Rheumatology News

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TORONTO — When it comes to using artificial intelligence (AI) in your practice, pediatric dermatologist Albert Yan, MD, professor of pediatrics and dermatology at the University of Pennsylvania, Philadelphia, suggests that dermatologists “just jump in” and become familiar with the various AI models.

He reminds doctors that many of their colleagues and patients and their families are already using these systems, “and you don’t want to be left behind.”

In an interview following his presentation on AI at the annual meeting of the Society for Pediatric Dermatology (SPD), Dr. Yan discussed his tips for using AI.
 

Changing Fast 

From the outset, most generative AI systems have been very good at processing language — for example, generating letters of medical necessity and summarizing disease processes into lay terms. But now they’re becoming “truly multimodal,” said Dr. Yan. “You can enter images; you could have it process audio; you can even start to have it refine video.”

To get started, he recommends signing up for a free account with ChatGPT, Gemini, Perplexity, Claude, and/or Microsoft Copilot. “To make the best choice, you have to try them out yourself because they each have their own kind of flavor and strengths and weaknesses,” said Dr. Yan.

Personally, he finds that ChatGPT is the most versatile, Gemini perhaps a little better in terms of image generation, and Perplexity probably the best at references because it was designed as an online library.

Once you figure out which platforms you prefer, consider signing up for a premium subscription, which is typically month to month and can be canceled at any time, Dr. Yan said. “This will allow you to get the most out of the AI model.”

As these AI systems are based on large language models, they are excellent at text, Dr. Yan noted. He suggests asking one to generate a letter or patient instruction sheet. “If you have a premium model, give it a PDF to summarize an article or take a photo of something that you want its opinion on.”

Privacy Critical

Always pay attention to privacy issues and avoid entering any private health information that would violate the Health Insurance Portability and Accountability Act (HIPAA), he said.

“We have to be very careful about how we interact with AI,” said Dr. Yan. “We can’t be posting private patient health information into these systems, no matter how useful these systems are.” Many academic institutions are creating “walled gardens” — private areas of AI access that don’t allow patient information to “leak out,” he said. “These AI models may have HIPAA protections in place and come with specific guidelines of use.”

The AI “scribe,” which helps with electronic health record documentation, is one of the most useful tools for clinicians, he said. He referred to a recent study showing that an AI scribe saved users an average of 1 hour at the keyboard every day, and a small patient survey showing 71% reported that it led to spending more time with their physician.

When entering requests into a prompt line with an AI system, Dr. Yan stressed that these prompts need to be clear and concise. For a complicated calculation or multistep problem, try adding the words “let’s do this step by step,” he said. “This is a technique invoking a ‘chain of thought’ that allows the system to enhance its accuracy when solving problems.”

If the response is not satisfactory, try being more detailed in the request, he advised, and consider giving the system examples of what you’re looking for and telling it what you don’t want in the output.

“For instance, if you’re asking for a differential diagnosis of rashes that affect the hands and feet, you can stipulate that you only want rashes that are vesicular or that arise in neonates, so you can get a more focused answer,” said Dr. Yan.

If there are “long-winded verbose” responses, add the phrase “be concise,” and it will shorten the response by about 50%, he added.
 

AI Hallucinations

Dr. Yan broached an issue that occasionally comes up, AI hallucinations, which refer to inaccurate or misleading responses on the basis of incomplete training or intrinsic biases within the model. He pointed to the case of a doctor discussing issues related to a patient’s hands, feet, and mouth, which the AI-generated model summarized as “the patient being diagnosed with hand, foot, and mouth disease.”

Another example he provided was a request to generate a letter of medical necessity for using ustekinumab (Stelara) for treating hidradenitis suppurative in a child that included references for its effectiveness and safety in children. The AI system generated “false references that sounded like they should be real because the authors are often people who have written in that field or on that subject,” said Dr. Yan.

When pressed, the system did acknowledge the references were hypothetical but were meant to illustrate the types of studies that would typically support the use of this drug in pediatric patients with HS. “ It’s well meaning, in the sense that it’s trying to help you achieve your goals using this training system,” said Dr. Yan.

“If you’re skeptical about a response, double-check the answer with a Google search or run the response through another AI [tool] asking it to check if the response is accurate,” he added.

While AI systems won’t replace the clinician, they are continuing to improve and becoming more sophisticated. Dr. Yan advises keeping up with emerging developments and engaging and adapting the most appropriate AI tool for an individual clinician’s work.

Asked to comment on the presentation at the SPD meeting, Sheilagh Maguiness, MD, director of the Division of Pediatric Dermatology at the University of Minnesota, Minneapolis, who, like other doctors, is increasingly testing AI, said she foresees a time when AI scribes fully replace humans for completing tasks during patient interactions.

“The hope is that if the AI scribes get good enough, we can just open our phone, have them translate the interaction, and create the notes for us.”

While she likes the idea of using ChatGPT to help with tasks like letters of recommendation for medications, Dr. Yan’s comments reiterated the importance of “checking and double-checking ChatGPT because it’s not correct all the time.” She particularly welcomed the advice “that we can just go back and ask it again to clarify, and that may improve its answers.”

Dr. Yan’s disclosures included an investment portfolio that includes companies working in the AI space, including Google, Apple, Nvidia, Amazon, Microsoft, and Arm. Dr. Maguiness had no relevant disclosures.

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

TORONTO — When it comes to using artificial intelligence (AI) in your practice, pediatric dermatologist Albert Yan, MD, professor of pediatrics and dermatology at the University of Pennsylvania, Philadelphia, suggests that dermatologists “just jump in” and become familiar with the various AI models.

He reminds doctors that many of their colleagues and patients and their families are already using these systems, “and you don’t want to be left behind.”

In an interview following his presentation on AI at the annual meeting of the Society for Pediatric Dermatology (SPD), Dr. Yan discussed his tips for using AI.
 

Changing Fast 

From the outset, most generative AI systems have been very good at processing language — for example, generating letters of medical necessity and summarizing disease processes into lay terms. But now they’re becoming “truly multimodal,” said Dr. Yan. “You can enter images; you could have it process audio; you can even start to have it refine video.”

To get started, he recommends signing up for a free account with ChatGPT, Gemini, Perplexity, Claude, and/or Microsoft Copilot. “To make the best choice, you have to try them out yourself because they each have their own kind of flavor and strengths and weaknesses,” said Dr. Yan.

Personally, he finds that ChatGPT is the most versatile, Gemini perhaps a little better in terms of image generation, and Perplexity probably the best at references because it was designed as an online library.

Once you figure out which platforms you prefer, consider signing up for a premium subscription, which is typically month to month and can be canceled at any time, Dr. Yan said. “This will allow you to get the most out of the AI model.”

As these AI systems are based on large language models, they are excellent at text, Dr. Yan noted. He suggests asking one to generate a letter or patient instruction sheet. “If you have a premium model, give it a PDF to summarize an article or take a photo of something that you want its opinion on.”

Privacy Critical

Always pay attention to privacy issues and avoid entering any private health information that would violate the Health Insurance Portability and Accountability Act (HIPAA), he said.

“We have to be very careful about how we interact with AI,” said Dr. Yan. “We can’t be posting private patient health information into these systems, no matter how useful these systems are.” Many academic institutions are creating “walled gardens” — private areas of AI access that don’t allow patient information to “leak out,” he said. “These AI models may have HIPAA protections in place and come with specific guidelines of use.”

The AI “scribe,” which helps with electronic health record documentation, is one of the most useful tools for clinicians, he said. He referred to a recent study showing that an AI scribe saved users an average of 1 hour at the keyboard every day, and a small patient survey showing 71% reported that it led to spending more time with their physician.

When entering requests into a prompt line with an AI system, Dr. Yan stressed that these prompts need to be clear and concise. For a complicated calculation or multistep problem, try adding the words “let’s do this step by step,” he said. “This is a technique invoking a ‘chain of thought’ that allows the system to enhance its accuracy when solving problems.”

If the response is not satisfactory, try being more detailed in the request, he advised, and consider giving the system examples of what you’re looking for and telling it what you don’t want in the output.

“For instance, if you’re asking for a differential diagnosis of rashes that affect the hands and feet, you can stipulate that you only want rashes that are vesicular or that arise in neonates, so you can get a more focused answer,” said Dr. Yan.

If there are “long-winded verbose” responses, add the phrase “be concise,” and it will shorten the response by about 50%, he added.
 

AI Hallucinations

Dr. Yan broached an issue that occasionally comes up, AI hallucinations, which refer to inaccurate or misleading responses on the basis of incomplete training or intrinsic biases within the model. He pointed to the case of a doctor discussing issues related to a patient’s hands, feet, and mouth, which the AI-generated model summarized as “the patient being diagnosed with hand, foot, and mouth disease.”

