MDedge Family Medicine

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

TOPLINE: 

Individuals with overweight and obesity who reach a weight-loss plateau at around 6 months on a healthy weight-loss diet may not achieve further weight reduction after switching to a different weight-loss diet.

METHODOLOGY:

• Dietary and lifestyle interventions initially result in rapid weight loss, followed by a weight-loss plateau after a few months and weight regain within a year or two, and diet fatigue has been proposed as a cause but not studied.
• This secondary analysis of a randomized trial assessed weight-loss trajectories before and after switching from a healthy low-carbohydrate (LC) diet to a healthy low-fat (LF) diet (or vice versa) in individuals with overweight and obesity.
• Overall, 42 participants (mean age, 42 years; 64% women; 87% White individuals) recruited from a local community in Palo Alto, California, were assigned to the LF or LC diet for the first 6 months, after which they were switched to the other diet for the remaining 6 months.
• Data from the DIETFITS trial, wherein participants remained either on the LF or LC diet for 12 months, were used as historical control.

The primary outcome was percent weight change at 3-6 months vs that observed at 6-9 months.

TAKEAWAY:

• The combined average weight loss was 7% (95% CI, 8%-6%) during the first 3 months, declining to 2% (95% CI, 3%-1%) between 3 and 6 months. On switching diets, the weight loss further slowed to 1% (95% CI, 2%-0.4%) between 6 and 9 months, with a modest increase in weight of 0.6% (95% CI, −0.1% to 1.3%) between 9 and 12 months.
• By diet order, participants in the LF first arm did not plateau and experienced a similar weight loss from 6 to 9 months as they had experienced from 3 to 6 months (relative change, −0.1%; 95% CI, −1.5% to 1.3%), while the LC first arm essentially nullified the 3-6 month weight loss during the 6-9 month LF phase (relative change, 2.2%; 95% CI, 0.7%-3.6%).
• For the LC first arm, low-density lipoprotein increased at 3 months and decreased when the participants switched to LF at 6 months, whereas the opposite effect was seen for the transition from LF to LC. Triglyceride levels decreased in both intervention arms.
• Insulin levels decreased in both dietary intervention arms between baseline and 6 months and plateaued following the 6-month dietary switch.

IN PRACTICE:

“This suggests that the weight-loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet,” wrote the authors. “As a person transitions from a weight loss to weight maintenance phase, a shift in the approach used may be required.”

SOURCE:

The study, led by Matthew J. Landry, Stanford Prevention Research Center, School of Medicine, Stanford University, California, was published in Scientific Reports.

LIMITATIONS:

The study results showed some possible differential trends but also highlighted the small sample size and large variability. Participants may have been unable to provide accurate estimates of self-reported energy intake. The authors also acknowledged that regular physical activity may have contributed to the maintenance of weight loss observed in this study.

DISCLOSURES:

The study was supported by the Hass Avocado Board; Human Health Service grant (General Clinical Research Centers and National Center for Research Resources, National Institutes of Health); National Heart, Lung, and Blood Institute; and Stanford Diabetes Research Center. The authors declared no conflicts of interest.

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

TOPLINE: 

Individuals with overweight and obesity who reach a weight-loss plateau at around 6 months on a healthy weight-loss diet may not achieve further weight reduction after switching to a different weight-loss diet.

METHODOLOGY:

• Dietary and lifestyle interventions initially result in rapid weight loss, followed by a weight-loss plateau after a few months and weight regain within a year or two, and diet fatigue has been proposed as a cause but not studied.
• This secondary analysis of a randomized trial assessed weight-loss trajectories before and after switching from a healthy low-carbohydrate (LC) diet to a healthy low-fat (LF) diet (or vice versa) in individuals with overweight and obesity.
• Overall, 42 participants (mean age, 42 years; 64% women; 87% White individuals) recruited from a local community in Palo Alto, California, were assigned to the LF or LC diet for the first 6 months, after which they were switched to the other diet for the remaining 6 months.
• Data from the DIETFITS trial, wherein participants remained either on the LF or LC diet for 12 months, were used as historical control.

The primary outcome was percent weight change at 3-6 months vs that observed at 6-9 months.

TAKEAWAY:

• The combined average weight loss was 7% (95% CI, 8%-6%) during the first 3 months, declining to 2% (95% CI, 3%-1%) between 3 and 6 months. On switching diets, the weight loss further slowed to 1% (95% CI, 2%-0.4%) between 6 and 9 months, with a modest increase in weight of 0.6% (95% CI, −0.1% to 1.3%) between 9 and 12 months.
• By diet order, participants in the LF first arm did not plateau and experienced a similar weight loss from 6 to 9 months as they had experienced from 3 to 6 months (relative change, −0.1%; 95% CI, −1.5% to 1.3%), while the LC first arm essentially nullified the 3-6 month weight loss during the 6-9 month LF phase (relative change, 2.2%; 95% CI, 0.7%-3.6%).
• For the LC first arm, low-density lipoprotein increased at 3 months and decreased when the participants switched to LF at 6 months, whereas the opposite effect was seen for the transition from LF to LC. Triglyceride levels decreased in both intervention arms.
• Insulin levels decreased in both dietary intervention arms between baseline and 6 months and plateaued following the 6-month dietary switch.

IN PRACTICE:

“This suggests that the weight-loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet,” wrote the authors. “As a person transitions from a weight loss to weight maintenance phase, a shift in the approach used may be required.”

SOURCE:

The study, led by Matthew J. Landry, Stanford Prevention Research Center, School of Medicine, Stanford University, California, was published in Scientific Reports.

LIMITATIONS:

The study results showed some possible differential trends but also highlighted the small sample size and large variability. Participants may have been unable to provide accurate estimates of self-reported energy intake. The authors also acknowledged that regular physical activity may have contributed to the maintenance of weight loss observed in this study.

DISCLOSURES:

The study was supported by the Hass Avocado Board; Human Health Service grant (General Clinical Research Centers and National Center for Research Resources, National Institutes of Health); National Heart, Lung, and Blood Institute; and Stanford Diabetes Research Center. The authors declared no conflicts of interest.

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

TOPLINE: 

Individuals with overweight and obesity who reach a weight-loss plateau at around 6 months on a healthy weight-loss diet may not achieve further weight reduction after switching to a different weight-loss diet.

METHODOLOGY:

• Dietary and lifestyle interventions initially result in rapid weight loss, followed by a weight-loss plateau after a few months and weight regain within a year or two, and diet fatigue has been proposed as a cause but not studied.
• This secondary analysis of a randomized trial assessed weight-loss trajectories before and after switching from a healthy low-carbohydrate (LC) diet to a healthy low-fat (LF) diet (or vice versa) in individuals with overweight and obesity.
• Overall, 42 participants (mean age, 42 years; 64% women; 87% White individuals) recruited from a local community in Palo Alto, California, were assigned to the LF or LC diet for the first 6 months, after which they were switched to the other diet for the remaining 6 months.
• Data from the DIETFITS trial, wherein participants remained either on the LF or LC diet for 12 months, were used as historical control.

The primary outcome was percent weight change at 3-6 months vs that observed at 6-9 months.

TAKEAWAY:

• The combined average weight loss was 7% (95% CI, 8%-6%) during the first 3 months, declining to 2% (95% CI, 3%-1%) between 3 and 6 months. On switching diets, the weight loss further slowed to 1% (95% CI, 2%-0.4%) between 6 and 9 months, with a modest increase in weight of 0.6% (95% CI, −0.1% to 1.3%) between 9 and 12 months.
• By diet order, participants in the LF first arm did not plateau and experienced a similar weight loss from 6 to 9 months as they had experienced from 3 to 6 months (relative change, −0.1%; 95% CI, −1.5% to 1.3%), while the LC first arm essentially nullified the 3-6 month weight loss during the 6-9 month LF phase (relative change, 2.2%; 95% CI, 0.7%-3.6%).
• For the LC first arm, low-density lipoprotein increased at 3 months and decreased when the participants switched to LF at 6 months, whereas the opposite effect was seen for the transition from LF to LC. Triglyceride levels decreased in both intervention arms.
• Insulin levels decreased in both dietary intervention arms between baseline and 6 months and plateaued following the 6-month dietary switch.

IN PRACTICE:

“This suggests that the weight-loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet,” wrote the authors. “As a person transitions from a weight loss to weight maintenance phase, a shift in the approach used may be required.”

SOURCE:

The study, led by Matthew J. Landry, Stanford Prevention Research Center, School of Medicine, Stanford University, California, was published in Scientific Reports.

LIMITATIONS:

The study results showed some possible differential trends but also highlighted the small sample size and large variability. Participants may have been unable to provide accurate estimates of self-reported energy intake. The authors also acknowledged that regular physical activity may have contributed to the maintenance of weight loss observed in this study.

DISCLOSURES:

The study was supported by the Hass Avocado Board; Human Health Service grant (General Clinical Research Centers and National Center for Research Resources, National Institutes of Health); National Heart, Lung, and Blood Institute; and Stanford Diabetes Research Center. The authors declared no conflicts of interest.

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

NEW YORK — Psychiatric comorbidities are highly prevalent in patients with eating disorders (EDs), a large study showed.

In a propensity-matched cohort of young adults with and without EDs, a wide variety of psychiatric disorders including depression and anxiety, as well as cannabis and alcohol use disorders, were more common in those with EDs, investigators found.

Comorbid psychiatric disorders should be “top of mind when working with someone with an eating disorder. If you are able to treat the comorbid psychiatric conditions, they might have a better recovery from the eating disorder,” study investigator Angela Liu, MD, with Northwell Health at Zucker Hillside Hospital, Glen Oaks, New York, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Data Gap

As previously reported by this news organization, more than one in five children worldwide are at risk for an ED and US medical admissions for adolescents with restrictive EDs more than doubled during the pandemic.

Yet there remains a “gap in the literature” about the prevalence of comorbid psychiatric conditions in people with EDs, specifically in young people, Dr. Liu explained.

“To our knowledge, this is the first study using a real-world, multistate administrative dataset to estimate the prevalence of psychiatric comorbidities in young people diagnosed with an eating disorder,” Dr. Liu said.

Using the TriNetX database, the researchers identified through ICD-10 codes 14,524 individuals with EDs (mean age, 15.9 years; 79% women) and 110,051 without EDs who were receiving antidepressants (mean age, 17.8 years; 65% women).

