Liam Davenport

Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.

But why? A new analysis finds that the difference can only partly be explained by risky behaviors and carcinogenic exposure.

“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.

“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.

The study was published online in the journal Cancer.

“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.

In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.

“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.

“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
 

Comprehensive analyses

The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.

This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”

However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.

The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.

Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.

“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
 

Details of the analysis 

In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.

However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.

Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.

They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).

The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.

After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).

After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.

The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.

After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.

In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.

The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.

Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.

These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.

There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.

Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”

“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.

“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.

The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.

The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.

No other relevant financial relationships were declared.

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

Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.

But why? A new analysis finds that the difference can only partly be explained by risky behaviors and carcinogenic exposure.

“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.

“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.

The study was published online in the journal Cancer.

“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.

In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.

“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.

“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
 

Comprehensive analyses

The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.

This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”

However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.

The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.

Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.

“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
 

Details of the analysis 

In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.

However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.

Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.

They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).

The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.

After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).

After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.

The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.

After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.

In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.

The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.

Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.

These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.

There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.

Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”

“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.

“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.

The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.

The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.

No other relevant financial relationships were declared.

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

Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.

But why? A new analysis finds that the difference can only partly be explained by risky behaviors and carcinogenic exposure.

“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.

“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.

The study was published online in the journal Cancer.

“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.

In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.

“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.

“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
 

Comprehensive analyses

The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.

This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”

However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.

The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.

Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.

“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
 

Details of the analysis 

In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.

However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.

Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.

They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).

The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.

After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).

After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.

The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.

After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.

In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.

The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.

Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.

These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.

There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.

Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”

“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.

“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.

The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.

The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.

No other relevant financial relationships were declared.

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

New research provides novel insight into how mindfulness alters pain-related activity in the brain, in findings that point to more targeted pain management.

In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.

Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.

A complex condition

Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.

“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”

The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”

Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.

“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
 

Thermal pain task

The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.

All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.

The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.

The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.

To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.

The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.

During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.

The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.

In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
 

Neural signatures

Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.

Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).

Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).

In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).

The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).

The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.

Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).

In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.

However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.

Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
 

‘We’re seeing the biology change’

Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.

However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.

He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.

However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.

He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.

“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.

“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.

The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.

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

New research provides novel insight into how mindfulness alters pain-related activity in the brain, in findings that point to more targeted pain management.

In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.

Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.

A complex condition

Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.

“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”

The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”

Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.

“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
 

Thermal pain task

The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.

All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.

The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.

The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.

To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.

The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.

During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.

The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.

In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
 

Neural signatures

Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.

Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).

Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).

In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).

The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).

The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.

Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).

In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.

However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.

Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
 

‘We’re seeing the biology change’

Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.

However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.

He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.

However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.

He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.

“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.

“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.

The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.

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

New research provides novel insight into how mindfulness alters pain-related activity in the brain, in findings that point to more targeted pain management.

In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.

Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.

A complex condition

Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.

“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”

The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”

Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.

“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
 

Thermal pain task

The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.

All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.

The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.

The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.

To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.

The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.

During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.

The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.

In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
 

Neural signatures

Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.

Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).

Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).

In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).

The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).

The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.

Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).

In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.

However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.

Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
 

‘We’re seeing the biology change’

Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.

However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.

He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.

However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.

He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.

“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.

“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.

The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.

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

Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.

Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.

Late bedtimes, snoring, and prolonged daytime napping were significantly associated with MAFLD, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.

In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.

The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.

Rise in unhealthy lifestyles leads to increase in MALFD

The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”

Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.

Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.

However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.

To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.

Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.

MAFLD was diagnosed in those with hepatic steatosis and one of the following:

• Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m².
• Presence of diabetes.
• Evidence of metabolic dysregulation.

After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m². Forty percent were male.

Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.

MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.

Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”

However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).

MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).

When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).

Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).

In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).

Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.

“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.

“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.

The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.

The authors report no relevant financial relationships.

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

Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.

Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.

Late bedtimes, snoring, and prolonged daytime napping were significantly associated with MAFLD, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.

In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.

The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.

Rise in unhealthy lifestyles leads to increase in MALFD

The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”

Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.

Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.

However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.

To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.

Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.

MAFLD was diagnosed in those with hepatic steatosis and one of the following:

• Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m².
• Presence of diabetes.
• Evidence of metabolic dysregulation.

After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m². Forty percent were male.

Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.

MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.

Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”

However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).

MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).

When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).

Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).

In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).

Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.

“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.

“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.

The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.

The authors report no relevant financial relationships.

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

Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.

Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.

Late bedtimes, snoring, and prolonged daytime napping were significantly associated with MAFLD, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.

In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.

The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.

Rise in unhealthy lifestyles leads to increase in MALFD

The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”

Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.

Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.

However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.

To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.

Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.

MAFLD was diagnosed in those with hepatic steatosis and one of the following:

• Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m².
• Presence of diabetes.
• Evidence of metabolic dysregulation.

After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m². Forty percent were male.

Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.

MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.

Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”

However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).

MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).

When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).

Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).

In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).

Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.

“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.

“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.

The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.

The authors report no relevant financial relationships.

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

For patients who experience endoscopic remission of ulcerative colitis (UC), signs of active disease on histology did not affect their risk of clinical relapse, according to a large prospective study that reinforces a low endoscopy score as the treatment target.

In the study of more than 250 patients in endoscopic remission from UC, 19% experienced a clinical relapse within 1 year. The researchers found that a lower baseline endoscopy score was linked to a lower risk of relapse.