Another example he provided was a request to generate a letter of medical necessity for using ustekinumab (Stelara) for treating hidradenitis suppurative in a child that included references for its effectiveness and safety in children. The AI system generated “false references that sounded like they should be real because the authors are often people who have written in that field or on that subject,” said Dr. Yan.

When pressed, the system did acknowledge the references were hypothetical but were meant to illustrate the types of studies that would typically support the use of this drug in pediatric patients with HS. “ It’s well meaning, in the sense that it’s trying to help you achieve your goals using this training system,” said Dr. Yan.

“If you’re skeptical about a response, double-check the answer with a Google search or run the response through another AI [tool] asking it to check if the response is accurate,” he added.

While AI systems won’t replace the clinician, they are continuing to improve and becoming more sophisticated. Dr. Yan advises keeping up with emerging developments and engaging and adapting the most appropriate AI tool for an individual clinician’s work.

Asked to comment on the presentation at the SPD meeting, Sheilagh Maguiness, MD, director of the Division of Pediatric Dermatology at the University of Minnesota, Minneapolis, who, like other doctors, is increasingly testing AI, said she foresees a time when AI scribes fully replace humans for completing tasks during patient interactions.

“The hope is that if the AI scribes get good enough, we can just open our phone, have them translate the interaction, and create the notes for us.”

While she likes the idea of using ChatGPT to help with tasks like letters of recommendation for medications, Dr. Yan’s comments reiterated the importance of “checking and double-checking ChatGPT because it’s not correct all the time.” She particularly welcomed the advice “that we can just go back and ask it again to clarify, and that may improve its answers.”

Dr. Yan’s disclosures included an investment portfolio that includes companies working in the AI space, including Google, Apple, Nvidia, Amazon, Microsoft, and Arm. Dr. Maguiness had no relevant disclosures.

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

TORONTO — When it comes to using artificial intelligence (AI) in your practice, pediatric dermatologist Albert Yan, MD, professor of pediatrics and dermatology at the University of Pennsylvania, Philadelphia, suggests that dermatologists “just jump in” and become familiar with the various AI models.

He reminds doctors that many of their colleagues and patients and their families are already using these systems, “and you don’t want to be left behind.”

In an interview following his presentation on AI at the annual meeting of the Society for Pediatric Dermatology (SPD), Dr. Yan discussed his tips for using AI.
 

Changing Fast 

From the outset, most generative AI systems have been very good at processing language — for example, generating letters of medical necessity and summarizing disease processes into lay terms. But now they’re becoming “truly multimodal,” said Dr. Yan. “You can enter images; you could have it process audio; you can even start to have it refine video.”

To get started, he recommends signing up for a free account with ChatGPT, Gemini, Perplexity, Claude, and/or Microsoft Copilot. “To make the best choice, you have to try them out yourself because they each have their own kind of flavor and strengths and weaknesses,” said Dr. Yan.

Personally, he finds that ChatGPT is the most versatile, Gemini perhaps a little better in terms of image generation, and Perplexity probably the best at references because it was designed as an online library.

Once you figure out which platforms you prefer, consider signing up for a premium subscription, which is typically month to month and can be canceled at any time, Dr. Yan said. “This will allow you to get the most out of the AI model.”

As these AI systems are based on large language models, they are excellent at text, Dr. Yan noted. He suggests asking one to generate a letter or patient instruction sheet. “If you have a premium model, give it a PDF to summarize an article or take a photo of something that you want its opinion on.”

Privacy Critical

Always pay attention to privacy issues and avoid entering any private health information that would violate the Health Insurance Portability and Accountability Act (HIPAA), he said.

“We have to be very careful about how we interact with AI,” said Dr. Yan. “We can’t be posting private patient health information into these systems, no matter how useful these systems are.” Many academic institutions are creating “walled gardens” — private areas of AI access that don’t allow patient information to “leak out,” he said. “These AI models may have HIPAA protections in place and come with specific guidelines of use.”

The AI “scribe,” which helps with electronic health record documentation, is one of the most useful tools for clinicians, he said. He referred to a recent study showing that an AI scribe saved users an average of 1 hour at the keyboard every day, and a small patient survey showing 71% reported that it led to spending more time with their physician.

When entering requests into a prompt line with an AI system, Dr. Yan stressed that these prompts need to be clear and concise. For a complicated calculation or multistep problem, try adding the words “let’s do this step by step,” he said. “This is a technique invoking a ‘chain of thought’ that allows the system to enhance its accuracy when solving problems.”

If the response is not satisfactory, try being more detailed in the request, he advised, and consider giving the system examples of what you’re looking for and telling it what you don’t want in the output.

“For instance, if you’re asking for a differential diagnosis of rashes that affect the hands and feet, you can stipulate that you only want rashes that are vesicular or that arise in neonates, so you can get a more focused answer,” said Dr. Yan.

If there are “long-winded verbose” responses, add the phrase “be concise,” and it will shorten the response by about 50%, he added.
 

AI Hallucinations

Dr. Yan broached an issue that occasionally comes up, AI hallucinations, which refer to inaccurate or misleading responses on the basis of incomplete training or intrinsic biases within the model. He pointed to the case of a doctor discussing issues related to a patient’s hands, feet, and mouth, which the AI-generated model summarized as “the patient being diagnosed with hand, foot, and mouth disease.”

Another example he provided was a request to generate a letter of medical necessity for using ustekinumab (Stelara) for treating hidradenitis suppurative in a child that included references for its effectiveness and safety in children. The AI system generated “false references that sounded like they should be real because the authors are often people who have written in that field or on that subject,” said Dr. Yan.

When pressed, the system did acknowledge the references were hypothetical but were meant to illustrate the types of studies that would typically support the use of this drug in pediatric patients with HS. “ It’s well meaning, in the sense that it’s trying to help you achieve your goals using this training system,” said Dr. Yan.

“If you’re skeptical about a response, double-check the answer with a Google search or run the response through another AI [tool] asking it to check if the response is accurate,” he added.

While AI systems won’t replace the clinician, they are continuing to improve and becoming more sophisticated. Dr. Yan advises keeping up with emerging developments and engaging and adapting the most appropriate AI tool for an individual clinician’s work.

Asked to comment on the presentation at the SPD meeting, Sheilagh Maguiness, MD, director of the Division of Pediatric Dermatology at the University of Minnesota, Minneapolis, who, like other doctors, is increasingly testing AI, said she foresees a time when AI scribes fully replace humans for completing tasks during patient interactions.

“The hope is that if the AI scribes get good enough, we can just open our phone, have them translate the interaction, and create the notes for us.”

While she likes the idea of using ChatGPT to help with tasks like letters of recommendation for medications, Dr. Yan’s comments reiterated the importance of “checking and double-checking ChatGPT because it’s not correct all the time.” She particularly welcomed the advice “that we can just go back and ask it again to clarify, and that may improve its answers.”

Dr. Yan’s disclosures included an investment portfolio that includes companies working in the AI space, including Google, Apple, Nvidia, Amazon, Microsoft, and Arm. Dr. Maguiness had no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

TOPLINE:

The estimated number of US adults who consumed at least one of the six most frequently reported hepatotoxic botanicals in the last 30 days is similar to the number of patients prescribed potentially hepatotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and simvastatin.

METHODOLOGY:

• Herbal and dietary supplements (HDS) are an increasingly common source of drug hepatotoxicity cases, but their prevalence and the reasons for their use among the general population are uncertain.
• This survey study evaluated nationally representative data from 9685 adults (mean age, 47.5 years; 51.8% women) enrolled in the National Health and Nutrition Examination Survey (NHANES) between January 2017 and March 2020.
• Participants reported their use of HDS and prescription drugs through personal interviews for a 30-day period prior to the survey date.
• Researchers compared the clinical features and baseline demographic characteristics of users of six potentially hepatotoxic botanicals (ie, turmeric, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha) with those of nonusers.
• The prevalence of use of these at-risk botanicals was compared with that of widely prescribed potentially hepatotoxic medications, including NSAIDs, simvastatin, and sertraline.

TAKEAWAY:

• In the cohort of 9685 participants, 4.7% of individuals reported consumption of at least one of the six potentially hepatotoxic botanicals in the past 30 days, with turmeric being the most common, followed by green tea.
• Extrapolating the survey data, researchers estimated that 15.6 million US adults use at least one of these six botanicals, which is comparable to the number of those prescribed potentially hepatotoxic drugs, including NSAIDs (14.8 million) and simvastatin (14.0 million). Sertraline use was lower (7.7 million).
• Most individuals used these botanicals without the recommendation of their healthcare provider.
• Those using botanicals were more likely to be older (adjusted odds ratio [aOR], 2.36; P = .04 for 40-59 years; aOR, 3.96; P = .001 for ≥ 60 years), to have some college education (aOR, 4.78; P < .001), and to have arthritis (aOR, 2.27; P < .001) than nonusers.
• The most common reasons for using any of these six potential hepatotoxic botanicals were to improve or maintain health or to prevent health problems or boost immunity.

