TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Depression, constipation, cystitis/urinary tract infections (UTIs), and sexual dysfunction may be early warning signs of multiple sclerosis (MS) 5 years prior to diagnosis, new research shows.

However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.

“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
 

Retracing MS Origins

The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.

Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.

Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.

After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:

• Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
• Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
• Constipation (OR, 1.5; 95% CI, 1.27-1.78)
• Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
• UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)

However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.

“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.

“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.

A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.

It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
 

Preventing Disease Evolution

In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.

“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.

“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.

The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.

A version of this article appeared on Medscape.com.

Depression, constipation, cystitis/urinary tract infections (UTIs), and sexual dysfunction may be early warning signs of multiple sclerosis (MS) 5 years prior to diagnosis, new research shows.

However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.

“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
 

Retracing MS Origins

The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.

Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.

Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.

After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:

• Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
• Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
• Constipation (OR, 1.5; 95% CI, 1.27-1.78)
• Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
• UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)

However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.

“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.

“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.

A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.

It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
 

Preventing Disease Evolution

In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.

“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.

“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.

The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.

A version of this article appeared on Medscape.com.

Depression, constipation, cystitis/urinary tract infections (UTIs), and sexual dysfunction may be early warning signs of multiple sclerosis (MS) 5 years prior to diagnosis, new research shows.

However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.

“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
 

Retracing MS Origins

The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.

Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.

Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.

After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:

• Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
• Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
• Constipation (OR, 1.5; 95% CI, 1.27-1.78)
• Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
• UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)

However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.

“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.

“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.

A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.

It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
 

Preventing Disease Evolution

In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.

“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.

“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.

The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).

I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.

ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.

How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.

What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.

For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.

To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.

So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.

What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.

I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.

In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.

Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.

What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.

“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.

Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.

But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.

Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.

Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).

I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.

ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.

How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.

What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.

For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.

To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.

So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.

What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.

I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.

In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.

Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.

What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.

“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.

Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.

But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.

Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.

Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).

I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.

ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.

How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.

What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.

For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.

To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.

So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.

What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.

I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.

In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.

Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.

What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.

“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.

Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.

But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.

Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.

Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

The positive results from the SELECT trial for the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were hailed as ushering in a “new era for patients with obesity.” In the trial of overweight and obese patients with cardiovascular disease (CVD), but no diabetes, semaglutide showed meaningful reductions in cardiovascular death, myocardial infarction, and stroke compared with placebo.

“I definitely see increasing adoption of GLP-1 RAs by cardiologists and expect the number to increase now that the data support its use in secondary prevention,” said Nicole L. Lohr, MD, PhD, chair of the American College of Cardiology (ACC) Board of Governors, and Mary G. Waters, chair of cardiovascular medicine at UAB, Birmingham.

But many cardiologists are more hesitant. “I think there’s going to be an increasing urgency for cardiologists to start prescribing these drugs, but I don’t think the comfort to do so is that widespread at this point,” said American Heart Association (AHA) volunteer Chiadi E. Ndumele, MD, PhD, an associate professor at Johns Hopkins Medicine in Baltimore and chair of the AHA’s recent presidential advisory on cardiovascular-kidney-metabolic health.

“Weight loss hasn’t been a central focus in our practice until recently, with the advent of these more powerful agents. There’s a need for more education around not only the use of these agents, but also around initiating weight loss discussions in a nonjudgmental way that reflects the complexity of obesity as a condition with multifactorial causes.”

The process will take time and may be similar to what happened with statins, he suggests. “Statins started in the endocrinology space, but as their cardiovascular benefits became more clear, they were increasingly adopted by cardiologists, primary care physicians, and others.”

Eugene Yang, MD, chair of the ACC Prevention of CVD Council and codirector of UW Medicine’s Cardiovascular Wellness and Prevention Program in Seattle, agrees that GLP-1 uptake by cardiologists will likely be slow. “It’s a bit premature to start prescribing right away,” he said. “Semaglutide hasn’t been approved for secondary prevention at this point, and until it’s approved specifically for that indication, I don’t think many cardiologists will prescribe it.”
 

Side Effects ‘Concerning’

Beyond the requisite approval, Dr. Yang is concerned about side effects such as gastroparesis, severe nausea, and vomiting. “I’m not sure cardiologists are going to feel comfortable helping patients deal with these effects.”

Because GLP-1 RAs are already being used widely in primary care, he says, “I personally would work in collaboration with either my primary care colleagues or with endocrinologists.”

Ambarish Pandey, MD, an associate professor of internal medicine (cardiology) and medical director of the heart failure with preserved ejection fraction (HFpEF) program at UT Southwestern Medical Center, Dallas, is already prescribing semaglutide to patients with HFpEF and obesity. “In terms of side effects, I just tell patients what to expect,” he says.