While histologic activity, as reflected in the Geboes Score, was not associated with clinical relapse, the presence of basal plasmacytosis independently doubled the risk of relapse.

“Our findings do not support the use of histology as a target for treatment in patients with ulcerative colitis who already achieved clinical and endoscopic remission,” say Talat Bessissow, MD, McGill University Health Center, Montreal, and colleagues.

They add that the results “support the use of the Mayo endoscopic subscore of zero as the optimal target for endoscopic remission.”

Further prospective data are needed to “define the role of histology activity and basal plasmacytosis in the management of ulcerative colitis,” the authors write.

The study was published online in The American Journal of Gastroenterology.
 

Uncertain role of histology

Dr. Bessissow told this news organization that “some studies have shown that histologic healing is associated with better long-term outcomes and less relapse, but this topic remains controversial because other studies have shown the opposite.”

“Our study does not support histology as a treatment target,” he continued, adding that therapy should not be changed solely on the basis of histology.

Dr. Bessissow clarified that although histology was not associated with less relapse over 1 year of follow-up, the role of histology on other, longer-term outcomes, such as surgery and colorectal cancer, still needs to be studied.

The natural history of UC is characterized by frequent relapse, the authors write, but “treating symptoms alone is not sufficient to prevent long-term complications.”

This led to a shift toward using endoscopic healing as a therapeutic goal, a move that was aided by the advent of novel medical therapies, including biologic agents. Crucially, endoscopic healing is associated with improved long-term outcomes, as well as improved quality of life.

The authors continue, however, that a “significant proportion” of patients experience relapse despite achieving endoscopic healing, which “could be explained in part by the fact that up to 40% of patients in endoscopic healing will have ongoing active histologic disease.”

However, in studies in which histologic activity was an endpoint, results have conflicted, and questions remain as to which parameters to include when assessing histologic activity.
 

Measuring the predictive values of endoscopy and histology

To investigate further, the researchers conducted a prospective observational study of consecutive adult patients with confirmed UC who presented to an endoscopy unit for colonoscopy for disease assessment or surveillance.

To qualify for the study, the patients’ conditions had to have been in clinical remission for at least 3 months prior to the colonoscopy. They were excluded if they had undergone prior surgical resection, had experienced disease remission for a period of over 10 years, or had used oral or rectal steroids within 90 days, among other criteria.

During an initial colonoscopy, two biopsies were performed, with specimens taken from the rectosigmoid and, when possible, from the right and left colon. Blood and stool samples were taken, and demographic and clinical data were collected.

The study enrolled 253 patients. Almost half (47.4%) were younger than 50 years, and 46.3% were women. They were followed for 12 months, during which 19% developed clinical relapse, defined as a partial Mayo endoscopic score (MES) of greater than 2.

When compared with patients with an MES of 0, the team found that patients with an MES of 1 or greater than or equal to 2 were at higher risk of relapse, with an adjusted hazard ratio of 2.65 and 2.57, respectively.

Interestingly, a lower baseline MES also was associated with a lower risk of relapse, and patients with proctitis were more likely to experience relapse than those with pancolitis.
 

No impact of histology on relapse risk

Further analysis revealed that there was no association between clinical relapse and age, sex, disease extent, and C-reactive protein, hemoglobin, and albumin levels. However, there was a significant association between relapse and the occurrence of at least one relapse in the 2 years prior to enrollment.

While the mean baseline fecal calprotectin (FC) level was numerically higher in patients who experienced relapse, compared with those who did not (306.9 mcg/g vs. 213.7 mcg/g), the difference was not significant.

FC of greater than 100 mcg/g was, however, significantly associated with relapse, at an odds ratio of 2.26, although the association was no longer significant when using the False Discovery Rate test.

Active histology was no more common among those who experienced relapse than among those who did not. But with regard to histologic factors, the team found that the presence of basal plasmacytosis was associated with clinical relapse, at an adjusted odds ratio of 2.07.

On the other hand, a Geboes Score of greater than or equal to 3.1, indicating the presence of epithelial neutrophils with or without crypt destruction or erosions, was not significantly associated with the risk of relapse, nor with the time to clinical relapse.
 

Clinical implications

Approached for comment, Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, said that this is “the largest prospective study assessing histologic activity or remission to predict future disease relapse in ulcerative colitis.”

He told this news organization that what the findings mean for clinical practice is that “patients who achieve an endoscopic and clinical remission are at a low likelihood of clinical relapse,” and added that “these should be the ‘treat-to-target’ endpoints.”

“Patients who have biopsy evidence, [such as] histologic activity based on the Geboes Score, do not require an escalation of therapy or a change in inflammatory bowel disease therapy,” Dr. Regueiro said.

He noted, however, that one primary question remains: Aside from surveillance of dysplasia, is there a role for biopsy in cases of UC in which the Mayo score is 0?

“In my practice, I still take biopsies from a previously involved colitis segment, even if Mayo 0,” he said.

“If there is histologic activity, I would not increase or optimize the current medications, but I also would not deescalate,” Dr. Regueiro added. “I would keep the patient on a regular surveillance colonoscopy regimen, too.”

