ORLANDO — “Itch may not be as sexy as Mohs surgery or aesthetic procedures,” but treating it is important and meaningful to patients, particularly those who’ve found little relief previously, Shawn G. Kwatra, MD, said at the annual ODAC Dermatology, Aesthetic & Surgery Conference.

Chronic itch is common, with presentations that range from annoying to debilitating. There are many over-the-counter and prescription treatments patients can and likely have tried by the time they seek a dermatologist for help.

In doctors’ defense, it can be highly challenging to know which approach is optimal for each individual with pruritus, added Dr. Kwatra, associate professor of dermatology at Johns Hopkins University, Baltimore, Maryland.

Cooling agents, topical capsaicin, topical anesthetics like pramoxine 1%, various forms of lidocaine, strontium, opioid modulators like naltrexone, oral Janus kinase inhibitor (JAK) inhibitors, and medical marijuana are among some of the “outside the box” tools in Dr. Kwatra’s itch toolbox.
 

Often a Medical Puzzle

Frequently, patients come to the dermatologist complaining of itch, “but you don’t see much on their skin.” After a trial of antihistamines, and some topical steroids, the doctor might put up their hands and think: I tried, but I don’t know what else to do. “This actually happens a lot,” said Dr. Kwatra, who is also director of the Johns Hopkins Itch Center.

This means itch can frustrate providers as well. But for patients, the impact on their quality of life can be on the same level as recovering from a stroke or living with heart failure, Dr. Kwatra said. Finding relief for their itch is where “we can make a big difference for patients.”
 

Consider Cooling Agents

Many of these therapies are inexpensive and widely available. Cooling agents like menthol, camphor, or calamine can reduce activity of the transient receptor potential (TRP) channels in the skin associated with itch. This ion channel also senses temperature, pressure, and other sensations.

Another option is topical capsaicin, which works through the same ion channels. It binds to the TRPV1 receptors in sensory nerve fibers and causes desensitization. Initially, four to six applications a day are required to reduce itch. After that, patients can apply the medication less frequently. “You have to tell folks we know it’s going to work, but it’s going to burn a lot initially,” Dr. Kwatra said. “In real world practice, I’m not using it often.”

A 1.8% capsaicin patch, approved for treating postherpetic neuralgia, can be used to treat pruritus as well. “You put the patch on for one hour and you can have a true clinical response,” he noted.

Another option for itch relief, the topical anesthetic pramoxine 1%, “is probably underutilized for our patients,” Dr. Kwatra said. Pramoxine 1% works fast — as quickly as 2 minutes — and lasts up to 8 hours and is well-tolerated with low toxicity, he added. The agent is applied three to four times a day and relieves itch by reducing the transmembrane permeability of sodium ions on the skin. “This is something widely available and cheap.”

Lidocaine, another topical anesthetic, is available compounded, over the counter, and as a spray or patch. “I would be careful before you use high doses, like 10%” because of tolerability issues, Dr. Kwatra cautioned. He generally starts with lower concentrations.

Topical strontium is really interesting as a strategy, Dr. Kwatra said. Strontium is a soft, white metal that competes with calcium for receptor binding. There are over-the-counter formulations available as a scalp solution or lotion, which, he said, “are ways to go with more episodic itching.”

Topical oatmeal can also relieve itch in some patients. “There is actually some good scientific evidence for topical oatmeal preparations,” he said.
 

Steroid-Sparing Novel Topicals

Topical ruxolitinib (a JAK inhibitor approved for atopic dermatitis and vitiligo); topical roflumilast (a phosphodiesterase-4 inhibitor) and topical tapinarof (an aryl hydrocarbon receptor agonist), both approved for treating psoriasis; and the atopic dermatitis drug crisaborole fall into this category of topicals with potential for treating itch, he said, noting that use for treating itch is off label.

Off-label use of biologic agents are also possible treatment options for itch, dupilumab and tralokinumab, both US Food and Drug Administration (FDA)–approved for treating atopic dermatitis. Emerging agents that may prove useful for treating itch include lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab, he said.

In terms of oral therapies, the FDA has approved two oral JAK inhibitors for atopic dermatitis, abrocitinib and upadacitinib, which could prove useful for itch as an off-label indication, according to Dr. Kwatra.
 

Naltrexone Off Label

An emerging therapeutic concept for treating itch is using an opioid antagonist like naltrexone. Morphine causes more itch, so the theory is a reversal agent might help reduce it. The challenge is that naltrexone only comes as a 50 mg tablet, “and I find the high dose makes people nauseous and vomit,” he added.

Don’t Forget Devices

He referred to a “great paper” that he said has been “totally overlooked,” published in 2001, which evaluated a device that stimulates C fibers in the skin to reduce itch. In the study, 19 patients used the device to treat local areas 20 minutes daily for 5 weeks. Punch biopsies of the affected areas were taken at baseline and after treatment. Mean itch ratings decreased from 78% to 42%, and the number of immunoreactive nerve fibers in the epidermis decreased by 40% at the end of treatment.

“Electrical neurostimulation is better for localized pruritus. There is limited case series evidence, but it’s something to think about,” Dr. Kwatra said.

He and his colleagues also have a case study in press that explored the use of injected botulinum toxin to relieve recalcitrant, chronic itch in a 65-year-old man “who failed everything.”

Dr. Kwatra is a consultant or advisory board member for AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Incyte Corporation, Johnson & Johnson, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi.

A version of this article appeared on Medscape.com.

ORLANDO — “Itch may not be as sexy as Mohs surgery or aesthetic procedures,” but treating it is important and meaningful to patients, particularly those who’ve found little relief previously, Shawn G. Kwatra, MD, said at the annual ODAC Dermatology, Aesthetic & Surgery Conference.

Chronic itch is common, with presentations that range from annoying to debilitating. There are many over-the-counter and prescription treatments patients can and likely have tried by the time they seek a dermatologist for help.

In doctors’ defense, it can be highly challenging to know which approach is optimal for each individual with pruritus, added Dr. Kwatra, associate professor of dermatology at Johns Hopkins University, Baltimore, Maryland.

Cooling agents, topical capsaicin, topical anesthetics like pramoxine 1%, various forms of lidocaine, strontium, opioid modulators like naltrexone, oral Janus kinase inhibitor (JAK) inhibitors, and medical marijuana are among some of the “outside the box” tools in Dr. Kwatra’s itch toolbox.
 

Often a Medical Puzzle

Frequently, patients come to the dermatologist complaining of itch, “but you don’t see much on their skin.” After a trial of antihistamines, and some topical steroids, the doctor might put up their hands and think: I tried, but I don’t know what else to do. “This actually happens a lot,” said Dr. Kwatra, who is also director of the Johns Hopkins Itch Center.

This means itch can frustrate providers as well. But for patients, the impact on their quality of life can be on the same level as recovering from a stroke or living with heart failure, Dr. Kwatra said. Finding relief for their itch is where “we can make a big difference for patients.”
 

Consider Cooling Agents

Many of these therapies are inexpensive and widely available. Cooling agents like menthol, camphor, or calamine can reduce activity of the transient receptor potential (TRP) channels in the skin associated with itch. This ion channel also senses temperature, pressure, and other sensations.

Another option is topical capsaicin, which works through the same ion channels. It binds to the TRPV1 receptors in sensory nerve fibers and causes desensitization. Initially, four to six applications a day are required to reduce itch. After that, patients can apply the medication less frequently. “You have to tell folks we know it’s going to work, but it’s going to burn a lot initially,” Dr. Kwatra said. “In real world practice, I’m not using it often.”

A 1.8% capsaicin patch, approved for treating postherpetic neuralgia, can be used to treat pruritus as well. “You put the patch on for one hour and you can have a true clinical response,” he noted.

Another option for itch relief, the topical anesthetic pramoxine 1%, “is probably underutilized for our patients,” Dr. Kwatra said. Pramoxine 1% works fast — as quickly as 2 minutes — and lasts up to 8 hours and is well-tolerated with low toxicity, he added. The agent is applied three to four times a day and relieves itch by reducing the transmembrane permeability of sodium ions on the skin. “This is something widely available and cheap.”

