Musculoskeletal Disorders

TOPLINE:

MRI-derived abdominal adipose tissue is linked to chronic musculoskeletal pain in multiple sites. The association is stronger in women, suggesting sex differences in fat distribution and hormones.

METHODOLOGY:

• Researchers used data from the UK Biobank, a large population-based cohort study, to investigate the associations between MRI-measured abdominal adipose tissue and chronic musculoskeletal pain.
• A total of 32,409 participants (50.8% women; mean age, 55.0 ± 7.4 years) were included in the analysis, with abdominal MRI scans performed at two imaging visits.
• Pain in the neck/shoulder, back, hip, knee, or “all over the body” was assessed, and participants were categorized based on the number of chronic pain sites.
• Mixed-effects ordinal, multinomial, and logistic regression models were used to analyze the associations between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and their ratio with chronic pain.

TAKEAWAY:

• According to the authors, there was a dose-response association between VAT, SAT, and their ratio with the number of chronic pain sites in both women and men.
• Higher levels of abdominal adipose tissue were associated with greater odds of reporting chronic pain in both sexes, with effect estimates being relatively larger in women.
• The researchers found that the VAT/SAT ratio was associated with the number of chronic pain sites and chronic pain in both sexes, reflecting differences in fat distribution and hormones.
• The study suggested that excessive abdominal adipose tissue may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain.

IN PRACTICE:

“Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain,” wrote the authors of the study.

SOURCE:

This study was led by Zemene Demelash Kifle, University of Tasmania Menzies Institute for Medical Research in Hobart, Australia. It was published online in Regional Anesthesia & Pain Medicine.

LIMITATIONS: 

The study’s limitations included the use of a pain questionnaire that did not assess pain severity, which limited the ability to examine the relationship between fat measures and pain severity. Additionally, MRI was conducted on only two occasions, which may have not captured patterns and fluctuations in chronic pain sites. The relatively small size of the imaging sample, compared with the original baseline sample limited the generalizability of the findings. The predominant White ethnicity of participants also limited the generalizability to diverse populations.

DISCLOSURES:

The study was supported by grants from the Australian National Health and Medical Research Council (NHMRC). Mr. Kifle disclosed receiving grants from the Australian NHMRC. Additional disclosures are noted in the original article.

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:

MRI-derived abdominal adipose tissue is linked to chronic musculoskeletal pain in multiple sites. The association is stronger in women, suggesting sex differences in fat distribution and hormones.

METHODOLOGY:

• Researchers used data from the UK Biobank, a large population-based cohort study, to investigate the associations between MRI-measured abdominal adipose tissue and chronic musculoskeletal pain.
• A total of 32,409 participants (50.8% women; mean age, 55.0 ± 7.4 years) were included in the analysis, with abdominal MRI scans performed at two imaging visits.
• Pain in the neck/shoulder, back, hip, knee, or “all over the body” was assessed, and participants were categorized based on the number of chronic pain sites.
• Mixed-effects ordinal, multinomial, and logistic regression models were used to analyze the associations between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and their ratio with chronic pain.

TAKEAWAY:

• According to the authors, there was a dose-response association between VAT, SAT, and their ratio with the number of chronic pain sites in both women and men.
• Higher levels of abdominal adipose tissue were associated with greater odds of reporting chronic pain in both sexes, with effect estimates being relatively larger in women.
• The researchers found that the VAT/SAT ratio was associated with the number of chronic pain sites and chronic pain in both sexes, reflecting differences in fat distribution and hormones.
• The study suggested that excessive abdominal adipose tissue may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain.

IN PRACTICE:

“Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain,” wrote the authors of the study.

SOURCE:

This study was led by Zemene Demelash Kifle, University of Tasmania Menzies Institute for Medical Research in Hobart, Australia. It was published online in Regional Anesthesia & Pain Medicine.

LIMITATIONS: 

The study’s limitations included the use of a pain questionnaire that did not assess pain severity, which limited the ability to examine the relationship between fat measures and pain severity. Additionally, MRI was conducted on only two occasions, which may have not captured patterns and fluctuations in chronic pain sites. The relatively small size of the imaging sample, compared with the original baseline sample limited the generalizability of the findings. The predominant White ethnicity of participants also limited the generalizability to diverse populations.

DISCLOSURES:

The study was supported by grants from the Australian National Health and Medical Research Council (NHMRC). Mr. Kifle disclosed receiving grants from the Australian NHMRC. Additional disclosures are noted in the original article.

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:

MRI-derived abdominal adipose tissue is linked to chronic musculoskeletal pain in multiple sites. The association is stronger in women, suggesting sex differences in fat distribution and hormones.

METHODOLOGY:

• Researchers used data from the UK Biobank, a large population-based cohort study, to investigate the associations between MRI-measured abdominal adipose tissue and chronic musculoskeletal pain.
• A total of 32,409 participants (50.8% women; mean age, 55.0 ± 7.4 years) were included in the analysis, with abdominal MRI scans performed at two imaging visits.
• Pain in the neck/shoulder, back, hip, knee, or “all over the body” was assessed, and participants were categorized based on the number of chronic pain sites.
• Mixed-effects ordinal, multinomial, and logistic regression models were used to analyze the associations between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and their ratio with chronic pain.

TAKEAWAY:

• According to the authors, there was a dose-response association between VAT, SAT, and their ratio with the number of chronic pain sites in both women and men.
• Higher levels of abdominal adipose tissue were associated with greater odds of reporting chronic pain in both sexes, with effect estimates being relatively larger in women.
• The researchers found that the VAT/SAT ratio was associated with the number of chronic pain sites and chronic pain in both sexes, reflecting differences in fat distribution and hormones.
• The study suggested that excessive abdominal adipose tissue may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain.