No funding for the study has been reported. Dr. Bessissow has relationships with AbbVie, Alimentiv (formerly Robarts), Amgen, Bristol-Myers-Squibb, Ferring, Gilead, Janssen, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris. Other authors have disclosed numerous financial relationships. Dr. Regueiro has disclosed no such relationships.

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

For patients who experience endoscopic remission of ulcerative colitis (UC), signs of active disease on histology did not affect their risk of clinical relapse, according to a large prospective study that reinforces a low endoscopy score as the treatment target.

In the study of more than 250 patients in endoscopic remission from UC, 19% experienced a clinical relapse within 1 year. The researchers found that a lower baseline endoscopy score was linked to a lower risk of relapse.

While histologic activity, as reflected in the Geboes Score, was not associated with clinical relapse, the presence of basal plasmacytosis independently doubled the risk of relapse.

“Our findings do not support the use of histology as a target for treatment in patients with ulcerative colitis who already achieved clinical and endoscopic remission,” say Talat Bessissow, MD, McGill University Health Center, Montreal, and colleagues.

They add that the results “support the use of the Mayo endoscopic subscore of zero as the optimal target for endoscopic remission.”

Further prospective data are needed to “define the role of histology activity and basal plasmacytosis in the management of ulcerative colitis,” the authors write.

The study was published online in The American Journal of Gastroenterology.
 

Uncertain role of histology

Dr. Bessissow told this news organization that “some studies have shown that histologic healing is associated with better long-term outcomes and less relapse, but this topic remains controversial because other studies have shown the opposite.”

“Our study does not support histology as a treatment target,” he continued, adding that therapy should not be changed solely on the basis of histology.

Dr. Bessissow clarified that although histology was not associated with less relapse over 1 year of follow-up, the role of histology on other, longer-term outcomes, such as surgery and colorectal cancer, still needs to be studied.

The natural history of UC is characterized by frequent relapse, the authors write, but “treating symptoms alone is not sufficient to prevent long-term complications.”

This led to a shift toward using endoscopic healing as a therapeutic goal, a move that was aided by the advent of novel medical therapies, including biologic agents. Crucially, endoscopic healing is associated with improved long-term outcomes, as well as improved quality of life.

The authors continue, however, that a “significant proportion” of patients experience relapse despite achieving endoscopic healing, which “could be explained in part by the fact that up to 40% of patients in endoscopic healing will have ongoing active histologic disease.”

However, in studies in which histologic activity was an endpoint, results have conflicted, and questions remain as to which parameters to include when assessing histologic activity.
 

Measuring the predictive values of endoscopy and histology

To investigate further, the researchers conducted a prospective observational study of consecutive adult patients with confirmed UC who presented to an endoscopy unit for colonoscopy for disease assessment or surveillance.

To qualify for the study, the patients’ conditions had to have been in clinical remission for at least 3 months prior to the colonoscopy. They were excluded if they had undergone prior surgical resection, had experienced disease remission for a period of over 10 years, or had used oral or rectal steroids within 90 days, among other criteria.

During an initial colonoscopy, two biopsies were performed, with specimens taken from the rectosigmoid and, when possible, from the right and left colon. Blood and stool samples were taken, and demographic and clinical data were collected.

The study enrolled 253 patients. Almost half (47.4%) were younger than 50 years, and 46.3% were women. They were followed for 12 months, during which 19% developed clinical relapse, defined as a partial Mayo endoscopic score (MES) of greater than 2.

When compared with patients with an MES of 0, the team found that patients with an MES of 1 or greater than or equal to 2 were at higher risk of relapse, with an adjusted hazard ratio of 2.65 and 2.57, respectively.

Interestingly, a lower baseline MES also was associated with a lower risk of relapse, and patients with proctitis were more likely to experience relapse than those with pancolitis.
 

No impact of histology on relapse risk

Further analysis revealed that there was no association between clinical relapse and age, sex, disease extent, and C-reactive protein, hemoglobin, and albumin levels. However, there was a significant association between relapse and the occurrence of at least one relapse in the 2 years prior to enrollment.

While the mean baseline fecal calprotectin (FC) level was numerically higher in patients who experienced relapse, compared with those who did not (306.9 mcg/g vs. 213.7 mcg/g), the difference was not significant.

FC of greater than 100 mcg/g was, however, significantly associated with relapse, at an odds ratio of 2.26, although the association was no longer significant when using the False Discovery Rate test.

Active histology was no more common among those who experienced relapse than among those who did not. But with regard to histologic factors, the team found that the presence of basal plasmacytosis was associated with clinical relapse, at an adjusted odds ratio of 2.07.

On the other hand, a Geboes Score of greater than or equal to 3.1, indicating the presence of epithelial neutrophils with or without crypt destruction or erosions, was not significantly associated with the risk of relapse, nor with the time to clinical relapse.
 

Clinical implications

Approached for comment, Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, said that this is “the largest prospective study assessing histologic activity or remission to predict future disease relapse in ulcerative colitis.”

He told this news organization that what the findings mean for clinical practice is that “patients who achieve an endoscopic and clinical remission are at a low likelihood of clinical relapse,” and added that “these should be the ‘treat-to-target’ endpoints.”

“Patients who have biopsy evidence, [such as] histologic activity based on the Geboes Score, do not require an escalation of therapy or a change in inflammatory bowel disease therapy,” Dr. Regueiro said.