Lidocaine, another topical anesthetic, is available compounded, over the counter, and as a spray or patch. “I would be careful before you use high doses, like 10%” because of tolerability issues, Dr. Kwatra cautioned. He generally starts with lower concentrations.

Topical strontium is really interesting as a strategy, Dr. Kwatra said. Strontium is a soft, white metal that competes with calcium for receptor binding. There are over-the-counter formulations available as a scalp solution or lotion, which, he said, “are ways to go with more episodic itching.”

Topical oatmeal can also relieve itch in some patients. “There is actually some good scientific evidence for topical oatmeal preparations,” he said.
 

Steroid-Sparing Novel Topicals

Topical ruxolitinib (a JAK inhibitor approved for atopic dermatitis and vitiligo); topical roflumilast (a phosphodiesterase-4 inhibitor) and topical tapinarof (an aryl hydrocarbon receptor agonist), both approved for treating psoriasis; and the atopic dermatitis drug crisaborole fall into this category of topicals with potential for treating itch, he said, noting that use for treating itch is off label.

Off-label use of biologic agents are also possible treatment options for itch, dupilumab and tralokinumab, both US Food and Drug Administration (FDA)–approved for treating atopic dermatitis. Emerging agents that may prove useful for treating itch include lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab, he said.

In terms of oral therapies, the FDA has approved two oral JAK inhibitors for atopic dermatitis, abrocitinib and upadacitinib, which could prove useful for itch as an off-label indication, according to Dr. Kwatra.
 

Naltrexone Off Label

An emerging therapeutic concept for treating itch is using an opioid antagonist like naltrexone. Morphine causes more itch, so the theory is a reversal agent might help reduce it. The challenge is that naltrexone only comes as a 50 mg tablet, “and I find the high dose makes people nauseous and vomit,” he added.

Don’t Forget Devices

He referred to a “great paper” that he said has been “totally overlooked,” published in 2001, which evaluated a device that stimulates C fibers in the skin to reduce itch. In the study, 19 patients used the device to treat local areas 20 minutes daily for 5 weeks. Punch biopsies of the affected areas were taken at baseline and after treatment. Mean itch ratings decreased from 78% to 42%, and the number of immunoreactive nerve fibers in the epidermis decreased by 40% at the end of treatment.

“Electrical neurostimulation is better for localized pruritus. There is limited case series evidence, but it’s something to think about,” Dr. Kwatra said.

He and his colleagues also have a case study in press that explored the use of injected botulinum toxin to relieve recalcitrant, chronic itch in a 65-year-old man “who failed everything.”

Dr. Kwatra is a consultant or advisory board member for AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Incyte Corporation, Johnson & Johnson, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi.

A version of this article appeared on Medscape.com.

ORLANDO — “Itch may not be as sexy as Mohs surgery or aesthetic procedures,” but treating it is important and meaningful to patients, particularly those who’ve found little relief previously, Shawn G. Kwatra, MD, said at the annual ODAC Dermatology, Aesthetic & Surgery Conference.

Chronic itch is common, with presentations that range from annoying to debilitating. There are many over-the-counter and prescription treatments patients can and likely have tried by the time they seek a dermatologist for help.

In doctors’ defense, it can be highly challenging to know which approach is optimal for each individual with pruritus, added Dr. Kwatra, associate professor of dermatology at Johns Hopkins University, Baltimore, Maryland.

Cooling agents, topical capsaicin, topical anesthetics like pramoxine 1%, various forms of lidocaine, strontium, opioid modulators like naltrexone, oral Janus kinase inhibitor (JAK) inhibitors, and medical marijuana are among some of the “outside the box” tools in Dr. Kwatra’s itch toolbox.
 

Often a Medical Puzzle

Frequently, patients come to the dermatologist complaining of itch, “but you don’t see much on their skin.” After a trial of antihistamines, and some topical steroids, the doctor might put up their hands and think: I tried, but I don’t know what else to do. “This actually happens a lot,” said Dr. Kwatra, who is also director of the Johns Hopkins Itch Center.

This means itch can frustrate providers as well. But for patients, the impact on their quality of life can be on the same level as recovering from a stroke or living with heart failure, Dr. Kwatra said. Finding relief for their itch is where “we can make a big difference for patients.”
 

Consider Cooling Agents

Many of these therapies are inexpensive and widely available. Cooling agents like menthol, camphor, or calamine can reduce activity of the transient receptor potential (TRP) channels in the skin associated with itch. This ion channel also senses temperature, pressure, and other sensations.

Another option is topical capsaicin, which works through the same ion channels. It binds to the TRPV1 receptors in sensory nerve fibers and causes desensitization. Initially, four to six applications a day are required to reduce itch. After that, patients can apply the medication less frequently. “You have to tell folks we know it’s going to work, but it’s going to burn a lot initially,” Dr. Kwatra said. “In real world practice, I’m not using it often.”

A 1.8% capsaicin patch, approved for treating postherpetic neuralgia, can be used to treat pruritus as well. “You put the patch on for one hour and you can have a true clinical response,” he noted.

Another option for itch relief, the topical anesthetic pramoxine 1%, “is probably underutilized for our patients,” Dr. Kwatra said. Pramoxine 1% works fast — as quickly as 2 minutes — and lasts up to 8 hours and is well-tolerated with low toxicity, he added. The agent is applied three to four times a day and relieves itch by reducing the transmembrane permeability of sodium ions on the skin. “This is something widely available and cheap.”

Lidocaine, another topical anesthetic, is available compounded, over the counter, and as a spray or patch. “I would be careful before you use high doses, like 10%” because of tolerability issues, Dr. Kwatra cautioned. He generally starts with lower concentrations.

Topical strontium is really interesting as a strategy, Dr. Kwatra said. Strontium is a soft, white metal that competes with calcium for receptor binding. There are over-the-counter formulations available as a scalp solution or lotion, which, he said, “are ways to go with more episodic itching.”

Topical oatmeal can also relieve itch in some patients. “There is actually some good scientific evidence for topical oatmeal preparations,” he said.
 

Steroid-Sparing Novel Topicals

Topical ruxolitinib (a JAK inhibitor approved for atopic dermatitis and vitiligo); topical roflumilast (a phosphodiesterase-4 inhibitor) and topical tapinarof (an aryl hydrocarbon receptor agonist), both approved for treating psoriasis; and the atopic dermatitis drug crisaborole fall into this category of topicals with potential for treating itch, he said, noting that use for treating itch is off label.

Off-label use of biologic agents are also possible treatment options for itch, dupilumab and tralokinumab, both US Food and Drug Administration (FDA)–approved for treating atopic dermatitis. Emerging agents that may prove useful for treating itch include lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab, he said.

In terms of oral therapies, the FDA has approved two oral JAK inhibitors for atopic dermatitis, abrocitinib and upadacitinib, which could prove useful for itch as an off-label indication, according to Dr. Kwatra.
 

Naltrexone Off Label

An emerging therapeutic concept for treating itch is using an opioid antagonist like naltrexone. Morphine causes more itch, so the theory is a reversal agent might help reduce it. The challenge is that naltrexone only comes as a 50 mg tablet, “and I find the high dose makes people nauseous and vomit,” he added.

Don’t Forget Devices

He referred to a “great paper” that he said has been “totally overlooked,” published in 2001, which evaluated a device that stimulates C fibers in the skin to reduce itch. In the study, 19 patients used the device to treat local areas 20 minutes daily for 5 weeks. Punch biopsies of the affected areas were taken at baseline and after treatment. Mean itch ratings decreased from 78% to 42%, and the number of immunoreactive nerve fibers in the epidermis decreased by 40% at the end of treatment.

“Electrical neurostimulation is better for localized pruritus. There is limited case series evidence, but it’s something to think about,” Dr. Kwatra said.

He and his colleagues also have a case study in press that explored the use of injected botulinum toxin to relieve recalcitrant, chronic itch in a 65-year-old man “who failed everything.”

Dr. Kwatra is a consultant or advisory board member for AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Incyte Corporation, Johnson & Johnson, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi.

