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Psychiatric Comorbidity Prevalent in Eating Disorders
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 .
Endoscopic Procedure Targets ‘Hunger Hormone’ for Weight Loss
WASHINGTON — .
“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.
“They generally described that their relationship with food had changed,” Dr. McGowan said at a May 8 press briefing during which his research (Abstract 516) was previewed for Digestive Disease Week® (DDW).
Researchers targeted the gastric fundus because its mucosal lining contains 80%-90% of the cells that produce ghrelin. When a person diets and/or loses weight, ghrelin levels increase, making the person hungrier and preventing sustained weight loss, Dr. McGowan said.
Previously, the only proven way to reduce ghrelin was to surgically remove or bypass the fundus. Weight-loss medications like Wegovy, Zepbound, and Ozempic target a different hormonal pathway, glucagon-like peptide 1 (GLP-1).
“What we’ve learned from the GLP-1 medications is the profound impact of reducing hunger,” Dr. McGowan said. “That’s what patients describe quite often — that it really changes their life and their quality of life. That’s really, really important.”
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.”
In a standard nutrient drink test, the maximum tolerated volume among participants dropped from a mean 27.3 oz at baseline to 15.8 oz at 6-month follow-up (P = .004).
Participants also completed three questionnaires. From baseline to 6 months, their DAILY EATS mean hunger score decreased from 6.2 to 4 (P = .002), mean Eating Drivers Index score dropped from 7 to 4 (P < .001), and WEL-SF score improved from 47.7 to 62.4 (P = .001).
Repeat endoscopy at 6 months showed that the gastric fundus contracted and healed. An unexpected and beneficial finding was fibrotic tissue, which made the fundus less able to expand, Dr. McGowan said. A smaller fundus “is critical for feeling full.”
No serious adverse events were reported. Participants described gas pressure, mild nausea, and cramping, all of which lasted 1-3 days, he said.
“The key here is preserving safety. This is why we use the technique of injecting a fluid cushion prior to ablating, so we’re not entering any deeper layers of the stomach,” Dr. McGowan said. “Importantly, there are no nerve receptors within the lining of the stomach, so there’s no pain from this procedure.”
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 — .
“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.
“They generally described that their relationship with food had changed,” Dr. McGowan said at a May 8 press briefing during which his research (Abstract 516) was previewed for Digestive Disease Week® (DDW).
Researchers targeted the gastric fundus because its mucosal lining contains 80%-90% of the cells that produce ghrelin. When a person diets and/or loses weight, ghrelin levels increase, making the person hungrier and preventing sustained weight loss, Dr. McGowan said.
Previously, the only proven way to reduce ghrelin was to surgically remove or bypass the fundus. Weight-loss medications like Wegovy, Zepbound, and Ozempic target a different hormonal pathway, glucagon-like peptide 1 (GLP-1).
“What we’ve learned from the GLP-1 medications is the profound impact of reducing hunger,” Dr. McGowan said. “That’s what patients describe quite often — that it really changes their life and their quality of life. That’s really, really important.”
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.”
In a standard nutrient drink test, the maximum tolerated volume among participants dropped from a mean 27.3 oz at baseline to 15.8 oz at 6-month follow-up (P = .004).
Participants also completed three questionnaires. From baseline to 6 months, their DAILY EATS mean hunger score decreased from 6.2 to 4 (P = .002), mean Eating Drivers Index score dropped from 7 to 4 (P < .001), and WEL-SF score improved from 47.7 to 62.4 (P = .001).
Repeat endoscopy at 6 months showed that the gastric fundus contracted and healed. An unexpected and beneficial finding was fibrotic tissue, which made the fundus less able to expand, Dr. McGowan said. A smaller fundus “is critical for feeling full.”
No serious adverse events were reported. Participants described gas pressure, mild nausea, and cramping, all of which lasted 1-3 days, he said.
“The key here is preserving safety. This is why we use the technique of injecting a fluid cushion prior to ablating, so we’re not entering any deeper layers of the stomach,” Dr. McGowan said. “Importantly, there are no nerve receptors within the lining of the stomach, so there’s no pain from this procedure.”