He noted, however, that one primary question remains: Aside from surveillance of dysplasia, is there a role for biopsy in cases of UC in which the Mayo score is 0?

“In my practice, I still take biopsies from a previously involved colitis segment, even if Mayo 0,” he said.

“If there is histologic activity, I would not increase or optimize the current medications, but I also would not deescalate,” Dr. Regueiro added. “I would keep the patient on a regular surveillance colonoscopy regimen, too.”

No funding for the study has been reported. Dr. Bessissow has relationships with AbbVie, Alimentiv (formerly Robarts), Amgen, Bristol-Myers-Squibb, Ferring, Gilead, Janssen, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris. Other authors have disclosed numerous financial relationships. Dr. Regueiro has disclosed no such relationships.

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

For patients who experience endoscopic remission of ulcerative colitis (UC), signs of active disease on histology did not affect their risk of clinical relapse, according to a large prospective study that reinforces a low endoscopy score as the treatment target.

In the study of more than 250 patients in endoscopic remission from UC, 19% experienced a clinical relapse within 1 year. The researchers found that a lower baseline endoscopy score was linked to a lower risk of relapse.

While histologic activity, as reflected in the Geboes Score, was not associated with clinical relapse, the presence of basal plasmacytosis independently doubled the risk of relapse.

“Our findings do not support the use of histology as a target for treatment in patients with ulcerative colitis who already achieved clinical and endoscopic remission,” say Talat Bessissow, MD, McGill University Health Center, Montreal, and colleagues.

They add that the results “support the use of the Mayo endoscopic subscore of zero as the optimal target for endoscopic remission.”

Further prospective data are needed to “define the role of histology activity and basal plasmacytosis in the management of ulcerative colitis,” the authors write.

The study was published online in The American Journal of Gastroenterology.
 

Uncertain role of histology

Dr. Bessissow told this news organization that “some studies have shown that histologic healing is associated with better long-term outcomes and less relapse, but this topic remains controversial because other studies have shown the opposite.”

“Our study does not support histology as a treatment target,” he continued, adding that therapy should not be changed solely on the basis of histology.

Dr. Bessissow clarified that although histology was not associated with less relapse over 1 year of follow-up, the role of histology on other, longer-term outcomes, such as surgery and colorectal cancer, still needs to be studied.

The natural history of UC is characterized by frequent relapse, the authors write, but “treating symptoms alone is not sufficient to prevent long-term complications.”

This led to a shift toward using endoscopic healing as a therapeutic goal, a move that was aided by the advent of novel medical therapies, including biologic agents. Crucially, endoscopic healing is associated with improved long-term outcomes, as well as improved quality of life.

The authors continue, however, that a “significant proportion” of patients experience relapse despite achieving endoscopic healing, which “could be explained in part by the fact that up to 40% of patients in endoscopic healing will have ongoing active histologic disease.”

However, in studies in which histologic activity was an endpoint, results have conflicted, and questions remain as to which parameters to include when assessing histologic activity.
 

Measuring the predictive values of endoscopy and histology

To investigate further, the researchers conducted a prospective observational study of consecutive adult patients with confirmed UC who presented to an endoscopy unit for colonoscopy for disease assessment or surveillance.

To qualify for the study, the patients’ conditions had to have been in clinical remission for at least 3 months prior to the colonoscopy. They were excluded if they had undergone prior surgical resection, had experienced disease remission for a period of over 10 years, or had used oral or rectal steroids within 90 days, among other criteria.

During an initial colonoscopy, two biopsies were performed, with specimens taken from the rectosigmoid and, when possible, from the right and left colon. Blood and stool samples were taken, and demographic and clinical data were collected.

The study enrolled 253 patients. Almost half (47.4%) were younger than 50 years, and 46.3% were women. They were followed for 12 months, during which 19% developed clinical relapse, defined as a partial Mayo endoscopic score (MES) of greater than 2.

When compared with patients with an MES of 0, the team found that patients with an MES of 1 or greater than or equal to 2 were at higher risk of relapse, with an adjusted hazard ratio of 2.65 and 2.57, respectively.

Interestingly, a lower baseline MES also was associated with a lower risk of relapse, and patients with proctitis were more likely to experience relapse than those with pancolitis.
 

No impact of histology on relapse risk

Further analysis revealed that there was no association between clinical relapse and age, sex, disease extent, and C-reactive protein, hemoglobin, and albumin levels. However, there was a significant association between relapse and the occurrence of at least one relapse in the 2 years prior to enrollment.

While the mean baseline fecal calprotectin (FC) level was numerically higher in patients who experienced relapse, compared with those who did not (306.9 mcg/g vs. 213.7 mcg/g), the difference was not significant.

FC of greater than 100 mcg/g was, however, significantly associated with relapse, at an odds ratio of 2.26, although the association was no longer significant when using the False Discovery Rate test.

Active histology was no more common among those who experienced relapse than among those who did not. But with regard to histologic factors, the team found that the presence of basal plasmacytosis was associated with clinical relapse, at an adjusted odds ratio of 2.07.

On the other hand, a Geboes Score of greater than or equal to 3.1, indicating the presence of epithelial neutrophils with or without crypt destruction or erosions, was not significantly associated with the risk of relapse, nor with the time to clinical relapse.
 

