Conference Coverage

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

The addition of dupilumab significantly reduced itching and hives, compared with placebo, in patients with chronic spontaneous urticaria (CSU) that was uncontrolled with H1-antihistamines, based on data from 151 individuals.

“Approximately 50% of patients with chronic spontaneous urticaria do not respond to antihistamines,” said Thomas B. Casale, MD, professor of internal medicine at the University of South Florida, Tampa, in an interview. Omalizumab, the only biologic approved for this condition, is not effective in all patients, and additional treatment options are needed, added Casale, the lead author who presented the new data, at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Annual Scientific Meeting.

Dupilumab (Dupixent), a fully human monoclonal antibody that targets the interleukin (IL)–4 and IL-13 pathways, is currently approved in the United States for the treatment of several allergy and dermatology indications, including atopic dermatitis, severe asthma exacerbations, chronic rhinosinusitis with nasal polyps, and prurigo nodularis.

In the study, known as LIBERTY-CSU CUPID Study C, researchers randomized 74 patients with CSU aged 6 years or older to add-on dupilumab subcutaneously every 2 weeks and 77 to placebo. (Patients were omalizumab-naive and had symptomatic CSU, despite treatment with up to four times the approved dose of standard-of-care H1-antihistamines.) Dupilumab doses were 300 mg for adults and adolescents weighing ≥ 60 kg or 200 mg for adolescents weighing < 60 kg and children weighing ≥ 30 kg.

The primary outcomes were Itch Severity Score over 7 days (ISS7; range, 0-21) and Urticaria Activity Score over 7 days (UAS7; range, 0-42).

Over the 24-week study period, patients in the dupilumab group showed significantly greater change from baseline than those in the placebo group on both measures, with least squares mean changes of 8.6 vs 6.1 for ISS7 and 15.9 vs 11.2 for UAS7 (P = .02 for both).

In addition, at 24 weeks, significantly more patients in the dupilumab group than in the placebo group achieved well-controlled disease based on a UAS of 6 or lower (41% vs 23%; P = .005). Significantly more dupilumab-treated patients also achieved a complete response (defined as a UAS of 0), compared with placebo-treated patients (30% vs 18%; P = .02).

Overall rates of treatment-emergent adverse events were 53% for both groups, and safety data were mainly consistent with dupilumab’s known safety profile, the researchers wrote.

The findings were not surprising, as a previous related study, LIBERTY-CSU CUPID Study A, showed that dupilumab was effective for CSU, Casale told this news organization. “This replicate study confirms the previous study and provides evidence for regulatory approval.”

If approved by the Food and Drug Administration (FDA), “dupilumab will provide another therapeutic option for patients with chronic urticaria unresponsive to antihistamines,” Casale commented.

No new safety signals occurred, and the ability to self-administer the medication at home provides an advantage for patients, he added. As for additional research, “analysis of patient characteristics and potential biomarkers that would predict responsiveness is needed.”

 

More Research Needed to Fine-Tune Management

An unmet need persists for patients with CSU whose disease is not adequately controlled by higher-dose H1-antihistamines, Robert G. Micheletti, MD, associate professor of dermatology and medicine at the University of Pennsylvania, Philadelphia, said in an interview. “It is important not only to identify effective add-on therapies for these patients but also to generate data to support insurance coverage and drug access,” said Micheletti, who was not involved in the study.

Also referring to the similar findings reported in the LIBERTY-CSU CUPID Study A, Micheletti said, “as in the earlier study, the results demonstrate significantly reduced itch and urticaria in treated patients compared to placebo.”

“While many providers currently prescribe dupilumab off-label for refractory CSU, FDA approval would improve access to the drug for patients who need it and provide an alternative for patients who may not be good candidates for omalizumab,” he added. However, more research is needed to define optimal management of patients with CSU with inadequate response to omalizumab.

“The LIBERTY-CSU CUPID Study B showed a small improvement in itch severity and urticaria activity among such patients receiving dupilumab,” he noted. “Future work should aim to identify biomarkers and other features predictive of response to various therapies.” 

Study B involved patients with CSU who were uncontrolled on standard-of-care antihistamines and refractory or intolerant to omalizumab, according to Regeneron. 

On November 15, after the ACAAI meeting had ended, the company announced that the FDA had accepted the resubmission of an application for approval of dupilumab for the treatment of CSU in adults and pediatric patients aged 12 years or older not adequately controlled with H1-antihistamines.