“There was a much higher prevalence of almost all other psychiatric conditions in those with an eating disorder compared to the general psychiatry population,” coinvestigator Binx Y. Lin, MD, MSc, with Virginia Tech Carilion School of Medicine in Roanoke, Virginia, told this news organization.

In the baseline comparison (before matching), psychiatric disorders seen more often in adults with than in those without EDs included (but were not limited to) mood disorders (51% vs 23%), generalized anxiety disorder (GAD; 30% vs 8%), posttraumatic stress disorder (PTSD; 10% vs 2%), obsessive-compulsive disorder (OCD; 8% vs 1%), panic disorder (6% vs 2%), substance use disorder (8% vs 5%), and adjustment disorders (5% vs 2%).

The results held after propensity score matching, with numerous psychiatric conditions significantly (P < .001) more prevalent in the ED cohort.

Understanding the burden of comorbid psychiatric disorders in young people with EDs is important to design comprehensive, evidence-based interventions, the researchers said.

Providing perspective on this topic, Petros Levounis, MD, professor and chair, Department of Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey, noted that “comorbidity between substance use disorders and other psychiatric disorders has both been grossly underestimated and grossly overestimated.

“I go around the country and see rehab programs, and there are people that very strongly believe that if you stop using the drugs, you won’t have problems with depression or anxiety or whatever,” Dr. Levounis, immediate past president of the APA, shared with this news organization.

“Others say they have never seen somebody who’s addicted to something that doesn’t also have some other psychiatric disorders and if you just scratch the surface, you always find some other psychological or psychiatric problem lying behind. Neither of them are true,” he cautioned.

Dr. Levounis said it’s important to recognize that “some people with addiction will also have another psychiatric disorder. But clearly there are people who just have a mental illness without addiction, and there are clearly people who will just have addiction without other mental illness.”

This research had no commercial funding and was supported in part by the American Psychiatric Association Research Fellowship. Dr. Liu, Dr. Lin, and Dr. Levounis had no relevant disclosures.

A version of this article appeared on Medscape.com .

NEW YORK — Psychiatric comorbidities are highly prevalent in patients with eating disorders (EDs), a large study showed.

In a propensity-matched cohort of young adults with and without EDs, a wide variety of psychiatric disorders including depression and anxiety, as well as cannabis and alcohol use disorders, were more common in those with EDs, investigators found.

Comorbid psychiatric disorders should be “top of mind when working with someone with an eating disorder. If you are able to treat the comorbid psychiatric conditions, they might have a better recovery from the eating disorder,” study investigator Angela Liu, MD, with Northwell Health at Zucker Hillside Hospital, Glen Oaks, New York, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Data Gap

As previously reported by this news organization, more than one in five children worldwide are at risk for an ED and US medical admissions for adolescents with restrictive EDs more than doubled during the pandemic.

Yet there remains a “gap in the literature” about the prevalence of comorbid psychiatric conditions in people with EDs, specifically in young people, Dr. Liu explained.

“To our knowledge, this is the first study using a real-world, multistate administrative dataset to estimate the prevalence of psychiatric comorbidities in young people diagnosed with an eating disorder,” Dr. Liu said.

Using the TriNetX database, the researchers identified through ICD-10 codes 14,524 individuals with EDs (mean age, 15.9 years; 79% women) and 110,051 without EDs who were receiving antidepressants (mean age, 17.8 years; 65% women).

“There was a much higher prevalence of almost all other psychiatric conditions in those with an eating disorder compared to the general psychiatry population,” coinvestigator Binx Y. Lin, MD, MSc, with Virginia Tech Carilion School of Medicine in Roanoke, Virginia, told this news organization.

In the baseline comparison (before matching), psychiatric disorders seen more often in adults with than in those without EDs included (but were not limited to) mood disorders (51% vs 23%), generalized anxiety disorder (GAD; 30% vs 8%), posttraumatic stress disorder (PTSD; 10% vs 2%), obsessive-compulsive disorder (OCD; 8% vs 1%), panic disorder (6% vs 2%), substance use disorder (8% vs 5%), and adjustment disorders (5% vs 2%).

The results held after propensity score matching, with numerous psychiatric conditions significantly (P < .001) more prevalent in the ED cohort.

Understanding the burden of comorbid psychiatric disorders in young people with EDs is important to design comprehensive, evidence-based interventions, the researchers said.

Providing perspective on this topic, Petros Levounis, MD, professor and chair, Department of Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey, noted that “comorbidity between substance use disorders and other psychiatric disorders has both been grossly underestimated and grossly overestimated.

“I go around the country and see rehab programs, and there are people that very strongly believe that if you stop using the drugs, you won’t have problems with depression or anxiety or whatever,” Dr. Levounis, immediate past president of the APA, shared with this news organization.

“Others say they have never seen somebody who’s addicted to something that doesn’t also have some other psychiatric disorders and if you just scratch the surface, you always find some other psychological or psychiatric problem lying behind. Neither of them are true,” he cautioned.

Dr. Levounis said it’s important to recognize that “some people with addiction will also have another psychiatric disorder. But clearly there are people who just have a mental illness without addiction, and there are clearly people who will just have addiction without other mental illness.”

This research had no commercial funding and was supported in part by the American Psychiatric Association Research Fellowship. Dr. Liu, Dr. Lin, and Dr. Levounis had no relevant disclosures.

A version of this article appeared on Medscape.com .

NEW YORK — Psychiatric comorbidities are highly prevalent in patients with eating disorders (EDs), a large study showed.

In a propensity-matched cohort of young adults with and without EDs, a wide variety of psychiatric disorders including depression and anxiety, as well as cannabis and alcohol use disorders, were more common in those with EDs, investigators found.

Comorbid psychiatric disorders should be “top of mind when working with someone with an eating disorder. If you are able to treat the comorbid psychiatric conditions, they might have a better recovery from the eating disorder,” study investigator Angela Liu, MD, with Northwell Health at Zucker Hillside Hospital, Glen Oaks, New York, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Data Gap

As previously reported by this news organization, more than one in five children worldwide are at risk for an ED and US medical admissions for adolescents with restrictive EDs more than doubled during the pandemic.

Yet there remains a “gap in the literature” about the prevalence of comorbid psychiatric conditions in people with EDs, specifically in young people, Dr. Liu explained.

“To our knowledge, this is the first study using a real-world, multistate administrative dataset to estimate the prevalence of psychiatric comorbidities in young people diagnosed with an eating disorder,” Dr. Liu said.

Using the TriNetX database, the researchers identified through ICD-10 codes 14,524 individuals with EDs (mean age, 15.9 years; 79% women) and 110,051 without EDs who were receiving antidepressants (mean age, 17.8 years; 65% women).

“There was a much higher prevalence of almost all other psychiatric conditions in those with an eating disorder compared to the general psychiatry population,” coinvestigator Binx Y. Lin, MD, MSc, with Virginia Tech Carilion School of Medicine in Roanoke, Virginia, told this news organization.

In the baseline comparison (before matching), psychiatric disorders seen more often in adults with than in those without EDs included (but were not limited to) mood disorders (51% vs 23%), generalized anxiety disorder (GAD; 30% vs 8%), posttraumatic stress disorder (PTSD; 10% vs 2%), obsessive-compulsive disorder (OCD; 8% vs 1%), panic disorder (6% vs 2%), substance use disorder (8% vs 5%), and adjustment disorders (5% vs 2%).

The results held after propensity score matching, with numerous psychiatric conditions significantly (P < .001) more prevalent in the ED cohort.

Understanding the burden of comorbid psychiatric disorders in young people with EDs is important to design comprehensive, evidence-based interventions, the researchers said.

Providing perspective on this topic, Petros Levounis, MD, professor and chair, Department of Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey, noted that “comorbidity between substance use disorders and other psychiatric disorders has both been grossly underestimated and grossly overestimated.

“I go around the country and see rehab programs, and there are people that very strongly believe that if you stop using the drugs, you won’t have problems with depression or anxiety or whatever,” Dr. Levounis, immediate past president of the APA, shared with this news organization.

“Others say they have never seen somebody who’s addicted to something that doesn’t also have some other psychiatric disorders and if you just scratch the surface, you always find some other psychological or psychiatric problem lying behind. Neither of them are true,” he cautioned.

Dr. Levounis said it’s important to recognize that “some people with addiction will also have another psychiatric disorder. But clearly there are people who just have a mental illness without addiction, and there are clearly people who will just have addiction without other mental illness.”

This research had no commercial funding and was supported in part by the American Psychiatric Association Research Fellowship. Dr. Liu, Dr. Lin, and Dr. Levounis had no relevant disclosures.

A version of this article appeared on Medscape.com .

WASHINGTON — Ablation of the gastric fundus to reduce production of the “hunger hormone” ghrelin resulted in decreased appetite and significant weight loss among participants in a small first-in-human trial.

“Patients reported a decrease in hunger, appetite, and cravings and an increase in control over [their] eating,” said senior study investigator Christopher McGowan, MD, AGAF, a gastroenterologist in private practice and medical director of True You Weight Loss in Cary, North Carolina.

jaspugugatocokusamoslouoruchesahufraswuvithotocokaslicragisojuchuthibisovujigichotelistuswojut

Major Findings

In the trial, 10 women (mean age, 38 years; mean body mass index, 40.2) underwent endoscopic fundic mucosal ablation via hybrid argon plasma coagulation in an ambulatory setting under general anesthesia from November 1, 2022, to April 14, 2023. The procedure took less than an hour on average, and the technique gave them easy access to the fundus, Dr. McGowan said.

Compared with baseline, there were multiple beneficial outcomes at 6 months:

• 45% less circulating ghrelin in the blood.
• 53% drop in ghrelin-producing cells in the fundus.
• 42% reduction in stomach capacity.
• 43% decrease in hunger, appetite, and cravings.
• 7.7% body weight loss.

Over the 6 months of the study, mean ghrelin concentrations dropped from 461.6 pg/mL at baseline to 254.8 pg/mL (P = .006).

It is fascinating that the hormone ghrelin decreased just by ablating, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024. “They used the same device that we use to treat bleeding ulcers or lesions in the stomach and applied it broadly over the whole upper part of the stomach.”

cesputhabravesa

Another Anti-Obesity Tool?

“We’re all familiar with the epidemic that is obesity affecting nearly one in two adults, and the profound impact that it has on patients’ health, their quality of life, as well as the healthcare system,” Dr. McGowan said. “It’s clear that we need every tool possible to address this because we know that obesity is not a matter of willpower. It’s a disease.”