Clinical implications

Approached for comment, Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, said that this is “the largest prospective study assessing histologic activity or remission to predict future disease relapse in ulcerative colitis.”

He told this news organization that what the findings mean for clinical practice is that “patients who achieve an endoscopic and clinical remission are at a low likelihood of clinical relapse,” and added that “these should be the ‘treat-to-target’ endpoints.”

“Patients who have biopsy evidence, [such as] histologic activity based on the Geboes Score, do not require an escalation of therapy or a change in inflammatory bowel disease therapy,” Dr. Regueiro said.

He noted, however, that one primary question remains: Aside from surveillance of dysplasia, is there a role for biopsy in cases of UC in which the Mayo score is 0?

“In my practice, I still take biopsies from a previously involved colitis segment, even if Mayo 0,” he said.

“If there is histologic activity, I would not increase or optimize the current medications, but I also would not deescalate,” Dr. Regueiro added. “I would keep the patient on a regular surveillance colonoscopy regimen, too.”

No funding for the study has been reported. Dr. Bessissow has relationships with AbbVie, Alimentiv (formerly Robarts), Amgen, Bristol-Myers-Squibb, Ferring, Gilead, Janssen, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris. Other authors have disclosed numerous financial relationships. Dr. Regueiro has disclosed no such relationships.

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

Among biologic agents, vedolizumab (Entyvio) and ustekinumab (Stelara) are associated with lower rates of infection-related hospitalizations than anti-tumor necrosis factor (TNF) agents in older patients with inflammatory bowel disease (IBD), but only if older patients also have comorbidities, U.S. researchers have found.

The researchers examined U.S. health insurance claims for three cohorts – patients with IBD who were treated with anti-TNF agents, vedolizumab, and ustekinumab – and found no overall difference in infection rates or infection-related hospitalizations between the groups.

But in patients with a greater burden of comorbidity, the monoclonal antibodies vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations, compared with anti-TNF agents, with 22% less for vedolizumab and 34% less for ustekinumab.

In the “first pharmacoepidemiologic study comparing all approved classes of biologic agents to treat IBD focused on older adults,” the authors say they “demonstrate that comorbidity is a mediator of infections requiring hospitalizations.”

“These data can help counsel older adults who are about to initiate a biologic agent in clinical practice,” they write.

The research was published online in The American Journal of Gastroenterology.

Co-lead author Bharati Kochar, MD, MS, a gastroenterologist at Massachusetts General Hospital, Boston, said that the real question, when we’re seeing an older patient, is which medications are safer.

“Not surprisingly, we found that there was no overall difference in the three classes of medications,” she said, adding that “if you take your healthy older adults without any serious comorbidities, anti-TNF agents are not different in terms of a safety profile.”

With the more selective biologics like vedolizumab and ustekinumab seeming to confer a lower risk for serious infections in patients with comorbidities, Dr. Kochar said the hope is that their study will help doctors feel more confident in prescribing and encourage thinking about the patient in a broader manner beyond chronological age.
 

Real-world study on older adults with IBD

The authors note that the number of older adults with IBD is rising rapidly. It is estimated that almost 1 million individuals aged 60 years and older in the United States are living with the disease.

They add that there has been a rapid proliferation of treatment options for both Crohn’s disease and ulcerative colitis, but the likelihood of achieving remission may vary by mechanism of immunosuppression.

Older adults have a higher baseline risk for infections than younger adults, regardless of treatment type, the authors underline; yet, older adults with IBD are disproportionately under-represented in clinical trials of IBD therapies.

Recognizing the need for real-world studies focused on older adults, Dr. Kochar and her colleagues gathered claims data from a commercial U.S. health insurance plan totaling nearly 86 million individuals between 2008 and 2019.

They identified patients with IBD aged 60 years or older (average age, 67 years) who had at least one claim for vedolizumab, ustekinumab, or anti-TNF agents, including adalimumab, infliximab, golimumab, or certolizumab pegol.

The cohorts included 2,369 patients treated with anti-TNF agents, 972 who were started on vedolizumab and 352 who were given ustekinumab.

Patients were excluded if they received vedolizumab or ustekinumab during the first 6 months of treatment and were then switched to anti-TNF therapy.

The on-treatment period was defined as starting with the index treatment date and ending with the date of treatment discontinuation. Treatment was required to last more than 90 days.

The overall incidence rates for any infection were similar across the three treatment groups, at 3,606 per 1,000 person-years in the anti-TNF group, 3,748 per 1,000 person-years in patients given vedolizumab, and 3,139 per 1,000 person-years in those treated with ustekinumab.

There were also no significant differences in the rate of infection-related hospitalizations, at a hazard ratio for vedolizumab versus anti-TNF agents of 0.94, and for ustekinumab, again versus anti-TNF agents, of 0.92.

However, the authors found that there was a “significant interaction” between comorbidities and treatment in terms of infection-related hospitalizations.

Among IBD patients older than 60 with a Charlson Comorbidity Index (CCI) score of greater than 1, treatment with vedolizumab and ustekinumab was associated with a significantly lower rate of infection-related hospitalizations versus anti-TNF agents, at hazard ratios of 0.78 and 0.66, respectively.

In contrast, the rates of hospitalization were similar between the treatment groups among patients without significant comorbidity.