The study was supported and sponsored by Sanofi and Regeneron Pharmaceuticals. Casale disclosed serving as a consultant for ALK, ARS Pharma, AstraZeneca, Bryn Pharma, Celgene, Eli Lilly, Genentech, GSK, Jasper, Novartis, Regeneron, and Sanofi and as a speaker for Genentech and Regeneron. Micheletti had no relevant financial conflicts to disclose.

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

The addition of dupilumab significantly reduced itching and hives, compared with placebo, in patients with chronic spontaneous urticaria (CSU) that was uncontrolled with H1-antihistamines, based on data from 151 individuals.

“Approximately 50% of patients with chronic spontaneous urticaria do not respond to antihistamines,” said Thomas B. Casale, MD, professor of internal medicine at the University of South Florida, Tampa, in an interview. Omalizumab, the only biologic approved for this condition, is not effective in all patients, and additional treatment options are needed, added Casale, the lead author who presented the new data, at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Annual Scientific Meeting.

Dupilumab (Dupixent), a fully human monoclonal antibody that targets the interleukin (IL)–4 and IL-13 pathways, is currently approved in the United States for the treatment of several allergy and dermatology indications, including atopic dermatitis, severe asthma exacerbations, chronic rhinosinusitis with nasal polyps, and prurigo nodularis.

In the study, known as LIBERTY-CSU CUPID Study C, researchers randomized 74 patients with CSU aged 6 years or older to add-on dupilumab subcutaneously every 2 weeks and 77 to placebo. (Patients were omalizumab-naive and had symptomatic CSU, despite treatment with up to four times the approved dose of standard-of-care H1-antihistamines.) Dupilumab doses were 300 mg for adults and adolescents weighing ≥ 60 kg or 200 mg for adolescents weighing < 60 kg and children weighing ≥ 30 kg.

The primary outcomes were Itch Severity Score over 7 days (ISS7; range, 0-21) and Urticaria Activity Score over 7 days (UAS7; range, 0-42).

Over the 24-week study period, patients in the dupilumab group showed significantly greater change from baseline than those in the placebo group on both measures, with least squares mean changes of 8.6 vs 6.1 for ISS7 and 15.9 vs 11.2 for UAS7 (P = .02 for both).

In addition, at 24 weeks, significantly more patients in the dupilumab group than in the placebo group achieved well-controlled disease based on a UAS of 6 or lower (41% vs 23%; P = .005). Significantly more dupilumab-treated patients also achieved a complete response (defined as a UAS of 0), compared with placebo-treated patients (30% vs 18%; P = .02).

Overall rates of treatment-emergent adverse events were 53% for both groups, and safety data were mainly consistent with dupilumab’s known safety profile, the researchers wrote.

The findings were not surprising, as a previous related study, LIBERTY-CSU CUPID Study A, showed that dupilumab was effective for CSU, Casale told this news organization. “This replicate study confirms the previous study and provides evidence for regulatory approval.”

If approved by the Food and Drug Administration (FDA), “dupilumab will provide another therapeutic option for patients with chronic urticaria unresponsive to antihistamines,” Casale commented.

No new safety signals occurred, and the ability to self-administer the medication at home provides an advantage for patients, he added. As for additional research, “analysis of patient characteristics and potential biomarkers that would predict responsiveness is needed.”

 

More Research Needed to Fine-Tune Management

An unmet need persists for patients with CSU whose disease is not adequately controlled by higher-dose H1-antihistamines, Robert G. Micheletti, MD, associate professor of dermatology and medicine at the University of Pennsylvania, Philadelphia, said in an interview. “It is important not only to identify effective add-on therapies for these patients but also to generate data to support insurance coverage and drug access,” said Micheletti, who was not involved in the study.

Also referring to the similar findings reported in the LIBERTY-CSU CUPID Study A, Micheletti said, “as in the earlier study, the results demonstrate significantly reduced itch and urticaria in treated patients compared to placebo.”

“While many providers currently prescribe dupilumab off-label for refractory CSU, FDA approval would improve access to the drug for patients who need it and provide an alternative for patients who may not be good candidates for omalizumab,” he added. However, more research is needed to define optimal management of patients with CSU with inadequate response to omalizumab.

“The LIBERTY-CSU CUPID Study B showed a small improvement in itch severity and urticaria activity among such patients receiving dupilumab,” he noted. “Future work should aim to identify biomarkers and other features predictive of response to various therapies.” 