Dr. Pandey prepares patients for appetite reduction, early satiety and fullness, abdominal discomfort, nausea, and other gastrointestinal symptoms. “Then I start low and slowly titrate to achieve enough weight loss. If they’re having adverse effects on a higher dose, I use a lower dose.”

The approach is working well for most patients, he says. “Obviously there’s some initial getting used to the drug, but once that has happened, patients like it because they see improvements in their exercise capacity and quality of life.”

But GLP-1 RAs are also associated with increased heart rate, which “is never good news,” notes Howard Weintraub, MD, a professor of medicine at NYU Grossman School of Medicine in New York City and clinical director of the NYU Center for the Prevention of Cardiovascular Disease. At least some of the elevation may be masked by beta-blocker use, he suggests. “The mechanism is not well elucidated, but it is something we’re going to need to keep an eye on, because we don’t want to get ambushed.”
 

Cost, Access ‘Significant Barriers’

All the cardiologists this news organization spoke with agreed that cost and access will be significant barriers to widespread prescribing, at least for now.

“Prescribing for individuals at very high cardiovascular risk will probably give a reasonable amount of bang for your buck. But individuals with more adverse social determinants of health, who are more likely to have challenges with obesity and related complications, are also least likely to be able to pay the exorbitant costs out of pocket. So, this is also an important health equity issue,” Dr. Ndumele says.

Furthermore, he adds, where GLP-1 RAs will fit for those with a lower absolute CVD risk “is still a clear question.”

“Access comes two ways,” Dr. Weintraub says. “One is the supply, which continues to be an issue. You can’t sell the drug if you don’t have it.”

The other access route is the insurance companies. “Will they throw down a gauntlet and make cardiologists prove that a patient failed other obesity drugs before they can prescribe a GLP-1 RA? Some of the old obesity drugs are not only unpleasant to use, but they’re ineffective and may have bad cardiac signals.”

If the new drugs are approved for secondary prevention, patients will want them and doctors will want them, he says. The demand will be “huge,” and it’s not clear how it will be handled.

Dr. Pandey agrees that getting the drug without “good insurance” to cover the cost is a big challenge. “ As more of these drugs become available, hopefully the cost will come down, and hopefully access will grow as companies are able to scale up production.”
 

Add-On or Substitute?

Anticipating approval, Dr. Yang says it’s not yet clear where the GLP-1 RAs stand among the various available cardiovascular therapies.

“Based on the results of SELECT, one could argue that maybe it’s more important to get the weight down and reduce blood pressure versus adding another cholesterol-lowering medication, for example, especially if a patient is already on a statin and ezetimibe. But maybe their low-density lipoprotein cholesterol is not exactly below the threshold of the current guideline. And maybe they’re overweight or prediabetic, and they can lose 10% or 15% of their body weight with a GLP-1 RA. You may have to pick and choose.”

That said, he adds, “Who’s going to be able to afford all of this? Some patients would be taking a PCSK9 inhibitor, bempedoic acid because their lipids are not optimized, then a GLP-1 receptor. Right there, we’re talking about at least $2000 a month for those three medications. That’s not feasible.”

“This is one of the things I’ve worried about, given all the drugs some of our patients are on,” Dr. Weintraub says. “The data on cholesterol-lowering drugs are so monumental, it’s hard to say you can do without it. The same is true of blood pressure-lowering medication. So to my mind, a GLP-1 RA is going to have to be an add-on.”

“The only good news is that unlike in the heart failure arena, patients are not paying for other drugs on top of it,” he says. “Statins, ACE inhibitors, ARBs, and beta-blockers are all generic; they’re not going to leave a huge hole in the patient’s pocket when the donut hole [Medicare payment gap] comes around. So in this case, if the GLP-1 RAs get included, which I hope they will, the added cost may not be that horrible.”
 

What About Lifestyle Changes?

Everyone agreed that the drugs are not a substitute for lifestyle changes.

“I have seen many patients who take these medications reach plateaus, and when discontinued, gain back the weight. I counsel patients to view the medication as an aid and not necessarily a magic wand,” Dr. Lohr says.

Dr. Ndumele agrees. “I advocate a lifestyle-first approach,” he says. “I imagine there will be busy clinicians who will prescribe medications as a first line, but that’s not going to be our most effective approach.”

The major challenge to such an approach, he says, is that lifestyle support has to be ongoing. “It’s not the kind of thing that just happens in a yearly doctor’s visit appointment, and it’s been under-supported in most coverage and reimbursement strategies.”

In his clinical practice, which includes ongoing support for lifestyle changes, Dr. Ndumele is seeing far greater weight loss than was shown in SELECT. “I think there’s a real benefit to having the two approaches come together,” he says.

Dr. Yang also favors an emphasis on lifestyle. “The success rate of a lifestyle approach may be low, but that doesn’t change the importance of it. We need to figure out better ways to do it.” Leveraging technology is one way, he suggests, such as cellphone reminders to walk more or alerts to tell you when to sleep.