Gastric fundus ablation “may represent, and frankly should represent, a treatment option for the greater than 100 million US adults with obesity,” he added.

Not every patient wants to or can access GLP-1 medications, Dr. McGowan said. Also, “there’s a difference between taking a medication long-term, requiring an injection every week, vs a single intervention in time that carries forward.”

Ablation could also help people transition after they stop GLP-1 medications to help them maintain their weight loss, he said.

Weight loss is the endpoint you care about the most, said Dr. Laine, who co-moderated the press briefing.

Though the weight loss of 7.7% was not a large percentage, it was only 10 patients. We will have to see whether the total body weight loss is different when they do the procedure in more patients or if they can combine different mechanisms, Dr. Laine said.

It remains unclear whether gastric fundus ablation would be a stand-alone procedure or used in combination with another endoscopic weight-management intervention, bariatric surgery, or medication.

The endoscopic sleeve, which is a stomach-reducing procedure, is very effective, but it doesn’t diminish hunger, Dr. McGowan said. Combining it with ablation may be “a best-of-both-worlds scenario.”

Dr. Laine added that another open question is whether the gastric fundal accommodation will be associated with any side effects such as dyspepsia.

Dr. McGowan reported consulting for Boston Scientific and Apollo Endosurgery. Dr. Laine reported no relevant financial relationships.

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

WASHINGTON — Ablation of the gastric fundus to reduce production of the “hunger hormone” ghrelin resulted in decreased appetite and significant weight loss among participants in a small first-in-human trial.

“Patients reported a decrease in hunger, appetite, and cravings and an increase in control over [their] eating,” said senior study investigator Christopher McGowan, MD, AGAF, a gastroenterologist in private practice and medical director of True You Weight Loss in Cary, North Carolina.

jaspugugatocokusamoslouoruchesahufraswuvithotocokaslicragisojuchuthibisovujigichotelistuswojut

Major Findings

In the trial, 10 women (mean age, 38 years; mean body mass index, 40.2) underwent endoscopic fundic mucosal ablation via hybrid argon plasma coagulation in an ambulatory setting under general anesthesia from November 1, 2022, to April 14, 2023. The procedure took less than an hour on average, and the technique gave them easy access to the fundus, Dr. McGowan said.

Compared with baseline, there were multiple beneficial outcomes at 6 months:

• 45% less circulating ghrelin in the blood.
• 53% drop in ghrelin-producing cells in the fundus.
• 42% reduction in stomach capacity.
• 43% decrease in hunger, appetite, and cravings.
• 7.7% body weight loss.

Over the 6 months of the study, mean ghrelin concentrations dropped from 461.6 pg/mL at baseline to 254.8 pg/mL (P = .006).

It is fascinating that the hormone ghrelin decreased just by ablating, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024. “They used the same device that we use to treat bleeding ulcers or lesions in the stomach and applied it broadly over the whole upper part of the stomach.”

cesputhabravesa

Another Anti-Obesity Tool?

“We’re all familiar with the epidemic that is obesity affecting nearly one in two adults, and the profound impact that it has on patients’ health, their quality of life, as well as the healthcare system,” Dr. McGowan said. “It’s clear that we need every tool possible to address this because we know that obesity is not a matter of willpower. It’s a disease.”

Gastric fundus ablation “may represent, and frankly should represent, a treatment option for the greater than 100 million US adults with obesity,” he added.

Not every patient wants to or can access GLP-1 medications, Dr. McGowan said. Also, “there’s a difference between taking a medication long-term, requiring an injection every week, vs a single intervention in time that carries forward.”

Ablation could also help people transition after they stop GLP-1 medications to help them maintain their weight loss, he said.

Weight loss is the endpoint you care about the most, said Dr. Laine, who co-moderated the press briefing.

Though the weight loss of 7.7% was not a large percentage, it was only 10 patients. We will have to see whether the total body weight loss is different when they do the procedure in more patients or if they can combine different mechanisms, Dr. Laine said.

It remains unclear whether gastric fundus ablation would be a stand-alone procedure or used in combination with another endoscopic weight-management intervention, bariatric surgery, or medication.

The endoscopic sleeve, which is a stomach-reducing procedure, is very effective, but it doesn’t diminish hunger, Dr. McGowan said. Combining it with ablation may be “a best-of-both-worlds scenario.”

Dr. Laine added that another open question is whether the gastric fundal accommodation will be associated with any side effects such as dyspepsia.

Dr. McGowan reported consulting for Boston Scientific and Apollo Endosurgery. Dr. Laine reported no relevant financial relationships.

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

WASHINGTON — Ablation of the gastric fundus to reduce production of the “hunger hormone” ghrelin resulted in decreased appetite and significant weight loss among participants in a small first-in-human trial.

“Patients reported a decrease in hunger, appetite, and cravings and an increase in control over [their] eating,” said senior study investigator Christopher McGowan, MD, AGAF, a gastroenterologist in private practice and medical director of True You Weight Loss in Cary, North Carolina.

jaspugugatocokusamoslouoruchesahufraswuvithotocokaslicragisojuchuthibisovujigichotelistuswojut

Major Findings

In the trial, 10 women (mean age, 38 years; mean body mass index, 40.2) underwent endoscopic fundic mucosal ablation via hybrid argon plasma coagulation in an ambulatory setting under general anesthesia from November 1, 2022, to April 14, 2023. The procedure took less than an hour on average, and the technique gave them easy access to the fundus, Dr. McGowan said.

Compared with baseline, there were multiple beneficial outcomes at 6 months:

• 45% less circulating ghrelin in the blood.
• 53% drop in ghrelin-producing cells in the fundus.
• 42% reduction in stomach capacity.
• 43% decrease in hunger, appetite, and cravings.
• 7.7% body weight loss.

Over the 6 months of the study, mean ghrelin concentrations dropped from 461.6 pg/mL at baseline to 254.8 pg/mL (P = .006).

It is fascinating that the hormone ghrelin decreased just by ablating, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024. “They used the same device that we use to treat bleeding ulcers or lesions in the stomach and applied it broadly over the whole upper part of the stomach.”

cesputhabravesa

Another Anti-Obesity Tool?

“We’re all familiar with the epidemic that is obesity affecting nearly one in two adults, and the profound impact that it has on patients’ health, their quality of life, as well as the healthcare system,” Dr. McGowan said. “It’s clear that we need every tool possible to address this because we know that obesity is not a matter of willpower. It’s a disease.”

Gastric fundus ablation “may represent, and frankly should represent, a treatment option for the greater than 100 million US adults with obesity,” he added.

Not every patient wants to or can access GLP-1 medications, Dr. McGowan said. Also, “there’s a difference between taking a medication long-term, requiring an injection every week, vs a single intervention in time that carries forward.”

Ablation could also help people transition after they stop GLP-1 medications to help them maintain their weight loss, he said.

Weight loss is the endpoint you care about the most, said Dr. Laine, who co-moderated the press briefing.

Though the weight loss of 7.7% was not a large percentage, it was only 10 patients. We will have to see whether the total body weight loss is different when they do the procedure in more patients or if they can combine different mechanisms, Dr. Laine said.

It remains unclear whether gastric fundus ablation would be a stand-alone procedure or used in combination with another endoscopic weight-management intervention, bariatric surgery, or medication.

The endoscopic sleeve, which is a stomach-reducing procedure, is very effective, but it doesn’t diminish hunger, Dr. McGowan said. Combining it with ablation may be “a best-of-both-worlds scenario.”

Dr. Laine added that another open question is whether the gastric fundal accommodation will be associated with any side effects such as dyspepsia.

Dr. McGowan reported consulting for Boston Scientific and Apollo Endosurgery. Dr. Laine reported no relevant financial relationships.

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

Screenings may not be the way to get needed resources to children and their caregivers, according to new research presented at the annual meeting of the Pediatric Academic Societies (PAS).

Caregivers and parents who were asked if they wanted assistance in several areas of need, including transportation and childcare, were nearly twice as likely to say they wanted such help than those who received a screening on current hardships. Generally, each questionnaire is administered in front of their children in primary care or pediatric hospital settings.

“Families have a lot of concern about being seen a different way by their healthcare team, being seen as unfit, and having child protective services involved in their childcare for issues related to poverty,” said Danielle Cullen, MD, a pediatric emergency medicine specialist at Children’s Hospital of Philadelphia (CHOP) and assistant professor of pediatrics at the University of Pennsylvania in Philadelphia.

Dr. Cullen and her colleagues analyzed data from nearly 4000 caregivers of children up to age 21 at emergency departments or primary care clinics at CHOP between 2021 and 2023.

Caregivers were randomly assigned to one of three arms — screening with a version of WE CARE (Well Child Care, Evaluation, Community Resources, Advocacy, Referral, Education), use of an online menu of options for help in areas like housing, or neither approach.

Caregivers in all three arms received a map of resources and a follow-up text from a resource navigator to assist them as needed.

Nearly 40% of caregivers who presented with the digital menu said they wanted resources compared with 29% of those who were screened (P < .001). Non-native English speakers given the menu were 2.5 times more likely to say yes to resources compared with those who were screened.

“We need to be thoughtful about these mandates to screen for social determinants of health: It’s not that straightforward,” said Esther K. Chung, MD, a pediatrician and professor of pediatrics at the University of Washington Medicine in Seattle, who was not involved in the study. “What we’re getting from this study is that patients want choice, and the menu provides them choice.”

Dr. Cullen said the menu option allows caregivers to make choices based on their priorities and not on whether they meet the screening thresholds for need.

While some health clinics utilize tablet forms for screenings to offer more privacy with questions, asking direct questions about income, food insecurity, and housing stability can be stigmatizing, Dr. Cullen said.

“Screening positive for social risk doesn’t mean that you actually want resources, and on the flip side, the literature shows that about half of the people who screen negative want resources,” she said.

Dr. Cullen and her team also conducted follow-up interviews with caregivers and found many feared that their clinician would assume a medical condition was connected to living conditions. They also had concerns about insurance companies gaining access to the data and using it to deny coverage or raise costs.

Spanish-speaking caregivers cited fears about their immigration status, experiences of discrimination, and language barriers when trying to access resources.

Participants said a few key strategies could make screening less intimidating, such as abstaining from screening during a serious medical visit, asking for consent to record answers in medical records, and communicating in an empathetic manner.