Interestingly, patients with ulcerative colitis treated with vedolizumab also had a lower rate of infection versus those given anti-TNF agents, at a hazard ratio of 0.96, while no such difference was seen in patients with Crohn’s disease.
 

Results will help refine clinical practice

Approached for comment, Dana J. Lukin, MD, PhD, clinical director of translational research at the Jill Roberts Center for Inflammatory Bowel Disease, New York, said the study is limited by the lack of granular data on disease activity.

Moreover, he told this news organization that since it is not a randomized controlled trial, the selection of medications in the claims database may have factored in some of the intangible contraindications to anti-TNF agents.

“It makes sense that comorbidity confers the biggest risk for hospitalization from infections,” Dr. Lukin said, adding that “what is interesting is that there is no difference overall in infection rates between any of the medication classes.”

He said the study therefore “rebuffs the traditional thinking” that, among older adults, anti-TNF agents will be associated with a higher risk of infections per se, “because really it’s specifically among those patients who have more comorbidities.”

Most importantly, Dr. Lukin said that the findings will help to refine clinical practice, as clinicians are specifically tasked with treating the inflammatory bowel disease but are not necessarily focused on comorbidities, which patients accrue more and more as they age.

Dr. Lukin continued that, for patients with comorbid conditions, “we should carefully consider using a non–anti-TNF agent.”

“We should also not be afraid to continue to use anti-TNF agents” in those without comorbidities, he added, as they are “very effective in patients who might need them for their disease-related characteristics.”

The study was supported in part by grants from the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Chleck Family Foundation.

Dr. Lukin declares relationships with Takeda, Abbvie, and Janssen. No other relevant financial relationships were declared.

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

Among biologic agents, vedolizumab (Entyvio) and ustekinumab (Stelara) are associated with lower rates of infection-related hospitalizations than anti-tumor necrosis factor (TNF) agents in older patients with inflammatory bowel disease (IBD), but only if older patients also have comorbidities, U.S. researchers have found.

The researchers examined U.S. health insurance claims for three cohorts – patients with IBD who were treated with anti-TNF agents, vedolizumab, and ustekinumab – and found no overall difference in infection rates or infection-related hospitalizations between the groups.

But in patients with a greater burden of comorbidity, the monoclonal antibodies vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations, compared with anti-TNF agents, with 22% less for vedolizumab and 34% less for ustekinumab.

In the “first pharmacoepidemiologic study comparing all approved classes of biologic agents to treat IBD focused on older adults,” the authors say they “demonstrate that comorbidity is a mediator of infections requiring hospitalizations.”

“These data can help counsel older adults who are about to initiate a biologic agent in clinical practice,” they write.

The research was published online in The American Journal of Gastroenterology.

Co-lead author Bharati Kochar, MD, MS, a gastroenterologist at Massachusetts General Hospital, Boston, said that the real question, when we’re seeing an older patient, is which medications are safer.

“Not surprisingly, we found that there was no overall difference in the three classes of medications,” she said, adding that “if you take your healthy older adults without any serious comorbidities, anti-TNF agents are not different in terms of a safety profile.”

With the more selective biologics like vedolizumab and ustekinumab seeming to confer a lower risk for serious infections in patients with comorbidities, Dr. Kochar said the hope is that their study will help doctors feel more confident in prescribing and encourage thinking about the patient in a broader manner beyond chronological age.
 

Real-world study on older adults with IBD

The authors note that the number of older adults with IBD is rising rapidly. It is estimated that almost 1 million individuals aged 60 years and older in the United States are living with the disease.

They add that there has been a rapid proliferation of treatment options for both Crohn’s disease and ulcerative colitis, but the likelihood of achieving remission may vary by mechanism of immunosuppression.

Older adults have a higher baseline risk for infections than younger adults, regardless of treatment type, the authors underline; yet, older adults with IBD are disproportionately under-represented in clinical trials of IBD therapies.

Recognizing the need for real-world studies focused on older adults, Dr. Kochar and her colleagues gathered claims data from a commercial U.S. health insurance plan totaling nearly 86 million individuals between 2008 and 2019.

They identified patients with IBD aged 60 years or older (average age, 67 years) who had at least one claim for vedolizumab, ustekinumab, or anti-TNF agents, including adalimumab, infliximab, golimumab, or certolizumab pegol.

The cohorts included 2,369 patients treated with anti-TNF agents, 972 who were started on vedolizumab and 352 who were given ustekinumab.

Patients were excluded if they received vedolizumab or ustekinumab during the first 6 months of treatment and were then switched to anti-TNF therapy.

The on-treatment period was defined as starting with the index treatment date and ending with the date of treatment discontinuation. Treatment was required to last more than 90 days.

The overall incidence rates for any infection were similar across the three treatment groups, at 3,606 per 1,000 person-years in the anti-TNF group, 3,748 per 1,000 person-years in patients given vedolizumab, and 3,139 per 1,000 person-years in those treated with ustekinumab.

There were also no significant differences in the rate of infection-related hospitalizations, at a hazard ratio for vedolizumab versus anti-TNF agents of 0.94, and for ustekinumab, again versus anti-TNF agents, of 0.92.

However, the authors found that there was a “significant interaction” between comorbidities and treatment in terms of infection-related hospitalizations.