A version of this article appeared on Medscape.com.

TOPLINE:

Circulating levels of serum 25-hydroxyvitamin D (25[OH]D) may be a marker of cardiovascular disease (CVD) risk in healthy young adults, small study finds.

METHODOLOGY:

• A secondary analysis of the Activating Brown Adipose Tissue Through Exercise (ACTIBATE) trial assessed the association between serum 25(OH)D levels and CVD risk factors.
• The cross-sectional study used baseline data of in 177 healthy sedentary adults ages 18-25 years (65% women; all White individuals), who were recruited between October 2015 and December 2016 from Granada, a region in the south of Spain.
• Study participants were nonsmokers, led a sedentary lifestyle, and did not have a prior history of CVD or chronic illnesses.
• The CVD risk factors included anthropometrical and body composition profiles, glucose and lipid metabolism, liver, and pro- and anti-inflammatory biomarkers.
• 25(OH)D serum concentrations were measured with a competitive chemiluminescence immunoassay and defined as deficient (< 20 ng/mL), insufficient (21-29 ng/mL), or normal (> 30 ng/mL).

TAKEAWAY:

• The  levels correlated inversely with body mass index (BMI; standardized regression coefficient [beta], −0.177; P = .018), fat mass index (beta, −0.195; P = .011), and systolic blood pressure (beta, −0.137; P = .038), after adjusting for sex.
• Glucose metabolism markers (serum glucose and insulin concentrations, insulin/glucose ratio, and homeostatic model assessment of  index) also correlated inversely with vitamin D levels.
• The trend was similar for liver markers serum γ-glutamyl transferase and alkaline phosphatase) and the anti-inflammatory marker interleukin-4.
• BMI, waist/hip ratio, fat mass index, blood pressure, and levels of glucose, insulin, , and liver markers were higher in the 44 participants with vitamin D deficiency vs 41 participants with normal vitamin D levels.

IN PRACTICE:

“Collectively, these findings support the idea that 25(OH)D concentrations may be used as a useful marker of CVD status, which can be easily monitored in young individuals,” the authors wrote.

SOURCE:

This study was led by first author Francisco J. AmaroGahete, MD, PhD, from the Department of Physiology, Faculty of Medicine, University of Granada, Spain, who also holds positions in other institutions. It was published online in the Journal of Endocrinological Investigation.

LIMITATIONS:

This study could not establish causal relationships due to its cross-sectional design. The results might not apply to younger or older people from different locations and ethnic backgrounds. The gold standard method for analyzing vitamin D levels, liquid chromatography–mass spectrometry, was not used in this study.

DISCLOSURES:

This study was supported by the Spanish Ministry of Economy and Competitiveness, Spanish Ministry of Education, AstraZeneca HealthCare Foundation, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Circulating levels of serum 25-hydroxyvitamin D (25[OH]D) may be a marker of cardiovascular disease (CVD) risk in healthy young adults, small study finds.

METHODOLOGY:

• A secondary analysis of the Activating Brown Adipose Tissue Through Exercise (ACTIBATE) trial assessed the association between serum 25(OH)D levels and CVD risk factors.
• The cross-sectional study used baseline data of in 177 healthy sedentary adults ages 18-25 years (65% women; all White individuals), who were recruited between October 2015 and December 2016 from Granada, a region in the south of Spain.
• Study participants were nonsmokers, led a sedentary lifestyle, and did not have a prior history of CVD or chronic illnesses.
• The CVD risk factors included anthropometrical and body composition profiles, glucose and lipid metabolism, liver, and pro- and anti-inflammatory biomarkers.
• 25(OH)D serum concentrations were measured with a competitive chemiluminescence immunoassay and defined as deficient (< 20 ng/mL), insufficient (21-29 ng/mL), or normal (> 30 ng/mL).

TAKEAWAY:

• The  levels correlated inversely with body mass index (BMI; standardized regression coefficient [beta], −0.177; P = .018), fat mass index (beta, −0.195; P = .011), and systolic blood pressure (beta, −0.137; P = .038), after adjusting for sex.
• Glucose metabolism markers (serum glucose and insulin concentrations, insulin/glucose ratio, and homeostatic model assessment of  index) also correlated inversely with vitamin D levels.
• The trend was similar for liver markers serum γ-glutamyl transferase and alkaline phosphatase) and the anti-inflammatory marker interleukin-4.
• BMI, waist/hip ratio, fat mass index, blood pressure, and levels of glucose, insulin, , and liver markers were higher in the 44 participants with vitamin D deficiency vs 41 participants with normal vitamin D levels.

IN PRACTICE:

“Collectively, these findings support the idea that 25(OH)D concentrations may be used as a useful marker of CVD status, which can be easily monitored in young individuals,” the authors wrote.

SOURCE:

This study was led by first author Francisco J. AmaroGahete, MD, PhD, from the Department of Physiology, Faculty of Medicine, University of Granada, Spain, who also holds positions in other institutions. It was published online in the Journal of Endocrinological Investigation.

LIMITATIONS:

This study could not establish causal relationships due to its cross-sectional design. The results might not apply to younger or older people from different locations and ethnic backgrounds. The gold standard method for analyzing vitamin D levels, liquid chromatography–mass spectrometry, was not used in this study.

DISCLOSURES:

This study was supported by the Spanish Ministry of Economy and Competitiveness, Spanish Ministry of Education, AstraZeneca HealthCare Foundation, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Circulating levels of serum 25-hydroxyvitamin D (25[OH]D) may be a marker of cardiovascular disease (CVD) risk in healthy young adults, small study finds.

METHODOLOGY:

• A secondary analysis of the Activating Brown Adipose Tissue Through Exercise (ACTIBATE) trial assessed the association between serum 25(OH)D levels and CVD risk factors.
• The cross-sectional study used baseline data of in 177 healthy sedentary adults ages 18-25 years (65% women; all White individuals), who were recruited between October 2015 and December 2016 from Granada, a region in the south of Spain.
• Study participants were nonsmokers, led a sedentary lifestyle, and did not have a prior history of CVD or chronic illnesses.
• The CVD risk factors included anthropometrical and body composition profiles, glucose and lipid metabolism, liver, and pro- and anti-inflammatory biomarkers.
• 25(OH)D serum concentrations were measured with a competitive chemiluminescence immunoassay and defined as deficient (< 20 ng/mL), insufficient (21-29 ng/mL), or normal (> 30 ng/mL).

TAKEAWAY:

• The  levels correlated inversely with body mass index (BMI; standardized regression coefficient [beta], −0.177; P = .018), fat mass index (beta, −0.195; P = .011), and systolic blood pressure (beta, −0.137; P = .038), after adjusting for sex.
• Glucose metabolism markers (serum glucose and insulin concentrations, insulin/glucose ratio, and homeostatic model assessment of  index) also correlated inversely with vitamin D levels.
• The trend was similar for liver markers serum γ-glutamyl transferase and alkaline phosphatase) and the anti-inflammatory marker interleukin-4.
• BMI, waist/hip ratio, fat mass index, blood pressure, and levels of glucose, insulin, , and liver markers were higher in the 44 participants with vitamin D deficiency vs 41 participants with normal vitamin D levels.

IN PRACTICE:

“Collectively, these findings support the idea that 25(OH)D concentrations may be used as a useful marker of CVD status, which can be easily monitored in young individuals,” the authors wrote.

SOURCE:

This study was led by first author Francisco J. AmaroGahete, MD, PhD, from the Department of Physiology, Faculty of Medicine, University of Granada, Spain, who also holds positions in other institutions. It was published online in the Journal of Endocrinological Investigation.

LIMITATIONS:

This study could not establish causal relationships due to its cross-sectional design. The results might not apply to younger or older people from different locations and ethnic backgrounds. The gold standard method for analyzing vitamin D levels, liquid chromatography–mass spectrometry, was not used in this study.

DISCLOSURES:

This study was supported by the Spanish Ministry of Economy and Competitiveness, Spanish Ministry of Education, AstraZeneca HealthCare Foundation, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Patients with back pain that has persisted for less than 12 weeks have a high probability of substantial pain reduction over time, but patients with back pain that has persisted for 12 or more weeks have a lower chance of improvement, new data suggest.