“Some families are a bit surprised when we ask about things like housing and food insecurity, but I think as long as we contextualize it, we can minimize the stigma associated with it,” Dr. Chung said. “That takes quite a bit of nuance and skill.”

The study was funded by the William T. Grant Foundation and the Emergency Medicine Foundation. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

Screenings may not be the way to get needed resources to children and their caregivers, according to new research presented at the annual meeting of the Pediatric Academic Societies (PAS).

Caregivers and parents who were asked if they wanted assistance in several areas of need, including transportation and childcare, were nearly twice as likely to say they wanted such help than those who received a screening on current hardships. Generally, each questionnaire is administered in front of their children in primary care or pediatric hospital settings.

“Families have a lot of concern about being seen a different way by their healthcare team, being seen as unfit, and having child protective services involved in their childcare for issues related to poverty,” said Danielle Cullen, MD, a pediatric emergency medicine specialist at Children’s Hospital of Philadelphia (CHOP) and assistant professor of pediatrics at the University of Pennsylvania in Philadelphia.

Dr. Cullen and her colleagues analyzed data from nearly 4000 caregivers of children up to age 21 at emergency departments or primary care clinics at CHOP between 2021 and 2023.

Caregivers were randomly assigned to one of three arms — screening with a version of WE CARE (Well Child Care, Evaluation, Community Resources, Advocacy, Referral, Education), use of an online menu of options for help in areas like housing, or neither approach.

Caregivers in all three arms received a map of resources and a follow-up text from a resource navigator to assist them as needed.

Nearly 40% of caregivers who presented with the digital menu said they wanted resources compared with 29% of those who were screened (P < .001). Non-native English speakers given the menu were 2.5 times more likely to say yes to resources compared with those who were screened.

“We need to be thoughtful about these mandates to screen for social determinants of health: It’s not that straightforward,” said Esther K. Chung, MD, a pediatrician and professor of pediatrics at the University of Washington Medicine in Seattle, who was not involved in the study. “What we’re getting from this study is that patients want choice, and the menu provides them choice.”

Dr. Cullen said the menu option allows caregivers to make choices based on their priorities and not on whether they meet the screening thresholds for need.

While some health clinics utilize tablet forms for screenings to offer more privacy with questions, asking direct questions about income, food insecurity, and housing stability can be stigmatizing, Dr. Cullen said.

“Screening positive for social risk doesn’t mean that you actually want resources, and on the flip side, the literature shows that about half of the people who screen negative want resources,” she said.

Dr. Cullen and her team also conducted follow-up interviews with caregivers and found many feared that their clinician would assume a medical condition was connected to living conditions. They also had concerns about insurance companies gaining access to the data and using it to deny coverage or raise costs.

Spanish-speaking caregivers cited fears about their immigration status, experiences of discrimination, and language barriers when trying to access resources.

Participants said a few key strategies could make screening less intimidating, such as abstaining from screening during a serious medical visit, asking for consent to record answers in medical records, and communicating in an empathetic manner.

“Some families are a bit surprised when we ask about things like housing and food insecurity, but I think as long as we contextualize it, we can minimize the stigma associated with it,” Dr. Chung said. “That takes quite a bit of nuance and skill.”

The study was funded by the William T. Grant Foundation and the Emergency Medicine Foundation. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

Screenings may not be the way to get needed resources to children and their caregivers, according to new research presented at the annual meeting of the Pediatric Academic Societies (PAS).

Caregivers and parents who were asked if they wanted assistance in several areas of need, including transportation and childcare, were nearly twice as likely to say they wanted such help than those who received a screening on current hardships. Generally, each questionnaire is administered in front of their children in primary care or pediatric hospital settings.

“Families have a lot of concern about being seen a different way by their healthcare team, being seen as unfit, and having child protective services involved in their childcare for issues related to poverty,” said Danielle Cullen, MD, a pediatric emergency medicine specialist at Children’s Hospital of Philadelphia (CHOP) and assistant professor of pediatrics at the University of Pennsylvania in Philadelphia.

Dr. Cullen and her colleagues analyzed data from nearly 4000 caregivers of children up to age 21 at emergency departments or primary care clinics at CHOP between 2021 and 2023.

Caregivers were randomly assigned to one of three arms — screening with a version of WE CARE (Well Child Care, Evaluation, Community Resources, Advocacy, Referral, Education), use of an online menu of options for help in areas like housing, or neither approach.

Caregivers in all three arms received a map of resources and a follow-up text from a resource navigator to assist them as needed.

Nearly 40% of caregivers who presented with the digital menu said they wanted resources compared with 29% of those who were screened (P < .001). Non-native English speakers given the menu were 2.5 times more likely to say yes to resources compared with those who were screened.

“We need to be thoughtful about these mandates to screen for social determinants of health: It’s not that straightforward,” said Esther K. Chung, MD, a pediatrician and professor of pediatrics at the University of Washington Medicine in Seattle, who was not involved in the study. “What we’re getting from this study is that patients want choice, and the menu provides them choice.”

Dr. Cullen said the menu option allows caregivers to make choices based on their priorities and not on whether they meet the screening thresholds for need.

While some health clinics utilize tablet forms for screenings to offer more privacy with questions, asking direct questions about income, food insecurity, and housing stability can be stigmatizing, Dr. Cullen said.

“Screening positive for social risk doesn’t mean that you actually want resources, and on the flip side, the literature shows that about half of the people who screen negative want resources,” she said.

Dr. Cullen and her team also conducted follow-up interviews with caregivers and found many feared that their clinician would assume a medical condition was connected to living conditions. They also had concerns about insurance companies gaining access to the data and using it to deny coverage or raise costs.

Spanish-speaking caregivers cited fears about their immigration status, experiences of discrimination, and language barriers when trying to access resources.

Participants said a few key strategies could make screening less intimidating, such as abstaining from screening during a serious medical visit, asking for consent to record answers in medical records, and communicating in an empathetic manner.

“Some families are a bit surprised when we ask about things like housing and food insecurity, but I think as long as we contextualize it, we can minimize the stigma associated with it,” Dr. Chung said. “That takes quite a bit of nuance and skill.”

The study was funded by the William T. Grant Foundation and the Emergency Medicine Foundation. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

No matter where one looks for the statistics, no matter what words one chooses to describe it, this country has a child and adolescent mental health crisis. Almost 20% of young people in the 3-17 age bracket have a mental, emotional, developmental, or behavioral disorder. COVID-19 has certainly exacerbated the problem, but the downward trend in the mental health of this nation has been going on for decades.

The voices calling for more services to address the problem are getting more numerous and louder. But, what exactly should those services look like and who should be delivering them?

Wilkoff_William_G_2_web.jpg

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

No matter where one looks for the statistics, no matter what words one chooses to describe it, this country has a child and adolescent mental health crisis. Almost 20% of young people in the 3-17 age bracket have a mental, emotional, developmental, or behavioral disorder. COVID-19 has certainly exacerbated the problem, but the downward trend in the mental health of this nation has been going on for decades.

The voices calling for more services to address the problem are getting more numerous and louder. But, what exactly should those services look like and who should be delivering them?

Wilkoff_William_G_2_web.jpg

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

No matter where one looks for the statistics, no matter what words one chooses to describe it, this country has a child and adolescent mental health crisis. Almost 20% of young people in the 3-17 age bracket have a mental, emotional, developmental, or behavioral disorder. COVID-19 has certainly exacerbated the problem, but the downward trend in the mental health of this nation has been going on for decades.

The voices calling for more services to address the problem are getting more numerous and louder. But, what exactly should those services look like and who should be delivering them?

Wilkoff_William_G_2_web.jpg

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

TOPLINE:

Adding arthroscopic surgery to nonoperative management neither delays nor accelerates the timing of total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA).

METHODOLOGY:

• Some case series show that arthroscopic surgery for knee OA may delay more invasive procedures, such as TKA or osteotomy, while longitudinal cohort studies often contradict this. Current OA guidelines are yet to address this issue.
• This secondary analysis of a randomized trial compared the long-term incidence of TKA in 178 patients (mean age, 59 years; 64.3% women) with knee OA who were referred for potential arthroscopic surgery at a tertiary care center in Canada.
• The patients received nonoperative care with or without additional arthroscopic surgery.
• Patients in the arthroscopic surgery group had specific knee procedures (resection of degenerative knee tissues) along with nonoperative management (physical therapy plus medications as required), while the control group received nonoperative management alone.
• The primary outcome was TKA on the knee being studied, and the secondary outcome was TKA or osteotomy on either knee.

TAKEAWAY:

• During a median follow-up of 13.8 years, 37.6% of patients underwent TKA, with comparable proportions of patients in the arthroscopic surgery and control groups undergoing TKA (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.52-1.40).
• The rates of TKA or osteotomy on either knee were similar in both groups (aHR, 0.91; 95% CI, 0.59-1.41).
• A time-stratified analysis done for 0-5 years, 5-10 years, and beyond 10 years of follow-up also showed a consistent interpretation.
• When patients with crossover to arthroscopic surgery during the follow-up were included, the results remained similar for both the primary (HR, 0.88; 95% CI, 0.53-1.44) and secondary (HR, 1.08; 95% CI, 0.69-1.68) outcomes.

IN PRACTICE:

“Our study findings do not support the use of arthroscopic surgery for OA of the knee.” “Arthroscopic surgery does not provide additional benefit to nonoperative management for improving pain, stiffness, and function and is likely not cost-effective at 2 years of follow-up,” the authors wrote.

SOURCE:

This study was led by Trevor B. Birmingham, PhD, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario, London, Ontario, Canada. It was published online in JAMA Network Open

LIMITATIONS:

The study was designed to assess differences in 2-year patient-reported outcomes rather than long-term TKA incidence. Factors influencing decisions to undergo TKA or osteotomy were not considered. Moreover, the effects observed in this study should be evaluated considering the estimated confidence intervals.

DISCLOSURES:

This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Some authors declared consulting, performing contracted services, or receiving grant funding, royalties, and nonfinancial support from various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Adding arthroscopic surgery to nonoperative management neither delays nor accelerates the timing of total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA).