Among IBD patients older than 60 with a Charlson Comorbidity Index (CCI) score of greater than 1, treatment with vedolizumab and ustekinumab was associated with a significantly lower rate of infection-related hospitalizations versus anti-TNF agents, at hazard ratios of 0.78 and 0.66, respectively.

In contrast, the rates of hospitalization were similar between the treatment groups among patients without significant comorbidity.

Interestingly, patients with ulcerative colitis treated with vedolizumab also had a lower rate of infection versus those given anti-TNF agents, at a hazard ratio of 0.96, while no such difference was seen in patients with Crohn’s disease.
 

Results will help refine clinical practice

Approached for comment, Dana J. Lukin, MD, PhD, clinical director of translational research at the Jill Roberts Center for Inflammatory Bowel Disease, New York, said the study is limited by the lack of granular data on disease activity.

Moreover, he told this news organization that since it is not a randomized controlled trial, the selection of medications in the claims database may have factored in some of the intangible contraindications to anti-TNF agents.

“It makes sense that comorbidity confers the biggest risk for hospitalization from infections,” Dr. Lukin said, adding that “what is interesting is that there is no difference overall in infection rates between any of the medication classes.”

He said the study therefore “rebuffs the traditional thinking” that, among older adults, anti-TNF agents will be associated with a higher risk of infections per se, “because really it’s specifically among those patients who have more comorbidities.”

Most importantly, Dr. Lukin said that the findings will help to refine clinical practice, as clinicians are specifically tasked with treating the inflammatory bowel disease but are not necessarily focused on comorbidities, which patients accrue more and more as they age.

Dr. Lukin continued that, for patients with comorbid conditions, “we should carefully consider using a non–anti-TNF agent.”

“We should also not be afraid to continue to use anti-TNF agents” in those without comorbidities, he added, as they are “very effective in patients who might need them for their disease-related characteristics.”

The study was supported in part by grants from the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Chleck Family Foundation.

Dr. Lukin declares relationships with Takeda, Abbvie, and Janssen. No other relevant financial relationships were declared.

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

Among biologic agents, vedolizumab (Entyvio) and ustekinumab (Stelara) are associated with lower rates of infection-related hospitalizations than anti-tumor necrosis factor (TNF) agents in older patients with inflammatory bowel disease (IBD), but only if older patients also have comorbidities, U.S. researchers have found.

The researchers examined U.S. health insurance claims for three cohorts – patients with IBD who were treated with anti-TNF agents, vedolizumab, and ustekinumab – and found no overall difference in infection rates or infection-related hospitalizations between the groups.

But in patients with a greater burden of comorbidity, the monoclonal antibodies vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations, compared with anti-TNF agents, with 22% less for vedolizumab and 34% less for ustekinumab.

In the “first pharmacoepidemiologic study comparing all approved classes of biologic agents to treat IBD focused on older adults,” the authors say they “demonstrate that comorbidity is a mediator of infections requiring hospitalizations.”

“These data can help counsel older adults who are about to initiate a biologic agent in clinical practice,” they write.

The research was published online in The American Journal of Gastroenterology.

Co-lead author Bharati Kochar, MD, MS, a gastroenterologist at Massachusetts General Hospital, Boston, said that the real question, when we’re seeing an older patient, is which medications are safer.

“Not surprisingly, we found that there was no overall difference in the three classes of medications,” she said, adding that “if you take your healthy older adults without any serious comorbidities, anti-TNF agents are not different in terms of a safety profile.”

With the more selective biologics like vedolizumab and ustekinumab seeming to confer a lower risk for serious infections in patients with comorbidities, Dr. Kochar said the hope is that their study will help doctors feel more confident in prescribing and encourage thinking about the patient in a broader manner beyond chronological age.
 

Real-world study on older adults with IBD

The authors note that the number of older adults with IBD is rising rapidly. It is estimated that almost 1 million individuals aged 60 years and older in the United States are living with the disease.

They add that there has been a rapid proliferation of treatment options for both Crohn’s disease and ulcerative colitis, but the likelihood of achieving remission may vary by mechanism of immunosuppression.

Older adults have a higher baseline risk for infections than younger adults, regardless of treatment type, the authors underline; yet, older adults with IBD are disproportionately under-represented in clinical trials of IBD therapies.

Recognizing the need for real-world studies focused on older adults, Dr. Kochar and her colleagues gathered claims data from a commercial U.S. health insurance plan totaling nearly 86 million individuals between 2008 and 2019.

They identified patients with IBD aged 60 years or older (average age, 67 years) who had at least one claim for vedolizumab, ustekinumab, or anti-TNF agents, including adalimumab, infliximab, golimumab, or certolizumab pegol.

The cohorts included 2,369 patients treated with anti-TNF agents, 972 who were started on vedolizumab and 352 who were given ustekinumab.

Patients were excluded if they received vedolizumab or ustekinumab during the first 6 months of treatment and were then switched to anti-TNF therapy.

The on-treatment period was defined as starting with the index treatment date and ending with the date of treatment discontinuation. Treatment was required to last more than 90 days.

The overall incidence rates for any infection were similar across the three treatment groups, at 3,606 per 1,000 person-years in the anti-TNF group, 3,748 per 1,000 person-years in patients given vedolizumab, and 3,139 per 1,000 person-years in those treated with ustekinumab.