IN PRACTICE:

“In light of the lack of regulatory oversight on the manufacturing and testing of botanical products, it is recommended that clinicians obtain a full medication and HDS use history when evaluating patients with unexplained symptoms or liver test abnormalities,” the authors wrote.

SOURCE:

The study, led by Alisa Likhitsup, MD, MPH, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, was published online in JAMA Network Open. 

LIMITATIONS:

The survey response rate was low at 43.9% for adults aged ≥ 20 years. As NHANES is a cross-sectional study, the causal relationship between consumption of the six botanicals of interest and the development of liver injury could not be determined. The use of HDS products and medications was self-reported in NHANES and not independently verified using source documents. 

DISCLOSURES:

This study did not report any source of funding. Two authors declared receiving grants from pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

The estimated number of US adults who consumed at least one of the six most frequently reported hepatotoxic botanicals in the last 30 days is similar to the number of patients prescribed potentially hepatotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and simvastatin.

METHODOLOGY:

• Herbal and dietary supplements (HDS) are an increasingly common source of drug hepatotoxicity cases, but their prevalence and the reasons for their use among the general population are uncertain.
• This survey study evaluated nationally representative data from 9685 adults (mean age, 47.5 years; 51.8% women) enrolled in the National Health and Nutrition Examination Survey (NHANES) between January 2017 and March 2020.
• Participants reported their use of HDS and prescription drugs through personal interviews for a 30-day period prior to the survey date.
• Researchers compared the clinical features and baseline demographic characteristics of users of six potentially hepatotoxic botanicals (ie, turmeric, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha) with those of nonusers.
• The prevalence of use of these at-risk botanicals was compared with that of widely prescribed potentially hepatotoxic medications, including NSAIDs, simvastatin, and sertraline.

TAKEAWAY:

• In the cohort of 9685 participants, 4.7% of individuals reported consumption of at least one of the six potentially hepatotoxic botanicals in the past 30 days, with turmeric being the most common, followed by green tea.
• Extrapolating the survey data, researchers estimated that 15.6 million US adults use at least one of these six botanicals, which is comparable to the number of those prescribed potentially hepatotoxic drugs, including NSAIDs (14.8 million) and simvastatin (14.0 million). Sertraline use was lower (7.7 million).
• Most individuals used these botanicals without the recommendation of their healthcare provider.
• Those using botanicals were more likely to be older (adjusted odds ratio [aOR], 2.36; P = .04 for 40-59 years; aOR, 3.96; P = .001 for ≥ 60 years), to have some college education (aOR, 4.78; P < .001), and to have arthritis (aOR, 2.27; P < .001) than nonusers.
• The most common reasons for using any of these six potential hepatotoxic botanicals were to improve or maintain health or to prevent health problems or boost immunity.

IN PRACTICE:

“In light of the lack of regulatory oversight on the manufacturing and testing of botanical products, it is recommended that clinicians obtain a full medication and HDS use history when evaluating patients with unexplained symptoms or liver test abnormalities,” the authors wrote.

SOURCE:

The study, led by Alisa Likhitsup, MD, MPH, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, was published online in JAMA Network Open. 

LIMITATIONS:

The survey response rate was low at 43.9% for adults aged ≥ 20 years. As NHANES is a cross-sectional study, the causal relationship between consumption of the six botanicals of interest and the development of liver injury could not be determined. The use of HDS products and medications was self-reported in NHANES and not independently verified using source documents. 

DISCLOSURES:

This study did not report any source of funding. Two authors declared receiving grants from pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

The estimated number of US adults who consumed at least one of the six most frequently reported hepatotoxic botanicals in the last 30 days is similar to the number of patients prescribed potentially hepatotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and simvastatin.

METHODOLOGY:

• Herbal and dietary supplements (HDS) are an increasingly common source of drug hepatotoxicity cases, but their prevalence and the reasons for their use among the general population are uncertain.
• This survey study evaluated nationally representative data from 9685 adults (mean age, 47.5 years; 51.8% women) enrolled in the National Health and Nutrition Examination Survey (NHANES) between January 2017 and March 2020.
• Participants reported their use of HDS and prescription drugs through personal interviews for a 30-day period prior to the survey date.
• Researchers compared the clinical features and baseline demographic characteristics of users of six potentially hepatotoxic botanicals (ie, turmeric, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha) with those of nonusers.
• The prevalence of use of these at-risk botanicals was compared with that of widely prescribed potentially hepatotoxic medications, including NSAIDs, simvastatin, and sertraline.

TAKEAWAY:

• In the cohort of 9685 participants, 4.7% of individuals reported consumption of at least one of the six potentially hepatotoxic botanicals in the past 30 days, with turmeric being the most common, followed by green tea.
• Extrapolating the survey data, researchers estimated that 15.6 million US adults use at least one of these six botanicals, which is comparable to the number of those prescribed potentially hepatotoxic drugs, including NSAIDs (14.8 million) and simvastatin (14.0 million). Sertraline use was lower (7.7 million).
• Most individuals used these botanicals without the recommendation of their healthcare provider.
• Those using botanicals were more likely to be older (adjusted odds ratio [aOR], 2.36; P = .04 for 40-59 years; aOR, 3.96; P = .001 for ≥ 60 years), to have some college education (aOR, 4.78; P < .001), and to have arthritis (aOR, 2.27; P < .001) than nonusers.
• The most common reasons for using any of these six potential hepatotoxic botanicals were to improve or maintain health or to prevent health problems or boost immunity.

IN PRACTICE:

“In light of the lack of regulatory oversight on the manufacturing and testing of botanical products, it is recommended that clinicians obtain a full medication and HDS use history when evaluating patients with unexplained symptoms or liver test abnormalities,” the authors wrote.

SOURCE:

The study, led by Alisa Likhitsup, MD, MPH, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, was published online in JAMA Network Open. 

LIMITATIONS:

The survey response rate was low at 43.9% for adults aged ≥ 20 years. As NHANES is a cross-sectional study, the causal relationship between consumption of the six botanicals of interest and the development of liver injury could not be determined. The use of HDS products and medications was self-reported in NHANES and not independently verified using source documents. 

DISCLOSURES:

This study did not report any source of funding. Two authors declared receiving grants from pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

A surprising therapy is showing promise for chronic pain, vision loss, and muscle recovery, among other conditions.

It’s not a pill, an injection, or surgery.

It’s light.

Yes, light. The thing that appears when you open the curtains, flip a switch, or strike a match.

Light illuminates our world and helps us see. Early human trials suggest it may help us heal in new ways as well.

“Phototherapy is still in its infancy,” said Mohab Ibrahim, MD, PhD, a professor of anesthesiology at the University of Arizona, Tucson, who studies the effects of light on chronic pain. “There are so many questions, a lot of things we do not understand yet. But that’s where it gets interesting. What we can conclude is that different colors of light can influence different biological functions.”

This growing field goes by several names. Light therapy. Phototherapy. Photobiomodulation.

It leverages known effects of light on human health — such as skin exposure to ultraviolet light producing vitamin D or blue light’s power to regulate human body clocks — to take light as medicine in surprising new directions.
 

New Science, Old Idea

The science is young, but the concept of using light to restore health is thousands of years old.

Hippocrates prescribed sunbathing to patients at his medical center on the Greek island of Kos in 400 BC. Florence Nightingale promoted sunshine, along with fresh air, as prerequisites for recovery in hospitals during the Civil War. A Danish doctor, Niels Finsen, won the Nobel Prize in 1903 for developing ultraviolet lamps to treat a tuberculosis-related skin condition. And worried parents of the 1930s sat their babies in front of mercury arc lamps, bought at the drugstore, to discourage rickets.

Today, light therapy is widely used in medicine for newborn jaundice, psoriasis, and seasonal affective disorder and in light-activated treatments for cancers of the esophagus and lungs, as well as for actinic keratosis, a skin condition that can lead to cancer.

But researchers are finding that light may be capable of far more, particularly in conditions with few treatment options or where available drugs have unwanted side effects.
 

How Red Light Could Restore Vision

When 100 midlife and older adults, aged 53-91, with the dry form of age-related macular degeneration (AMD) were treated with an experimental red-light therapy or a sham therapy, the light treatment group showed signs of improved vision, as measured on a standard eye chart.

Volunteers received the therapy three times a week for 3-5 weeks, every 4 months for 2 years. By the study’s end, 67% of those treated with light could read an additional five letters on the chart, and 20% could read 10 or more. About 7% developed geographic atrophy — the most advanced, vision-threatening stage of dry AMD — compared with 24% in the sham group.