IN PRACTICE:

“Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain,” wrote the authors of the study.

SOURCE:

This study was led by Zemene Demelash Kifle, University of Tasmania Menzies Institute for Medical Research in Hobart, Australia. It was published online in Regional Anesthesia & Pain Medicine.

LIMITATIONS: 

The study’s limitations included the use of a pain questionnaire that did not assess pain severity, which limited the ability to examine the relationship between fat measures and pain severity. Additionally, MRI was conducted on only two occasions, which may have not captured patterns and fluctuations in chronic pain sites. The relatively small size of the imaging sample, compared with the original baseline sample limited the generalizability of the findings. The predominant White ethnicity of participants also limited the generalizability to diverse populations.

DISCLOSURES:

The study was supported by grants from the Australian National Health and Medical Research Council (NHMRC). Mr. Kifle disclosed receiving grants from the Australian NHMRC. Additional disclosures are noted in the original article.

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.

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

TOPLINE:

A smartphone app that delivers acceptance and commitment therapy (ACT), a type of cognitive behavioral therapy, improves overall well-being and reduces the severity of pain, fatigue, sleep issues, and depression to a greater extent than daily symptom tracking in patients with fibromyalgia.

METHODOLOGY:

• Researchers conducted the phase 3 PROSPER-FM trial at 25 community sites in the United States to assess the efficacy and safety of digital ACT for patients with fibromyalgia.
• A total of 275 adult patients aged 22-75 years with fibromyalgia were randomly assigned to either the digital ACT group (n = 140) or the active control group (n = 135) for 12 weeks.
• Patients in the digital ACT group received a self-guided, smartphone-delivered program in which they learned and practiced the core ACT skills of acceptance, values, mindfulness, defusion, self as context, and willingness and committed action to build psychological flexibility, while the control group underwent daily symptom tracking and received educational materials.
• The primary endpoint was the response rate on the Patient Global Impression of Change (PGIC) at week 12, which is an indicator of patient well-being.
• The secondary endpoints included changes in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) total score and pain intensity, pain interference, and sleep interference scores.

TAKEAWAY:

• At week 12, 71% of the patients in the digital ACT group responded with a minimally improved or better change in the PGIC response, compared with only 22% of the patients in the control group (P < .0001).
• The digital ACT group showed a significant reduction in the impact of fibromyalgia, with a between-group effect size of d = 0.65 (P < .0001) at week 12. The FIQ-R total score significantly improved within 3 weeks of using the self-guided digital ACT app.
• The use of digital ACT also demonstrated positive effects on the levels of weekly pain intensity (P = .001) and depression (P < .0001), compared with the control group.
• No serious adverse effects related to the app were reported, and both groups demonstrated high rates of adherence, with most (72%) participants in the digital ACT group completing at least 42 sessions.

IN PRACTICE:

“The results found in the study are essential for professionals who care for patients with fibromyalgia as they present a new viable treatment alternative,” Guilherme Torres Vilarino, PhD, Santa Catarina State University, Florianópolis, Brazil, wrote in an accompanying editorial.

SOURCE:

This study was led by R. Michael Gendreau, MD, PhD, Gendreau Consulting, Poway, California. It was published online  in The Lancet.

LIMITATIONS:

The study population predominantly consisted of women and White individuals, which may limit the generalizability of the findings to more diverse populations. Additionally, the study was conducted in the United States, and the results may thus not be applicable to other countries with different racial, ethnic, educational, and economic characteristics. The study duration was 12 weeks, and the long-term benefits of digital ACT have not yet been shown.

DISCLOSURES:

This study was funded by Swing Therapeutics. Seven authors declared having stock options and/or receiving salary from Swing Therapeutics. Other authors reported having many ties with several sources, including Swing Therapeutics.

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:

A smartphone app that delivers acceptance and commitment therapy (ACT), a type of cognitive behavioral therapy, improves overall well-being and reduces the severity of pain, fatigue, sleep issues, and depression to a greater extent than daily symptom tracking in patients with fibromyalgia.

METHODOLOGY:

• Researchers conducted the phase 3 PROSPER-FM trial at 25 community sites in the United States to assess the efficacy and safety of digital ACT for patients with fibromyalgia.
• A total of 275 adult patients aged 22-75 years with fibromyalgia were randomly assigned to either the digital ACT group (n = 140) or the active control group (n = 135) for 12 weeks.
• Patients in the digital ACT group received a self-guided, smartphone-delivered program in which they learned and practiced the core ACT skills of acceptance, values, mindfulness, defusion, self as context, and willingness and committed action to build psychological flexibility, while the control group underwent daily symptom tracking and received educational materials.
• The primary endpoint was the response rate on the Patient Global Impression of Change (PGIC) at week 12, which is an indicator of patient well-being.
• The secondary endpoints included changes in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) total score and pain intensity, pain interference, and sleep interference scores.

TAKEAWAY:

• At week 12, 71% of the patients in the digital ACT group responded with a minimally improved or better change in the PGIC response, compared with only 22% of the patients in the control group (P < .0001).
• The digital ACT group showed a significant reduction in the impact of fibromyalgia, with a between-group effect size of d = 0.65 (P < .0001) at week 12. The FIQ-R total score significantly improved within 3 weeks of using the self-guided digital ACT app.
• The use of digital ACT also demonstrated positive effects on the levels of weekly pain intensity (P = .001) and depression (P < .0001), compared with the control group.
• No serious adverse effects related to the app were reported, and both groups demonstrated high rates of adherence, with most (72%) participants in the digital ACT group completing at least 42 sessions.

IN PRACTICE:

“The results found in the study are essential for professionals who care for patients with fibromyalgia as they present a new viable treatment alternative,” Guilherme Torres Vilarino, PhD, Santa Catarina State University, Florianópolis, Brazil, wrote in an accompanying editorial.