There were also no significant differences in the rate of infection-related hospitalizations, at a hazard ratio for vedolizumab versus anti-TNF agents of 0.94, and for ustekinumab, again versus anti-TNF agents, of 0.92.

However, the authors found that there was a “significant interaction” between comorbidities and treatment in terms of infection-related hospitalizations.

Among IBD patients older than 60 with a Charlson Comorbidity Index (CCI) score of greater than 1, treatment with vedolizumab and ustekinumab was associated with a significantly lower rate of infection-related hospitalizations versus anti-TNF agents, at hazard ratios of 0.78 and 0.66, respectively.

In contrast, the rates of hospitalization were similar between the treatment groups among patients without significant comorbidity.

Interestingly, patients with ulcerative colitis treated with vedolizumab also had a lower rate of infection versus those given anti-TNF agents, at a hazard ratio of 0.96, while no such difference was seen in patients with Crohn’s disease.
 

Results will help refine clinical practice

Approached for comment, Dana J. Lukin, MD, PhD, clinical director of translational research at the Jill Roberts Center for Inflammatory Bowel Disease, New York, said the study is limited by the lack of granular data on disease activity.

Moreover, he told this news organization that since it is not a randomized controlled trial, the selection of medications in the claims database may have factored in some of the intangible contraindications to anti-TNF agents.

“It makes sense that comorbidity confers the biggest risk for hospitalization from infections,” Dr. Lukin said, adding that “what is interesting is that there is no difference overall in infection rates between any of the medication classes.”

He said the study therefore “rebuffs the traditional thinking” that, among older adults, anti-TNF agents will be associated with a higher risk of infections per se, “because really it’s specifically among those patients who have more comorbidities.”

Most importantly, Dr. Lukin said that the findings will help to refine clinical practice, as clinicians are specifically tasked with treating the inflammatory bowel disease but are not necessarily focused on comorbidities, which patients accrue more and more as they age.

Dr. Lukin continued that, for patients with comorbid conditions, “we should carefully consider using a non–anti-TNF agent.”

“We should also not be afraid to continue to use anti-TNF agents” in those without comorbidities, he added, as they are “very effective in patients who might need them for their disease-related characteristics.”

The study was supported in part by grants from the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Chleck Family Foundation.

Dr. Lukin declares relationships with Takeda, Abbvie, and Janssen. No other relevant financial relationships were declared.

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

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

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

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

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

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

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

*This article was updated on July 27, 2022.

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

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

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

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

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

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

When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.

Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.

However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.

“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.

The research was published online by Clinical Gastroenterology and Hepatology.
 

Real-world evidence

“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.

They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”

“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”

The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.

While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”

To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.

They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.

Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.

There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
 

Early difference fades

Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.

Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.

Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.

The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.

Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.

The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.

But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.

“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
 

‘Interesting’ efficacy data

Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.

“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.

While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.

“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”

The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”

Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.

“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.

Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.

The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.

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

When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.

Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.

However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.

“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.

The research was published online by Clinical Gastroenterology and Hepatology.
 

Real-world evidence

“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.

They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”

“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”

The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.

While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”

To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.

They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.

Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.

There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
 

Early difference fades

Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.

Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.

Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.

The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.

Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.

The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.

But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.

“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
 

‘Interesting’ efficacy data

Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.

“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.

While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.

“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”

The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”

Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.

“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.

Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.

The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.

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

When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.

Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.

However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.

“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.

The research was published online by Clinical Gastroenterology and Hepatology.
 

Real-world evidence

“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.

They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”

“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”

The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.

While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”

To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.

They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.

Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.

There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
 

Early difference fades

Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.

Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.

Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.

The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.

Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.

The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.

But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.

“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
 

‘Interesting’ efficacy data

Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.

“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.

While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.

“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”

The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”

Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.

“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.

Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.

The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.

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

GLASGOW, Scotland – The wound-healing benefits seen with a topical agent containing the bark derivative oleogel-S10 (Filsuvez) for patients with epidermolysis bullosa (EB) continue to accrue with continued use, suggests data from an open-label extension of EASE, the phase 3 safety and efficacy study of the treatment.

Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.

Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.

The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.

In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.

However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.

In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”

Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”

He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”

“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.

Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.

During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.

While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.

To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.

The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).

However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.

Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.

In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.

Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.

Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.

Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.

Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.

Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.

Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.

The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.

The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.

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

GLASGOW, Scotland – The wound-healing benefits seen with a topical agent containing the bark derivative oleogel-S10 (Filsuvez) for patients with epidermolysis bullosa (EB) continue to accrue with continued use, suggests data from an open-label extension of EASE, the phase 3 safety and efficacy study of the treatment.

Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.

Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.

The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.

In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.

However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.

In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”

Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”

He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”

“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.

Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.

During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.

While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.

To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.

The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).

However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.

Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.

In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.

Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.

Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.

Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.

Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.

Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.

Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.

The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.

The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.

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

GLASGOW, Scotland – The wound-healing benefits seen with a topical agent containing the bark derivative oleogel-S10 (Filsuvez) for patients with epidermolysis bullosa (EB) continue to accrue with continued use, suggests data from an open-label extension of EASE, the phase 3 safety and efficacy study of the treatment.

Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.

Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.

The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.

In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.

However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.

In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”

Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”

He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”

“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.

Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.

During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.

While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.

To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.

The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).

However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.

Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.

In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.

Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.

Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.

Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.

Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.

Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.

Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.

The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.

The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.

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

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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