The study, called LIGHTSITE III, was conducted at 10 ophthalmology centers across the United States. The device they used — the Valeda Light Delivery System from medical device company LumiThera — is available in Europe and now being reviewed by the Food and Drug Administration (FDA).

courtesy LumiThera

Exposure to red light at the wavelengths used in the study likely revitalizes failing mitochondria — the power plants inside cells — so they produce more energy, the researchers say.

“This is the first therapy for dry AMD that’s actually shown a benefit in improving vision,” said study coauthor Richard Rosen, MD, chair of ophthalmology at the Icahn School of Medicine at Mount Sinai and chief of Retinal Services at the New York Eye and Ear Infirmary in New York City. “Supplements called AREDS can reduce progression, and in wet AMD we can improve vision loss with injections. But in dry AMD, none of the treatments studied in the past have improved it.”

AMD develops when the eyes can’t break down natural by-products, which glom together as clumps of protein called drusen. Drusen can lodge under the retina, eventually damaging tissue.

“Retinal epithelial cells, a single layer of cells that cares for the photoreceptors in the eyes, are there for life,” Dr. Rosen said. “They have a tremendous capacity to repair themselves, but things [such as aging and smoking] get in the way.”

“I’m proposing,” Dr. Rosen said, “that by boosting energy levels in cells [with red light], we’re improving normal repair mechanisms.”

Lab studies support this idea.

In a 2017 mouse study from the University College London Institute of Ophthalmology in England, retinal function improved by 25% in old mice exposed to red light. And a 2019 study from the Ophthalmological Research Foundation, Oviedo, Spain, found that exposure to blue light harmed the mitochondria in retina cells, while red light somewhat counteracted the losses.

If cleared by the FDA — which the company anticipated could happen in 2024 — LumiThera’s light delivery device will likely be most useful in the beginning stages of dry AMD, Dr. Rosen said. “I think treatment of early dry AMD will be huge.”

Eventually, light therapy may also be valuable in treating or managing glaucoma and diabetic retinopathy.

For now, Dr. Rosen recommended that clinicians and consumers with AMD skip over-the-counter (OTC) red-light therapy devices currently on the market.

“We don’t know what kind of light the devices produce,” he said. “The wavelengths can vary. The eyes are delicate. Experimenting on your own may be hazardous to your vision.”
 

Green Light for Pain Relief

On his way to the pharmacy to pick up pain relievers for a headache, Dr. Ibrahim passed Gene C. Reid Park in Tucson. Recalling how his brother eased headaches by sitting in his backyard, Dr. Ibrahim pulled over.

“Reid Park is probably one of the greenest areas of Tucson,” said Dr. Ibrahim, who also serves as medical director of the Comprehensive Center for Pain & Addiction at Banner-University Medical Center Phoenix in Arizona. “I spent a half hour or 40 minutes there, and my headache felt better.”

Being outdoors in a green space may be soothing for lots of reasons, like the quiet or the fresh air. But there’s also sunlight reflected off and shining through greenery. The experience inspired Dr. Ibrahim to take a closer look at the effects of green light on chronic pain.

In his 2021 study of 29 people with migraines, participants reported that, after daily exposure to green light for 10 weeks, the number of days per month when they had headaches fell from 7.9 to 2.4 for those who had episodic migraines and from 22.3 to 9.4 for those with chronic migraines. In another 2021 study, 21 people with fibromyalgia who had green light therapy for 10 weeks said their average, self-reported pain intensity fell from 8.4 to 4.9 on a 10-point scale used at the University of Arizona’s pain clinic.

Volunteers in both studies got their light therapy at home, switching on green LED lights while they listened to music, read a book, relaxed, or exercised for 1 or 2 hours daily. The lights were within their field of vision, but they did not look directly at them.

Dr. Ibrahim now has funding from the Department of Defense and Department of Veterans Affairs to find out why green light alters pain perception.

“What we know is that the visual system is connected to certain areas of the brain that also modulate pain,” he said. “We are trying to understand the connection.”

Padma Gulur, MD, a professor of anesthesiology and population health and director of Pain Management Strategy and Opioid Surveillance at Duke University, Durham, North Carolina, saw similar results in a 2023 study of 45 people with fibromyalgia. But instead of using a light source, volunteers wore glasses with clear, green, or blue lenses for 4 hours a day.

After 2 weeks, 33% in the green lens group reduced their use of opioids by 10% or more, compared with 11% in the blue lens group and 8% who wore clear lenses. Previous studies have found green light affects levels of the feel-good brain chemical serotonin and stimulates the body’s own opioid system, the authors noted.

“Green light helps your body control and reduce pain,” Dr. Gulur said. It “seems to help with pain relief by affecting the body’s natural pain management system. This effect appears to play a crucial role in antinociception — reducing the sensation of pain; antiallodynia — preventing normal, nonpainful stimuli from causing pain; and antihyperalgesia — reducing heightened sensitivity to pain.”

Light therapy could help pain patients reduce their dose of opioids or even forgo the drugs altogether, Dr. Gulur said. “It is our hope this will become a useful adjuvant therapy to manage pain.”

In the University of Arizona studies, some patients on green-light therapy stopped their medications completely. Even if they didn’t, other benefits appeared. “They had improved quality of life, decreased depression and anxiety, and improved sleep,” Dr. Ibrahim said.

But not just any green light or green-tinted glasses will work, both researchers said. “We have found there are specific frequencies of green light that give this benefit,” Dr. Gulur said. “OTC products may not be helpful for that reason.”

While Dr. Ibrahim said it could be possible for healthcare practitioners and consumers to consult his studies and put together an inexpensive green-light device at home while carefully following the protocol participants used in the studies , it would first be a good idea for patients to talk with their family doctor or a pain specialist.

“A headache is not always just a headache,” Dr. Ibrahim said. “It could be some other abnormality that needs diagnosis and treatment. If you have long-lasting pain or pain that’s getting worse, it’s always better to discuss it with your physician.”
 

Helping Muscles Recover With Red Light

Intense exercise — whether it’s a sprint at the end of a morning run, an extra set of biceps curls, or a weekend of all-day DIY home improvement projects — can temporarily damage muscle, causing soreness, inflammation, and even swelling. Phototherapy with red and near-infrared light is widely used by sports trainers, physical therapists, and athletes to aid in recovery. It may even work better than a trendy plunge in an ice bath, according to a 2019 Texas State University review.

But how does it work? Jamie Ghigiarelli, PhD, professor of Allied Health & Kinesiology at Hofstra University in Hempstead, New York, looked closely at signs of inflammation and muscle damage in 12 athletes to find out.

Study participants overtaxed their muscles with rounds of chin-ups, high-speed sprints, and repeated bench presses. Afterward, they relaxed in a full-body red-light therapy bed or in a similar bed without lights.

The results, published in 2020, showed that blood levels of creatine kinase — an enzyme that’s elevated by muscle damage — were 18% lower 1-3 days after exercising for the light-bed group than for the control group.

“Photobiomodulation seems to help with muscle recovery,” Dr. Ghigiarelli said.

Red light at wavelengths from 650 to 820 nm can enter muscle cells, where it is absorbed by mitochondria and boosts their energy production, he said. At the time of his research, some exercise science researchers and athletes thought using light therapy before an event might also increase athletic performance, but according to Dr. Ghigiarelli, that use has not panned out.

Handheld red light and near-infrared light devices for muscle recovery are widely available, but it’s important to do your homework before buying one.

“You want to choose a device with the right energy production — the right wavelength of light, the right power — to be safe and effective,” he said.

For details, he recommends consulting a 2019 paper in The Brazilian Journal of Physical Therapy called “Clinical and scientific recommendations for the use of photobiomodulation therapy in exercise performance enhancement and post-exercise recovery: Current evidence and future directions.”

The paper, from the Laboratory of Phototherapy and Innovative Technologies in Health at the Universidade Nove de Julho in Sao Paulo, Brazil, recommends that for small muscle groups like the biceps or triceps, use red-light lasers or LED devices with a wavelength of 640 nm for red light or 950 nm for infrared light, at a power of 50-200 mW per diode for single-probe device types, at a dose of 20-60 J, given 5-10 minutes after exercise.

A version of this article appeared on Medscape.com.

A surprising therapy is showing promise for chronic pain, vision loss, and muscle recovery, among other conditions.

It’s not a pill, an injection, or surgery.

It’s light.

Yes, light. The thing that appears when you open the curtains, flip a switch, or strike a match.

Light illuminates our world and helps us see. Early human trials suggest it may help us heal in new ways as well.