SOURCE:

This study was led by R. Michael Gendreau, MD, PhD, Gendreau Consulting, Poway, California. It was published online  in The Lancet.

LIMITATIONS:

The study population predominantly consisted of women and White individuals, which may limit the generalizability of the findings to more diverse populations. Additionally, the study was conducted in the United States, and the results may thus not be applicable to other countries with different racial, ethnic, educational, and economic characteristics. The study duration was 12 weeks, and the long-term benefits of digital ACT have not yet been shown.

DISCLOSURES:

This study was funded by Swing Therapeutics. Seven authors declared having stock options and/or receiving salary from Swing Therapeutics. Other authors reported having many ties with several sources, including Swing Therapeutics.

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:

A smartphone app that delivers acceptance and commitment therapy (ACT), a type of cognitive behavioral therapy, improves overall well-being and reduces the severity of pain, fatigue, sleep issues, and depression to a greater extent than daily symptom tracking in patients with fibromyalgia.

METHODOLOGY:

• Researchers conducted the phase 3 PROSPER-FM trial at 25 community sites in the United States to assess the efficacy and safety of digital ACT for patients with fibromyalgia.
• A total of 275 adult patients aged 22-75 years with fibromyalgia were randomly assigned to either the digital ACT group (n = 140) or the active control group (n = 135) for 12 weeks.
• Patients in the digital ACT group received a self-guided, smartphone-delivered program in which they learned and practiced the core ACT skills of acceptance, values, mindfulness, defusion, self as context, and willingness and committed action to build psychological flexibility, while the control group underwent daily symptom tracking and received educational materials.
• The primary endpoint was the response rate on the Patient Global Impression of Change (PGIC) at week 12, which is an indicator of patient well-being.
• The secondary endpoints included changes in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) total score and pain intensity, pain interference, and sleep interference scores.

TAKEAWAY:

• At week 12, 71% of the patients in the digital ACT group responded with a minimally improved or better change in the PGIC response, compared with only 22% of the patients in the control group (P < .0001).
• The digital ACT group showed a significant reduction in the impact of fibromyalgia, with a between-group effect size of d = 0.65 (P < .0001) at week 12. The FIQ-R total score significantly improved within 3 weeks of using the self-guided digital ACT app.
• The use of digital ACT also demonstrated positive effects on the levels of weekly pain intensity (P = .001) and depression (P < .0001), compared with the control group.
• No serious adverse effects related to the app were reported, and both groups demonstrated high rates of adherence, with most (72%) participants in the digital ACT group completing at least 42 sessions.

IN PRACTICE:

“The results found in the study are essential for professionals who care for patients with fibromyalgia as they present a new viable treatment alternative,” Guilherme Torres Vilarino, PhD, Santa Catarina State University, Florianópolis, Brazil, wrote in an accompanying editorial.

SOURCE:

This study was led by R. Michael Gendreau, MD, PhD, Gendreau Consulting, Poway, California. It was published online  in The Lancet.

LIMITATIONS:

The study population predominantly consisted of women and White individuals, which may limit the generalizability of the findings to more diverse populations. Additionally, the study was conducted in the United States, and the results may thus not be applicable to other countries with different racial, ethnic, educational, and economic characteristics. The study duration was 12 weeks, and the long-term benefits of digital ACT have not yet been shown.

DISCLOSURES:

This study was funded by Swing Therapeutics. Seven authors declared having stock options and/or receiving salary from Swing Therapeutics. Other authors reported having many ties with several sources, including Swing Therapeutics.

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.

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

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

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

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

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

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

Poorer physical function, not poorer bone mineral density (BMD), could be the principal reason for the increased fracture risk in older women with type 2 diabetes (T2D), according to a Swedish prospective observational study in JAMA Network Open.

The study was conducted in more than 3000 Swedish women by Mattias Lorentzon, MD, a professor of geriatric medicine at Gothenburg University, and chief physician at the Osteoporosis Clinic at Sahlgrenska University Hospital in Mölndal, and colleagues.

Study Details

A fractures study was performed in the Gothenburg area from March 2013 to May 2016 with follow-up of incident fracture data completed in March 2023. Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using dual-energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess BMSi.

Among the cohort’s 3008 women, ages 75-80 (mean, 77.8), 294 patients with T2D were compared with 2714 same-age unaffected women.

During a median follow-up of 7.3 years, 1071 incident fractures, 853 major osteoporotic fractures, and 232 hip fractures occurred. In models adjusted for age, BMI, clinical risk factors, and femoral neck BMD, T2D was associated with an increased risk of any fracture: hazard ratio (HR), 1.26; (95% CI, 1.04-1.54), and major osteoporotic fracture (HR, 1.25; 95% CI, 1.00-1.56).

Most fractures were due to falls, with the most common affected sites being the forearm, upper arm, spine, and hip, Dr. Lorentzon said.

Among the findings:

• In bone microarchitecture, women with T2D had higher BMD at all sites: total hip, 4.4% higher; femoral neck, 4.9% higher; and lumbar spine, 5.2% higher.
• At the tibia, the T2D group had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction.

“Our findings regarding BMD are consistent with previous publications showing higher BMD in individuals with T2D compared with those without diabetes,” Dr. Lorentzon said. A 2012 meta-analysis, for example, showed higher BMD levels in T2D patients. “Some smaller studies, however, have found worse bone microstructure and lower bone material strength in contrast to the results from our study,” Dr. Lorentzon said.

• There was no difference in BMSi, with a mean of 78 in both groups.
• The T2D group had lower performance on all physical function tests: a 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes.