METHODOLOGY:

• Some case series show that arthroscopic surgery for knee OA may delay more invasive procedures, such as TKA or osteotomy, while longitudinal cohort studies often contradict this. Current OA guidelines are yet to address this issue.
• This secondary analysis of a randomized trial compared the long-term incidence of TKA in 178 patients (mean age, 59 years; 64.3% women) with knee OA who were referred for potential arthroscopic surgery at a tertiary care center in Canada.
• The patients received nonoperative care with or without additional arthroscopic surgery.
• Patients in the arthroscopic surgery group had specific knee procedures (resection of degenerative knee tissues) along with nonoperative management (physical therapy plus medications as required), while the control group received nonoperative management alone.
• The primary outcome was TKA on the knee being studied, and the secondary outcome was TKA or osteotomy on either knee.

TAKEAWAY:

• During a median follow-up of 13.8 years, 37.6% of patients underwent TKA, with comparable proportions of patients in the arthroscopic surgery and control groups undergoing TKA (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.52-1.40).
• The rates of TKA or osteotomy on either knee were similar in both groups (aHR, 0.91; 95% CI, 0.59-1.41).
• A time-stratified analysis done for 0-5 years, 5-10 years, and beyond 10 years of follow-up also showed a consistent interpretation.
• When patients with crossover to arthroscopic surgery during the follow-up were included, the results remained similar for both the primary (HR, 0.88; 95% CI, 0.53-1.44) and secondary (HR, 1.08; 95% CI, 0.69-1.68) outcomes.

IN PRACTICE:

“Our study findings do not support the use of arthroscopic surgery for OA of the knee.” “Arthroscopic surgery does not provide additional benefit to nonoperative management for improving pain, stiffness, and function and is likely not cost-effective at 2 years of follow-up,” the authors wrote.

SOURCE:

This study was led by Trevor B. Birmingham, PhD, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario, London, Ontario, Canada. It was published online in JAMA Network Open

LIMITATIONS:

The study was designed to assess differences in 2-year patient-reported outcomes rather than long-term TKA incidence. Factors influencing decisions to undergo TKA or osteotomy were not considered. Moreover, the effects observed in this study should be evaluated considering the estimated confidence intervals.

DISCLOSURES:

This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Some authors declared consulting, performing contracted services, or receiving grant funding, royalties, and nonfinancial support from various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Adding arthroscopic surgery to nonoperative management neither delays nor accelerates the timing of total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA).

METHODOLOGY:

• Some case series show that arthroscopic surgery for knee OA may delay more invasive procedures, such as TKA or osteotomy, while longitudinal cohort studies often contradict this. Current OA guidelines are yet to address this issue.
• This secondary analysis of a randomized trial compared the long-term incidence of TKA in 178 patients (mean age, 59 years; 64.3% women) with knee OA who were referred for potential arthroscopic surgery at a tertiary care center in Canada.
• The patients received nonoperative care with or without additional arthroscopic surgery.
• Patients in the arthroscopic surgery group had specific knee procedures (resection of degenerative knee tissues) along with nonoperative management (physical therapy plus medications as required), while the control group received nonoperative management alone.
• The primary outcome was TKA on the knee being studied, and the secondary outcome was TKA or osteotomy on either knee.

TAKEAWAY:

• During a median follow-up of 13.8 years, 37.6% of patients underwent TKA, with comparable proportions of patients in the arthroscopic surgery and control groups undergoing TKA (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.52-1.40).
• The rates of TKA or osteotomy on either knee were similar in both groups (aHR, 0.91; 95% CI, 0.59-1.41).
• A time-stratified analysis done for 0-5 years, 5-10 years, and beyond 10 years of follow-up also showed a consistent interpretation.
• When patients with crossover to arthroscopic surgery during the follow-up were included, the results remained similar for both the primary (HR, 0.88; 95% CI, 0.53-1.44) and secondary (HR, 1.08; 95% CI, 0.69-1.68) outcomes.

IN PRACTICE:

“Our study findings do not support the use of arthroscopic surgery for OA of the knee.” “Arthroscopic surgery does not provide additional benefit to nonoperative management for improving pain, stiffness, and function and is likely not cost-effective at 2 years of follow-up,” the authors wrote.

SOURCE:

This study was led by Trevor B. Birmingham, PhD, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario, London, Ontario, Canada. It was published online in JAMA Network Open

LIMITATIONS:

The study was designed to assess differences in 2-year patient-reported outcomes rather than long-term TKA incidence. Factors influencing decisions to undergo TKA or osteotomy were not considered. Moreover, the effects observed in this study should be evaluated considering the estimated confidence intervals.

DISCLOSURES:

This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Some authors declared consulting, performing contracted services, or receiving grant funding, royalties, and nonfinancial support from various sources.

A version of this article appeared on Medscape.com.

NEW YORK — Urate, the culprit of gout, affects the vasculature in multiple ways that can raise cardiovascular risk (CV) in an individual with gout, and following guidelines for gout treatment, including the use of colchicine, can be the key to reducing those risks.

“Guideline-concordant gout treatment, which is essentially an anti-inflammatory urate-lowering strategy, at least improves arterial physiology and likely reduces cardiovascular risk,” Michael H. Pillinger, MD, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference. Dr. Pillinger is professor of medicine and biochemistry and molecular pharmacology at New York University Grossman School of Medicine, New York City, who has published multiple studies on gout.

brojideclewrapricrewronicrauodespeposaprelarewrinochatinestubolephiuuclegesposhutihibrotimathorakichalerucluceneswuvugapishifrabraswajurespasorulobrumuresp

He cited evidence that has shown soluble urate stimulates the production of C-reactive protein (CRP), which is a predictor of cardiovascular disease (CVD). Another study, in which Dr. Pillinger participated, demonstrated that gout patients have impaired vascular endothelial function associated with a chronic, low-level inflammatory state, he said.

“There’s good evidence that urate itself affects the vasculature in multiple ways, and I suspect this may be a model for other metabolic effects on vasculature,” Dr. Pillinger said. “Patients with gout have abnormal endothelium in ways that really convey vascular risk.”
 

Gout, Inflammation, and CVD

However, for rheumatologists to study the association between gout-related inflammation and CVD is “very, very hard,” Dr. Pillinger added. “But I do think that the mechanisms by which gout induces biological changes in the vasculature may provide insights into cardiovascular disease in general.”

One way to evaluate the effects of gout on the endothelium in the clinic is to measure flow-mediated dilation. This technique involves placing an ultrasound probe over the brachial artery and measuring the baseline artery diameter. Then, with the blood pressure cuff over the forearm, inflate it to reduce flow, then release the cuff and measure the brachial artery diameter after the endothelium releases vasodilators.

Dr. Pillinger and colleagues evaluated this technique in 34 patients with gout and 64 controls and found that patients with gout had an almost 50% decrease in flow-mediated dilation, he said. “Interestingly, the higher the urate, the worse the flow; the more the inflammation, the worse the flow, so seemingly corresponding with the severity of the gout,” he said. That raised an obvious question, Dr. Pillinger continued: “If you can treat the gout, can you improve the flow-mediated dilation?”

His group answered that question with a study in 38 previously untreated patients with gout, giving them colchicine 0.6 mg twice daily for a month plus a urate-lowering xanthine oxidase inhibitor (allopurinol or febuxostat) to treat them to a target urate level of < 6 mg/dL. “We saw an increase in endothelial function, and it normalized,” Dr. Pillinger said.

However, some study participants didn’t respond. “They were people with well-established other cardiovascular comorbidities — hypertension, hyperlipidemia,” he said. “I think some people just have vessels that are too damaged to get at them just by fixing their gout problem or their inflammation.”

That means patients with gout need to be treated with colchicine early on to avoid CV problems, Dr. Pillinger added. “We ought to get to them before they have the other problems,” he said.

Managing gout, and the concomitant CV problems, requires vigilance both during and in between flares, Dr. Pillinger said after his presentation.

“We have always taught that patients between flares basically look like people with no gout, but we do know now that patients with gout between flares tend to have what you might call ‘subclinical’ inflammation: CRPs and ESRs [erythrocyte sedimentation rates] that are higher than those of the general population, though not so excessive that they might grab attention,” he said. “We also know that many, if not all, patients between flares have urate deposited in or around their joints, but how these two relate is not fully established.”

Better treatment within 3 months of an acute gout flare may reduce the risk for CV events, he said, but that’s based on speculation more so than clinical data.
 

Potential Benefits of Targeting Inflammation

“More chronically, we know from the cardiologists’ studies that anti-inflammatory therapy should reduce risk in the high-risk general population,” Dr. Pillinger said. “There are no prospective studies confirming that this approach will work among gout patients, but there is no reason why it shouldn’t work — except perhaps that gout patients may have higher inflammation than the general population and also have more comorbidities, so they could perhaps be more resistant.”

Dr. Pillinger said that his group’s studies and another led by Daniel Solomon, MD, at Brigham and Women’s Hospital in Boston, have indicated that anti-inflammatory strategies in gout will lower CV risk.

“And interestingly,” he added, “our data suggest that colchicine use may lower risk not only in high-risk gout patients but also in gout patients who start with no CAD [coronary artery disease] but who seem to have less incident CAD on colchicine. I see this as identifying that gout patients are intrinsically at high risk for CAD, even if they don’t actually have any, so they represent a population for whom lowering chronic inflammation may help prevent incident disease.”

Dr. Pillinger provided more evidence that the understanding of the relationship between gout, gout flares, and CV risk is evolving, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone, New York City.

Garshick_Michael_NY_web.JPG

“There’s epidemiologic evidence supporting the association,” Dr. Garshick told this news organization after the conference. “We think that most conditions with immune system activation do tend to have an increased risk of some form of cardiovascular disease, but I think the relationship with gout has been highly underpublicized.”

Many patients with gout tend to have a higher prevalence of traditional cardiometabolic issues, which may compound the relationship, Dr. Garshick added. “However, I would argue that with this patient subset that it doesn’t matter because gout patients have a higher risk of traditional risk factors, and you have to [treat-to-target] those traditional risk factors.”

While the clinical evidence of a link between gout and atherosclerosis may not be conclusive, enough circumstantial evidence exists to believe that treating gout will reduce CV risks, he said. “Some of the imaging techniques do suggest that gouty crystals [are] in the atherosclerotic plaque of gout patients,” Dr. Garshick added. Dr. Pillinger’s work, he said, “is showing us that there are different pathways to develop atherosclerosis.”

Dr. Pillinger disclosed relationships with Federation Bio, Fortress Biotech, Amgen, Scilex, Hikma Pharmaceuticals, LG Chem, and Olatec Therapeutics. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
 

A version of this article appeared on Medscape.com.