“I also encourage patients to monitor their own blood pressure, and they do.” Dr. Yang acknowledges that his patient population is highly educated with access to resources to purchase the technological devices. However, he adds, “if the clinician is negative, and doesn’t really believe these interventions will work, the patient can sense that, and then they won’t work.” It’s up to the clinician to promote the importance of these lifestyle changes in order to be successful. Is it discouraging at times? Yes. But don’t let the patient know.”

Dr. Pandey approaches the issue differently. “Our healthcare system is such that patients don’t get to see us that often, so I think we should start the lifestyle intervention, but also start the medication at the same time, in parallel, because we don’t have time to take a stepwise approach.”

“Lifestyle interventions are better received if patients see positive improvements, and the medication actually induces a positive improvement,” he says. He is concerned that if a lifestyle first approach doesn’t work “that can affect the willingness to try future therapies. And we don’t want to lose like 6 or 8 months just trying lifestyle when they could have benefited from the weight-loss medication, as well.”

Dr. Lohr, Dr. Ndumele, and Dr. Yang report no conflicts of interest. Dr. Weintraub reports being an investigator in the SELECT trial and a consultant for NovoNordisk. Dr. Pandey reports receiving research support from the National Institutes of Health; grant funding from Applied Therapeutics and Gilead Sciences; honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon therapies, Medtronic, Edwards Lifesciences, Science 37 Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, Emmi Solutions; and has received nonfinancial support from Pfizer and Merck; and serving as a consultant for Palomarin Inc. with stocks compensation.

A version of this article appeared on Medscape.com.

The positive results from the SELECT trial for the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were hailed as ushering in a “new era for patients with obesity.” In the trial of overweight and obese patients with cardiovascular disease (CVD), but no diabetes, semaglutide showed meaningful reductions in cardiovascular death, myocardial infarction, and stroke compared with placebo.

“I definitely see increasing adoption of GLP-1 RAs by cardiologists and expect the number to increase now that the data support its use in secondary prevention,” said Nicole L. Lohr, MD, PhD, chair of the American College of Cardiology (ACC) Board of Governors, and Mary G. Waters, chair of cardiovascular medicine at UAB, Birmingham.

But many cardiologists are more hesitant. “I think there’s going to be an increasing urgency for cardiologists to start prescribing these drugs, but I don’t think the comfort to do so is that widespread at this point,” said American Heart Association (AHA) volunteer Chiadi E. Ndumele, MD, PhD, an associate professor at Johns Hopkins Medicine in Baltimore and chair of the AHA’s recent presidential advisory on cardiovascular-kidney-metabolic health.

“Weight loss hasn’t been a central focus in our practice until recently, with the advent of these more powerful agents. There’s a need for more education around not only the use of these agents, but also around initiating weight loss discussions in a nonjudgmental way that reflects the complexity of obesity as a condition with multifactorial causes.”

The process will take time and may be similar to what happened with statins, he suggests. “Statins started in the endocrinology space, but as their cardiovascular benefits became more clear, they were increasingly adopted by cardiologists, primary care physicians, and others.”

Eugene Yang, MD, chair of the ACC Prevention of CVD Council and codirector of UW Medicine’s Cardiovascular Wellness and Prevention Program in Seattle, agrees that GLP-1 uptake by cardiologists will likely be slow. “It’s a bit premature to start prescribing right away,” he said. “Semaglutide hasn’t been approved for secondary prevention at this point, and until it’s approved specifically for that indication, I don’t think many cardiologists will prescribe it.”
 

Side Effects ‘Concerning’

Beyond the requisite approval, Dr. Yang is concerned about side effects such as gastroparesis, severe nausea, and vomiting. “I’m not sure cardiologists are going to feel comfortable helping patients deal with these effects.”

Because GLP-1 RAs are already being used widely in primary care, he says, “I personally would work in collaboration with either my primary care colleagues or with endocrinologists.”

Ambarish Pandey, MD, an associate professor of internal medicine (cardiology) and medical director of the heart failure with preserved ejection fraction (HFpEF) program at UT Southwestern Medical Center, Dallas, is already prescribing semaglutide to patients with HFpEF and obesity. “In terms of side effects, I just tell patients what to expect,” he says.

Dr. Pandey prepares patients for appetite reduction, early satiety and fullness, abdominal discomfort, nausea, and other gastrointestinal symptoms. “Then I start low and slowly titrate to achieve enough weight loss. If they’re having adverse effects on a higher dose, I use a lower dose.”

The approach is working well for most patients, he says. “Obviously there’s some initial getting used to the drug, but once that has happened, patients like it because they see improvements in their exercise capacity and quality of life.”