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 — .
“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.
“They generally described that their relationship with food had changed,” Dr. McGowan said at a May 8 press briefing during which his research (Abstract 516) was previewed for Digestive Disease Week® (DDW).
Researchers targeted the gastric fundus because its mucosal lining contains 80%-90% of the cells that produce ghrelin. When a person diets and/or loses weight, ghrelin levels increase, making the person hungrier and preventing sustained weight loss, Dr. McGowan said.
Previously, the only proven way to reduce ghrelin was to surgically remove or bypass the fundus. Weight-loss medications like Wegovy, Zepbound, and Ozempic target a different hormonal pathway, glucagon-like peptide 1 (GLP-1).
“What we’ve learned from the GLP-1 medications is the profound impact of reducing hunger,” Dr. McGowan said. “That’s what patients describe quite often — that it really changes their life and their quality of life. That’s really, really important.”
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.”
In a standard nutrient drink test, the maximum tolerated volume among participants dropped from a mean 27.3 oz at baseline to 15.8 oz at 6-month follow-up (P = .004).
Participants also completed three questionnaires. From baseline to 6 months, their DAILY EATS mean hunger score decreased from 6.2 to 4 (P = .002), mean Eating Drivers Index score dropped from 7 to 4 (P < .001), and WEL-SF score improved from 47.7 to 62.4 (P = .001).
Repeat endoscopy at 6 months showed that the gastric fundus contracted and healed. An unexpected and beneficial finding was fibrotic tissue, which made the fundus less able to expand, Dr. McGowan said. A smaller fundus “is critical for feeling full.”
No serious adverse events were reported. Participants described gas pressure, mild nausea, and cramping, all of which lasted 1-3 days, he said.
“The key here is preserving safety. This is why we use the technique of injecting a fluid cushion prior to ablating, so we’re not entering any deeper layers of the stomach,” Dr. McGowan said. “Importantly, there are no nerve receptors within the lining of the stomach, so there’s no pain from this procedure.”
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.
FROM DDW 2024
No Improvement in OS With Atezolizumab in Early Relapsing TNBC
Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
“These patients have a dismal prognosis and represent a high unmet need,” she added.
The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.
Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.
“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”
IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.
Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.
Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.
The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.
The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.
After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).
A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.
Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”
The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.
There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.
“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”
The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.
Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse.
This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.”
The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.
IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.
“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”
The study was sponsored by Hoffmann-La Roche.
Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.
A version of this article appeared on Medscape.com .
Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
“These patients have a dismal prognosis and represent a high unmet need,” she added.
The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.
Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.
“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”
IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.
Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.
Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.
The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.
The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.
After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).
A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.
Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”
The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.
There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.
“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”
The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.
Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse.
This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.”
The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.
IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.
“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”
The study was sponsored by Hoffmann-La Roche.
Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.
A version of this article appeared on Medscape.com .
Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
“These patients have a dismal prognosis and represent a high unmet need,” she added.
The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.
Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.
“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”
IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.
Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.
Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.
The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.
The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.
After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).
A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.
Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”
The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.
There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.
“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”
The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.
Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse.
This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.”
The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.
IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.
“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”
The study was sponsored by Hoffmann-La Roche.
Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.
A version of this article appeared on Medscape.com .
FROM ESMO BREAST CANCER 2024
Vigilance Needed in Gout Treatment to Reduce CVD Risks
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.
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.
“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.
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.
“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.
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.
“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.
Don’t Leave CVD Risk in RA Undertreated Despite Unresolved Questions
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).
“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.
“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).
“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.
“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).
“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.
“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.
What Does Natural Healing of ACL Ruptures Mean for Long-Term Outcomes?
VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress.
At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.
“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.
“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.
She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”
At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
Healing Without Surgery
The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.
Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.
However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
What Happens Long Term?
Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.
ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.
But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.
In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.
The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
ACL Continuity and Long-Term Outcomes
At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.
Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.
“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.
However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.
Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.
By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).
These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
Posttraumatic OA After ACL Surgery
Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.
Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.
“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.
“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.
The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.
Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.
The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.
Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.
A version of this article appeared on Medscape.com.
VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress.
At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.
“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.
“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.
She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”
At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
Healing Without Surgery
The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.
Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.
However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
What Happens Long Term?
Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.
ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.
But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.
In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.
The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
ACL Continuity and Long-Term Outcomes
At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.
Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.
“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.
However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.
Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.
By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).
These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
Posttraumatic OA After ACL Surgery
Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.
Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.
“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.
“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.
The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.
Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.
The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.
Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.
A version of this article appeared on Medscape.com.
VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress.
At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.
“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.
“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.
She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”
At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
Healing Without Surgery
The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.
Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.
However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
What Happens Long Term?
Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.
ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.
But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.
In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.
The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
ACL Continuity and Long-Term Outcomes
At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.
Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.
“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.
However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.
Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.
By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).
These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
Posttraumatic OA After ACL Surgery
Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.
Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.
“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.
“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.
The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.
Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.
The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.
Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.
A version of this article appeared on Medscape.com.
FROM OARSI 2024
Is Meningitis a Risk Factor for Trigeminal Neuralgia? New Data
In multivariate analysis, the odds of meningitis were threefold higher in patients admitted with trigeminal neuralgia than in matched controls without trigeminal neuralgia.
This is the first nationwide population-based study of the rare, chronic pain disorder to identify the prevalence of trigeminal neuralgia admissions in the United States and risk factors contributing to trigeminal neuralgia development.
“Our results affirm known associations between trigeminal neuralgia and comorbidities like multiple sclerosis, and they also identify meningitis as a novel risk factor for trigeminal neuralgia,” said investigator Megan Tang, BS, a medical student at the Icahn School of Medicine at Mount Sinai, New York City.
The findings were presented at the American Association of Neurological Surgeons (AANS) 2024 annual meeting.
Strong Clinical Risk Factors
Trigeminal neuralgia is a rare pain disorder involving neurovascular compression of the trigeminal nerve. Its etiology and risk factors are poorly understood. Current literature is based on limited datasets and reports inconsistent risk factors across studies.
To better understand the disorder, researchers used International Classification of Diseases (ICD)-9 codes to identify trigeminal neuralgia admissions in the National Inpatient Sample from 2016 to 2019, and then propensity matched them 1:1 to non-trigeminal neuralgia admissions based on demographics, socioeconomic status, and Charlson comorbidity index scores.
Univariate analysis identified 136,345 trigeminal neuralgia admissions or an overall prevalence of 0.096%.
Trigeminal neuralgia admissions had lower morbidity than non-trigeminal neuralgia admissions and a higher prevalence of non-White patients, private insurance, and prolonged length of stay, Ms. Tang said.
Patients admitted for trigeminal neuralgia also had a higher prevalence of several chronic conditions, including hypertension, hyperlipidemia, and osteoarthritis; inflammatory conditions like lupus, meningitis, rheumatoid arthritis, and inflammatory bowel disease; and neurologic conditions including multiple sclerosis, epilepsy, stroke, and neurovascular compression disorders.
In multivariate analysis, investigators identified meningitis as a previously unknown risk factor for trigeminal neuralgia (odds ratio [OR], 3.1; P < .001).
Other strong risk factors were neurovascular compression disorders (OR, 39.82; P < .001) and multiple sclerosis (OR, 12.41; P < .001). Non-White race (Black; OR, 1.09; Hispanic; OR, 1.23; Other; OR, 1.24) and use of Medicaid (OR, 1.07) and other insurance (OR, 1.17) were demographic risk factors for trigeminal neuralgia.
“This finding points us toward future work exploring the potential mechanisms of predictors, most notably inflammatory conditions in trigeminal neuralgia development,” Ms. Tang concluded.
She declined to comment further on the findings, noting the investigators are still finalizing the results and interpretation.
Ask About Meningitis, Fever
Commenting on the findings, Michael D. Staudt, MD, MSc, University Hospitals Cleveland Medical Center, said that many patients who present with classical trigeminal neuralgia will have a blood vessel on MRI that is pressing on the trigeminal nerve.