In a systematic review and meta-analysis of 95 studies, pain score decreased by 35 points on a 100-point scale from baseline to 52 weeks among patients with acute pain (ie, pain lasting for less than 6 weeks). Patients with persistent pain (ie, pain lasting for more than 12 weeks but less than 52 weeks) had smaller improvements at 52 weeks, however. 

“The outcomes for acute pain are better than we thought they were,” study author Lorimer Moseley, AO, DSc, PhD, professor of clinical neurosciences and chair of physiotherapy at the University of South Australia in Adelaide, told this news organization. 

The study was published in the Canadian Medical Association Journal. 

Good Prognoses 

The current analysis represents an update to and advance on a 2012 systematic review and meta-analysis, said Moseley. That study found that patients with subacute low back pain and those with persistent low back pain had similar decreases in pain over 6 weeks. The previous analysis “may have resulted in improved outcomes in the persistent group,” the investigators wrote in the current analysis.

For the current study, the researchers examined 95 studies to understand the clinical course of acute, subacute (ie, lasting for 6 to less than 12 weeks), and persistent low back pain. They excluded retrospective cohorts and interventional studies, as well as studies of patients with low back pain for more than 12 months. The researchers also conducted meta-analyses on aggregate data, where possible, using pain and disability outcome data. 

In patients with acute pain, the mean pain score improved from 56 at baseline to 26 at 6 weeks and 21 at 52 weeks. Patients with subacute pain had a mean pain score of 63 at baseline that improved to 29 at 6 weeks and was maintained at 31 at 52 weeks. Patients with persistent pain had a mean pain score of 56 at baseline that improved to 48 at six weeks and 40 at 52 weeks.

“I don’t think we need to do any more studies to clarify recovery from acute back pain,” said Dr. Moseley. “For subacute back pain, I think there is a moderate to high level of certainty, so the prognosis is pretty good there. The bad news is that the data suggest that if someone’s got back pain 3 months after onset, the likelihood of recovery is much less, but those data are the ones we can’t be certain of on the basis of this meta-analysis.”

Dr. Moseley noted that the current analysis is not highly detailed, because individual patient data are absent. This is “the biggest limitation from a methodological perspective,” he said. “Individual patient analysis is a lot more powerful.”

Comprehensive Literature Search 

Commenting on the findings for this news organization, David Borenstein, MD, clinical professor of rheumatology at the George Washington University Medical Center and partner at Arthritis and Rheumatism Associates in Washington, DC, described the literature search as comprehensive. Dr. Borenstein did not participate in the study. The assessment of low back pain as either short-lived or lasting is worth investigating, he added, given that low back pain impairs a patient’s function and carries a hefty price tag at a societal level.

The study results suggest “that people with acute low back pain do pretty well, and people with subacute low back pain will do less well but still have a chance of healing,” said Dr. Borenstein. “People who have chronic low back pain do not do as well, and they have some increase in disability.” It would be important to develop ways to identify patients whose low back pain will persist beyond 3 months, as well as ways to identify the criteria or characteristics that might prevent those patients from having prolonged difficulties and persistent low back pain, he added.

Dr. Borenstein noted that the authors failed to mention specific approaches that could decrease progression from subacute to persistent low back pain. “They really don’t point anyone in a direction to what would make a difference,” he said. “It would have really improved the impact of the paper if they had seen anything along the way in their review of these articles that might have suggested how someone or a group might have been able to impact this progression.” 

The study was funded by supported by a National Health and Medical Research Council Leadership Investigator Grant to Dr. Moseley. Dr. Moseley and Dr. Borenstein reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Patients with back pain that has persisted for less than 12 weeks have a high probability of substantial pain reduction over time, but patients with back pain that has persisted for 12 or more weeks have a lower chance of improvement, new data suggest.

In a systematic review and meta-analysis of 95 studies, pain score decreased by 35 points on a 100-point scale from baseline to 52 weeks among patients with acute pain (ie, pain lasting for less than 6 weeks). Patients with persistent pain (ie, pain lasting for more than 12 weeks but less than 52 weeks) had smaller improvements at 52 weeks, however. 

“The outcomes for acute pain are better than we thought they were,” study author Lorimer Moseley, AO, DSc, PhD, professor of clinical neurosciences and chair of physiotherapy at the University of South Australia in Adelaide, told this news organization. 

The study was published in the Canadian Medical Association Journal. 

Good Prognoses 

The current analysis represents an update to and advance on a 2012 systematic review and meta-analysis, said Moseley. That study found that patients with subacute low back pain and those with persistent low back pain had similar decreases in pain over 6 weeks. The previous analysis “may have resulted in improved outcomes in the persistent group,” the investigators wrote in the current analysis.

For the current study, the researchers examined 95 studies to understand the clinical course of acute, subacute (ie, lasting for 6 to less than 12 weeks), and persistent low back pain. They excluded retrospective cohorts and interventional studies, as well as studies of patients with low back pain for more than 12 months. The researchers also conducted meta-analyses on aggregate data, where possible, using pain and disability outcome data. 

In patients with acute pain, the mean pain score improved from 56 at baseline to 26 at 6 weeks and 21 at 52 weeks. Patients with subacute pain had a mean pain score of 63 at baseline that improved to 29 at 6 weeks and was maintained at 31 at 52 weeks. Patients with persistent pain had a mean pain score of 56 at baseline that improved to 48 at six weeks and 40 at 52 weeks.

“I don’t think we need to do any more studies to clarify recovery from acute back pain,” said Dr. Moseley. “For subacute back pain, I think there is a moderate to high level of certainty, so the prognosis is pretty good there. The bad news is that the data suggest that if someone’s got back pain 3 months after onset, the likelihood of recovery is much less, but those data are the ones we can’t be certain of on the basis of this meta-analysis.”

Dr. Moseley noted that the current analysis is not highly detailed, because individual patient data are absent. This is “the biggest limitation from a methodological perspective,” he said. “Individual patient analysis is a lot more powerful.”

Comprehensive Literature Search 

Commenting on the findings for this news organization, David Borenstein, MD, clinical professor of rheumatology at the George Washington University Medical Center and partner at Arthritis and Rheumatism Associates in Washington, DC, described the literature search as comprehensive. Dr. Borenstein did not participate in the study. The assessment of low back pain as either short-lived or lasting is worth investigating, he added, given that low back pain impairs a patient’s function and carries a hefty price tag at a societal level.

The study results suggest “that people with acute low back pain do pretty well, and people with subacute low back pain will do less well but still have a chance of healing,” said Dr. Borenstein. “People who have chronic low back pain do not do as well, and they have some increase in disability.” It would be important to develop ways to identify patients whose low back pain will persist beyond 3 months, as well as ways to identify the criteria or characteristics that might prevent those patients from having prolonged difficulties and persistent low back pain, he added.

Dr. Borenstein noted that the authors failed to mention specific approaches that could decrease progression from subacute to persistent low back pain. “They really don’t point anyone in a direction to what would make a difference,” he said. “It would have really improved the impact of the paper if they had seen anything along the way in their review of these articles that might have suggested how someone or a group might have been able to impact this progression.” 

The study was funded by supported by a National Health and Medical Research Council Leadership Investigator Grant to Dr. Moseley. Dr. Moseley and Dr. Borenstein reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Patients with back pain that has persisted for less than 12 weeks have a high probability of substantial pain reduction over time, but patients with back pain that has persisted for 12 or more weeks have a lower chance of improvement, new data suggest.

In a systematic review and meta-analysis of 95 studies, pain score decreased by 35 points on a 100-point scale from baseline to 52 weeks among patients with acute pain (ie, pain lasting for less than 6 weeks). Patients with persistent pain (ie, pain lasting for more than 12 weeks but less than 52 weeks) had smaller improvements at 52 weeks, however. 

“The outcomes for acute pain are better than we thought they were,” study author Lorimer Moseley, AO, DSc, PhD, professor of clinical neurosciences and chair of physiotherapy at the University of South Australia in Adelaide, told this news organization. 