But GLP-1 RAs are also associated with increased heart rate, which “is never good news,” notes Howard Weintraub, MD, a professor of medicine at NYU Grossman School of Medicine in New York City and clinical director of the NYU Center for the Prevention of Cardiovascular Disease. At least some of the elevation may be masked by beta-blocker use, he suggests. “The mechanism is not well elucidated, but it is something we’re going to need to keep an eye on, because we don’t want to get ambushed.”
 

Cost, Access ‘Significant Barriers’

All the cardiologists this news organization spoke with agreed that cost and access will be significant barriers to widespread prescribing, at least for now.

“Prescribing for individuals at very high cardiovascular risk will probably give a reasonable amount of bang for your buck. But individuals with more adverse social determinants of health, who are more likely to have challenges with obesity and related complications, are also least likely to be able to pay the exorbitant costs out of pocket. So, this is also an important health equity issue,” Dr. Ndumele says.

Furthermore, he adds, where GLP-1 RAs will fit for those with a lower absolute CVD risk “is still a clear question.”

“Access comes two ways,” Dr. Weintraub says. “One is the supply, which continues to be an issue. You can’t sell the drug if you don’t have it.”

The other access route is the insurance companies. “Will they throw down a gauntlet and make cardiologists prove that a patient failed other obesity drugs before they can prescribe a GLP-1 RA? Some of the old obesity drugs are not only unpleasant to use, but they’re ineffective and may have bad cardiac signals.”

If the new drugs are approved for secondary prevention, patients will want them and doctors will want them, he says. The demand will be “huge,” and it’s not clear how it will be handled.

Dr. Pandey agrees that getting the drug without “good insurance” to cover the cost is a big challenge. “ As more of these drugs become available, hopefully the cost will come down, and hopefully access will grow as companies are able to scale up production.”
 

Add-On or Substitute?

Anticipating approval, Dr. Yang says it’s not yet clear where the GLP-1 RAs stand among the various available cardiovascular therapies.

“Based on the results of SELECT, one could argue that maybe it’s more important to get the weight down and reduce blood pressure versus adding another cholesterol-lowering medication, for example, especially if a patient is already on a statin and ezetimibe. But maybe their low-density lipoprotein cholesterol is not exactly below the threshold of the current guideline. And maybe they’re overweight or prediabetic, and they can lose 10% or 15% of their body weight with a GLP-1 RA. You may have to pick and choose.”

That said, he adds, “Who’s going to be able to afford all of this? Some patients would be taking a PCSK9 inhibitor, bempedoic acid because their lipids are not optimized, then a GLP-1 receptor. Right there, we’re talking about at least $2000 a month for those three medications. That’s not feasible.”

“This is one of the things I’ve worried about, given all the drugs some of our patients are on,” Dr. Weintraub says. “The data on cholesterol-lowering drugs are so monumental, it’s hard to say you can do without it. The same is true of blood pressure-lowering medication. So to my mind, a GLP-1 RA is going to have to be an add-on.”

“The only good news is that unlike in the heart failure arena, patients are not paying for other drugs on top of it,” he says. “Statins, ACE inhibitors, ARBs, and beta-blockers are all generic; they’re not going to leave a huge hole in the patient’s pocket when the donut hole [Medicare payment gap] comes around. So in this case, if the GLP-1 RAs get included, which I hope they will, the added cost may not be that horrible.”
 

What About Lifestyle Changes?

Everyone agreed that the drugs are not a substitute for lifestyle changes.

“I have seen many patients who take these medications reach plateaus, and when discontinued, gain back the weight. I counsel patients to view the medication as an aid and not necessarily a magic wand,” Dr. Lohr says.

Dr. Ndumele agrees. “I advocate a lifestyle-first approach,” he says. “I imagine there will be busy clinicians who will prescribe medications as a first line, but that’s not going to be our most effective approach.”

The major challenge to such an approach, he says, is that lifestyle support has to be ongoing. “It’s not the kind of thing that just happens in a yearly doctor’s visit appointment, and it’s been under-supported in most coverage and reimbursement strategies.”

In his clinical practice, which includes ongoing support for lifestyle changes, Dr. Ndumele is seeing far greater weight loss than was shown in SELECT. “I think there’s a real benefit to having the two approaches come together,” he says.

Dr. Yang also favors an emphasis on lifestyle. “The success rate of a lifestyle approach may be low, but that doesn’t change the importance of it. We need to figure out better ways to do it.” Leveraging technology is one way, he suggests, such as cellphone reminders to walk more or alerts to tell you when to sleep.

“I also encourage patients to monitor their own blood pressure, and they do.” Dr. Yang acknowledges that his patient population is highly educated with access to resources to purchase the technological devices. However, he adds, “if the clinician is negative, and doesn’t really believe these interventions will work, the patient can sense that, and then they won’t work.” It’s up to the clinician to promote the importance of these lifestyle changes in order to be successful. Is it discouraging at times? Yes. But don’t let the patient know.”

