds compared with the same period in 2019. Between March 2021 and February 2022, such emergency visits rose by 22% for teen girls, while falling by 15% for boys ages 5-12 years and 9% for older boys. Most visits occur during the school year.

But staffing shortages and limited physical space are taxing the capacity of the healthcare system to screen, diagnose, and manage these patients, according to a 2023 report published in Pediatrics.
 

Urgent Care: A Misnomer?

Some in the mental health community said the label “urgent” in these centers’ titles is misleading. Brighter Days and similar facilities do not conduct involuntary holds, administer medication, or handle serious cases like psychotic episodes.

David Mathison, MD, senior vice president of clinic operations at PM Pediatrics, a chain of pediatric urgent care clinics in Maryland, said patients and their families may mistakenly believe the centers will address mental health problems quickly.

“It’s really not urgent behavioral health. It’s really just another access point to get behavioral health,” Dr. Mathison said. “Crises in pediatrics are so much more complex” than physical injuries or acute infections, which are the bread and butter of urgent care centers.

“An urgent care center almost implies you’re going to come in for a solution to a simple problem, and it’s going to be done relatively quickly on demand, and it’s just not what the behavioral health centers do,” he said.

Dr. Mathison, who also serves on the executive committee for the section on urgent care at the American Academy of Pediatrics, likened the centers to in-person versions of crisis center hotlines, which offer virtual counseling and talk therapy and may refer individuals to specialists who can provide clinical care over the long term.

Instead, Brighter Days and other centers provide crisis de-escalation for individuals experiencing an exacerbation of a diagnosed mental illness, such a manic episode from bipolar disorder.

“Most places aren’t just going to change their therapy without either contacting their psychiatrist or having psychiatrists on staff,” Dr. Mathison said.

Other challenges at Brighter Days and similar centers include staffing with appropriately trained mental health professionals, given the nationwide shortage of child and adolescent psychiatrists, Dr. Scharf said.

The number of child and adolescent psychiatrists per 100,000 children varies significantly across states. Nationally, the average stands at 14 psychiatrists per 100,000 children, but ranges from as low as 4 to 65, according to the American Academy of Child & Adolescent Psychiatry.

For now, Dr. Scharf said, patients who visit Brighter Days are billed as if they are having a routine pediatric office visit as opposed to a pricier trip to the emergency department. And the center accepts all individuals, regardless of their insurance status.

Ms. Opladen said the urgent care center represents a significant improvement over her experience at the emergency department’s psychiatric triage.

“I saw how awful it was and just the environment,” she said. “The first thing I thought was, what do I need to do to get out of here?”

She said the pediatric mental health urgent care centers are “the complete opposite.” Like Brighter Days, these centers are designed to look more like a pediatrician’s office, with bright welcoming colors and games and toys.

“It’s separated from everything else. There’s a welcome, relaxed space,” she said. “The welcoming feel is just a whole different environment, and that’s really how it should be.”
 

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

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Since the European Alliance of Associations for Rheumatology (EULAR) published its 2019 recommendations, the range of therapeutic options in the management of psoriatic arthritis (PsA) has expanded significantly. Univadis France spoke to Laure Gossec, MD, PhD, a rheumatologist at Pitié-Salpêtrière Hospital and Sorbonne University in Paris, about the updates to these recommendations. 

What is the role of nonsteroidal anti-inflammatory drugs (NSAIDs) today?

NSAIDs remain the first-line treatment, but their place as monotherapy without background treatment has been mainly limited to patients with mild peripheral disease. For them, NSAIDs are recommended as monotherapy for a short duration, 2-4 weeks, while the clinician assesses and promptly introduces background treatment. We have a window of opportunity. Inflammation must be targeted quickly, especially if the patient has a form of disease associated with poor prognosis. Such patients include those with polyarticular forms or high C-reactive protein (CRP).

The two criteria of at least four swollen joints and/or a CRP greater than 5 mg/L should prompt the physician to introduce background treatment.

When prescribing NSAIDs, clinicians must rigorously evaluate the benefit-risk ratio because patients with PsA often have comorbidities. In France, one third of them have obesity, 20% have hypertension, and 20% have diabetes.
 

What is the recommended hierarchy for other treatments?

In the second phase of treatment, synthetic conventional treatments (like methotrexate, leflunomide, or sulfasalazine) are recommended. Methotrexate is by far the most used. This choice is based on efficacy, the efficacy-safety ratio, and cost.

A biologic therapy has no place as a first-line treatment because most PsA cases are moderate. In this regard, our European recommendations differ from American recommendations, which leave the choice between conventional or targeted therapies as a first-line treatment.

We have opted for a step-up approach. Although there is no study comparing a biologic therapy vs methotrexate as a first-line treatment, we have many data showing that more than half of patients will never need a biologic therapy.