“We found all parameters regarding physical function, such as muscle strength, balance, and performance, were much worse in women with diabetes than in those without,” Dr. Lorentzon said. “Dizziness could also be a contributor to the increased risk of falls, but this factor was not investigated in our study.”

Commenting on the study but not involved in it, Anthony J. Pick, MD, an endocrinologist at Northwestern Medicine Lake Forest Hospital in Lake Forest, Illinois, said sarcopenia is a common and often under-recognized problem in older adults and is especially prevalent in T2D, obesity, and heart failure. “I believe that ‘exercise is medicine’ is a key concept for metabolic and osteoporosis patients — and wellness and longevity in general — and I certainly hope studies like this drive awareness of the importance of engaging in strengthening exercises.”

Poorer physical function, not poorer bone mineral density (BMD), could be the principal reason for the increased fracture risk in older women with type 2 diabetes (T2D), according to a Swedish prospective observational study in JAMA Network Open.

The study was conducted in more than 3000 Swedish women by Mattias Lorentzon, MD, a professor of geriatric medicine at Gothenburg University, and chief physician at the Osteoporosis Clinic at Sahlgrenska University Hospital in Mölndal, and colleagues.

Study Details

A fractures study was performed in the Gothenburg area from March 2013 to May 2016 with follow-up of incident fracture data completed in March 2023. Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using dual-energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess BMSi.

Among the cohort’s 3008 women, ages 75-80 (mean, 77.8), 294 patients with T2D were compared with 2714 same-age unaffected women.

During a median follow-up of 7.3 years, 1071 incident fractures, 853 major osteoporotic fractures, and 232 hip fractures occurred. In models adjusted for age, BMI, clinical risk factors, and femoral neck BMD, T2D was associated with an increased risk of any fracture: hazard ratio (HR), 1.26; (95% CI, 1.04-1.54), and major osteoporotic fracture (HR, 1.25; 95% CI, 1.00-1.56).

Most fractures were due to falls, with the most common affected sites being the forearm, upper arm, spine, and hip, Dr. Lorentzon said.

Among the findings:

• In bone microarchitecture, women with T2D had higher BMD at all sites: total hip, 4.4% higher; femoral neck, 4.9% higher; and lumbar spine, 5.2% higher.
• At the tibia, the T2D group had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction.

“Our findings regarding BMD are consistent with previous publications showing higher BMD in individuals with T2D compared with those without diabetes,” Dr. Lorentzon said. A 2012 meta-analysis, for example, showed higher BMD levels in T2D patients. “Some smaller studies, however, have found worse bone microstructure and lower bone material strength in contrast to the results from our study,” Dr. Lorentzon said.

• There was no difference in BMSi, with a mean of 78 in both groups.
• The T2D group had lower performance on all physical function tests: a 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes.

“We found all parameters regarding physical function, such as muscle strength, balance, and performance, were much worse in women with diabetes than in those without,” Dr. Lorentzon said. “Dizziness could also be a contributor to the increased risk of falls, but this factor was not investigated in our study.”

Commenting on the study but not involved in it, Anthony J. Pick, MD, an endocrinologist at Northwestern Medicine Lake Forest Hospital in Lake Forest, Illinois, said sarcopenia is a common and often under-recognized problem in older adults and is especially prevalent in T2D, obesity, and heart failure. “I believe that ‘exercise is medicine’ is a key concept for metabolic and osteoporosis patients — and wellness and longevity in general — and I certainly hope studies like this drive awareness of the importance of engaging in strengthening exercises.”

Poorer physical function, not poorer bone mineral density (BMD), could be the principal reason for the increased fracture risk in older women with type 2 diabetes (T2D), according to a Swedish prospective observational study in JAMA Network Open.

The study was conducted in more than 3000 Swedish women by Mattias Lorentzon, MD, a professor of geriatric medicine at Gothenburg University, and chief physician at the Osteoporosis Clinic at Sahlgrenska University Hospital in Mölndal, and colleagues.

Study Details

A fractures study was performed in the Gothenburg area from March 2013 to May 2016 with follow-up of incident fracture data completed in March 2023. Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using dual-energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess BMSi.

Among the cohort’s 3008 women, ages 75-80 (mean, 77.8), 294 patients with T2D were compared with 2714 same-age unaffected women.

During a median follow-up of 7.3 years, 1071 incident fractures, 853 major osteoporotic fractures, and 232 hip fractures occurred. In models adjusted for age, BMI, clinical risk factors, and femoral neck BMD, T2D was associated with an increased risk of any fracture: hazard ratio (HR), 1.26; (95% CI, 1.04-1.54), and major osteoporotic fracture (HR, 1.25; 95% CI, 1.00-1.56).

Most fractures were due to falls, with the most common affected sites being the forearm, upper arm, spine, and hip, Dr. Lorentzon said.

Among the findings:

• In bone microarchitecture, women with T2D had higher BMD at all sites: total hip, 4.4% higher; femoral neck, 4.9% higher; and lumbar spine, 5.2% higher.
• At the tibia, the T2D group had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction.

“Our findings regarding BMD are consistent with previous publications showing higher BMD in individuals with T2D compared with those without diabetes,” Dr. Lorentzon said. A 2012 meta-analysis, for example, showed higher BMD levels in T2D patients. “Some smaller studies, however, have found worse bone microstructure and lower bone material strength in contrast to the results from our study,” Dr. Lorentzon said.

• There was no difference in BMSi, with a mean of 78 in both groups.
• The T2D group had lower performance on all physical function tests: a 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes.

“We found all parameters regarding physical function, such as muscle strength, balance, and performance, were much worse in women with diabetes than in those without,” Dr. Lorentzon said. “Dizziness could also be a contributor to the increased risk of falls, but this factor was not investigated in our study.”