Dr. Pandey approaches the issue differently. “Our healthcare system is such that patients don’t get to see us that often, so I think we should start the lifestyle intervention, but also start the medication at the same time, in parallel, because we don’t have time to take a stepwise approach.”

“Lifestyle interventions are better received if patients see positive improvements, and the medication actually induces a positive improvement,” he says. He is concerned that if a lifestyle first approach doesn’t work “that can affect the willingness to try future therapies. And we don’t want to lose like 6 or 8 months just trying lifestyle when they could have benefited from the weight-loss medication, as well.”

Dr. Lohr, Dr. Ndumele, and Dr. Yang report no conflicts of interest. Dr. Weintraub reports being an investigator in the SELECT trial and a consultant for NovoNordisk. Dr. Pandey reports receiving research support from the National Institutes of Health; grant funding from Applied Therapeutics and Gilead Sciences; honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon therapies, Medtronic, Edwards Lifesciences, Science 37 Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, Emmi Solutions; and has received nonfinancial support from Pfizer and Merck; and serving as a consultant for Palomarin Inc. with stocks compensation.

A version of this article appeared on Medscape.com.

The positive results from the SELECT trial for the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were hailed as ushering in a “new era for patients with obesity.” In the trial of overweight and obese patients with cardiovascular disease (CVD), but no diabetes, semaglutide showed meaningful reductions in cardiovascular death, myocardial infarction, and stroke compared with placebo.

“I definitely see increasing adoption of GLP-1 RAs by cardiologists and expect the number to increase now that the data support its use in secondary prevention,” said Nicole L. Lohr, MD, PhD, chair of the American College of Cardiology (ACC) Board of Governors, and Mary G. Waters, chair of cardiovascular medicine at UAB, Birmingham.

But many cardiologists are more hesitant. “I think there’s going to be an increasing urgency for cardiologists to start prescribing these drugs, but I don’t think the comfort to do so is that widespread at this point,” said American Heart Association (AHA) volunteer Chiadi E. Ndumele, MD, PhD, an associate professor at Johns Hopkins Medicine in Baltimore and chair of the AHA’s recent presidential advisory on cardiovascular-kidney-metabolic health.

“Weight loss hasn’t been a central focus in our practice until recently, with the advent of these more powerful agents. There’s a need for more education around not only the use of these agents, but also around initiating weight loss discussions in a nonjudgmental way that reflects the complexity of obesity as a condition with multifactorial causes.”

The process will take time and may be similar to what happened with statins, he suggests. “Statins started in the endocrinology space, but as their cardiovascular benefits became more clear, they were increasingly adopted by cardiologists, primary care physicians, and others.”

Eugene Yang, MD, chair of the ACC Prevention of CVD Council and codirector of UW Medicine’s Cardiovascular Wellness and Prevention Program in Seattle, agrees that GLP-1 uptake by cardiologists will likely be slow. “It’s a bit premature to start prescribing right away,” he said. “Semaglutide hasn’t been approved for secondary prevention at this point, and until it’s approved specifically for that indication, I don’t think many cardiologists will prescribe it.”
 

Side Effects ‘Concerning’

Beyond the requisite approval, Dr. Yang is concerned about side effects such as gastroparesis, severe nausea, and vomiting. “I’m not sure cardiologists are going to feel comfortable helping patients deal with these effects.”

Because GLP-1 RAs are already being used widely in primary care, he says, “I personally would work in collaboration with either my primary care colleagues or with endocrinologists.”

Ambarish Pandey, MD, an associate professor of internal medicine (cardiology) and medical director of the heart failure with preserved ejection fraction (HFpEF) program at UT Southwestern Medical Center, Dallas, is already prescribing semaglutide to patients with HFpEF and obesity. “In terms of side effects, I just tell patients what to expect,” he says.

Dr. Pandey prepares patients for appetite reduction, early satiety and fullness, abdominal discomfort, nausea, and other gastrointestinal symptoms. “Then I start low and slowly titrate to achieve enough weight loss. If they’re having adverse effects on a higher dose, I use a lower dose.”

The approach is working well for most patients, he says. “Obviously there’s some initial getting used to the drug, but once that has happened, patients like it because they see improvements in their exercise capacity and quality of life.”

But GLP-1 RAs are also associated with increased heart rate, which “is never good news,” notes Howard Weintraub, MD, a professor of medicine at NYU Grossman School of Medicine in New York City and clinical director of the NYU Center for the Prevention of Cardiovascular Disease. At least some of the elevation may be masked by beta-blocker use, he suggests. “The mechanism is not well elucidated, but it is something we’re going to need to keep an eye on, because we don’t want to get ambushed.”
 

Cost, Access ‘Significant Barriers’

All the cardiologists this news organization spoke with agreed that cost and access will be significant barriers to widespread prescribing, at least for now.