“Obviously, the nerve is bathed in cerebrospinal fluid. So, if there’s an inflammatory marker, inflammation, or infection that could be injuring the nerve in a way that we don’t yet understand, that could be something that could cause trigeminal neuralgia without having to see a blood vessel,” said Dr. Staudt, who was not involved in the study. “It makes sense, theoretically. Something that’s inflammatory, something that’s irritating, that’s novel.”
Currently, predictive markers include clinical history, response to classical medications such as carbamazepine, and MRI findings, Dr. Staudt noted.
“Someone shows up with symptoms and MRI, and it’s basically do they have a blood vessel or not,” he said. “Treatments are generally within the same categories, but we don’t think it’s the same sort of success rate as seeing a blood vessel.”
Further research is needed, but, in the meantime, Dr. Staudt said, “We can ask patients who show up with facial pain if they’ve ever had meningitis or some sort of fever that preceded their onset of pain.”
The study had no specific funding. Ms. Tang and coauthor Jack Y. Zhang, MS, reported no relevant financial disclosures. Dr. Staudt reported serving as a consultant for Abbott and as a scientific adviser and consultant for Boston Scientific.
A version of this article appeared on Medscape.com.
In multivariate analysis, the odds of meningitis were threefold higher in patients admitted with trigeminal neuralgia than in matched controls without trigeminal neuralgia.
This is the first nationwide population-based study of the rare, chronic pain disorder to identify the prevalence of trigeminal neuralgia admissions in the United States and risk factors contributing to trigeminal neuralgia development.
“Our results affirm known associations between trigeminal neuralgia and comorbidities like multiple sclerosis, and they also identify meningitis as a novel risk factor for trigeminal neuralgia,” said investigator Megan Tang, BS, a medical student at the Icahn School of Medicine at Mount Sinai, New York City.
The findings were presented at the American Association of Neurological Surgeons (AANS) 2024 annual meeting.
Strong Clinical Risk Factors
Trigeminal neuralgia is a rare pain disorder involving neurovascular compression of the trigeminal nerve. Its etiology and risk factors are poorly understood. Current literature is based on limited datasets and reports inconsistent risk factors across studies.
To better understand the disorder, researchers used International Classification of Diseases (ICD)-9 codes to identify trigeminal neuralgia admissions in the National Inpatient Sample from 2016 to 2019, and then propensity matched them 1:1 to non-trigeminal neuralgia admissions based on demographics, socioeconomic status, and Charlson comorbidity index scores.
Univariate analysis identified 136,345 trigeminal neuralgia admissions or an overall prevalence of 0.096%.
Trigeminal neuralgia admissions had lower morbidity than non-trigeminal neuralgia admissions and a higher prevalence of non-White patients, private insurance, and prolonged length of stay, Ms. Tang said.
Patients admitted for trigeminal neuralgia also had a higher prevalence of several chronic conditions, including hypertension, hyperlipidemia, and osteoarthritis; inflammatory conditions like lupus, meningitis, rheumatoid arthritis, and inflammatory bowel disease; and neurologic conditions including multiple sclerosis, epilepsy, stroke, and neurovascular compression disorders.
In multivariate analysis, investigators identified meningitis as a previously unknown risk factor for trigeminal neuralgia (odds ratio [OR], 3.1; P < .001).
Other strong risk factors were neurovascular compression disorders (OR, 39.82; P < .001) and multiple sclerosis (OR, 12.41; P < .001). Non-White race (Black; OR, 1.09; Hispanic; OR, 1.23; Other; OR, 1.24) and use of Medicaid (OR, 1.07) and other insurance (OR, 1.17) were demographic risk factors for trigeminal neuralgia.
“This finding points us toward future work exploring the potential mechanisms of predictors, most notably inflammatory conditions in trigeminal neuralgia development,” Ms. Tang concluded.
She declined to comment further on the findings, noting the investigators are still finalizing the results and interpretation.
Ask About Meningitis, Fever
Commenting on the findings, Michael D. Staudt, MD, MSc, University Hospitals Cleveland Medical Center, said that many patients who present with classical trigeminal neuralgia will have a blood vessel on MRI that is pressing on the trigeminal nerve.