NEW YORK — Urate, the culprit of gout, affects the vasculature in multiple ways that can raise cardiovascular risk (CV) in an individual with gout, and following guidelines for gout treatment, including the use of colchicine, can be the key to reducing those risks.

“Guideline-concordant gout treatment, which is essentially an anti-inflammatory urate-lowering strategy, at least improves arterial physiology and likely reduces cardiovascular risk,” Michael H. Pillinger, MD, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference. Dr. Pillinger is professor of medicine and biochemistry and molecular pharmacology at New York University Grossman School of Medicine, New York City, who has published multiple studies on gout.

brojideclewrapricrewronicrauodespeposaprelarewrinochatinestubolephiuuclegesposhutihibrotimathorakichalerucluceneswuvugapishifrabraswajurespasorulobrumuresp

He cited evidence that has shown soluble urate stimulates the production of C-reactive protein (CRP), which is a predictor of cardiovascular disease (CVD). Another study, in which Dr. Pillinger participated, demonstrated that gout patients have impaired vascular endothelial function associated with a chronic, low-level inflammatory state, he said.

“There’s good evidence that urate itself affects the vasculature in multiple ways, and I suspect this may be a model for other metabolic effects on vasculature,” Dr. Pillinger said. “Patients with gout have abnormal endothelium in ways that really convey vascular risk.”
 

Gout, Inflammation, and CVD

However, for rheumatologists to study the association between gout-related inflammation and CVD is “very, very hard,” Dr. Pillinger added. “But I do think that the mechanisms by which gout induces biological changes in the vasculature may provide insights into cardiovascular disease in general.”

One way to evaluate the effects of gout on the endothelium in the clinic is to measure flow-mediated dilation. This technique involves placing an ultrasound probe over the brachial artery and measuring the baseline artery diameter. Then, with the blood pressure cuff over the forearm, inflate it to reduce flow, then release the cuff and measure the brachial artery diameter after the endothelium releases vasodilators.

Dr. Pillinger and colleagues evaluated this technique in 34 patients with gout and 64 controls and found that patients with gout had an almost 50% decrease in flow-mediated dilation, he said. “Interestingly, the higher the urate, the worse the flow; the more the inflammation, the worse the flow, so seemingly corresponding with the severity of the gout,” he said. That raised an obvious question, Dr. Pillinger continued: “If you can treat the gout, can you improve the flow-mediated dilation?”

His group answered that question with a study in 38 previously untreated patients with gout, giving them colchicine 0.6 mg twice daily for a month plus a urate-lowering xanthine oxidase inhibitor (allopurinol or febuxostat) to treat them to a target urate level of < 6 mg/dL. “We saw an increase in endothelial function, and it normalized,” Dr. Pillinger said.

However, some study participants didn’t respond. “They were people with well-established other cardiovascular comorbidities — hypertension, hyperlipidemia,” he said. “I think some people just have vessels that are too damaged to get at them just by fixing their gout problem or their inflammation.”

That means patients with gout need to be treated with colchicine early on to avoid CV problems, Dr. Pillinger added. “We ought to get to them before they have the other problems,” he said.

Managing gout, and the concomitant CV problems, requires vigilance both during and in between flares, Dr. Pillinger said after his presentation.

“We have always taught that patients between flares basically look like people with no gout, but we do know now that patients with gout between flares tend to have what you might call ‘subclinical’ inflammation: CRPs and ESRs [erythrocyte sedimentation rates] that are higher than those of the general population, though not so excessive that they might grab attention,” he said. “We also know that many, if not all, patients between flares have urate deposited in or around their joints, but how these two relate is not fully established.”

Better treatment within 3 months of an acute gout flare may reduce the risk for CV events, he said, but that’s based on speculation more so than clinical data.
 

Potential Benefits of Targeting Inflammation

“More chronically, we know from the cardiologists’ studies that anti-inflammatory therapy should reduce risk in the high-risk general population,” Dr. Pillinger said. “There are no prospective studies confirming that this approach will work among gout patients, but there is no reason why it shouldn’t work — except perhaps that gout patients may have higher inflammation than the general population and also have more comorbidities, so they could perhaps be more resistant.”

Dr. Pillinger said that his group’s studies and another led by Daniel Solomon, MD, at Brigham and Women’s Hospital in Boston, have indicated that anti-inflammatory strategies in gout will lower CV risk.

“And interestingly,” he added, “our data suggest that colchicine use may lower risk not only in high-risk gout patients but also in gout patients who start with no CAD [coronary artery disease] but who seem to have less incident CAD on colchicine. I see this as identifying that gout patients are intrinsically at high risk for CAD, even if they don’t actually have any, so they represent a population for whom lowering chronic inflammation may help prevent incident disease.”

Dr. Pillinger provided more evidence that the understanding of the relationship between gout, gout flares, and CV risk is evolving, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone, New York City.

Garshick_Michael_NY_web.JPG

“There’s epidemiologic evidence supporting the association,” Dr. Garshick told this news organization after the conference. “We think that most conditions with immune system activation do tend to have an increased risk of some form of cardiovascular disease, but I think the relationship with gout has been highly underpublicized.”

Many patients with gout tend to have a higher prevalence of traditional cardiometabolic issues, which may compound the relationship, Dr. Garshick added. “However, I would argue that with this patient subset that it doesn’t matter because gout patients have a higher risk of traditional risk factors, and you have to [treat-to-target] those traditional risk factors.”

While the clinical evidence of a link between gout and atherosclerosis may not be conclusive, enough circumstantial evidence exists to believe that treating gout will reduce CV risks, he said. “Some of the imaging techniques do suggest that gouty crystals [are] in the atherosclerotic plaque of gout patients,” Dr. Garshick added. Dr. Pillinger’s work, he said, “is showing us that there are different pathways to develop atherosclerosis.”

Dr. Pillinger disclosed relationships with Federation Bio, Fortress Biotech, Amgen, Scilex, Hikma Pharmaceuticals, LG Chem, and Olatec Therapeutics. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
 

A version of this article appeared on Medscape.com.

NEW YORK — Urate, the culprit of gout, affects the vasculature in multiple ways that can raise cardiovascular risk (CV) in an individual with gout, and following guidelines for gout treatment, including the use of colchicine, can be the key to reducing those risks.

“Guideline-concordant gout treatment, which is essentially an anti-inflammatory urate-lowering strategy, at least improves arterial physiology and likely reduces cardiovascular risk,” Michael H. Pillinger, MD, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference. Dr. Pillinger is professor of medicine and biochemistry and molecular pharmacology at New York University Grossman School of Medicine, New York City, who has published multiple studies on gout.

brojideclewrapricrewronicrauodespeposaprelarewrinochatinestubolephiuuclegesposhutihibrotimathorakichalerucluceneswuvugapishifrabraswajurespasorulobrumuresp

He cited evidence that has shown soluble urate stimulates the production of C-reactive protein (CRP), which is a predictor of cardiovascular disease (CVD). Another study, in which Dr. Pillinger participated, demonstrated that gout patients have impaired vascular endothelial function associated with a chronic, low-level inflammatory state, he said.

“There’s good evidence that urate itself affects the vasculature in multiple ways, and I suspect this may be a model for other metabolic effects on vasculature,” Dr. Pillinger said. “Patients with gout have abnormal endothelium in ways that really convey vascular risk.”
 

Gout, Inflammation, and CVD

However, for rheumatologists to study the association between gout-related inflammation and CVD is “very, very hard,” Dr. Pillinger added. “But I do think that the mechanisms by which gout induces biological changes in the vasculature may provide insights into cardiovascular disease in general.”

One way to evaluate the effects of gout on the endothelium in the clinic is to measure flow-mediated dilation. This technique involves placing an ultrasound probe over the brachial artery and measuring the baseline artery diameter. Then, with the blood pressure cuff over the forearm, inflate it to reduce flow, then release the cuff and measure the brachial artery diameter after the endothelium releases vasodilators.

Dr. Pillinger and colleagues evaluated this technique in 34 patients with gout and 64 controls and found that patients with gout had an almost 50% decrease in flow-mediated dilation, he said. “Interestingly, the higher the urate, the worse the flow; the more the inflammation, the worse the flow, so seemingly corresponding with the severity of the gout,” he said. That raised an obvious question, Dr. Pillinger continued: “If you can treat the gout, can you improve the flow-mediated dilation?”

His group answered that question with a study in 38 previously untreated patients with gout, giving them colchicine 0.6 mg twice daily for a month plus a urate-lowering xanthine oxidase inhibitor (allopurinol or febuxostat) to treat them to a target urate level of < 6 mg/dL. “We saw an increase in endothelial function, and it normalized,” Dr. Pillinger said.

However, some study participants didn’t respond. “They were people with well-established other cardiovascular comorbidities — hypertension, hyperlipidemia,” he said. “I think some people just have vessels that are too damaged to get at them just by fixing their gout problem or their inflammation.”

That means patients with gout need to be treated with colchicine early on to avoid CV problems, Dr. Pillinger added. “We ought to get to them before they have the other problems,” he said.

Managing gout, and the concomitant CV problems, requires vigilance both during and in between flares, Dr. Pillinger said after his presentation.

“We have always taught that patients between flares basically look like people with no gout, but we do know now that patients with gout between flares tend to have what you might call ‘subclinical’ inflammation: CRPs and ESRs [erythrocyte sedimentation rates] that are higher than those of the general population, though not so excessive that they might grab attention,” he said. “We also know that many, if not all, patients between flares have urate deposited in or around their joints, but how these two relate is not fully established.”

Better treatment within 3 months of an acute gout flare may reduce the risk for CV events, he said, but that’s based on speculation more so than clinical data.
 

Potential Benefits of Targeting Inflammation

“More chronically, we know from the cardiologists’ studies that anti-inflammatory therapy should reduce risk in the high-risk general population,” Dr. Pillinger said. “There are no prospective studies confirming that this approach will work among gout patients, but there is no reason why it shouldn’t work — except perhaps that gout patients may have higher inflammation than the general population and also have more comorbidities, so they could perhaps be more resistant.”

Dr. Pillinger said that his group’s studies and another led by Daniel Solomon, MD, at Brigham and Women’s Hospital in Boston, have indicated that anti-inflammatory strategies in gout will lower CV risk.