“Prescribing for individuals at very high cardiovascular risk will probably give a reasonable amount of bang for your buck. But individuals with more adverse social determinants of health, who are more likely to have challenges with obesity and related complications, are also least likely to be able to pay the exorbitant costs out of pocket. So, this is also an important health equity issue,” Dr. Ndumele says.

Furthermore, he adds, where GLP-1 RAs will fit for those with a lower absolute CVD risk “is still a clear question.”

“Access comes two ways,” Dr. Weintraub says. “One is the supply, which continues to be an issue. You can’t sell the drug if you don’t have it.”

The other access route is the insurance companies. “Will they throw down a gauntlet and make cardiologists prove that a patient failed other obesity drugs before they can prescribe a GLP-1 RA? Some of the old obesity drugs are not only unpleasant to use, but they’re ineffective and may have bad cardiac signals.”

If the new drugs are approved for secondary prevention, patients will want them and doctors will want them, he says. The demand will be “huge,” and it’s not clear how it will be handled.

Dr. Pandey agrees that getting the drug without “good insurance” to cover the cost is a big challenge. “ As more of these drugs become available, hopefully the cost will come down, and hopefully access will grow as companies are able to scale up production.”
 

Add-On or Substitute?

Anticipating approval, Dr. Yang says it’s not yet clear where the GLP-1 RAs stand among the various available cardiovascular therapies.

“Based on the results of SELECT, one could argue that maybe it’s more important to get the weight down and reduce blood pressure versus adding another cholesterol-lowering medication, for example, especially if a patient is already on a statin and ezetimibe. But maybe their low-density lipoprotein cholesterol is not exactly below the threshold of the current guideline. And maybe they’re overweight or prediabetic, and they can lose 10% or 15% of their body weight with a GLP-1 RA. You may have to pick and choose.”

That said, he adds, “Who’s going to be able to afford all of this? Some patients would be taking a PCSK9 inhibitor, bempedoic acid because their lipids are not optimized, then a GLP-1 receptor. Right there, we’re talking about at least $2000 a month for those three medications. That’s not feasible.”

“This is one of the things I’ve worried about, given all the drugs some of our patients are on,” Dr. Weintraub says. “The data on cholesterol-lowering drugs are so monumental, it’s hard to say you can do without it. The same is true of blood pressure-lowering medication. So to my mind, a GLP-1 RA is going to have to be an add-on.”

“The only good news is that unlike in the heart failure arena, patients are not paying for other drugs on top of it,” he says. “Statins, ACE inhibitors, ARBs, and beta-blockers are all generic; they’re not going to leave a huge hole in the patient’s pocket when the donut hole [Medicare payment gap] comes around. So in this case, if the GLP-1 RAs get included, which I hope they will, the added cost may not be that horrible.”
 

What About Lifestyle Changes?

Everyone agreed that the drugs are not a substitute for lifestyle changes.

“I have seen many patients who take these medications reach plateaus, and when discontinued, gain back the weight. I counsel patients to view the medication as an aid and not necessarily a magic wand,” Dr. Lohr says.

Dr. Ndumele agrees. “I advocate a lifestyle-first approach,” he says. “I imagine there will be busy clinicians who will prescribe medications as a first line, but that’s not going to be our most effective approach.”

The major challenge to such an approach, he says, is that lifestyle support has to be ongoing. “It’s not the kind of thing that just happens in a yearly doctor’s visit appointment, and it’s been under-supported in most coverage and reimbursement strategies.”

In his clinical practice, which includes ongoing support for lifestyle changes, Dr. Ndumele is seeing far greater weight loss than was shown in SELECT. “I think there’s a real benefit to having the two approaches come together,” he says.

Dr. Yang also favors an emphasis on lifestyle. “The success rate of a lifestyle approach may be low, but that doesn’t change the importance of it. We need to figure out better ways to do it.” Leveraging technology is one way, he suggests, such as cellphone reminders to walk more or alerts to tell you when to sleep.

“I also encourage patients to monitor their own blood pressure, and they do.” Dr. Yang acknowledges that his patient population is highly educated with access to resources to purchase the technological devices. However, he adds, “if the clinician is negative, and doesn’t really believe these interventions will work, the patient can sense that, and then they won’t work.” It’s up to the clinician to promote the importance of these lifestyle changes in order to be successful. Is it discouraging at times? Yes. But don’t let the patient know.”

Dr. Pandey approaches the issue differently. “Our healthcare system is such that patients don’t get to see us that often, so I think we should start the lifestyle intervention, but also start the medication at the same time, in parallel, because we don’t have time to take a stepwise approach.”

“Lifestyle interventions are better received if patients see positive improvements, and the medication actually induces a positive improvement,” he says. He is concerned that if a lifestyle first approach doesn’t work “that can affect the willingness to try future therapies. And we don’t want to lose like 6 or 8 months just trying lifestyle when they could have benefited from the weight-loss medication, as well.”