“Phototherapy is still in its infancy,” said Mohab Ibrahim, MD, PhD, a professor of anesthesiology at the University of Arizona, Tucson, who studies the effects of light on chronic pain. “There are so many questions, a lot of things we do not understand yet. But that’s where it gets interesting. What we can conclude is that different colors of light can influence different biological functions.”

This growing field goes by several names. Light therapy. Phototherapy. Photobiomodulation.

It leverages known effects of light on human health — such as skin exposure to ultraviolet light producing vitamin D or blue light’s power to regulate human body clocks — to take light as medicine in surprising new directions.
 

New Science, Old Idea

The science is young, but the concept of using light to restore health is thousands of years old.

Hippocrates prescribed sunbathing to patients at his medical center on the Greek island of Kos in 400 BC. Florence Nightingale promoted sunshine, along with fresh air, as prerequisites for recovery in hospitals during the Civil War. A Danish doctor, Niels Finsen, won the Nobel Prize in 1903 for developing ultraviolet lamps to treat a tuberculosis-related skin condition. And worried parents of the 1930s sat their babies in front of mercury arc lamps, bought at the drugstore, to discourage rickets.

Today, light therapy is widely used in medicine for newborn jaundice, psoriasis, and seasonal affective disorder and in light-activated treatments for cancers of the esophagus and lungs, as well as for actinic keratosis, a skin condition that can lead to cancer.

But researchers are finding that light may be capable of far more, particularly in conditions with few treatment options or where available drugs have unwanted side effects.
 

How Red Light Could Restore Vision

When 100 midlife and older adults, aged 53-91, with the dry form of age-related macular degeneration (AMD) were treated with an experimental red-light therapy or a sham therapy, the light treatment group showed signs of improved vision, as measured on a standard eye chart.

Volunteers received the therapy three times a week for 3-5 weeks, every 4 months for 2 years. By the study’s end, 67% of those treated with light could read an additional five letters on the chart, and 20% could read 10 or more. About 7% developed geographic atrophy — the most advanced, vision-threatening stage of dry AMD — compared with 24% in the sham group.

The study, called LIGHTSITE III, was conducted at 10 ophthalmology centers across the United States. The device they used — the Valeda Light Delivery System from medical device company LumiThera — is available in Europe and now being reviewed by the Food and Drug Administration (FDA).

courtesy LumiThera

Exposure to red light at the wavelengths used in the study likely revitalizes failing mitochondria — the power plants inside cells — so they produce more energy, the researchers say.

“This is the first therapy for dry AMD that’s actually shown a benefit in improving vision,” said study coauthor Richard Rosen, MD, chair of ophthalmology at the Icahn School of Medicine at Mount Sinai and chief of Retinal Services at the New York Eye and Ear Infirmary in New York City. “Supplements called AREDS can reduce progression, and in wet AMD we can improve vision loss with injections. But in dry AMD, none of the treatments studied in the past have improved it.”

AMD develops when the eyes can’t break down natural by-products, which glom together as clumps of protein called drusen. Drusen can lodge under the retina, eventually damaging tissue.

“Retinal epithelial cells, a single layer of cells that cares for the photoreceptors in the eyes, are there for life,” Dr. Rosen said. “They have a tremendous capacity to repair themselves, but things [such as aging and smoking] get in the way.”

“I’m proposing,” Dr. Rosen said, “that by boosting energy levels in cells [with red light], we’re improving normal repair mechanisms.”

Lab studies support this idea.

In a 2017 mouse study from the University College London Institute of Ophthalmology in England, retinal function improved by 25% in old mice exposed to red light. And a 2019 study from the Ophthalmological Research Foundation, Oviedo, Spain, found that exposure to blue light harmed the mitochondria in retina cells, while red light somewhat counteracted the losses.

If cleared by the FDA — which the company anticipated could happen in 2024 — LumiThera’s light delivery device will likely be most useful in the beginning stages of dry AMD, Dr. Rosen said. “I think treatment of early dry AMD will be huge.”

Eventually, light therapy may also be valuable in treating or managing glaucoma and diabetic retinopathy.

For now, Dr. Rosen recommended that clinicians and consumers with AMD skip over-the-counter (OTC) red-light therapy devices currently on the market.

“We don’t know what kind of light the devices produce,” he said. “The wavelengths can vary. The eyes are delicate. Experimenting on your own may be hazardous to your vision.”
 

Green Light for Pain Relief

On his way to the pharmacy to pick up pain relievers for a headache, Dr. Ibrahim passed Gene C. Reid Park in Tucson. Recalling how his brother eased headaches by sitting in his backyard, Dr. Ibrahim pulled over.

“Reid Park is probably one of the greenest areas of Tucson,” said Dr. Ibrahim, who also serves as medical director of the Comprehensive Center for Pain & Addiction at Banner-University Medical Center Phoenix in Arizona. “I spent a half hour or 40 minutes there, and my headache felt better.”

Being outdoors in a green space may be soothing for lots of reasons, like the quiet or the fresh air. But there’s also sunlight reflected off and shining through greenery. The experience inspired Dr. Ibrahim to take a closer look at the effects of green light on chronic pain.

In his 2021 study of 29 people with migraines, participants reported that, after daily exposure to green light for 10 weeks, the number of days per month when they had headaches fell from 7.9 to 2.4 for those who had episodic migraines and from 22.3 to 9.4 for those with chronic migraines. In another 2021 study, 21 people with fibromyalgia who had green light therapy for 10 weeks said their average, self-reported pain intensity fell from 8.4 to 4.9 on a 10-point scale used at the University of Arizona’s pain clinic.

Volunteers in both studies got their light therapy at home, switching on green LED lights while they listened to music, read a book, relaxed, or exercised for 1 or 2 hours daily. The lights were within their field of vision, but they did not look directly at them.

Dr. Ibrahim now has funding from the Department of Defense and Department of Veterans Affairs to find out why green light alters pain perception.

“What we know is that the visual system is connected to certain areas of the brain that also modulate pain,” he said. “We are trying to understand the connection.”

Padma Gulur, MD, a professor of anesthesiology and population health and director of Pain Management Strategy and Opioid Surveillance at Duke University, Durham, North Carolina, saw similar results in a 2023 study of 45 people with fibromyalgia. But instead of using a light source, volunteers wore glasses with clear, green, or blue lenses for 4 hours a day.

After 2 weeks, 33% in the green lens group reduced their use of opioids by 10% or more, compared with 11% in the blue lens group and 8% who wore clear lenses. Previous studies have found green light affects levels of the feel-good brain chemical serotonin and stimulates the body’s own opioid system, the authors noted.

“Green light helps your body control and reduce pain,” Dr. Gulur said. It “seems to help with pain relief by affecting the body’s natural pain management system. This effect appears to play a crucial role in antinociception — reducing the sensation of pain; antiallodynia — preventing normal, nonpainful stimuli from causing pain; and antihyperalgesia — reducing heightened sensitivity to pain.”

Light therapy could help pain patients reduce their dose of opioids or even forgo the drugs altogether, Dr. Gulur said. “It is our hope this will become a useful adjuvant therapy to manage pain.”

In the University of Arizona studies, some patients on green-light therapy stopped their medications completely. Even if they didn’t, other benefits appeared. “They had improved quality of life, decreased depression and anxiety, and improved sleep,” Dr. Ibrahim said.

But not just any green light or green-tinted glasses will work, both researchers said. “We have found there are specific frequencies of green light that give this benefit,” Dr. Gulur said. “OTC products may not be helpful for that reason.”

While Dr. Ibrahim said it could be possible for healthcare practitioners and consumers to consult his studies and put together an inexpensive green-light device at home while carefully following the protocol participants used in the studies , it would first be a good idea for patients to talk with their family doctor or a pain specialist.

“A headache is not always just a headache,” Dr. Ibrahim said. “It could be some other abnormality that needs diagnosis and treatment. If you have long-lasting pain or pain that’s getting worse, it’s always better to discuss it with your physician.”
 

Helping Muscles Recover With Red Light

Intense exercise — whether it’s a sprint at the end of a morning run, an extra set of biceps curls, or a weekend of all-day DIY home improvement projects — can temporarily damage muscle, causing soreness, inflammation, and even swelling. Phototherapy with red and near-infrared light is widely used by sports trainers, physical therapists, and athletes to aid in recovery. It may even work better than a trendy plunge in an ice bath, according to a 2019 Texas State University review.

But how does it work? Jamie Ghigiarelli, PhD, professor of Allied Health & Kinesiology at Hofstra University in Hempstead, New York, looked closely at signs of inflammation and muscle damage in 12 athletes to find out.

Study participants overtaxed their muscles with rounds of chin-ups, high-speed sprints, and repeated bench presses. Afterward, they relaxed in a full-body red-light therapy bed or in a similar bed without lights.