“Obviously, the nerve is bathed in cerebrospinal fluid. So, if there’s an inflammatory marker, inflammation, or infection that could be injuring the nerve in a way that we don’t yet understand, that could be something that could cause trigeminal neuralgia without having to see a blood vessel,” said Dr. Staudt, who was not involved in the study. “It makes sense, theoretically. Something that’s inflammatory, something that’s irritating, that’s novel.”
Currently, predictive markers include clinical history, response to classical medications such as carbamazepine, and MRI findings, Dr. Staudt noted.
“Someone shows up with symptoms and MRI, and it’s basically do they have a blood vessel or not,” he said. “Treatments are generally within the same categories, but we don’t think it’s the same sort of success rate as seeing a blood vessel.”
Further research is needed, but, in the meantime, Dr. Staudt said, “We can ask patients who show up with facial pain if they’ve ever had meningitis or some sort of fever that preceded their onset of pain.”
The study had no specific funding. Ms. Tang and coauthor Jack Y. Zhang, MS, reported no relevant financial disclosures. Dr. Staudt reported serving as a consultant for Abbott and as a scientific adviser and consultant for Boston Scientific.
A version of this article appeared on Medscape.com.
In multivariate analysis, the odds of meningitis were threefold higher in patients admitted with trigeminal neuralgia than in matched controls without trigeminal neuralgia.
This is the first nationwide population-based study of the rare, chronic pain disorder to identify the prevalence of trigeminal neuralgia admissions in the United States and risk factors contributing to trigeminal neuralgia development.
“Our results affirm known associations between trigeminal neuralgia and comorbidities like multiple sclerosis, and they also identify meningitis as a novel risk factor for trigeminal neuralgia,” said investigator Megan Tang, BS, a medical student at the Icahn School of Medicine at Mount Sinai, New York City.
The findings were presented at the American Association of Neurological Surgeons (AANS) 2024 annual meeting.
Strong Clinical Risk Factors
Trigeminal neuralgia is a rare pain disorder involving neurovascular compression of the trigeminal nerve. Its etiology and risk factors are poorly understood. Current literature is based on limited datasets and reports inconsistent risk factors across studies.
To better understand the disorder, researchers used International Classification of Diseases (ICD)-9 codes to identify trigeminal neuralgia admissions in the National Inpatient Sample from 2016 to 2019, and then propensity matched them 1:1 to non-trigeminal neuralgia admissions based on demographics, socioeconomic status, and Charlson comorbidity index scores.
Univariate analysis identified 136,345 trigeminal neuralgia admissions or an overall prevalence of 0.096%.
Trigeminal neuralgia admissions had lower morbidity than non-trigeminal neuralgia admissions and a higher prevalence of non-White patients, private insurance, and prolonged length of stay, Ms. Tang said.
Patients admitted for trigeminal neuralgia also had a higher prevalence of several chronic conditions, including hypertension, hyperlipidemia, and osteoarthritis; inflammatory conditions like lupus, meningitis, rheumatoid arthritis, and inflammatory bowel disease; and neurologic conditions including multiple sclerosis, epilepsy, stroke, and neurovascular compression disorders.
In multivariate analysis, investigators identified meningitis as a previously unknown risk factor for trigeminal neuralgia (odds ratio [OR], 3.1; P < .001).
Other strong risk factors were neurovascular compression disorders (OR, 39.82; P < .001) and multiple sclerosis (OR, 12.41; P < .001). Non-White race (Black; OR, 1.09; Hispanic; OR, 1.23; Other; OR, 1.24) and use of Medicaid (OR, 1.07) and other insurance (OR, 1.17) were demographic risk factors for trigeminal neuralgia.
“This finding points us toward future work exploring the potential mechanisms of predictors, most notably inflammatory conditions in trigeminal neuralgia development,” Ms. Tang concluded.
She declined to comment further on the findings, noting the investigators are still finalizing the results and interpretation.