Dr. Lohr, Dr. Ndumele, and Dr. Yang report no conflicts of interest. Dr. Weintraub reports being an investigator in the SELECT trial and a consultant for NovoNordisk. Dr. Pandey reports receiving research support from the National Institutes of Health; grant funding from Applied Therapeutics and Gilead Sciences; honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon therapies, Medtronic, Edwards Lifesciences, Science 37 Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, Emmi Solutions; and has received nonfinancial support from Pfizer and Merck; and serving as a consultant for Palomarin Inc. with stocks compensation.

A version of this article appeared on Medscape.com.

UnitedHealth Group, the parent company of the nation’s largest private insurer, UnitedHealthcare (UHC), is now affiliated with or employs approximately 10% of the US physician workforce, raising anti-trust and noncompete concerns as more payers and private equity firms pursue medical practice acquisitions.

The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.

Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care. 

Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied. 

Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization. 

Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh. 

A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce. 

The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized. 

According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws. 

The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care. 

“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.” 

Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee. 

Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers. 

UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders. 

At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.

A version of this article appeared on Medscape.com.

UnitedHealth Group, the parent company of the nation’s largest private insurer, UnitedHealthcare (UHC), is now affiliated with or employs approximately 10% of the US physician workforce, raising anti-trust and noncompete concerns as more payers and private equity firms pursue medical practice acquisitions.

The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.

Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care. 

Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied. 

Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization. 

Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh. 

A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce. 

The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized. 

According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws. 

The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care. 

“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.” 

Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee. 

Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers. 

UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders. 

At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.

A version of this article appeared on Medscape.com.

UnitedHealth Group, the parent company of the nation’s largest private insurer, UnitedHealthcare (UHC), is now affiliated with or employs approximately 10% of the US physician workforce, raising anti-trust and noncompete concerns as more payers and private equity firms pursue medical practice acquisitions.

The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.

Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care. 

Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied. 

Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization. 

Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh. 

A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce. 

The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized. 

According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws. 

The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care. 

“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.” 

Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee. 

Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers. 

UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders. 

At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.

A version of this article appeared on Medscape.com.

TOPLINE

Babies born to mothers living in disadvantaged neighborhoods have a higher risk of being diagnosed with autism spectrum disorder (ASD), but only if they are White, a population-based prospective cohort study shows. 

METHODOLOGY

• Investigators analyzed data from a large cohort of singleton children with insurance born in Kaiser Permanente Southern California hospitals between 2001 and 2014.
• They ascertained ASD diagnosis, maternal race and ethnicity, and maternal address at time of birth.
• Neighborhood disadvantage was determined by the percentage of families in the mother’s neighborhood considered to be living in poverty, unemployed, have female-headed households with children, using public assistance, less than a high school education, among other variables.

TAKEAWAY

• Among 318,300 mothers who delivered babies during the study period, 6350 children were diagnosed with ASD during follow-up, and median age at diagnosis was 3.5 years.
• Greater neighborhood disadvantage at birth was associated with a higher likelihood of ASD diagnosis (adjusted hazard ratio [aHR], 1.07; 95% CI, 1.02-1.11)
• ASD diagnoses were more likely among children of mothers who were Black (aHR, 1.13; 95% CI, 1.02-1.25), Asian/Pacific Islander (aHR, 1.11; 95% CI, 1.02-1.20), or Hispanic (aHR, 1.07; 95% CI, 1.00-1.15), even after the researchers controlled for neighborhood.
• While odds of an ASD diagnosis were higher among children from minority racial and ethnic groups, neighborhood disadvantage was significantly associated with ASD diagnosis only for children of White mothers (aHR, 1.17; 95% CI, 1.09-1.26).

IN PRACTICE

Investigators noted that they could only speculate about the factors driving the association between neighborhood disadvantage and a stronger risk for ASD diagnosis in children of White mothers. “They may be due to systemic racism, discrimination, and their impact on maternal health during pregnancy,” they wrote.

SOURCE

Xin Yu, MS, and Daniel Hackman, PhD, of the University of Southern California Los Angeles, led the study, which was published online November 15 in JAMA Psychiatry. 

LIMITATIONS

The research was limited by a lack of information on fathers and variables such as incomes, which may have confounded the findings. The authors also acknowledged that the study should be replicated in other health service settings. 

DISCLOSURES

The study was funded by the National Institutes on Environmental Health Sciences, the National Institutes of Health (NIH), and the Environmental Protection Agency. Dr. Hackman reported receiving grant funding from NIH during the conduct of the study. Other disclosures are available in the original study. 
 

A version of this article appeared on Medscape.com.

TOPLINE

Babies born to mothers living in disadvantaged neighborhoods have a higher risk of being diagnosed with autism spectrum disorder (ASD), but only if they are White, a population-based prospective cohort study shows. 