The results, published in 2020, showed that blood levels of creatine kinase — an enzyme that’s elevated by muscle damage — were 18% lower 1-3 days after exercising for the light-bed group than for the control group.

“Photobiomodulation seems to help with muscle recovery,” Dr. Ghigiarelli said.

Red light at wavelengths from 650 to 820 nm can enter muscle cells, where it is absorbed by mitochondria and boosts their energy production, he said. At the time of his research, some exercise science researchers and athletes thought using light therapy before an event might also increase athletic performance, but according to Dr. Ghigiarelli, that use has not panned out.

Handheld red light and near-infrared light devices for muscle recovery are widely available, but it’s important to do your homework before buying one.

“You want to choose a device with the right energy production — the right wavelength of light, the right power — to be safe and effective,” he said.

For details, he recommends consulting a 2019 paper in The Brazilian Journal of Physical Therapy called “Clinical and scientific recommendations for the use of photobiomodulation therapy in exercise performance enhancement and post-exercise recovery: Current evidence and future directions.”

The paper, from the Laboratory of Phototherapy and Innovative Technologies in Health at the Universidade Nove de Julho in Sao Paulo, Brazil, recommends that for small muscle groups like the biceps or triceps, use red-light lasers or LED devices with a wavelength of 640 nm for red light or 950 nm for infrared light, at a power of 50-200 mW per diode for single-probe device types, at a dose of 20-60 J, given 5-10 minutes after exercise.

A version of this article appeared on Medscape.com.

A surprising therapy is showing promise for chronic pain, vision loss, and muscle recovery, among other conditions.

It’s not a pill, an injection, or surgery.

It’s light.

Yes, light. The thing that appears when you open the curtains, flip a switch, or strike a match.

Light illuminates our world and helps us see. Early human trials suggest it may help us heal in new ways as well.

“Phototherapy is still in its infancy,” said Mohab Ibrahim, MD, PhD, a professor of anesthesiology at the University of Arizona, Tucson, who studies the effects of light on chronic pain. “There are so many questions, a lot of things we do not understand yet. But that’s where it gets interesting. What we can conclude is that different colors of light can influence different biological functions.”

This growing field goes by several names. Light therapy. Phototherapy. Photobiomodulation.

It leverages known effects of light on human health — such as skin exposure to ultraviolet light producing vitamin D or blue light’s power to regulate human body clocks — to take light as medicine in surprising new directions.
 

New Science, Old Idea

The science is young, but the concept of using light to restore health is thousands of years old.

Hippocrates prescribed sunbathing to patients at his medical center on the Greek island of Kos in 400 BC. Florence Nightingale promoted sunshine, along with fresh air, as prerequisites for recovery in hospitals during the Civil War. A Danish doctor, Niels Finsen, won the Nobel Prize in 1903 for developing ultraviolet lamps to treat a tuberculosis-related skin condition. And worried parents of the 1930s sat their babies in front of mercury arc lamps, bought at the drugstore, to discourage rickets.

Today, light therapy is widely used in medicine for newborn jaundice, psoriasis, and seasonal affective disorder and in light-activated treatments for cancers of the esophagus and lungs, as well as for actinic keratosis, a skin condition that can lead to cancer.

But researchers are finding that light may be capable of far more, particularly in conditions with few treatment options or where available drugs have unwanted side effects.
 

How Red Light Could Restore Vision

When 100 midlife and older adults, aged 53-91, with the dry form of age-related macular degeneration (AMD) were treated with an experimental red-light therapy or a sham therapy, the light treatment group showed signs of improved vision, as measured on a standard eye chart.

Volunteers received the therapy three times a week for 3-5 weeks, every 4 months for 2 years. By the study’s end, 67% of those treated with light could read an additional five letters on the chart, and 20% could read 10 or more. About 7% developed geographic atrophy — the most advanced, vision-threatening stage of dry AMD — compared with 24% in the sham group.

The study, called LIGHTSITE III, was conducted at 10 ophthalmology centers across the United States. The device they used — the Valeda Light Delivery System from medical device company LumiThera — is available in Europe and now being reviewed by the Food and Drug Administration (FDA).

courtesy LumiThera

Exposure to red light at the wavelengths used in the study likely revitalizes failing mitochondria — the power plants inside cells — so they produce more energy, the researchers say.

“This is the first therapy for dry AMD that’s actually shown a benefit in improving vision,” said study coauthor Richard Rosen, MD, chair of ophthalmology at the Icahn School of Medicine at Mount Sinai and chief of Retinal Services at the New York Eye and Ear Infirmary in New York City. “Supplements called AREDS can reduce progression, and in wet AMD we can improve vision loss with injections. But in dry AMD, none of the treatments studied in the past have improved it.”

AMD develops when the eyes can’t break down natural by-products, which glom together as clumps of protein called drusen. Drusen can lodge under the retina, eventually damaging tissue.

“Retinal epithelial cells, a single layer of cells that cares for the photoreceptors in the eyes, are there for life,” Dr. Rosen said. “They have a tremendous capacity to repair themselves, but things [such as aging and smoking] get in the way.”

“I’m proposing,” Dr. Rosen said, “that by boosting energy levels in cells [with red light], we’re improving normal repair mechanisms.”

Lab studies support this idea.

In a 2017 mouse study from the University College London Institute of Ophthalmology in England, retinal function improved by 25% in old mice exposed to red light. And a 2019 study from the Ophthalmological Research Foundation, Oviedo, Spain, found that exposure to blue light harmed the mitochondria in retina cells, while red light somewhat counteracted the losses.

If cleared by the FDA — which the company anticipated could happen in 2024 — LumiThera’s light delivery device will likely be most useful in the beginning stages of dry AMD, Dr. Rosen said. “I think treatment of early dry AMD will be huge.”

Eventually, light therapy may also be valuable in treating or managing glaucoma and diabetic retinopathy.

For now, Dr. Rosen recommended that clinicians and consumers with AMD skip over-the-counter (OTC) red-light therapy devices currently on the market.

“We don’t know what kind of light the devices produce,” he said. “The wavelengths can vary. The eyes are delicate. Experimenting on your own may be hazardous to your vision.”
 

Green Light for Pain Relief

On his way to the pharmacy to pick up pain relievers for a headache, Dr. Ibrahim passed Gene C. Reid Park in Tucson. Recalling how his brother eased headaches by sitting in his backyard, Dr. Ibrahim pulled over.

“Reid Park is probably one of the greenest areas of Tucson,” said Dr. Ibrahim, who also serves as medical director of the Comprehensive Center for Pain & Addiction at Banner-University Medical Center Phoenix in Arizona. “I spent a half hour or 40 minutes there, and my headache felt better.”

Being outdoors in a green space may be soothing for lots of reasons, like the quiet or the fresh air. But there’s also sunlight reflected off and shining through greenery. The experience inspired Dr. Ibrahim to take a closer look at the effects of green light on chronic pain.

In his 2021 study of 29 people with migraines, participants reported that, after daily exposure to green light for 10 weeks, the number of days per month when they had headaches fell from 7.9 to 2.4 for those who had episodic migraines and from 22.3 to 9.4 for those with chronic migraines. In another 2021 study, 21 people with fibromyalgia who had green light therapy for 10 weeks said their average, self-reported pain intensity fell from 8.4 to 4.9 on a 10-point scale used at the University of Arizona’s pain clinic.

Volunteers in both studies got their light therapy at home, switching on green LED lights while they listened to music, read a book, relaxed, or exercised for 1 or 2 hours daily. The lights were within their field of vision, but they did not look directly at them.

Dr. Ibrahim now has funding from the Department of Defense and Department of Veterans Affairs to find out why green light alters pain perception.

“What we know is that the visual system is connected to certain areas of the brain that also modulate pain,” he said. “We are trying to understand the connection.”

Padma Gulur, MD, a professor of anesthesiology and population health and director of Pain Management Strategy and Opioid Surveillance at Duke University, Durham, North Carolina, saw similar results in a 2023 study of 45 people with fibromyalgia. But instead of using a light source, volunteers wore glasses with clear, green, or blue lenses for 4 hours a day.

After 2 weeks, 33% in the green lens group reduced their use of opioids by 10% or more, compared with 11% in the blue lens group and 8% who wore clear lenses. Previous studies have found green light affects levels of the feel-good brain chemical serotonin and stimulates the body’s own opioid system, the authors noted.

“Green light helps your body control and reduce pain,” Dr. Gulur said. It “seems to help with pain relief by affecting the body’s natural pain management system. This effect appears to play a crucial role in antinociception — reducing the sensation of pain; antiallodynia — preventing normal, nonpainful stimuli from causing pain; and antihyperalgesia — reducing heightened sensitivity to pain.”