Commenting on the study but not involved in it, Anthony J. Pick, MD, an endocrinologist at Northwestern Medicine Lake Forest Hospital in Lake Forest, Illinois, said sarcopenia is a common and often under-recognized problem in older adults and is especially prevalent in T2D, obesity, and heart failure. “I believe that ‘exercise is medicine’ is a key concept for metabolic and osteoporosis patients — and wellness and longevity in general — and I certainly hope studies like this drive awareness of the importance of engaging in strengthening exercises.”

TOPLINE:

Uptake of infliximab biosimilars rose slowly across private insurance, Medicaid, and Medicare when two were available in the United States during 2016-2020 but increased significantly through 2022 after the third biosimilar became available in July 2020. However, prescriptions in Medicare still lagged behind those in private insurance and Medicaid.

METHODOLOGY:

• Researchers analyzed electronic health records from over 1100 US rheumatologists who participated in a national registry, the Rheumatology Informatics System for Effectiveness (RISE), for all infliximab administrations (bio-originator or biosimilar) to patients older than 18 years from April 2016 to September 2022.
• They conducted an interrupted time series to account for autocorrelation and model the effect of each infliximab biosimilar release (infliximab-dyyb in November 2016, infliximab-abda in July 2017, and infliximab-axxq in July 2020) on uptake across Medicare, Medicaid, and private insurers.

TAKEAWAY:

• The researchers identified 659,988 infliximab administrations for 37,560 unique patients, with 52% on Medicare, 4.8% on Medicaid, and 43% on private insurance.
• Biosimilar uptake rose slowly with average annual increases < 5% from 2016 to June 2020 (Medicare, 3.2%; Medicaid, 5.2%; private insurance, 1.8%).
• After the third biosimilar release in July 2020, the average annual increase reached 13% for Medicaid and 16.4% for private insurance but remained low for Medicare (5.6%).
• By September 2022, biosimilar uptake was higher for Medicaid (43.8%) and private insurance (38.5%) than for Medicare (24%).

IN PRACTICE:

“Our results suggest policymakers may need to do more to allow biosimilars to get a foothold in the market by incentivizing the development and entry of multiple biosimilars, address anticompetitive pricing strategies, and may need to amend Medicare policy to [incentivize] uptake in order to ensure a competitive and sustainable biosimilar market that gradually reduces total drug expenditures and out-of-pocket costs over time,” wrote the authors of the study.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco. It was published online on July 30, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

First, while the biosimilar introductions are likely catalysts for many changes in the market, some changes in slopes may also be attributable to the natural growth of the market over time. Second, this study may neither be generalizable to academic medical centers, which are underrepresented in RISE, nor be generalizable to infliximab prescriptions from other specialties. Third, uptake among privately insured patients changed shortly after November-December 2020, raising the possibility that the delay reflected negotiations between insurance companies and relevant entities regarding formulary coverage.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author disclosed receiving consulting fees from Pfizer, AstraZeneca, and Bristol-Myers Squibb and grant funding from AstraZeneca, the Bristol-Myers Squibb Foundation, and Aurinia.

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:

Uptake of infliximab biosimilars rose slowly across private insurance, Medicaid, and Medicare when two were available in the United States during 2016-2020 but increased significantly through 2022 after the third biosimilar became available in July 2020. However, prescriptions in Medicare still lagged behind those in private insurance and Medicaid.

METHODOLOGY:

• Researchers analyzed electronic health records from over 1100 US rheumatologists who participated in a national registry, the Rheumatology Informatics System for Effectiveness (RISE), for all infliximab administrations (bio-originator or biosimilar) to patients older than 18 years from April 2016 to September 2022.
• They conducted an interrupted time series to account for autocorrelation and model the effect of each infliximab biosimilar release (infliximab-dyyb in November 2016, infliximab-abda in July 2017, and infliximab-axxq in July 2020) on uptake across Medicare, Medicaid, and private insurers.

TAKEAWAY:

• The researchers identified 659,988 infliximab administrations for 37,560 unique patients, with 52% on Medicare, 4.8% on Medicaid, and 43% on private insurance.
• Biosimilar uptake rose slowly with average annual increases < 5% from 2016 to June 2020 (Medicare, 3.2%; Medicaid, 5.2%; private insurance, 1.8%).
• After the third biosimilar release in July 2020, the average annual increase reached 13% for Medicaid and 16.4% for private insurance but remained low for Medicare (5.6%).
• By September 2022, biosimilar uptake was higher for Medicaid (43.8%) and private insurance (38.5%) than for Medicare (24%).

IN PRACTICE:

“Our results suggest policymakers may need to do more to allow biosimilars to get a foothold in the market by incentivizing the development and entry of multiple biosimilars, address anticompetitive pricing strategies, and may need to amend Medicare policy to [incentivize] uptake in order to ensure a competitive and sustainable biosimilar market that gradually reduces total drug expenditures and out-of-pocket costs over time,” wrote the authors of the study.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco. It was published online on July 30, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

First, while the biosimilar introductions are likely catalysts for many changes in the market, some changes in slopes may also be attributable to the natural growth of the market over time. Second, this study may neither be generalizable to academic medical centers, which are underrepresented in RISE, nor be generalizable to infliximab prescriptions from other specialties. Third, uptake among privately insured patients changed shortly after November-December 2020, raising the possibility that the delay reflected negotiations between insurance companies and relevant entities regarding formulary coverage.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author disclosed receiving consulting fees from Pfizer, AstraZeneca, and Bristol-Myers Squibb and grant funding from AstraZeneca, the Bristol-Myers Squibb Foundation, and Aurinia.

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:

Uptake of infliximab biosimilars rose slowly across private insurance, Medicaid, and Medicare when two were available in the United States during 2016-2020 but increased significantly through 2022 after the third biosimilar became available in July 2020. However, prescriptions in Medicare still lagged behind those in private insurance and Medicaid.