We have a lot of experience with molecules like methotrexate. The benefit-risk ratio of this treatment as a first-line option is favorable, with efficacy for the skin. However, in axial forms, methotrexate is ineffective and calls for the use of biologic therapy.
 

Are there selection criteria for second-line biologic therapies?

Five classes of molecules are authorized and reimbursed in France: anti-TNF (tumor necrosis factor), anti–IL (interleukin)-17A, anti–IL-17A, -F, and -AF (bimekizumab), anti–IL-12/23 (ustekinumab), and anti–IL-23. All these treatments are effective in about two thirds of patients.

Unfortunately, we are not yet practicing personalized medicine to choose the most appropriate treatment for each patient, because we cannot predict this response. However, there are specific cases. Anti–IL-17 and anti–IL-23 can be favored in patients with bothersome skin involvement, either because it is extensive or located on the face or genital area. If a patient also has chronic inflammatory bowel disease, anti-TNF, anti–IL-23, or Janus kinase (JAK) inhibitors should be prioritized. In axial forms, anti-TNF or anti–IL-17 is recommended. But these cases concern only a minority of our patients. 

We have kept a place for JAK inhibitors in patients for whom biologic therapies are not suitable or effective. It is important to follow the recommendations of the European Medicines Agency, avoiding the use of JAK inhibitors after age 60 years, in smokers, or in those with cardiovascular risk. Oncologic monitoring is also important for patients treated with this therapeutic class.

Let’s also remember the role of apremilast, which is an alternative to biologic therapies in patients with moderate forms of the disease.

In the next 2 or 3 years, new modes of action or new molecules should be available, such as tyrosine kinase 2 (TYK2) inhibitors; izokibep, an oral nanomolecule targeting IL-17; or a new injectable anti–IL-17 with an affinity with interleukin that is incomparable to that of previous antibodies.
 

What message should be conveyed to the general practitioner?

PsA treatments are prescribed initially in hospitals, but rheumatologists will be able to prescribe them in the coming months. The general practitioner cannot initiate targeted treatment but has the role of starting methotrexate and referring the patient to specialized follow-up.

The most important thing to know is that in France, about half of patients will be on targeted treatment. The median maintenance of such therapy is only 3 years, which means that half of the patients will have replaced it with another therapy after 3 years. This switch could indicate a loss of efficacy or escape. It is therefore important for a specialist to follow the patient and to continue biologic monitoring every 2-6 months, as well as imaging every 2-5 years to check radiographic progression.

In cases of prolonged remission of more than 6 months, a gradual and cautious decrease in background treatments can be considered in a shared medical decision. However, treatment discontinuation leads to a systemic relapse in the short or long term, and a gradual decrease results in relapse in about half of the patients.
 

And in terms of monitoring?

The management of comorbidities is crucial. It is essential to keep vaccinations up to date, especially because of the increased risk for potential infections with targeted treatments. Regular screening for infections, including dental follow-up, is also recommended.

Preventive medicine is also important, especially regarding breast and colon cancer screening. General population recommendations apply.

Cardiovascular risk, which is doubled in patients with PsA compared with the general population due to chronic inflammation, should prompt monitoring of blood pressure and metabolic diseases. It should be noted that there is an 11% higher mortality rate after 8 years of follow-up, mainly due to cardiovascular and neoplastic risks.

Dr. Gossec reported receiving research grants from AbbVie, Biogen, Lilly, Novartis, and UCB and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB.
 

This story was translated from Univadis France, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Since the European Alliance of Associations for Rheumatology (EULAR) published its 2019 recommendations, the range of therapeutic options in the management of psoriatic arthritis (PsA) has expanded significantly. Univadis France spoke to Laure Gossec, MD, PhD, a rheumatologist at Pitié-Salpêtrière Hospital and Sorbonne University in Paris, about the updates to these recommendations. 

What is the role of nonsteroidal anti-inflammatory drugs (NSAIDs) today?

NSAIDs remain the first-line treatment, but their place as monotherapy without background treatment has been mainly limited to patients with mild peripheral disease. For them, NSAIDs are recommended as monotherapy for a short duration, 2-4 weeks, while the clinician assesses and promptly introduces background treatment. We have a window of opportunity. Inflammation must be targeted quickly, especially if the patient has a form of disease associated with poor prognosis. Such patients include those with polyarticular forms or high C-reactive protein (CRP).

The two criteria of at least four swollen joints and/or a CRP greater than 5 mg/L should prompt the physician to introduce background treatment.

When prescribing NSAIDs, clinicians must rigorously evaluate the benefit-risk ratio because patients with PsA often have comorbidities. In France, one third of them have obesity, 20% have hypertension, and 20% have diabetes.
 