The study was published in the Canadian Medical Association Journal. 

Good Prognoses 

The current analysis represents an update to and advance on a 2012 systematic review and meta-analysis, said Moseley. That study found that patients with subacute low back pain and those with persistent low back pain had similar decreases in pain over 6 weeks. The previous analysis “may have resulted in improved outcomes in the persistent group,” the investigators wrote in the current analysis.

For the current study, the researchers examined 95 studies to understand the clinical course of acute, subacute (ie, lasting for 6 to less than 12 weeks), and persistent low back pain. They excluded retrospective cohorts and interventional studies, as well as studies of patients with low back pain for more than 12 months. The researchers also conducted meta-analyses on aggregate data, where possible, using pain and disability outcome data. 

In patients with acute pain, the mean pain score improved from 56 at baseline to 26 at 6 weeks and 21 at 52 weeks. Patients with subacute pain had a mean pain score of 63 at baseline that improved to 29 at 6 weeks and was maintained at 31 at 52 weeks. Patients with persistent pain had a mean pain score of 56 at baseline that improved to 48 at six weeks and 40 at 52 weeks.

“I don’t think we need to do any more studies to clarify recovery from acute back pain,” said Dr. Moseley. “For subacute back pain, I think there is a moderate to high level of certainty, so the prognosis is pretty good there. The bad news is that the data suggest that if someone’s got back pain 3 months after onset, the likelihood of recovery is much less, but those data are the ones we can’t be certain of on the basis of this meta-analysis.”

Dr. Moseley noted that the current analysis is not highly detailed, because individual patient data are absent. This is “the biggest limitation from a methodological perspective,” he said. “Individual patient analysis is a lot more powerful.”

Comprehensive Literature Search 

Commenting on the findings for this news organization, David Borenstein, MD, clinical professor of rheumatology at the George Washington University Medical Center and partner at Arthritis and Rheumatism Associates in Washington, DC, described the literature search as comprehensive. Dr. Borenstein did not participate in the study. The assessment of low back pain as either short-lived or lasting is worth investigating, he added, given that low back pain impairs a patient’s function and carries a hefty price tag at a societal level.

The study results suggest “that people with acute low back pain do pretty well, and people with subacute low back pain will do less well but still have a chance of healing,” said Dr. Borenstein. “People who have chronic low back pain do not do as well, and they have some increase in disability.” It would be important to develop ways to identify patients whose low back pain will persist beyond 3 months, as well as ways to identify the criteria or characteristics that might prevent those patients from having prolonged difficulties and persistent low back pain, he added.

Dr. Borenstein noted that the authors failed to mention specific approaches that could decrease progression from subacute to persistent low back pain. “They really don’t point anyone in a direction to what would make a difference,” he said. “It would have really improved the impact of the paper if they had seen anything along the way in their review of these articles that might have suggested how someone or a group might have been able to impact this progression.” 

The study was funded by supported by a National Health and Medical Research Council Leadership Investigator Grant to Dr. Moseley. Dr. Moseley and Dr. Borenstein reported no relevant disclosures.

A version of this article appeared on Medscape.com.

People who mainly sit while on the job increase their risk of dying of cardiovascular disease (CVD) by more than one third compared with peers who largely don’t sit at work, new research shows. 

However, daily breaks from sitting and leisure-time activity can help mitigate the “serious” risks associated with prolonged occupational sitting, the researchers say. 

“As part of modern lifestyles, prolonged occupational sitting is considered normal and has not received due attention, even though its deleterious effect on health outcomes has been demonstrated,” wrote the authors, led by Wayne Gao, PhD, with Taipei Medical University College of Public Health, Taipei City, Taiwan. 

“The importance of physical activity and moving around can never be overstated,” Michelle Bloom, MD, director of the cardio-oncology program at NYU Langone Health in New York, who wasn’t involved in the study, told this news organization. 

“As a cardiologist, I bring this up at almost every visit with every patient regardless of why they’re seeing me, because I think that patients respond better when their doctor says it than when they just kind of know it in the back of their mind,” said Dr. Bloom, who is also a professor in the Division of Cardiology, NYU Grossman Long Island School of Medicine, New York. 

The study was published online in JAMA Network Open.

Prolonged Sitting Hard on the Heart 

2020 marked the first time that guidelines on physical activity from the World Health Organization recommended reducing sedentary behaviors owing to their health consequences. Less is known on the specific association of prolonged occupational sitting with health outcomes, especially in the context of low physical activity. 

For their study, Dr. Gao and colleagues quantified health risks associated with prolonged sitting on the job and determined whether a certain threshold of physical activity may attenuate this risk. 

Participants included 481,688 adults (mean age, 39 years; 53% women) in a health surveillance program in Taiwan. Data on occupational sitting, leisure-time physical activity, lifestyle, and metabolic parameters were collected. 

During an average follow up of nearly 13 years, 26,257 participants died; more than half (57%) of the deaths occurred in individuals who mostly sat at work. There were 5371 CVD-related deaths, with 60% occurring in the mostly sitting group. 

In multivariate analysis that adjusted for sex, age, education, smoking, drinking, and body mass index, adults who mostly sat at work had a 16% higher risk of dying of any cause (hazard ratio [HR], 1.16; 95% CI, 1.11-1.20) and a 34% increased risk of dying of CVD (HR, 1.34; 95% CI, 1.22-1.46) compared with those who mostly did not sit at work. 

Adults who mostly alternated between sitting and not sitting at work were not at increased risk of all-cause mortality compared with individuals who mostly did not at work (HR, 1.01; 95% CI, 0.97-1.05). 

Among adults who mostly sat at work and engaged in low (15-29 minutes) or no (< 15 minutes) daily leisure-time activity, increasing activity by 15 and 30 minutes per day, respectively, lowered the risk for mortality to a level similar to that of inactive individuals who mostly do not sit at work. 

“Overall, our findings from a large prospective cohort help to strengthen the increasingly accumulating evidence linking a sedentary lifestyle and health risks,” the authors wrote. 

“Systemic changes, such as more frequent breaks, standing desks, designated workplace areas for physical activity, and gym membership benefits, can help reduce risk,” they added. 

Simple Yet Profound Message 

Reached for comment, Anu Lala, MD, with Icahn School of Medicine at Mount Sinai and Mount Sinai Fuster Heart Hospital in New York, said this study provides a “simple yet profound message” about the dangers of prolonged sitting. 

The finding of a 16% higher all-cause mortality in those who mostly sat at work after adjustment for major risk factors is “pretty remarkable. And for CVD mortality, it’s double that,” Dr. Lala told this news organization.

“I think we undervalue the importance of movement, however simple it is. Even simple actions, like squatting and standing up have benefits for the heart,” Dr. Lala added. 

Dr. Bloom said she tells her patients, “You don’t have to go out tomorrow and run a marathon. Just get up a few times a day, walk a few laps in your office, walk back and forth from the mailbox, walk up and down your steps a couple of times — just do something more than you’re doing already.”

The study had no commercial funding. Dr. Gao and Dr. Bloom have no relevant disclosures. Dr. Lala has serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Novartis, AstraZeneca, Merck, Bayer, Novo Nordisk, Cordio, Zoll, and Sequana Medical.

A version of this article appeared on Medscape.com.

People who mainly sit while on the job increase their risk of dying of cardiovascular disease (CVD) by more than one third compared with peers who largely don’t sit at work, new research shows. 

However, daily breaks from sitting and leisure-time activity can help mitigate the “serious” risks associated with prolonged occupational sitting, the researchers say. 

“As part of modern lifestyles, prolonged occupational sitting is considered normal and has not received due attention, even though its deleterious effect on health outcomes has been demonstrated,” wrote the authors, led by Wayne Gao, PhD, with Taipei Medical University College of Public Health, Taipei City, Taiwan. 

“The importance of physical activity and moving around can never be overstated,” Michelle Bloom, MD, director of the cardio-oncology program at NYU Langone Health in New York, who wasn’t involved in the study, told this news organization. 