METHODOLOGY:

• Researchers analyzed electronic health records from over 1100 US rheumatologists who participated in a national registry, the Rheumatology Informatics System for Effectiveness (RISE), for all infliximab administrations (bio-originator or biosimilar) to patients older than 18 years from April 2016 to September 2022.
• They conducted an interrupted time series to account for autocorrelation and model the effect of each infliximab biosimilar release (infliximab-dyyb in November 2016, infliximab-abda in July 2017, and infliximab-axxq in July 2020) on uptake across Medicare, Medicaid, and private insurers.

TAKEAWAY:

• The researchers identified 659,988 infliximab administrations for 37,560 unique patients, with 52% on Medicare, 4.8% on Medicaid, and 43% on private insurance.
• Biosimilar uptake rose slowly with average annual increases < 5% from 2016 to June 2020 (Medicare, 3.2%; Medicaid, 5.2%; private insurance, 1.8%).
• After the third biosimilar release in July 2020, the average annual increase reached 13% for Medicaid and 16.4% for private insurance but remained low for Medicare (5.6%).
• By September 2022, biosimilar uptake was higher for Medicaid (43.8%) and private insurance (38.5%) than for Medicare (24%).

IN PRACTICE:

“Our results suggest policymakers may need to do more to allow biosimilars to get a foothold in the market by incentivizing the development and entry of multiple biosimilars, address anticompetitive pricing strategies, and may need to amend Medicare policy to [incentivize] uptake in order to ensure a competitive and sustainable biosimilar market that gradually reduces total drug expenditures and out-of-pocket costs over time,” wrote the authors of the study.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco. It was published online on July 30, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

First, while the biosimilar introductions are likely catalysts for many changes in the market, some changes in slopes may also be attributable to the natural growth of the market over time. Second, this study may neither be generalizable to academic medical centers, which are underrepresented in RISE, nor be generalizable to infliximab prescriptions from other specialties. Third, uptake among privately insured patients changed shortly after November-December 2020, raising the possibility that the delay reflected negotiations between insurance companies and relevant entities regarding formulary coverage.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author disclosed receiving consulting fees from Pfizer, AstraZeneca, and Bristol-Myers Squibb and grant funding from AstraZeneca, the Bristol-Myers Squibb Foundation, and Aurinia.

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:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

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:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

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:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

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.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome to The Curbsiders. I’m here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. We’re going to be talking about the evaluation of chronic neck pain, which is a really common complaint in primary care. So, Paul, what are the three buckets of neck pain? 

Paul N. Williams, MD: Well, as our listeners probably know, neck pain is extraordinarily common. There are three big buckets. There is mechanical neck pain, which is sort of the bread-and-butter “my neck just hurts” — probably the one you’re going to see most commonly in the office. We’ll get into that in just a second. 

The second bucket is cervical radiculopathy. We see a little bit more neurologic symptoms as part of the presentation. They may have weakness. They may have pain.

The third type of neck pain is cervical myelopathy, which is the one that probably warrants more aggressive follow-up and evaluation, and potentially even management. And that is typically your older patients in nontraumatic cases, who have bony impingement on the central spinal cord, often with upper motor neuron signs, and it can ultimately be very devastating. It’s almost a spectrum of presentations to worry about in terms of severity and outcomes.

We’ll start with the mechanical neck pain. It’s the one that we see the most commonly in the primary care office. We’ve all dealt with this. This is the patient who’s got localized neck pain that doesn’t really radiate anywhere; it kind of sits in the middle of the neck. In fact, if you actually poke back there where the patient says “ouch,” you’re probably in the right ballpark. The etiology and pathophysiology, weirdly, are still not super well-defined, but it’s probably mostly myofascial in etiology. And as such, it often gets better no matter what you do. It will probably get better with time.

You are not going to have neurologic deficits with this type of neck pain. There’s not going to be weakness, or radiation down the arm, or upper motor neuron signs. No one is mentioning the urinary symptoms with this. You can treat it with NSAIDs and physical therapy, which may be necessary if it persists. Massage can sometimes be helpful, but basically you’re just kind of supporting the patients through their own natural healing process. Physical therapy might help with the ergonomics and help make sure that they position themselves and move in a way that does not exacerbate the underlying structures. That is probably the one that we see the most and in some ways is probably the easiest to manage. 

Dr. Watto: This is the one that we generally should be least worried about. But cervical radiculopathy, which is the second bucket, is not as severe as cervical myelopathy, so it’s kind of in between the two. Cervical radiculopathy is basically the patient who has neck pain that’s going down one arm or the other, usually not both arms because that would be weird for them to have symmetric radiculopathy. It’s a nerve being pinched somewhere, usually more on one side than the other. 

The good news for patients is that the natural history is that it’s going to get better over time, almost no matter what we do. I almost think of this akin to sciatica. Usually sciatica and cervical radiculopathy do not have any motor weakness along with them. It’s really just the pain and maybe a little bit of mild sensory symptoms. So, you can reassure the patient that this usually goes away. Our guest said he sometimes gives gabapentin for this. That’s not my practice. I would be more likely to refer to physical therapy or try some NSAIDs if they’re really having trouble functioning or maybe some muscle relaxants. But they aren’t going to need to go to surgery. 

What about cervical myelopathy, Paul? Do those patients need surgery? 