Ask About Meningitis, Fever
Commenting on the findings, Michael D. Staudt, MD, MSc, University Hospitals Cleveland Medical Center, said that many patients who present with classical trigeminal neuralgia will have a blood vessel on MRI that is pressing on the trigeminal nerve.
“Obviously, the nerve is bathed in cerebrospinal fluid. So, if there’s an inflammatory marker, inflammation, or infection that could be injuring the nerve in a way that we don’t yet understand, that could be something that could cause trigeminal neuralgia without having to see a blood vessel,” said Dr. Staudt, who was not involved in the study. “It makes sense, theoretically. Something that’s inflammatory, something that’s irritating, that’s novel.”
Currently, predictive markers include clinical history, response to classical medications such as carbamazepine, and MRI findings, Dr. Staudt noted.
“Someone shows up with symptoms and MRI, and it’s basically do they have a blood vessel or not,” he said. “Treatments are generally within the same categories, but we don’t think it’s the same sort of success rate as seeing a blood vessel.”
Further research is needed, but, in the meantime, Dr. Staudt said, “We can ask patients who show up with facial pain if they’ve ever had meningitis or some sort of fever that preceded their onset of pain.”
The study had no specific funding. Ms. Tang and coauthor Jack Y. Zhang, MS, reported no relevant financial disclosures. Dr. Staudt reported serving as a consultant for Abbott and as a scientific adviser and consultant for Boston Scientific.
A version of this article appeared on Medscape.com.
FROM AANS 2024
Will Diabetes Drugs Advance Osteoarthritis Management?
VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?
“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.
Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.
“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
Weight Loss Benefits
Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.
In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.
It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.
“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
Weight Rebound
Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.
“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.
Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.
“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
Weight Loss Affects Bone
Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.
Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.
Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.
Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
GLP-1 and Bone Effects
Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.
Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”
The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.
These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
New Role for Dipeptidyl Transferase Inhibitors?
Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.
Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.
“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”
For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.
Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).
DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.
Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?
So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.
“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.
He presented data from a large analysis of new users of SGLT2 inhibitors and GLP-1 receptor agonists within two claims databases — Merative (n = 603,471) and TriNetX (n = 1,202,972) — showing that SGLT2 inhibitors were associated with significantly lower risks for OA and the need for TKR.
Comparing new users of SGLT2 inhibitors and GLP-1 receptor agonists in the Merative dataset, the relative risks and odds ratios for OA were a respective 0.96 and 0.80, and having a TKR, 0.88 and 0.76.
Similar results were seen using the TriNetX dataset, with respective relative risks and hazard ratios of 0.90 and 0.85 for OA, and 0.81 and 0.78 for TKR.
In an interview, Dr. Jafarzadeh said that the initial hypothesis was that because SGLT2 inhibitors have only a modest effect on weight loss, there would be no effect on OA outcomes.
“But we were surprised that it actually looked like they reduced the risk of OA outcomes even more than GLP-1 receptor agonists,” Dr. Jafarzadeh said.
Further work is needed to understand these data, but they could mean that SLGT2 inhibitors, like GLP-1 receptor agonists, may have a role to play outside their current use in type 2 diabetes.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com .
VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?
“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.
Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.
“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
Weight Loss Benefits
Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.
In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.
It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.
“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
Weight Rebound
Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.
“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.
Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.
“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
Weight Loss Affects Bone
Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.
Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.
Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.
Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
GLP-1 and Bone Effects
Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.
Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”
The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.
These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
New Role for Dipeptidyl Transferase Inhibitors?
Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.
Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.
“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”
For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.
Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).
DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.
Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?
So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.
“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.
He presented data from a large analysis of new users of SGLT2 inhibitors and GLP-1 receptor agonists within two claims databases — Merative (n = 603,471) and TriNetX (n = 1,202,972) — showing that SGLT2 inhibitors were associated with significantly lower risks for OA and the need for TKR.
Comparing new users of SGLT2 inhibitors and GLP-1 receptor agonists in the Merative dataset, the relative risks and odds ratios for OA were a respective 0.96 and 0.80, and having a TKR, 0.88 and 0.76.