“And interestingly,” he added, “our data suggest that colchicine use may lower risk not only in high-risk gout patients but also in gout patients who start with no CAD [coronary artery disease] but who seem to have less incident CAD on colchicine. I see this as identifying that gout patients are intrinsically at high risk for CAD, even if they don’t actually have any, so they represent a population for whom lowering chronic inflammation may help prevent incident disease.”

Dr. Pillinger provided more evidence that the understanding of the relationship between gout, gout flares, and CV risk is evolving, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone, New York City.

Garshick_Michael_NY_web.JPG

“There’s epidemiologic evidence supporting the association,” Dr. Garshick told this news organization after the conference. “We think that most conditions with immune system activation do tend to have an increased risk of some form of cardiovascular disease, but I think the relationship with gout has been highly underpublicized.”

Many patients with gout tend to have a higher prevalence of traditional cardiometabolic issues, which may compound the relationship, Dr. Garshick added. “However, I would argue that with this patient subset that it doesn’t matter because gout patients have a higher risk of traditional risk factors, and you have to [treat-to-target] those traditional risk factors.”

While the clinical evidence of a link between gout and atherosclerosis may not be conclusive, enough circumstantial evidence exists to believe that treating gout will reduce CV risks, he said. “Some of the imaging techniques do suggest that gouty crystals [are] in the atherosclerotic plaque of gout patients,” Dr. Garshick added. Dr. Pillinger’s work, he said, “is showing us that there are different pathways to develop atherosclerosis.”

Dr. Pillinger disclosed relationships with Federation Bio, Fortress Biotech, Amgen, Scilex, Hikma Pharmaceuticals, LG Chem, and Olatec Therapeutics. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
 

A version of this article appeared on Medscape.com.

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

NEW YORK — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreated to manage that risk. Rheumatologists should consider a patient with RA’s cardiovascular disease (CVD) status before deciding on RA treatments, a researcher of cardiometabolic disorders advised.

“The ORAL Surveillance trial suggests that we need to consider cardiovascular risk factors and maybe do additional screening in these patients before we use RA therapies,” Jon T. Giles, MD, PhD, director of the Cedars-Sinai Inflammatory Arthritis Clinical Center at Cedars-Sinai in Los Angeles, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
 

Underuse of Statins

ORAL Surveillance enrolled 4362 patients with RA aged 50 years and older with at least one cardiovascular risk factor. About 23% of all patients were taking statins, as were about half of patients with a history of atherosclerotic CVD (ASCVD).

Giles_Jon_NY_web.jpg

“A lot of those people should have been on statins,” Dr. Giles said in an interview. “Not because of their RA but because of their risk factors, and then RA brings it up another notch.” In the population with ASCVD, Dr. Giles added, “It should have been more like 70% and 80%. If we’re talking about a disease that has enhanced cardiovascular risk, then the adoption of standard care that you would do for anybody in the general population should be at that standard and maybe above.”

Multiple studies have documented the underlying risk for CVD events, CV mortality, and subclinical atherosclerosis in people with RA, Dr. Giles noted in his presentation. Physiologically, the RA-specific risk factors most linked to CVD risk are systemic inflammation/cytokine excess and specific circulating T-cell and intermediate monocyte subsets, or both, Dr. Giles said.
 

Disease-Modifying Antirheumatic Drugs (DMARDs) and CVD Risk

Likewise, research in the past decade has linked methotrexate and tumor necrosis factor (TNF) inhibitors to reduced ASCVD events in RA. Another study showed that abatacept had an effect similar to that of etanercept in patients with RA, and the ENTRACTE trial, for which Dr. Giles was the lead author, demonstrated that tocilizumab matched etanercept in reducing CV events.

The ORAL Surveillance investigators also reported that patients with RA who were receiving the Janus kinase (JAK) inhibitor tofacitinib had a higher risk for major adverse cardiovascular events and cancers than those on TNF therapy, Dr. Giles noted. While statins in combination with JAK inhibitors may have the potential to provide a balance for controlling CV risk in patients with RA, he said later that the potential of JAK inhibitors in reducing CVD risk in RA “is still unsettled.”

The ongoing TARGET trial is further evaluating the impact of DMARDs on vascular inflammation in RA, said Dr. Giles, who’s also a trial principal investigator. TARGET is randomizing 115 patients with RA who didn’t respond to methotrexate to a TNF inhibitor or the addition of sulfasalazine and hydroxychloroquine to their methotrexate. Patients can be on low-intensity but not high-intensity statin therapy, Dr. Giles said.

TARGET results reported last year demonstrated an 8% decrease in arterial fluorodeoxyglucose (FDG) uptake on PET-CT in both treatment arms. Previous studies, Dr. Giles noted, have shown a potential link between FDG and histologic markers of inflammation. “An 8% decrease in vascular FDG is in line with what you would expect from statin treatment,” he said.

TARGET results published in April showed that a measure of a cluster of 12 cytokines and other inflammatory mediators, known as the multibiomarker disease activity (MBDA) score and marketed under the brand name Vectra DA, may help determine arterial FDG uptake. “Those who had a low MBDA score at week 24 actually had the greatest reduction in the arterial FDG,” he said.

Those results were driven entirely by low serum amyloid A (SAA) levels, Dr. Giles said. Those same results didn’t hold for patients in whom SAA and C-reactive protein were correlated.

“So, there’s more to come here,” Dr. Giles said. “We’re looking at other, much larger biomarker panels.”

Nonetheless, he said, sufficient evidence exists to conclude that treating RA to target reduces CV events. “The idea is that at every visit that you see an RA patient, you measure their disease activity, and if they’re not at the target of low disease activity or remission, then you change their therapy to improve that,” he said in an interview.

But an evidence-based guideline is needed to improve coverage of CVD risks in patients with RA, Dr. Giles said. “There is a movement afoot” for a guideline, he said. “If you just did what is supposed to happen for a general population, you would make some improvements. The risk-benefit [ratio] for statins for people with RA has been looked at, and it’s very favorable.”
 

Unanswered Questions

Dr. Giles noted that the ORAL Surveillance trial has left a number of questions unanswered about the role of JAK inhibitors in managing CVD risk in patients with RA. “The issue that we’re trying to ask is, is it just the TNF inhibitors may be better? Is this a subpopulation issue, or was it just bad luck from the purposes of this one trial? Granted, it was a very large trial, but you can still have luck in terms of getting an effect that’s not accurate.”

Dr. Giles’ “gut feeling” on JAK inhibitors is that they’re not causing harm, but that they’re not as effective as TNF inhibitors in ameliorating CV risks in patients with RA.

Michael S. Garshick, MD, who attended the conference and is head of the cardio-rheumatology program at NYU Langone Health, concurred that a number of unanswered questions persist over the treatment of CVD risk in RA — and autoimmune disease in general.

Garshick_Michael_NY_web.JPG

“I think we’re still trying to prove that DMARDs reduce cardiovascular risk in autoimmune conditions,” he said. “The epidemiologic data would suggest, yes, that inflammation prevention is beneficial for cardiovascular disease, but the TARGET trial suggested that vascular inflammation improved by treating RA, but that biologic therapy wasn’t better than traditional triple therapy.”

Other questions remain unanswered, Dr. Garshick said.

“Is there a specific immunotherapy that is most beneficial to reduce heart disease in patients with an autoimmune condition, whether it’s rheumatoid arthritis, psoriasis, or lupus?”

Dr. Garshick said he’s specifically interested in the residual risk that exists after treating the autoimmunity. “Do you still have a higher risk for heart disease, and if so, why? Is there something else going on that we can’t see?”

The biggest unanswered question, he said, is “How can we do a better job of recognizing heart disease risk in these patients? That’s the low-hanging fruit that people are studying, but across many of those studies, patients have higher rates of blood pressure, cholesterol issues, obesity, diabetes, and many times, we’re not adequately treating these comorbidities.”

That, Dr. Garshick said, may be a result of physician fatigue. “And so [treatment of these comorbidities is] kicked down the road for a year or years,” he added.

Dr. Giles disclosed financial relationships with Pfizer, AbbVie, Eli Lilly, and Novartis. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.

A version of this article appeared on Medscape.com.

NEW YORK — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreated to manage that risk. Rheumatologists should consider a patient with RA’s cardiovascular disease (CVD) status before deciding on RA treatments, a researcher of cardiometabolic disorders advised.

“The ORAL Surveillance trial suggests that we need to consider cardiovascular risk factors and maybe do additional screening in these patients before we use RA therapies,” Jon T. Giles, MD, PhD, director of the Cedars-Sinai Inflammatory Arthritis Clinical Center at Cedars-Sinai in Los Angeles, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
 

Underuse of Statins

ORAL Surveillance enrolled 4362 patients with RA aged 50 years and older with at least one cardiovascular risk factor. About 23% of all patients were taking statins, as were about half of patients with a history of atherosclerotic CVD (ASCVD).

Giles_Jon_NY_web.jpg

“A lot of those people should have been on statins,” Dr. Giles said in an interview. “Not because of their RA but because of their risk factors, and then RA brings it up another notch.” In the population with ASCVD, Dr. Giles added, “It should have been more like 70% and 80%. If we’re talking about a disease that has enhanced cardiovascular risk, then the adoption of standard care that you would do for anybody in the general population should be at that standard and maybe above.”

Multiple studies have documented the underlying risk for CVD events, CV mortality, and subclinical atherosclerosis in people with RA, Dr. Giles noted in his presentation. Physiologically, the RA-specific risk factors most linked to CVD risk are systemic inflammation/cytokine excess and specific circulating T-cell and intermediate monocyte subsets, or both, Dr. Giles said.
 

Disease-Modifying Antirheumatic Drugs (DMARDs) and CVD Risk

Likewise, research in the past decade has linked methotrexate and tumor necrosis factor (TNF) inhibitors to reduced ASCVD events in RA. Another study showed that abatacept had an effect similar to that of etanercept in patients with RA, and the ENTRACTE trial, for which Dr. Giles was the lead author, demonstrated that tocilizumab matched etanercept in reducing CV events.

The ORAL Surveillance investigators also reported that patients with RA who were receiving the Janus kinase (JAK) inhibitor tofacitinib had a higher risk for major adverse cardiovascular events and cancers than those on TNF therapy, Dr. Giles noted. While statins in combination with JAK inhibitors may have the potential to provide a balance for controlling CV risk in patients with RA, he said later that the potential of JAK inhibitors in reducing CVD risk in RA “is still unsettled.”