Dr. Williams: Yes. The idea with cervical myelopathy is to keep it from progressing. It typically occurs in older patients. It’s like arthritis — a sort of bony buildup that compresses on the spinal cord itself. These patients will often have neck pain but not always. It’s also associated with impairments in motor function and other neurologic deficits. So, the patients may report that they have difficulty buttoning their buttons or managing fine-motor skills. They may have radicular symptoms down their arms. They may have an abnormal physical examination. They may have weakness on exam, but they’ll have a positive Hoffmann’s test where you flick the middle finger and look for flexion of the first finger and the thumb. They may have abnormal tandem gait, or patellar or Achilles hyperreflexia. Their neuro exam will not be normal much of the time, and in later cases because it’s upper motor neuron disease, they may even report urinary symptoms like urinary hesitancy or just a feeling of general unsteadiness of the gait, even though we’re at the cervical level. If you suspect myelopathy — and the trick is to think about it and recognize it when you see it — then you should send them for an MRI. If it persists or they have rapid regression, you get the MRI and refer them to neurosurgery. It’s not necessarily a neurosurgical emergency, but things should move along fairly briskly once you’ve actually identified it. 

Dr. Watto: Dr. Mikula made the point that if someone comes to you in a wheelchair, they are probably not going to regain the ability to walk. You’re really trying to prevent progression. If they are already severely disabled, they’re probably not going to get totally back to full functioning, even with surgery. You’re just trying to prevent things from getting worse. That’s the main reason to identify this and get the patient to surgery. 

We covered a lot more about neck pain. This was a very superficial review of what we talked about with Dr. Anthony Mikula. Click here to listen to the full podcast.

Matthew F. Watto is clinical assistant professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania, and internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Paul N. Williams is associate professor of clinical medicine, Department of General Internal Medicine, Lewis Katz School of Medicine, and staff physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for The Curbsiders; received income in an amount equal to or greater than $250 from The Curbsiders.

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

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome to The Curbsiders. I’m here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. We’re going to be talking about the evaluation of chronic neck pain, which is a really common complaint in primary care. So, Paul, what are the three buckets of neck pain? 

Paul N. Williams, MD: Well, as our listeners probably know, neck pain is extraordinarily common. There are three big buckets. There is mechanical neck pain, which is sort of the bread-and-butter “my neck just hurts” — probably the one you’re going to see most commonly in the office. We’ll get into that in just a second. 

The second bucket is cervical radiculopathy. We see a little bit more neurologic symptoms as part of the presentation. They may have weakness. They may have pain.

The third type of neck pain is cervical myelopathy, which is the one that probably warrants more aggressive follow-up and evaluation, and potentially even management. And that is typically your older patients in nontraumatic cases, who have bony impingement on the central spinal cord, often with upper motor neuron signs, and it can ultimately be very devastating. It’s almost a spectrum of presentations to worry about in terms of severity and outcomes.

We’ll start with the mechanical neck pain. It’s the one that we see the most commonly in the primary care office. We’ve all dealt with this. This is the patient who’s got localized neck pain that doesn’t really radiate anywhere; it kind of sits in the middle of the neck. In fact, if you actually poke back there where the patient says “ouch,” you’re probably in the right ballpark. The etiology and pathophysiology, weirdly, are still not super well-defined, but it’s probably mostly myofascial in etiology. And as such, it often gets better no matter what you do. It will probably get better with time.

You are not going to have neurologic deficits with this type of neck pain. There’s not going to be weakness, or radiation down the arm, or upper motor neuron signs. No one is mentioning the urinary symptoms with this. You can treat it with NSAIDs and physical therapy, which may be necessary if it persists. Massage can sometimes be helpful, but basically you’re just kind of supporting the patients through their own natural healing process. Physical therapy might help with the ergonomics and help make sure that they position themselves and move in a way that does not exacerbate the underlying structures. That is probably the one that we see the most and in some ways is probably the easiest to manage. 

Dr. Watto: This is the one that we generally should be least worried about. But cervical radiculopathy, which is the second bucket, is not as severe as cervical myelopathy, so it’s kind of in between the two. Cervical radiculopathy is basically the patient who has neck pain that’s going down one arm or the other, usually not both arms because that would be weird for them to have symmetric radiculopathy. It’s a nerve being pinched somewhere, usually more on one side than the other. 

The good news for patients is that the natural history is that it’s going to get better over time, almost no matter what we do. I almost think of this akin to sciatica. Usually sciatica and cervical radiculopathy do not have any motor weakness along with them. It’s really just the pain and maybe a little bit of mild sensory symptoms. So, you can reassure the patient that this usually goes away. Our guest said he sometimes gives gabapentin for this. That’s not my practice. I would be more likely to refer to physical therapy or try some NSAIDs if they’re really having trouble functioning or maybe some muscle relaxants. But they aren’t going to need to go to surgery. 

What about cervical myelopathy, Paul? Do those patients need surgery? 

Dr. Williams: Yes. The idea with cervical myelopathy is to keep it from progressing. It typically occurs in older patients. It’s like arthritis — a sort of bony buildup that compresses on the spinal cord itself. These patients will often have neck pain but not always. It’s also associated with impairments in motor function and other neurologic deficits. So, the patients may report that they have difficulty buttoning their buttons or managing fine-motor skills. They may have radicular symptoms down their arms. They may have an abnormal physical examination. They may have weakness on exam, but they’ll have a positive Hoffmann’s test where you flick the middle finger and look for flexion of the first finger and the thumb. They may have abnormal tandem gait, or patellar or Achilles hyperreflexia. Their neuro exam will not be normal much of the time, and in later cases because it’s upper motor neuron disease, they may even report urinary symptoms like urinary hesitancy or just a feeling of general unsteadiness of the gait, even though we’re at the cervical level. If you suspect myelopathy — and the trick is to think about it and recognize it when you see it — then you should send them for an MRI. If it persists or they have rapid regression, you get the MRI and refer them to neurosurgery. It’s not necessarily a neurosurgical emergency, but things should move along fairly briskly once you’ve actually identified it. 