METHODOLOGY

• Investigators analyzed data from a large cohort of singleton children with insurance born in Kaiser Permanente Southern California hospitals between 2001 and 2014.
• They ascertained ASD diagnosis, maternal race and ethnicity, and maternal address at time of birth.
• Neighborhood disadvantage was determined by the percentage of families in the mother’s neighborhood considered to be living in poverty, unemployed, have female-headed households with children, using public assistance, less than a high school education, among other variables.

TAKEAWAY

• Among 318,300 mothers who delivered babies during the study period, 6350 children were diagnosed with ASD during follow-up, and median age at diagnosis was 3.5 years.
• Greater neighborhood disadvantage at birth was associated with a higher likelihood of ASD diagnosis (adjusted hazard ratio [aHR], 1.07; 95% CI, 1.02-1.11)
• ASD diagnoses were more likely among children of mothers who were Black (aHR, 1.13; 95% CI, 1.02-1.25), Asian/Pacific Islander (aHR, 1.11; 95% CI, 1.02-1.20), or Hispanic (aHR, 1.07; 95% CI, 1.00-1.15), even after the researchers controlled for neighborhood.
• While odds of an ASD diagnosis were higher among children from minority racial and ethnic groups, neighborhood disadvantage was significantly associated with ASD diagnosis only for children of White mothers (aHR, 1.17; 95% CI, 1.09-1.26).

IN PRACTICE

Investigators noted that they could only speculate about the factors driving the association between neighborhood disadvantage and a stronger risk for ASD diagnosis in children of White mothers. “They may be due to systemic racism, discrimination, and their impact on maternal health during pregnancy,” they wrote.

SOURCE

Xin Yu, MS, and Daniel Hackman, PhD, of the University of Southern California Los Angeles, led the study, which was published online November 15 in JAMA Psychiatry. 

LIMITATIONS

The research was limited by a lack of information on fathers and variables such as incomes, which may have confounded the findings. The authors also acknowledged that the study should be replicated in other health service settings. 

DISCLOSURES

The study was funded by the National Institutes on Environmental Health Sciences, the National Institutes of Health (NIH), and the Environmental Protection Agency. Dr. Hackman reported receiving grant funding from NIH during the conduct of the study. Other disclosures are available in the original study. 
 

A version of this article appeared on Medscape.com.

TOPLINE

Babies born to mothers living in disadvantaged neighborhoods have a higher risk of being diagnosed with autism spectrum disorder (ASD), but only if they are White, a population-based prospective cohort study shows. 

METHODOLOGY

• Investigators analyzed data from a large cohort of singleton children with insurance born in Kaiser Permanente Southern California hospitals between 2001 and 2014.
• They ascertained ASD diagnosis, maternal race and ethnicity, and maternal address at time of birth.
• Neighborhood disadvantage was determined by the percentage of families in the mother’s neighborhood considered to be living in poverty, unemployed, have female-headed households with children, using public assistance, less than a high school education, among other variables.

TAKEAWAY

• Among 318,300 mothers who delivered babies during the study period, 6350 children were diagnosed with ASD during follow-up, and median age at diagnosis was 3.5 years.
• Greater neighborhood disadvantage at birth was associated with a higher likelihood of ASD diagnosis (adjusted hazard ratio [aHR], 1.07; 95% CI, 1.02-1.11)
• ASD diagnoses were more likely among children of mothers who were Black (aHR, 1.13; 95% CI, 1.02-1.25), Asian/Pacific Islander (aHR, 1.11; 95% CI, 1.02-1.20), or Hispanic (aHR, 1.07; 95% CI, 1.00-1.15), even after the researchers controlled for neighborhood.
• While odds of an ASD diagnosis were higher among children from minority racial and ethnic groups, neighborhood disadvantage was significantly associated with ASD diagnosis only for children of White mothers (aHR, 1.17; 95% CI, 1.09-1.26).

IN PRACTICE

Investigators noted that they could only speculate about the factors driving the association between neighborhood disadvantage and a stronger risk for ASD diagnosis in children of White mothers. “They may be due to systemic racism, discrimination, and their impact on maternal health during pregnancy,” they wrote.

SOURCE

Xin Yu, MS, and Daniel Hackman, PhD, of the University of Southern California Los Angeles, led the study, which was published online November 15 in JAMA Psychiatry. 

LIMITATIONS

The research was limited by a lack of information on fathers and variables such as incomes, which may have confounded the findings. The authors also acknowledged that the study should be replicated in other health service settings. 

DISCLOSURES

The study was funded by the National Institutes on Environmental Health Sciences, the National Institutes of Health (NIH), and the Environmental Protection Agency. Dr. Hackman reported receiving grant funding from NIH during the conduct of the study. Other disclosures are available in the original study. 
 

A version of this article appeared on Medscape.com.