What is the recommended hierarchy for other treatments?

In the second phase of treatment, synthetic conventional treatments (like methotrexate, leflunomide, or sulfasalazine) are recommended. Methotrexate is by far the most used. This choice is based on efficacy, the efficacy-safety ratio, and cost.

A biologic therapy has no place as a first-line treatment because most PsA cases are moderate. In this regard, our European recommendations differ from American recommendations, which leave the choice between conventional or targeted therapies as a first-line treatment.

We have opted for a step-up approach. Although there is no study comparing a biologic therapy vs methotrexate as a first-line treatment, we have many data showing that more than half of patients will never need a biologic therapy.

We have a lot of experience with molecules like methotrexate. The benefit-risk ratio of this treatment as a first-line option is favorable, with efficacy for the skin. However, in axial forms, methotrexate is ineffective and calls for the use of biologic therapy.
 

Are there selection criteria for second-line biologic therapies?

Five classes of molecules are authorized and reimbursed in France: anti-TNF (tumor necrosis factor), anti–IL (interleukin)-17A, anti–IL-17A, -F, and -AF (bimekizumab), anti–IL-12/23 (ustekinumab), and anti–IL-23. All these treatments are effective in about two thirds of patients.

Unfortunately, we are not yet practicing personalized medicine to choose the most appropriate treatment for each patient, because we cannot predict this response. However, there are specific cases. Anti–IL-17 and anti–IL-23 can be favored in patients with bothersome skin involvement, either because it is extensive or located on the face or genital area. If a patient also has chronic inflammatory bowel disease, anti-TNF, anti–IL-23, or Janus kinase (JAK) inhibitors should be prioritized. In axial forms, anti-TNF or anti–IL-17 is recommended. But these cases concern only a minority of our patients. 

We have kept a place for JAK inhibitors in patients for whom biologic therapies are not suitable or effective. It is important to follow the recommendations of the European Medicines Agency, avoiding the use of JAK inhibitors after age 60 years, in smokers, or in those with cardiovascular risk. Oncologic monitoring is also important for patients treated with this therapeutic class.

Let’s also remember the role of apremilast, which is an alternative to biologic therapies in patients with moderate forms of the disease.

In the next 2 or 3 years, new modes of action or new molecules should be available, such as tyrosine kinase 2 (TYK2) inhibitors; izokibep, an oral nanomolecule targeting IL-17; or a new injectable anti–IL-17 with an affinity with interleukin that is incomparable to that of previous antibodies.
 

What message should be conveyed to the general practitioner?

PsA treatments are prescribed initially in hospitals, but rheumatologists will be able to prescribe them in the coming months. The general practitioner cannot initiate targeted treatment but has the role of starting methotrexate and referring the patient to specialized follow-up.

The most important thing to know is that in France, about half of patients will be on targeted treatment. The median maintenance of such therapy is only 3 years, which means that half of the patients will have replaced it with another therapy after 3 years. This switch could indicate a loss of efficacy or escape. It is therefore important for a specialist to follow the patient and to continue biologic monitoring every 2-6 months, as well as imaging every 2-5 years to check radiographic progression.

In cases of prolonged remission of more than 6 months, a gradual and cautious decrease in background treatments can be considered in a shared medical decision. However, treatment discontinuation leads to a systemic relapse in the short or long term, and a gradual decrease results in relapse in about half of the patients.
 

And in terms of monitoring?

The management of comorbidities is crucial. It is essential to keep vaccinations up to date, especially because of the increased risk for potential infections with targeted treatments. Regular screening for infections, including dental follow-up, is also recommended.

Preventive medicine is also important, especially regarding breast and colon cancer screening. General population recommendations apply.

Cardiovascular risk, which is doubled in patients with PsA compared with the general population due to chronic inflammation, should prompt monitoring of blood pressure and metabolic diseases. It should be noted that there is an 11% higher mortality rate after 8 years of follow-up, mainly due to cardiovascular and neoplastic risks.

Dr. Gossec reported receiving research grants from AbbVie, Biogen, Lilly, Novartis, and UCB and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB.
 

This story was translated from Univadis France, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Since the European Alliance of Associations for Rheumatology (EULAR) published its 2019 recommendations, the range of therapeutic options in the management of psoriatic arthritis (PsA) has expanded significantly. Univadis France spoke to Laure Gossec, MD, PhD, a rheumatologist at Pitié-Salpêtrière Hospital and Sorbonne University in Paris, about the updates to these recommendations. 

What is the role of nonsteroidal anti-inflammatory drugs (NSAIDs) today?