The ongoing TARGET trial is further evaluating the impact of DMARDs on vascular inflammation in RA, said Dr. Giles, who’s also a trial principal investigator. TARGET is randomizing 115 patients with RA who didn’t respond to methotrexate to a TNF inhibitor or the addition of sulfasalazine and hydroxychloroquine to their methotrexate. Patients can be on low-intensity but not high-intensity statin therapy, Dr. Giles said.

TARGET results reported last year demonstrated an 8% decrease in arterial fluorodeoxyglucose (FDG) uptake on PET-CT in both treatment arms. Previous studies, Dr. Giles noted, have shown a potential link between FDG and histologic markers of inflammation. “An 8% decrease in vascular FDG is in line with what you would expect from statin treatment,” he said.

TARGET results published in April showed that a measure of a cluster of 12 cytokines and other inflammatory mediators, known as the multibiomarker disease activity (MBDA) score and marketed under the brand name Vectra DA, may help determine arterial FDG uptake. “Those who had a low MBDA score at week 24 actually had the greatest reduction in the arterial FDG,” he said.

Those results were driven entirely by low serum amyloid A (SAA) levels, Dr. Giles said. Those same results didn’t hold for patients in whom SAA and C-reactive protein were correlated.

“So, there’s more to come here,” Dr. Giles said. “We’re looking at other, much larger biomarker panels.”

Nonetheless, he said, sufficient evidence exists to conclude that treating RA to target reduces CV events. “The idea is that at every visit that you see an RA patient, you measure their disease activity, and if they’re not at the target of low disease activity or remission, then you change their therapy to improve that,” he said in an interview.

But an evidence-based guideline is needed to improve coverage of CVD risks in patients with RA, Dr. Giles said. “There is a movement afoot” for a guideline, he said. “If you just did what is supposed to happen for a general population, you would make some improvements. The risk-benefit [ratio] for statins for people with RA has been looked at, and it’s very favorable.”
 

Unanswered Questions

Dr. Giles noted that the ORAL Surveillance trial has left a number of questions unanswered about the role of JAK inhibitors in managing CVD risk in patients with RA. “The issue that we’re trying to ask is, is it just the TNF inhibitors may be better? Is this a subpopulation issue, or was it just bad luck from the purposes of this one trial? Granted, it was a very large trial, but you can still have luck in terms of getting an effect that’s not accurate.”

Dr. Giles’ “gut feeling” on JAK inhibitors is that they’re not causing harm, but that they’re not as effective as TNF inhibitors in ameliorating CV risks in patients with RA.

Michael S. Garshick, MD, who attended the conference and is head of the cardio-rheumatology program at NYU Langone Health, concurred that a number of unanswered questions persist over the treatment of CVD risk in RA — and autoimmune disease in general.

Garshick_Michael_NY_web.JPG

“I think we’re still trying to prove that DMARDs reduce cardiovascular risk in autoimmune conditions,” he said. “The epidemiologic data would suggest, yes, that inflammation prevention is beneficial for cardiovascular disease, but the TARGET trial suggested that vascular inflammation improved by treating RA, but that biologic therapy wasn’t better than traditional triple therapy.”

Other questions remain unanswered, Dr. Garshick said.

“Is there a specific immunotherapy that is most beneficial to reduce heart disease in patients with an autoimmune condition, whether it’s rheumatoid arthritis, psoriasis, or lupus?”

Dr. Garshick said he’s specifically interested in the residual risk that exists after treating the autoimmunity. “Do you still have a higher risk for heart disease, and if so, why? Is there something else going on that we can’t see?”

The biggest unanswered question, he said, is “How can we do a better job of recognizing heart disease risk in these patients? That’s the low-hanging fruit that people are studying, but across many of those studies, patients have higher rates of blood pressure, cholesterol issues, obesity, diabetes, and many times, we’re not adequately treating these comorbidities.”

That, Dr. Garshick said, may be a result of physician fatigue. “And so [treatment of these comorbidities is] kicked down the road for a year or years,” he added.

Dr. Giles disclosed financial relationships with Pfizer, AbbVie, Eli Lilly, and Novartis. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.

A version of this article appeared on Medscape.com.

NEW YORK — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreated to manage that risk. Rheumatologists should consider a patient with RA’s cardiovascular disease (CVD) status before deciding on RA treatments, a researcher of cardiometabolic disorders advised.

“The ORAL Surveillance trial suggests that we need to consider cardiovascular risk factors and maybe do additional screening in these patients before we use RA therapies,” Jon T. Giles, MD, PhD, director of the Cedars-Sinai Inflammatory Arthritis Clinical Center at Cedars-Sinai in Los Angeles, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
 

Underuse of Statins

ORAL Surveillance enrolled 4362 patients with RA aged 50 years and older with at least one cardiovascular risk factor. About 23% of all patients were taking statins, as were about half of patients with a history of atherosclerotic CVD (ASCVD).

Giles_Jon_NY_web.jpg

“A lot of those people should have been on statins,” Dr. Giles said in an interview. “Not because of their RA but because of their risk factors, and then RA brings it up another notch.” In the population with ASCVD, Dr. Giles added, “It should have been more like 70% and 80%. If we’re talking about a disease that has enhanced cardiovascular risk, then the adoption of standard care that you would do for anybody in the general population should be at that standard and maybe above.”

Multiple studies have documented the underlying risk for CVD events, CV mortality, and subclinical atherosclerosis in people with RA, Dr. Giles noted in his presentation. Physiologically, the RA-specific risk factors most linked to CVD risk are systemic inflammation/cytokine excess and specific circulating T-cell and intermediate monocyte subsets, or both, Dr. Giles said.
 

Disease-Modifying Antirheumatic Drugs (DMARDs) and CVD Risk

Likewise, research in the past decade has linked methotrexate and tumor necrosis factor (TNF) inhibitors to reduced ASCVD events in RA. Another study showed that abatacept had an effect similar to that of etanercept in patients with RA, and the ENTRACTE trial, for which Dr. Giles was the lead author, demonstrated that tocilizumab matched etanercept in reducing CV events.

The ORAL Surveillance investigators also reported that patients with RA who were receiving the Janus kinase (JAK) inhibitor tofacitinib had a higher risk for major adverse cardiovascular events and cancers than those on TNF therapy, Dr. Giles noted. While statins in combination with JAK inhibitors may have the potential to provide a balance for controlling CV risk in patients with RA, he said later that the potential of JAK inhibitors in reducing CVD risk in RA “is still unsettled.”

The ongoing TARGET trial is further evaluating the impact of DMARDs on vascular inflammation in RA, said Dr. Giles, who’s also a trial principal investigator. TARGET is randomizing 115 patients with RA who didn’t respond to methotrexate to a TNF inhibitor or the addition of sulfasalazine and hydroxychloroquine to their methotrexate. Patients can be on low-intensity but not high-intensity statin therapy, Dr. Giles said.

TARGET results reported last year demonstrated an 8% decrease in arterial fluorodeoxyglucose (FDG) uptake on PET-CT in both treatment arms. Previous studies, Dr. Giles noted, have shown a potential link between FDG and histologic markers of inflammation. “An 8% decrease in vascular FDG is in line with what you would expect from statin treatment,” he said.

TARGET results published in April showed that a measure of a cluster of 12 cytokines and other inflammatory mediators, known as the multibiomarker disease activity (MBDA) score and marketed under the brand name Vectra DA, may help determine arterial FDG uptake. “Those who had a low MBDA score at week 24 actually had the greatest reduction in the arterial FDG,” he said.

Those results were driven entirely by low serum amyloid A (SAA) levels, Dr. Giles said. Those same results didn’t hold for patients in whom SAA and C-reactive protein were correlated.

“So, there’s more to come here,” Dr. Giles said. “We’re looking at other, much larger biomarker panels.”

Nonetheless, he said, sufficient evidence exists to conclude that treating RA to target reduces CV events. “The idea is that at every visit that you see an RA patient, you measure their disease activity, and if they’re not at the target of low disease activity or remission, then you change their therapy to improve that,” he said in an interview.

But an evidence-based guideline is needed to improve coverage of CVD risks in patients with RA, Dr. Giles said. “There is a movement afoot” for a guideline, he said. “If you just did what is supposed to happen for a general population, you would make some improvements. The risk-benefit [ratio] for statins for people with RA has been looked at, and it’s very favorable.”
 

Unanswered Questions

Dr. Giles noted that the ORAL Surveillance trial has left a number of questions unanswered about the role of JAK inhibitors in managing CVD risk in patients with RA. “The issue that we’re trying to ask is, is it just the TNF inhibitors may be better? Is this a subpopulation issue, or was it just bad luck from the purposes of this one trial? Granted, it was a very large trial, but you can still have luck in terms of getting an effect that’s not accurate.”

Dr. Giles’ “gut feeling” on JAK inhibitors is that they’re not causing harm, but that they’re not as effective as TNF inhibitors in ameliorating CV risks in patients with RA.

Michael S. Garshick, MD, who attended the conference and is head of the cardio-rheumatology program at NYU Langone Health, concurred that a number of unanswered questions persist over the treatment of CVD risk in RA — and autoimmune disease in general.

Garshick_Michael_NY_web.JPG

“I think we’re still trying to prove that DMARDs reduce cardiovascular risk in autoimmune conditions,” he said. “The epidemiologic data would suggest, yes, that inflammation prevention is beneficial for cardiovascular disease, but the TARGET trial suggested that vascular inflammation improved by treating RA, but that biologic therapy wasn’t better than traditional triple therapy.”

Other questions remain unanswered, Dr. Garshick said.

“Is there a specific immunotherapy that is most beneficial to reduce heart disease in patients with an autoimmune condition, whether it’s rheumatoid arthritis, psoriasis, or lupus?”

Dr. Garshick said he’s specifically interested in the residual risk that exists after treating the autoimmunity. “Do you still have a higher risk for heart disease, and if so, why? Is there something else going on that we can’t see?”

The biggest unanswered question, he said, is “How can we do a better job of recognizing heart disease risk in these patients? That’s the low-hanging fruit that people are studying, but across many of those studies, patients have higher rates of blood pressure, cholesterol issues, obesity, diabetes, and many times, we’re not adequately treating these comorbidities.”

That, Dr. Garshick said, may be a result of physician fatigue. “And so [treatment of these comorbidities is] kicked down the road for a year or years,” he added.

Dr. Giles disclosed financial relationships with Pfizer, AbbVie, Eli Lilly, and Novartis. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.

A version of this article appeared on Medscape.com.