Dr. Watto: Dr. Mikula made the point that if someone comes to you in a wheelchair, they are probably not going to regain the ability to walk. You’re really trying to prevent progression. If they are already severely disabled, they’re probably not going to get totally back to full functioning, even with surgery. You’re just trying to prevent things from getting worse. That’s the main reason to identify this and get the patient to surgery. 

We covered a lot more about neck pain. This was a very superficial review of what we talked about with Dr. Anthony Mikula. Click here to listen to the full podcast.

Matthew F. Watto is clinical assistant professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania, and internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Paul N. Williams is associate professor of clinical medicine, Department of General Internal Medicine, Lewis Katz School of Medicine, and staff physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for The Curbsiders; received income in an amount equal to or greater than $250 from The Curbsiders.

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

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome to The Curbsiders. I’m here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. We’re going to be talking about the evaluation of chronic neck pain, which is a really common complaint in primary care. So, Paul, what are the three buckets of neck pain? 

Paul N. Williams, MD: Well, as our listeners probably know, neck pain is extraordinarily common. There are three big buckets. There is mechanical neck pain, which is sort of the bread-and-butter “my neck just hurts” — probably the one you’re going to see most commonly in the office. We’ll get into that in just a second. 

The second bucket is cervical radiculopathy. We see a little bit more neurologic symptoms as part of the presentation. They may have weakness. They may have pain.

The third type of neck pain is cervical myelopathy, which is the one that probably warrants more aggressive follow-up and evaluation, and potentially even management. And that is typically your older patients in nontraumatic cases, who have bony impingement on the central spinal cord, often with upper motor neuron signs, and it can ultimately be very devastating. It’s almost a spectrum of presentations to worry about in terms of severity and outcomes.

We’ll start with the mechanical neck pain. It’s the one that we see the most commonly in the primary care office. We’ve all dealt with this. This is the patient who’s got localized neck pain that doesn’t really radiate anywhere; it kind of sits in the middle of the neck. In fact, if you actually poke back there where the patient says “ouch,” you’re probably in the right ballpark. The etiology and pathophysiology, weirdly, are still not super well-defined, but it’s probably mostly myofascial in etiology. And as such, it often gets better no matter what you do. It will probably get better with time.

You are not going to have neurologic deficits with this type of neck pain. There’s not going to be weakness, or radiation down the arm, or upper motor neuron signs. No one is mentioning the urinary symptoms with this. You can treat it with NSAIDs and physical therapy, which may be necessary if it persists. Massage can sometimes be helpful, but basically you’re just kind of supporting the patients through their own natural healing process. Physical therapy might help with the ergonomics and help make sure that they position themselves and move in a way that does not exacerbate the underlying structures. That is probably the one that we see the most and in some ways is probably the easiest to manage. 

Dr. Watto: This is the one that we generally should be least worried about. But cervical radiculopathy, which is the second bucket, is not as severe as cervical myelopathy, so it’s kind of in between the two. Cervical radiculopathy is basically the patient who has neck pain that’s going down one arm or the other, usually not both arms because that would be weird for them to have symmetric radiculopathy. It’s a nerve being pinched somewhere, usually more on one side than the other. 

The good news for patients is that the natural history is that it’s going to get better over time, almost no matter what we do. I almost think of this akin to sciatica. Usually sciatica and cervical radiculopathy do not have any motor weakness along with them. It’s really just the pain and maybe a little bit of mild sensory symptoms. So, you can reassure the patient that this usually goes away. Our guest said he sometimes gives gabapentin for this. That’s not my practice. I would be more likely to refer to physical therapy or try some NSAIDs if they’re really having trouble functioning or maybe some muscle relaxants. But they aren’t going to need to go to surgery. 

What about cervical myelopathy, Paul? Do those patients need surgery? 

Dr. Williams: Yes. The idea with cervical myelopathy is to keep it from progressing. It typically occurs in older patients. It’s like arthritis — a sort of bony buildup that compresses on the spinal cord itself. These patients will often have neck pain but not always. It’s also associated with impairments in motor function and other neurologic deficits. So, the patients may report that they have difficulty buttoning their buttons or managing fine-motor skills. They may have radicular symptoms down their arms. They may have an abnormal physical examination. They may have weakness on exam, but they’ll have a positive Hoffmann’s test where you flick the middle finger and look for flexion of the first finger and the thumb. They may have abnormal tandem gait, or patellar or Achilles hyperreflexia. Their neuro exam will not be normal much of the time, and in later cases because it’s upper motor neuron disease, they may even report urinary symptoms like urinary hesitancy or just a feeling of general unsteadiness of the gait, even though we’re at the cervical level. If you suspect myelopathy — and the trick is to think about it and recognize it when you see it — then you should send them for an MRI. If it persists or they have rapid regression, you get the MRI and refer them to neurosurgery. It’s not necessarily a neurosurgical emergency, but things should move along fairly briskly once you’ve actually identified it. 

Dr. Watto: Dr. Mikula made the point that if someone comes to you in a wheelchair, they are probably not going to regain the ability to walk. You’re really trying to prevent progression. If they are already severely disabled, they’re probably not going to get totally back to full functioning, even with surgery. You’re just trying to prevent things from getting worse. That’s the main reason to identify this and get the patient to surgery. 

We covered a lot more about neck pain. This was a very superficial review of what we talked about with Dr. Anthony Mikula. Click here to listen to the full podcast.

Matthew F. Watto is clinical assistant professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania, and internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Paul N. Williams is associate professor of clinical medicine, Department of General Internal Medicine, Lewis Katz School of Medicine, and staff physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for The Curbsiders; received income in an amount equal to or greater than $250 from The Curbsiders.

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

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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