“As a cardiologist, I bring this up at almost every visit with every patient regardless of why they’re seeing me, because I think that patients respond better when their doctor says it than when they just kind of know it in the back of their mind,” said Dr. Bloom, who is also a professor in the Division of Cardiology, NYU Grossman Long Island School of Medicine, New York. 

The study was published online in JAMA Network Open.

Prolonged Sitting Hard on the Heart 

2020 marked the first time that guidelines on physical activity from the World Health Organization recommended reducing sedentary behaviors owing to their health consequences. Less is known on the specific association of prolonged occupational sitting with health outcomes, especially in the context of low physical activity. 

For their study, Dr. Gao and colleagues quantified health risks associated with prolonged sitting on the job and determined whether a certain threshold of physical activity may attenuate this risk. 

Participants included 481,688 adults (mean age, 39 years; 53% women) in a health surveillance program in Taiwan. Data on occupational sitting, leisure-time physical activity, lifestyle, and metabolic parameters were collected. 

During an average follow up of nearly 13 years, 26,257 participants died; more than half (57%) of the deaths occurred in individuals who mostly sat at work. There were 5371 CVD-related deaths, with 60% occurring in the mostly sitting group. 

In multivariate analysis that adjusted for sex, age, education, smoking, drinking, and body mass index, adults who mostly sat at work had a 16% higher risk of dying of any cause (hazard ratio [HR], 1.16; 95% CI, 1.11-1.20) and a 34% increased risk of dying of CVD (HR, 1.34; 95% CI, 1.22-1.46) compared with those who mostly did not sit at work. 

Adults who mostly alternated between sitting and not sitting at work were not at increased risk of all-cause mortality compared with individuals who mostly did not at work (HR, 1.01; 95% CI, 0.97-1.05). 

Among adults who mostly sat at work and engaged in low (15-29 minutes) or no (< 15 minutes) daily leisure-time activity, increasing activity by 15 and 30 minutes per day, respectively, lowered the risk for mortality to a level similar to that of inactive individuals who mostly do not sit at work. 

“Overall, our findings from a large prospective cohort help to strengthen the increasingly accumulating evidence linking a sedentary lifestyle and health risks,” the authors wrote. 

“Systemic changes, such as more frequent breaks, standing desks, designated workplace areas for physical activity, and gym membership benefits, can help reduce risk,” they added. 

Simple Yet Profound Message 

Reached for comment, Anu Lala, MD, with Icahn School of Medicine at Mount Sinai and Mount Sinai Fuster Heart Hospital in New York, said this study provides a “simple yet profound message” about the dangers of prolonged sitting. 

The finding of a 16% higher all-cause mortality in those who mostly sat at work after adjustment for major risk factors is “pretty remarkable. And for CVD mortality, it’s double that,” Dr. Lala told this news organization.

“I think we undervalue the importance of movement, however simple it is. Even simple actions, like squatting and standing up have benefits for the heart,” Dr. Lala added. 

Dr. Bloom said she tells her patients, “You don’t have to go out tomorrow and run a marathon. Just get up a few times a day, walk a few laps in your office, walk back and forth from the mailbox, walk up and down your steps a couple of times — just do something more than you’re doing already.”

The study had no commercial funding. Dr. Gao and Dr. Bloom have no relevant disclosures. Dr. Lala has serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Novartis, AstraZeneca, Merck, Bayer, Novo Nordisk, Cordio, Zoll, and Sequana Medical.

A version of this article appeared on Medscape.com.

People who mainly sit while on the job increase their risk of dying of cardiovascular disease (CVD) by more than one third compared with peers who largely don’t sit at work, new research shows. 

However, daily breaks from sitting and leisure-time activity can help mitigate the “serious” risks associated with prolonged occupational sitting, the researchers say. 

“As part of modern lifestyles, prolonged occupational sitting is considered normal and has not received due attention, even though its deleterious effect on health outcomes has been demonstrated,” wrote the authors, led by Wayne Gao, PhD, with Taipei Medical University College of Public Health, Taipei City, Taiwan. 

“The importance of physical activity and moving around can never be overstated,” Michelle Bloom, MD, director of the cardio-oncology program at NYU Langone Health in New York, who wasn’t involved in the study, told this news organization. 

“As a cardiologist, I bring this up at almost every visit with every patient regardless of why they’re seeing me, because I think that patients respond better when their doctor says it than when they just kind of know it in the back of their mind,” said Dr. Bloom, who is also a professor in the Division of Cardiology, NYU Grossman Long Island School of Medicine, New York. 

The study was published online in JAMA Network Open.

Prolonged Sitting Hard on the Heart 

2020 marked the first time that guidelines on physical activity from the World Health Organization recommended reducing sedentary behaviors owing to their health consequences. Less is known on the specific association of prolonged occupational sitting with health outcomes, especially in the context of low physical activity. 

For their study, Dr. Gao and colleagues quantified health risks associated with prolonged sitting on the job and determined whether a certain threshold of physical activity may attenuate this risk. 

Participants included 481,688 adults (mean age, 39 years; 53% women) in a health surveillance program in Taiwan. Data on occupational sitting, leisure-time physical activity, lifestyle, and metabolic parameters were collected. 

During an average follow up of nearly 13 years, 26,257 participants died; more than half (57%) of the deaths occurred in individuals who mostly sat at work. There were 5371 CVD-related deaths, with 60% occurring in the mostly sitting group. 

In multivariate analysis that adjusted for sex, age, education, smoking, drinking, and body mass index, adults who mostly sat at work had a 16% higher risk of dying of any cause (hazard ratio [HR], 1.16; 95% CI, 1.11-1.20) and a 34% increased risk of dying of CVD (HR, 1.34; 95% CI, 1.22-1.46) compared with those who mostly did not sit at work. 

Adults who mostly alternated between sitting and not sitting at work were not at increased risk of all-cause mortality compared with individuals who mostly did not at work (HR, 1.01; 95% CI, 0.97-1.05). 

Among adults who mostly sat at work and engaged in low (15-29 minutes) or no (< 15 minutes) daily leisure-time activity, increasing activity by 15 and 30 minutes per day, respectively, lowered the risk for mortality to a level similar to that of inactive individuals who mostly do not sit at work. 

“Overall, our findings from a large prospective cohort help to strengthen the increasingly accumulating evidence linking a sedentary lifestyle and health risks,” the authors wrote. 

“Systemic changes, such as more frequent breaks, standing desks, designated workplace areas for physical activity, and gym membership benefits, can help reduce risk,” they added. 

Simple Yet Profound Message 

Reached for comment, Anu Lala, MD, with Icahn School of Medicine at Mount Sinai and Mount Sinai Fuster Heart Hospital in New York, said this study provides a “simple yet profound message” about the dangers of prolonged sitting. 

The finding of a 16% higher all-cause mortality in those who mostly sat at work after adjustment for major risk factors is “pretty remarkable. And for CVD mortality, it’s double that,” Dr. Lala told this news organization.

“I think we undervalue the importance of movement, however simple it is. Even simple actions, like squatting and standing up have benefits for the heart,” Dr. Lala added. 

Dr. Bloom said she tells her patients, “You don’t have to go out tomorrow and run a marathon. Just get up a few times a day, walk a few laps in your office, walk back and forth from the mailbox, walk up and down your steps a couple of times — just do something more than you’re doing already.”

The study had no commercial funding. Dr. Gao and Dr. Bloom have no relevant disclosures. Dr. Lala has serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Novartis, AstraZeneca, Merck, Bayer, Novo Nordisk, Cordio, Zoll, and Sequana Medical.

A version of this article appeared on Medscape.com.

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

TOPLINE:

Artificial intelligence (AI) boosts the screening rate for potentially blinding diabetes eye disorders in a diabetes clinic compared with referral to an eye care provider (ECP) in a racially and ethnically diverse youth population with diabetes.