NSAIDs remain the first-line treatment, but their place as monotherapy without background treatment has been mainly limited to patients with mild peripheral disease. For them, NSAIDs are recommended as monotherapy for a short duration, 2-4 weeks, while the clinician assesses and promptly introduces background treatment. We have a window of opportunity. Inflammation must be targeted quickly, especially if the patient has a form of disease associated with poor prognosis. Such patients include those with polyarticular forms or high C-reactive protein (CRP).

The two criteria of at least four swollen joints and/or a CRP greater than 5 mg/L should prompt the physician to introduce background treatment.

When prescribing NSAIDs, clinicians must rigorously evaluate the benefit-risk ratio because patients with PsA often have comorbidities. In France, one third of them have obesity, 20% have hypertension, and 20% have diabetes.
 

What is the recommended hierarchy for other treatments?

In the second phase of treatment, synthetic conventional treatments (like methotrexate, leflunomide, or sulfasalazine) are recommended. Methotrexate is by far the most used. This choice is based on efficacy, the efficacy-safety ratio, and cost.

A biologic therapy has no place as a first-line treatment because most PsA cases are moderate. In this regard, our European recommendations differ from American recommendations, which leave the choice between conventional or targeted therapies as a first-line treatment.

We have opted for a step-up approach. Although there is no study comparing a biologic therapy vs methotrexate as a first-line treatment, we have many data showing that more than half of patients will never need a biologic therapy.

We have a lot of experience with molecules like methotrexate. The benefit-risk ratio of this treatment as a first-line option is favorable, with efficacy for the skin. However, in axial forms, methotrexate is ineffective and calls for the use of biologic therapy.
 

Are there selection criteria for second-line biologic therapies?

Five classes of molecules are authorized and reimbursed in France: anti-TNF (tumor necrosis factor), anti–IL (interleukin)-17A, anti–IL-17A, -F, and -AF (bimekizumab), anti–IL-12/23 (ustekinumab), and anti–IL-23. All these treatments are effective in about two thirds of patients.

Unfortunately, we are not yet practicing personalized medicine to choose the most appropriate treatment for each patient, because we cannot predict this response. However, there are specific cases. Anti–IL-17 and anti–IL-23 can be favored in patients with bothersome skin involvement, either because it is extensive or located on the face or genital area. If a patient also has chronic inflammatory bowel disease, anti-TNF, anti–IL-23, or Janus kinase (JAK) inhibitors should be prioritized. In axial forms, anti-TNF or anti–IL-17 is recommended. But these cases concern only a minority of our patients. 

We have kept a place for JAK inhibitors in patients for whom biologic therapies are not suitable or effective. It is important to follow the recommendations of the European Medicines Agency, avoiding the use of JAK inhibitors after age 60 years, in smokers, or in those with cardiovascular risk. Oncologic monitoring is also important for patients treated with this therapeutic class.

Let’s also remember the role of apremilast, which is an alternative to biologic therapies in patients with moderate forms of the disease.

In the next 2 or 3 years, new modes of action or new molecules should be available, such as tyrosine kinase 2 (TYK2) inhibitors; izokibep, an oral nanomolecule targeting IL-17; or a new injectable anti–IL-17 with an affinity with interleukin that is incomparable to that of previous antibodies.
 

What message should be conveyed to the general practitioner?

PsA treatments are prescribed initially in hospitals, but rheumatologists will be able to prescribe them in the coming months. The general practitioner cannot initiate targeted treatment but has the role of starting methotrexate and referring the patient to specialized follow-up.

The most important thing to know is that in France, about half of patients will be on targeted treatment. The median maintenance of such therapy is only 3 years, which means that half of the patients will have replaced it with another therapy after 3 years. This switch could indicate a loss of efficacy or escape. It is therefore important for a specialist to follow the patient and to continue biologic monitoring every 2-6 months, as well as imaging every 2-5 years to check radiographic progression.

In cases of prolonged remission of more than 6 months, a gradual and cautious decrease in background treatments can be considered in a shared medical decision. However, treatment discontinuation leads to a systemic relapse in the short or long term, and a gradual decrease results in relapse in about half of the patients.
 

And in terms of monitoring?

The management of comorbidities is crucial. It is essential to keep vaccinations up to date, especially because of the increased risk for potential infections with targeted treatments. Regular screening for infections, including dental follow-up, is also recommended.

Preventive medicine is also important, especially regarding breast and colon cancer screening. General population recommendations apply.

Cardiovascular risk, which is doubled in patients with PsA compared with the general population due to chronic inflammation, should prompt monitoring of blood pressure and metabolic diseases. It should be noted that there is an 11% higher mortality rate after 8 years of follow-up, mainly due to cardiovascular and neoplastic risks.

Dr. Gossec reported receiving research grants from AbbVie, Biogen, Lilly, Novartis, and UCB and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB.
 

This story was translated from Univadis France, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.