Light therapy could help pain patients reduce their dose of opioids or even forgo the drugs altogether, Dr. Gulur said. “It is our hope this will become a useful adjuvant therapy to manage pain.”

In the University of Arizona studies, some patients on green-light therapy stopped their medications completely. Even if they didn’t, other benefits appeared. “They had improved quality of life, decreased depression and anxiety, and improved sleep,” Dr. Ibrahim said.

But not just any green light or green-tinted glasses will work, both researchers said. “We have found there are specific frequencies of green light that give this benefit,” Dr. Gulur said. “OTC products may not be helpful for that reason.”

While Dr. Ibrahim said it could be possible for healthcare practitioners and consumers to consult his studies and put together an inexpensive green-light device at home while carefully following the protocol participants used in the studies , it would first be a good idea for patients to talk with their family doctor or a pain specialist.

“A headache is not always just a headache,” Dr. Ibrahim said. “It could be some other abnormality that needs diagnosis and treatment. If you have long-lasting pain or pain that’s getting worse, it’s always better to discuss it with your physician.”
 

Helping Muscles Recover With Red Light

Intense exercise — whether it’s a sprint at the end of a morning run, an extra set of biceps curls, or a weekend of all-day DIY home improvement projects — can temporarily damage muscle, causing soreness, inflammation, and even swelling. Phototherapy with red and near-infrared light is widely used by sports trainers, physical therapists, and athletes to aid in recovery. It may even work better than a trendy plunge in an ice bath, according to a 2019 Texas State University review.

But how does it work? Jamie Ghigiarelli, PhD, professor of Allied Health & Kinesiology at Hofstra University in Hempstead, New York, looked closely at signs of inflammation and muscle damage in 12 athletes to find out.

Study participants overtaxed their muscles with rounds of chin-ups, high-speed sprints, and repeated bench presses. Afterward, they relaxed in a full-body red-light therapy bed or in a similar bed without lights.

The results, published in 2020, showed that blood levels of creatine kinase — an enzyme that’s elevated by muscle damage — were 18% lower 1-3 days after exercising for the light-bed group than for the control group.

“Photobiomodulation seems to help with muscle recovery,” Dr. Ghigiarelli said.

Red light at wavelengths from 650 to 820 nm can enter muscle cells, where it is absorbed by mitochondria and boosts their energy production, he said. At the time of his research, some exercise science researchers and athletes thought using light therapy before an event might also increase athletic performance, but according to Dr. Ghigiarelli, that use has not panned out.

Handheld red light and near-infrared light devices for muscle recovery are widely available, but it’s important to do your homework before buying one.

“You want to choose a device with the right energy production — the right wavelength of light, the right power — to be safe and effective,” he said.

For details, he recommends consulting a 2019 paper in The Brazilian Journal of Physical Therapy called “Clinical and scientific recommendations for the use of photobiomodulation therapy in exercise performance enhancement and post-exercise recovery: Current evidence and future directions.”

The paper, from the Laboratory of Phototherapy and Innovative Technologies in Health at the Universidade Nove de Julho in Sao Paulo, Brazil, recommends that for small muscle groups like the biceps or triceps, use red-light lasers or LED devices with a wavelength of 640 nm for red light or 950 nm for infrared light, at a power of 50-200 mW per diode for single-probe device types, at a dose of 20-60 J, given 5-10 minutes after exercise.

A version of this article appeared on Medscape.com.

TOPLINE:

Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, showed an 80% complete response rate in patients with granulomatous cheilitis, with no serious adverse events, in a small retrospective case series.

METHODOLOGY:

• Granulomatous cheilitis is a rare, nonnecrotizing granulomatous inflammatory disorder characterized by intermittent or persistent swelling of the lips.
• In a retrospective case series of five patients (median age, 30 years; four women) with granulomatous cheilitis resistant to systemic treatments at a Belgian hospital between June 2023 and March 2024, all five were treated with a high dose of upadacitinib (30 mg daily).
• The primary endpoint was objective clinical improvement in lip swelling and infiltration over a median follow-up of 7.2 months.
• Three patients had concomitant dormant Crohn’s disease (CD); a secondary outcome was disease activity in these patients.

TAKEAWAY:

• Upadacitinib treatment resulted in a complete response in four patients (80%) within a median of 3.8 months and a partial response in one patient.
• CD remained dormant in the three patients with CD.
• The safety profile of upadacitinib was favorable, and no serious adverse events were reported. Two patients experienced headaches, acne, mild changes in lipids, and/or transaminitis.

IN PRACTICE:

“Upadacitinib was effective in treating patients with recalcitrant and long-lasting granulomatous cheilitis, even in cases of concomitant CD, which could substantially improve the quality of life of affected patients,” the authors wrote. More studies are needed to confirm these results in larger groups of patients over longer periods of time, “and with other JAK inhibitors.”

SOURCE:

The study was led by Axel De Greef, MD, Department of Dermatology, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium. It was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and short follow-up may limit the generalizability of the findings to a larger population of patients with granulomatous cheilitis.

DISCLOSURES:

The study did not report any funding sources. Some authors reported receiving nonfinancial support and personal fees from various pharmaceutical companies outside the submitted work.

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

TOPLINE:

Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, showed an 80% complete response rate in patients with granulomatous cheilitis, with no serious adverse events, in a small retrospective case series.

METHODOLOGY:

• Granulomatous cheilitis is a rare, nonnecrotizing granulomatous inflammatory disorder characterized by intermittent or persistent swelling of the lips.
• In a retrospective case series of five patients (median age, 30 years; four women) with granulomatous cheilitis resistant to systemic treatments at a Belgian hospital between June 2023 and March 2024, all five were treated with a high dose of upadacitinib (30 mg daily).
• The primary endpoint was objective clinical improvement in lip swelling and infiltration over a median follow-up of 7.2 months.
• Three patients had concomitant dormant Crohn’s disease (CD); a secondary outcome was disease activity in these patients.

TAKEAWAY:

• Upadacitinib treatment resulted in a complete response in four patients (80%) within a median of 3.8 months and a partial response in one patient.
• CD remained dormant in the three patients with CD.
• The safety profile of upadacitinib was favorable, and no serious adverse events were reported. Two patients experienced headaches, acne, mild changes in lipids, and/or transaminitis.

IN PRACTICE:

“Upadacitinib was effective in treating patients with recalcitrant and long-lasting granulomatous cheilitis, even in cases of concomitant CD, which could substantially improve the quality of life of affected patients,” the authors wrote. More studies are needed to confirm these results in larger groups of patients over longer periods of time, “and with other JAK inhibitors.”

SOURCE:

The study was led by Axel De Greef, MD, Department of Dermatology, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium. It was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and short follow-up may limit the generalizability of the findings to a larger population of patients with granulomatous cheilitis.

DISCLOSURES:

The study did not report any funding sources. Some authors reported receiving nonfinancial support and personal fees from various pharmaceutical companies outside the submitted work.

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

TOPLINE:

Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, showed an 80% complete response rate in patients with granulomatous cheilitis, with no serious adverse events, in a small retrospective case series.

METHODOLOGY:

• Granulomatous cheilitis is a rare, nonnecrotizing granulomatous inflammatory disorder characterized by intermittent or persistent swelling of the lips.
• In a retrospective case series of five patients (median age, 30 years; four women) with granulomatous cheilitis resistant to systemic treatments at a Belgian hospital between June 2023 and March 2024, all five were treated with a high dose of upadacitinib (30 mg daily).
• The primary endpoint was objective clinical improvement in lip swelling and infiltration over a median follow-up of 7.2 months.
• Three patients had concomitant dormant Crohn’s disease (CD); a secondary outcome was disease activity in these patients.

TAKEAWAY:

• Upadacitinib treatment resulted in a complete response in four patients (80%) within a median of 3.8 months and a partial response in one patient.
• CD remained dormant in the three patients with CD.
• The safety profile of upadacitinib was favorable, and no serious adverse events were reported. Two patients experienced headaches, acne, mild changes in lipids, and/or transaminitis.

IN PRACTICE:

“Upadacitinib was effective in treating patients with recalcitrant and long-lasting granulomatous cheilitis, even in cases of concomitant CD, which could substantially improve the quality of life of affected patients,” the authors wrote. More studies are needed to confirm these results in larger groups of patients over longer periods of time, “and with other JAK inhibitors.”

SOURCE:

The study was led by Axel De Greef, MD, Department of Dermatology, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium. It was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and short follow-up may limit the generalizability of the findings to a larger population of patients with granulomatous cheilitis.

DISCLOSURES:

The study did not report any funding sources. Some authors reported receiving nonfinancial support and personal fees from various pharmaceutical companies outside the submitted work.