METHODOLOGY:

• Although early screening and treatment can prevent diabetic eye diseases (DEDs), many people with diabetes in the United States lack access to and knowledge about diabetic eye exams.
• The  trial included 164 patients aged 8-21 years (58% female, 35% Black, and 6% Hispanic) with type 1 or 2 diabetes with no known DED and no diabetic eye exam in the last 6 months.
• In a diabetes clinic, patients were randomly assigned to an AI diabetic eye exam (intervention arm) then and there or to standard of care, referred to an ECP with scripted educational material (control).
• Participants in the intervention arm underwent the 5- to 10-minute autonomous AI diabetic eye exam without pharmacologic dilation. The results were generated immediately as either “DED present” or “DED absent.”
• The primary outcome was the completion rate of documented diabetic eye exams within 6 months (“primary gap closure rate”), either by AI or going to the ECP. The secondary outcome was ECP follow-up by intervention participants with DED (intervention) and all control patients.

TAKEAWAY:

• Within 6 months, all the participants (100%) in the intervention arm completed their diabetic eye exam, a primary care gap closure rate of 100% (95% CI, 96%-100%).
• The rate of primary care gap closure was significantly higher in the intervention vs control arm (100% vs 22%; P < .001).
• In the intervention arm, 64% of patients with DED followed up with an eye care provider within 6 months compared with a mere 22% participants in the control arm (P < .001).
• Participants reported high levels of satisfaction with autonomous AI, with 92.5% expressing satisfaction with the exam’s duration and 96% expressing satisfaction with the whole experience.

IN PRACTICE:

“Autonomous AI increases diabetic eye exam completion rates and closes this care gap in a racially and ethnically diverse population of youth with diabetes, compared to standard of care,” the authors wrote.

SOURCE:

This study, which was led by Risa M. Wolf, MD, department of pediatrics, division of endocrinology, Johns Hopkins School of Medicine, Baltimore, was published online on January 11, 2024, in Nature Communications.

LIMITATIONS:

This study used autonomous AI in the youth although it’s not approved by the US Food and Drug Administration for use in individuals aged 21 years and younger. Some of the participants in this study were already familiar with autonomous AI diabetic eye exams, which might have contributed to their willingness to participate in the current study. The autonomous AI used in the study was shown to have a lack of racial and ethnic bias, but any AI bias caused by differences in retinal pigment has potential to increase rather than decrease health disparities.

DISCLOSURES:

The clinical trial was supported by the National Eye Institute of the National Institutes of Health and the Diabetes Research Connection. Wolf, the lead author, declared receiving research support from Boehringer Ingelheim and Novo Nordisk outside the submitted work. Coauthor Michael D. Abramoff, MD, declared serving in various roles such as investor, director, and consultant for Digital Diagnostics Inc., as well as other ties with many sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Artificial intelligence (AI) boosts the screening rate for potentially blinding diabetes eye disorders in a diabetes clinic compared with referral to an eye care provider (ECP) in a racially and ethnically diverse youth population with diabetes.

METHODOLOGY:

• Although early screening and treatment can prevent diabetic eye diseases (DEDs), many people with diabetes in the United States lack access to and knowledge about diabetic eye exams.
• The  trial included 164 patients aged 8-21 years (58% female, 35% Black, and 6% Hispanic) with type 1 or 2 diabetes with no known DED and no diabetic eye exam in the last 6 months.
• In a diabetes clinic, patients were randomly assigned to an AI diabetic eye exam (intervention arm) then and there or to standard of care, referred to an ECP with scripted educational material (control).
• Participants in the intervention arm underwent the 5- to 10-minute autonomous AI diabetic eye exam without pharmacologic dilation. The results were generated immediately as either “DED present” or “DED absent.”
• The primary outcome was the completion rate of documented diabetic eye exams within 6 months (“primary gap closure rate”), either by AI or going to the ECP. The secondary outcome was ECP follow-up by intervention participants with DED (intervention) and all control patients.

TAKEAWAY:

• Within 6 months, all the participants (100%) in the intervention arm completed their diabetic eye exam, a primary care gap closure rate of 100% (95% CI, 96%-100%).
• The rate of primary care gap closure was significantly higher in the intervention vs control arm (100% vs 22%; P < .001).
• In the intervention arm, 64% of patients with DED followed up with an eye care provider within 6 months compared with a mere 22% participants in the control arm (P < .001).
• Participants reported high levels of satisfaction with autonomous AI, with 92.5% expressing satisfaction with the exam’s duration and 96% expressing satisfaction with the whole experience.

IN PRACTICE:

“Autonomous AI increases diabetic eye exam completion rates and closes this care gap in a racially and ethnically diverse population of youth with diabetes, compared to standard of care,” the authors wrote.

SOURCE:

This study, which was led by Risa M. Wolf, MD, department of pediatrics, division of endocrinology, Johns Hopkins School of Medicine, Baltimore, was published online on January 11, 2024, in Nature Communications.

LIMITATIONS:

This study used autonomous AI in the youth although it’s not approved by the US Food and Drug Administration for use in individuals aged 21 years and younger. Some of the participants in this study were already familiar with autonomous AI diabetic eye exams, which might have contributed to their willingness to participate in the current study. The autonomous AI used in the study was shown to have a lack of racial and ethnic bias, but any AI bias caused by differences in retinal pigment has potential to increase rather than decrease health disparities.

DISCLOSURES:

The clinical trial was supported by the National Eye Institute of the National Institutes of Health and the Diabetes Research Connection. Wolf, the lead author, declared receiving research support from Boehringer Ingelheim and Novo Nordisk outside the submitted work. Coauthor Michael D. Abramoff, MD, declared serving in various roles such as investor, director, and consultant for Digital Diagnostics Inc., as well as other ties with many sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Artificial intelligence (AI) boosts the screening rate for potentially blinding diabetes eye disorders in a diabetes clinic compared with referral to an eye care provider (ECP) in a racially and ethnically diverse youth population with diabetes.

METHODOLOGY:

• Although early screening and treatment can prevent diabetic eye diseases (DEDs), many people with diabetes in the United States lack access to and knowledge about diabetic eye exams.
• The  trial included 164 patients aged 8-21 years (58% female, 35% Black, and 6% Hispanic) with type 1 or 2 diabetes with no known DED and no diabetic eye exam in the last 6 months.
• In a diabetes clinic, patients were randomly assigned to an AI diabetic eye exam (intervention arm) then and there or to standard of care, referred to an ECP with scripted educational material (control).
• Participants in the intervention arm underwent the 5- to 10-minute autonomous AI diabetic eye exam without pharmacologic dilation. The results were generated immediately as either “DED present” or “DED absent.”
• The primary outcome was the completion rate of documented diabetic eye exams within 6 months (“primary gap closure rate”), either by AI or going to the ECP. The secondary outcome was ECP follow-up by intervention participants with DED (intervention) and all control patients.

TAKEAWAY:

• Within 6 months, all the participants (100%) in the intervention arm completed their diabetic eye exam, a primary care gap closure rate of 100% (95% CI, 96%-100%).
• The rate of primary care gap closure was significantly higher in the intervention vs control arm (100% vs 22%; P < .001).
• In the intervention arm, 64% of patients with DED followed up with an eye care provider within 6 months compared with a mere 22% participants in the control arm (P < .001).
• Participants reported high levels of satisfaction with autonomous AI, with 92.5% expressing satisfaction with the exam’s duration and 96% expressing satisfaction with the whole experience.

IN PRACTICE:

“Autonomous AI increases diabetic eye exam completion rates and closes this care gap in a racially and ethnically diverse population of youth with diabetes, compared to standard of care,” the authors wrote.

SOURCE:

This study, which was led by Risa M. Wolf, MD, department of pediatrics, division of endocrinology, Johns Hopkins School of Medicine, Baltimore, was published online on January 11, 2024, in Nature Communications.

LIMITATIONS:

This study used autonomous AI in the youth although it’s not approved by the US Food and Drug Administration for use in individuals aged 21 years and younger. Some of the participants in this study were already familiar with autonomous AI diabetic eye exams, which might have contributed to their willingness to participate in the current study. The autonomous AI used in the study was shown to have a lack of racial and ethnic bias, but any AI bias caused by differences in retinal pigment has potential to increase rather than decrease health disparities.