Similar results were seen using the TriNetX dataset, with respective relative risks and hazard ratios of 0.90 and 0.85 for OA, and 0.81 and 0.78 for TKR.
In an interview, Dr. Jafarzadeh said that the initial hypothesis was that because SGLT2 inhibitors have only a modest effect on weight loss, there would be no effect on OA outcomes.
“But we were surprised that it actually looked like they reduced the risk of OA outcomes even more than GLP-1 receptor agonists,” Dr. Jafarzadeh said.
Further work is needed to understand these data, but they could mean that SLGT2 inhibitors, like GLP-1 receptor agonists, may have a role to play outside their current use in type 2 diabetes.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com .
VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?
“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.
Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.
“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
Weight Loss Benefits
Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.
In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.
It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.
“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
Weight Rebound
Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.
“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.
Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.
“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
Weight Loss Affects Bone
Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.
Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.
Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.
Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
GLP-1 and Bone Effects
Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.
Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”
The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.
These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
New Role for Dipeptidyl Transferase Inhibitors?
Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.
Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.
“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”
For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.
Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).
DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.
Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?
So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.
“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.
He presented data from a large analysis of new users of SGLT2 inhibitors and GLP-1 receptor agonists within two claims databases — Merative (n = 603,471) and TriNetX (n = 1,202,972) — showing that SGLT2 inhibitors were associated with significantly lower risks for OA and the need for TKR.
Comparing new users of SGLT2 inhibitors and GLP-1 receptor agonists in the Merative dataset, the relative risks and odds ratios for OA were a respective 0.96 and 0.80, and having a TKR, 0.88 and 0.76.
Similar results were seen using the TriNetX dataset, with respective relative risks and hazard ratios of 0.90 and 0.85 for OA, and 0.81 and 0.78 for TKR.
In an interview, Dr. Jafarzadeh said that the initial hypothesis was that because SGLT2 inhibitors have only a modest effect on weight loss, there would be no effect on OA outcomes.
“But we were surprised that it actually looked like they reduced the risk of OA outcomes even more than GLP-1 receptor agonists,” Dr. Jafarzadeh said.
Further work is needed to understand these data, but they could mean that SLGT2 inhibitors, like GLP-1 receptor agonists, may have a role to play outside their current use in type 2 diabetes.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com .
FROM OARSI 2024
Lecanemab’s Promise and Peril: Alzheimer’s Treatment Dilemma
Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS).
Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.
But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.
The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.
Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic.
The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh.
“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.
Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.
Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.
Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.
The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab.
“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.
Neither speaker reported any financial conflicts of interest.
A version of this article first appeared on Medscape.com.
Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS).
Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.
But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.
The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.
Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic.
The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh.
“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.
Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.
Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.
Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.
The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab.
“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.
Neither speaker reported any financial conflicts of interest.
A version of this article first appeared on Medscape.com.
Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS).
Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.
But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.
The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.
Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic.
The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh.
“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.
Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.
Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.
Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.
The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab.
“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.
Neither speaker reported any financial conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM AGS 2024
Pediatricians Face Competing Goals in Well Visits for LGBTQ+ Adolescents
TORONTO — , and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.
In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.
Based on his work, there are two aims.
“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”
Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.
This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.
These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
Revealing Sensitive Information
With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).
The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.
These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.
The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.
“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.
The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.
For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.
For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.
As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.
In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.
When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.
“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
Protecting Patients
The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.
“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.
“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.
She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.
Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.
Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.
TORONTO — , and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.
In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.
Based on his work, there are two aims.
“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”
Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.
This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.
These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
Revealing Sensitive Information
With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).
The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.
These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.
The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.
“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.
The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.
For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.
For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.
As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.
In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.
When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.
“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
Protecting Patients
The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.
“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.
“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.
She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.
Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.
Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.
TORONTO — , and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.
In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.
Based on his work, there are two aims.
“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”
Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.
This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.
These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
Revealing Sensitive Information
With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).
The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.
These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.
The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.
“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.
The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.
For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.
For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.
As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.
In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.
When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.
“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
Protecting Patients
The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.
“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.
“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.
She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.
Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.
Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.
FROM PAS 2024