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

TOPLINE:

Patients with alopecia areata (AA) had a higher prevalence of several psychiatric and autoimmune comorbidities at baseline and were at greater risk of developing those comorbidities after diagnosis.

METHODOLOGY:

• Researchers evaluated 63,384 patients with AA and 3,309,107 individuals without AA (aged 12-64 years) from the Merative MarketScan Research Databases.
• The matched cohorts included 16,512 patients with AA and 66,048 control individuals.
• Outcomes were the prevalence of psychiatric and autoimmune diseases at baseline and the incidence of new-onset psychiatric and autoimmune diseases during the year after diagnosis.

TAKEAWAY:

• Overall, patients with AA showed a greater prevalence of any psychiatric disease (30.9% vs 26.8%; P < .001) and any immune-mediated or autoimmune disease (16.1% vs 8.9%; P < .0001) than those with controls.
• In matched cohorts, patients with AA also showed a higher incidence of any new-onset psychiatric diseases (10.2% vs 6.8%; P < .001) or immune-mediated or autoimmune disease (6.2% vs 1.5%; P <.001) within the first 12 months of AA diagnosis than those with controls.
• Among patients with AA, the risk of developing a psychiatric comorbidity was higher (adjusted hazard ratio [aHR], 1.3; 95% CI, 1.3-1.4). The highest risks were seen for adjustment disorder (aHR, 1.5), panic disorder (aHR, 1.4), and sexual dysfunction (aHR, 1.4).
• Compared with controls, patients with AA were also at an increased risk of developing immune-mediated or autoimmune comorbidities (aHR, 2.7; 95% CI, 2.5-2.8), with the highest for systemic lupus (aHR, 5.7), atopic dermatitis (aHR, 4.3), and vitiligo (aHR, 3.8).

IN PRACTICE:

“Routine monitoring of patients with AA, especially those at risk of developing comorbidities, may permit earlier and more effective intervention,” the authors wrote.

SOURCE:

The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital and Harvard University, Boston. It was published online on July 31, 2024, in JAMA Dermatology.

LIMITATIONS:

Causality could not be inferred because of the retrospective nature of the study. Comorbidities were solely diagnosed on the basis of diagnostic codes, and researchers did not have access to characteristics such as lab values that could have indicated any underlying comorbidity before the AA diagnosis. This study also did not account for the varying levels of severity of the disease, which may have led to an underestimation of disease burden and the risk for comorbidities.

DISCLOSURES:

AbbVie provided funding for this study. Mostaghimi disclosed receiving personal fees from Abbvie and several other companies outside of this work. The other four authors were current or former employees of Abbvie and have or may have stock and/or stock options in AbbVie.

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

TOPLINE:

Patients with alopecia areata (AA) had a higher prevalence of several psychiatric and autoimmune comorbidities at baseline and were at greater risk of developing those comorbidities after diagnosis.

METHODOLOGY:

• Researchers evaluated 63,384 patients with AA and 3,309,107 individuals without AA (aged 12-64 years) from the Merative MarketScan Research Databases.
• The matched cohorts included 16,512 patients with AA and 66,048 control individuals.
• Outcomes were the prevalence of psychiatric and autoimmune diseases at baseline and the incidence of new-onset psychiatric and autoimmune diseases during the year after diagnosis.

TAKEAWAY:

• Overall, patients with AA showed a greater prevalence of any psychiatric disease (30.9% vs 26.8%; P < .001) and any immune-mediated or autoimmune disease (16.1% vs 8.9%; P < .0001) than those with controls.
• In matched cohorts, patients with AA also showed a higher incidence of any new-onset psychiatric diseases (10.2% vs 6.8%; P < .001) or immune-mediated or autoimmune disease (6.2% vs 1.5%; P <.001) within the first 12 months of AA diagnosis than those with controls.
• Among patients with AA, the risk of developing a psychiatric comorbidity was higher (adjusted hazard ratio [aHR], 1.3; 95% CI, 1.3-1.4). The highest risks were seen for adjustment disorder (aHR, 1.5), panic disorder (aHR, 1.4), and sexual dysfunction (aHR, 1.4).
• Compared with controls, patients with AA were also at an increased risk of developing immune-mediated or autoimmune comorbidities (aHR, 2.7; 95% CI, 2.5-2.8), with the highest for systemic lupus (aHR, 5.7), atopic dermatitis (aHR, 4.3), and vitiligo (aHR, 3.8).

IN PRACTICE:

“Routine monitoring of patients with AA, especially those at risk of developing comorbidities, may permit earlier and more effective intervention,” the authors wrote.

SOURCE:

The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital and Harvard University, Boston. It was published online on July 31, 2024, in JAMA Dermatology.

LIMITATIONS:

Causality could not be inferred because of the retrospective nature of the study. Comorbidities were solely diagnosed on the basis of diagnostic codes, and researchers did not have access to characteristics such as lab values that could have indicated any underlying comorbidity before the AA diagnosis. This study also did not account for the varying levels of severity of the disease, which may have led to an underestimation of disease burden and the risk for comorbidities.

DISCLOSURES:

AbbVie provided funding for this study. Mostaghimi disclosed receiving personal fees from Abbvie and several other companies outside of this work. The other four authors were current or former employees of Abbvie and have or may have stock and/or stock options in AbbVie.

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

TOPLINE:

Patients with alopecia areata (AA) had a higher prevalence of several psychiatric and autoimmune comorbidities at baseline and were at greater risk of developing those comorbidities after diagnosis.

METHODOLOGY:

• Researchers evaluated 63,384 patients with AA and 3,309,107 individuals without AA (aged 12-64 years) from the Merative MarketScan Research Databases.
• The matched cohorts included 16,512 patients with AA and 66,048 control individuals.
• Outcomes were the prevalence of psychiatric and autoimmune diseases at baseline and the incidence of new-onset psychiatric and autoimmune diseases during the year after diagnosis.

TAKEAWAY:

• Overall, patients with AA showed a greater prevalence of any psychiatric disease (30.9% vs 26.8%; P < .001) and any immune-mediated or autoimmune disease (16.1% vs 8.9%; P < .0001) than those with controls.
• In matched cohorts, patients with AA also showed a higher incidence of any new-onset psychiatric diseases (10.2% vs 6.8%; P < .001) or immune-mediated or autoimmune disease (6.2% vs 1.5%; P <.001) within the first 12 months of AA diagnosis than those with controls.
• Among patients with AA, the risk of developing a psychiatric comorbidity was higher (adjusted hazard ratio [aHR], 1.3; 95% CI, 1.3-1.4). The highest risks were seen for adjustment disorder (aHR, 1.5), panic disorder (aHR, 1.4), and sexual dysfunction (aHR, 1.4).
• Compared with controls, patients with AA were also at an increased risk of developing immune-mediated or autoimmune comorbidities (aHR, 2.7; 95% CI, 2.5-2.8), with the highest for systemic lupus (aHR, 5.7), atopic dermatitis (aHR, 4.3), and vitiligo (aHR, 3.8).

IN PRACTICE:

“Routine monitoring of patients with AA, especially those at risk of developing comorbidities, may permit earlier and more effective intervention,” the authors wrote.

SOURCE:

The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital and Harvard University, Boston. It was published online on July 31, 2024, in JAMA Dermatology.

LIMITATIONS:

Causality could not be inferred because of the retrospective nature of the study. Comorbidities were solely diagnosed on the basis of diagnostic codes, and researchers did not have access to characteristics such as lab values that could have indicated any underlying comorbidity before the AA diagnosis. This study also did not account for the varying levels of severity of the disease, which may have led to an underestimation of disease burden and the risk for comorbidities.

DISCLOSURES:

AbbVie provided funding for this study. Mostaghimi disclosed receiving personal fees from Abbvie and several other companies outside of this work. The other four authors were current or former employees of Abbvie and have or may have stock and/or stock options in AbbVie.

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government’s complaint “serves as a warning” to healthcare providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to this news organization, Erlanger denied the allegations and said it would “vigorously” defend the lawsuit. 

“Erlanger paid physicians based on amounts that outside experts advised was fair market value,” Erlanger officials said in the statement. “Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims.”

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

“There is a tendency by physicians when contracting ... to rely on [hospitals’] perceived compliance and legal expertise,” Mr. Sarraille told this news organization. “This case illustrates the risks in doing so. Sometimes bigger doesn’t translate into more sophisticated or more effective from a compliance perspective.” 
 

Stark Law Prohibits Kickbacks

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

“HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase healthcare costs, and erode public trust in the healthcare system,” Ms. Miles said in a statement. 
 

Suit: Health System’s Money Woes Led to Illegal Arrangements

Erlanger’s financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government’s complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger’s agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government’s lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger’s physicians were expected to treat patients at Erlanger’s hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger’s CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.