DISCLOSURES:

The clinical trial was supported by the National Eye Institute of the National Institutes of Health and the Diabetes Research Connection. Wolf, the lead author, declared receiving research support from Boehringer Ingelheim and Novo Nordisk outside the submitted work. Coauthor Michael D. Abramoff, MD, declared serving in various roles such as investor, director, and consultant for Digital Diagnostics Inc., as well as other ties with many sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

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

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

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

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

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

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

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

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

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

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

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

TOPLINE:

Less than half of patients with rheumatoid arthritis (RA) initiating a first-line tumor necrosis factor inhibitor (TNFi) in clinical practice had a recorded composite disease activity assessment at the start of the treatment, and many remained on that treatment for years without evidence recorded in their electronic medical record of achieving low-disease activity or remission.

METHODOLOGY:

• Researchers reviewed data from 1651 adults aged 18 years and older with moderate to severe RA at baseline or follow-up in the electronic medical record database of the American Rheumatology Network, a large community network of independent practices with > 200 rheumatologists across the United States.
• Patients received a TNFi as their first advanced therapy between January 2014 and August 2021 and were assessed for measurement of disease activity with the Clinical Disease Activity Index (CDAI) or Routine Assessment of Patient Index Data 3 (RAPID3) at baseline and follow-up visits.

TAKEAWAY:

• Among the patients with moderate to severe RA, 47.2% of patients remained on first-line TNFi therapy 1 year after initiation despite no evidence of achieving treatment targets of low disease activity or remission (defined as CDAI ≤ 10 and/or RAPID3 ≤ 2).
• Approximately one third of patients remained on TNFi therapy for 2 (38.1%) or 3 (35.4%) years after initiation despite not achieving these targets. The median times to TNFi discontinuation was 30.4 months and to subsequent therapy initiation 68.3 months.
• A total of 52% discontinued their initial TNFi during the study period; among those who started a second therapy, 15% restarted the same TNFi, 45.6% started another TNFi, 27.6% started a non-TNFi biologic, and 11.5% started a Janus kinase inhibitor.
• The most common reported reasons for discontinuation were a combination of efficacy and intolerance, efficacy only, and intolerance only (26.9%, 25.3%, and 20.3%, respectively).
• Persistent pain was the most common reason for efficacy-related discontinuation (39.0%), followed by persistent inflammation/swelling and overall general discomfort (31.8% for both).

IN PRACTICE:

“Consistent monitoring of treatment response and timely switch to effective therapy as appropriate is needed in patients with RA initiating their first advanced therapies,” the researchers wrote.

SOURCE:

First author Colin Edgerton, MD, of Articularis Healthcare Group and American Rheumatology Network, Charleston, South Carolina, reported their work on January 14, 2024, in ACR Open Rheumatology.

LIMITATIONS:

The findings were limited by several factors including the retrospective design, incomplete data from electronic medical records, and reliance on physician documentation for drivers of discontinuation.

DISCLOSURES:

The study was supported by AbbVie. Lead author Edgerton also disclosed relationships with Novartis and Boehringer Ingelheim.

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

TOPLINE:

Less than half of patients with rheumatoid arthritis (RA) initiating a first-line tumor necrosis factor inhibitor (TNFi) in clinical practice had a recorded composite disease activity assessment at the start of the treatment, and many remained on that treatment for years without evidence recorded in their electronic medical record of achieving low-disease activity or remission.

METHODOLOGY:

• Researchers reviewed data from 1651 adults aged 18 years and older with moderate to severe RA at baseline or follow-up in the electronic medical record database of the American Rheumatology Network, a large community network of independent practices with > 200 rheumatologists across the United States.
• Patients received a TNFi as their first advanced therapy between January 2014 and August 2021 and were assessed for measurement of disease activity with the Clinical Disease Activity Index (CDAI) or Routine Assessment of Patient Index Data 3 (RAPID3) at baseline and follow-up visits.

TAKEAWAY:

• Among the patients with moderate to severe RA, 47.2% of patients remained on first-line TNFi therapy 1 year after initiation despite no evidence of achieving treatment targets of low disease activity or remission (defined as CDAI ≤ 10 and/or RAPID3 ≤ 2).
• Approximately one third of patients remained on TNFi therapy for 2 (38.1%) or 3 (35.4%) years after initiation despite not achieving these targets. The median times to TNFi discontinuation was 30.4 months and to subsequent therapy initiation 68.3 months.
• A total of 52% discontinued their initial TNFi during the study period; among those who started a second therapy, 15% restarted the same TNFi, 45.6% started another TNFi, 27.6% started a non-TNFi biologic, and 11.5% started a Janus kinase inhibitor.
• The most common reported reasons for discontinuation were a combination of efficacy and intolerance, efficacy only, and intolerance only (26.9%, 25.3%, and 20.3%, respectively).
• Persistent pain was the most common reason for efficacy-related discontinuation (39.0%), followed by persistent inflammation/swelling and overall general discomfort (31.8% for both).

IN PRACTICE:

“Consistent monitoring of treatment response and timely switch to effective therapy as appropriate is needed in patients with RA initiating their first advanced therapies,” the researchers wrote.

SOURCE:

First author Colin Edgerton, MD, of Articularis Healthcare Group and American Rheumatology Network, Charleston, South Carolina, reported their work on January 14, 2024, in ACR Open Rheumatology.

LIMITATIONS:

The findings were limited by several factors including the retrospective design, incomplete data from electronic medical records, and reliance on physician documentation for drivers of discontinuation.

DISCLOSURES:

The study was supported by AbbVie. Lead author Edgerton also disclosed relationships with Novartis and Boehringer Ingelheim.

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

TOPLINE:

Less than half of patients with rheumatoid arthritis (RA) initiating a first-line tumor necrosis factor inhibitor (TNFi) in clinical practice had a recorded composite disease activity assessment at the start of the treatment, and many remained on that treatment for years without evidence recorded in their electronic medical record of achieving low-disease activity or remission.

METHODOLOGY:

• Researchers reviewed data from 1651 adults aged 18 years and older with moderate to severe RA at baseline or follow-up in the electronic medical record database of the American Rheumatology Network, a large community network of independent practices with > 200 rheumatologists across the United States.
• Patients received a TNFi as their first advanced therapy between January 2014 and August 2021 and were assessed for measurement of disease activity with the Clinical Disease Activity Index (CDAI) or Routine Assessment of Patient Index Data 3 (RAPID3) at baseline and follow-up visits.

TAKEAWAY:

• Among the patients with moderate to severe RA, 47.2% of patients remained on first-line TNFi therapy 1 year after initiation despite no evidence of achieving treatment targets of low disease activity or remission (defined as CDAI ≤ 10 and/or RAPID3 ≤ 2).
• Approximately one third of patients remained on TNFi therapy for 2 (38.1%) or 3 (35.4%) years after initiation despite not achieving these targets. The median times to TNFi discontinuation was 30.4 months and to subsequent therapy initiation 68.3 months.
• A total of 52% discontinued their initial TNFi during the study period; among those who started a second therapy, 15% restarted the same TNFi, 45.6% started another TNFi, 27.6% started a non-TNFi biologic, and 11.5% started a Janus kinase inhibitor.
• The most common reported reasons for discontinuation were a combination of efficacy and intolerance, efficacy only, and intolerance only (26.9%, 25.3%, and 20.3%, respectively).
• Persistent pain was the most common reason for efficacy-related discontinuation (39.0%), followed by persistent inflammation/swelling and overall general discomfort (31.8% for both).

IN PRACTICE:

“Consistent monitoring of treatment response and timely switch to effective therapy as appropriate is needed in patients with RA initiating their first advanced therapies,” the researchers wrote.

SOURCE:

First author Colin Edgerton, MD, of Articularis Healthcare Group and American Rheumatology Network, Charleston, South Carolina, reported their work on January 14, 2024, in ACR Open Rheumatology.

LIMITATIONS:

The findings were limited by several factors including the retrospective design, incomplete data from electronic medical records, and reliance on physician documentation for drivers of discontinuation.

DISCLOSURES:

The study was supported by AbbVie. Lead author Edgerton also disclosed relationships with Novartis and Boehringer Ingelheim.

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