Study B involved patients with CSU who were uncontrolled on standard-of-care antihistamines and refractory or intolerant to omalizumab, according to Regeneron. 

On November 15, after the ACAAI meeting had ended, the company announced that the FDA had accepted the resubmission of an application for approval of dupilumab for the treatment of CSU in adults and pediatric patients aged 12 years or older not adequately controlled with H1-antihistamines.

The study was supported and sponsored by Sanofi and Regeneron Pharmaceuticals. Casale disclosed serving as a consultant for ALK, ARS Pharma, AstraZeneca, Bryn Pharma, Celgene, Eli Lilly, Genentech, GSK, Jasper, Novartis, Regeneron, and Sanofi and as a speaker for Genentech and Regeneron. Micheletti had no relevant financial conflicts to disclose.

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

The addition of dupilumab significantly reduced itching and hives, compared with placebo, in patients with chronic spontaneous urticaria (CSU) that was uncontrolled with H1-antihistamines, based on data from 151 individuals.

“Approximately 50% of patients with chronic spontaneous urticaria do not respond to antihistamines,” said Thomas B. Casale, MD, professor of internal medicine at the University of South Florida, Tampa, in an interview. Omalizumab, the only biologic approved for this condition, is not effective in all patients, and additional treatment options are needed, added Casale, the lead author who presented the new data, at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Annual Scientific Meeting.

Dupilumab (Dupixent), a fully human monoclonal antibody that targets the interleukin (IL)–4 and IL-13 pathways, is currently approved in the United States for the treatment of several allergy and dermatology indications, including atopic dermatitis, severe asthma exacerbations, chronic rhinosinusitis with nasal polyps, and prurigo nodularis.

In the study, known as LIBERTY-CSU CUPID Study C, researchers randomized 74 patients with CSU aged 6 years or older to add-on dupilumab subcutaneously every 2 weeks and 77 to placebo. (Patients were omalizumab-naive and had symptomatic CSU, despite treatment with up to four times the approved dose of standard-of-care H1-antihistamines.) Dupilumab doses were 300 mg for adults and adolescents weighing ≥ 60 kg or 200 mg for adolescents weighing < 60 kg and children weighing ≥ 30 kg.

The primary outcomes were Itch Severity Score over 7 days (ISS7; range, 0-21) and Urticaria Activity Score over 7 days (UAS7; range, 0-42).

Over the 24-week study period, patients in the dupilumab group showed significantly greater change from baseline than those in the placebo group on both measures, with least squares mean changes of 8.6 vs 6.1 for ISS7 and 15.9 vs 11.2 for UAS7 (P = .02 for both).

In addition, at 24 weeks, significantly more patients in the dupilumab group than in the placebo group achieved well-controlled disease based on a UAS of 6 or lower (41% vs 23%; P = .005). Significantly more dupilumab-treated patients also achieved a complete response (defined as a UAS of 0), compared with placebo-treated patients (30% vs 18%; P = .02).

Overall rates of treatment-emergent adverse events were 53% for both groups, and safety data were mainly consistent with dupilumab’s known safety profile, the researchers wrote.

The findings were not surprising, as a previous related study, LIBERTY-CSU CUPID Study A, showed that dupilumab was effective for CSU, Casale told this news organization. “This replicate study confirms the previous study and provides evidence for regulatory approval.”

If approved by the Food and Drug Administration (FDA), “dupilumab will provide another therapeutic option for patients with chronic urticaria unresponsive to antihistamines,” Casale commented.

No new safety signals occurred, and the ability to self-administer the medication at home provides an advantage for patients, he added. As for additional research, “analysis of patient characteristics and potential biomarkers that would predict responsiveness is needed.”

 

More Research Needed to Fine-Tune Management

An unmet need persists for patients with CSU whose disease is not adequately controlled by higher-dose H1-antihistamines, Robert G. Micheletti, MD, associate professor of dermatology and medicine at the University of Pennsylvania, Philadelphia, said in an interview. “It is important not only to identify effective add-on therapies for these patients but also to generate data to support insurance coverage and drug access,” said Micheletti, who was not involved in the study.

Also referring to the similar findings reported in the LIBERTY-CSU CUPID Study A, Micheletti said, “as in the earlier study, the results demonstrate significantly reduced itch and urticaria in treated patients compared to placebo.”

“While many providers currently prescribe dupilumab off-label for refractory CSU, FDA approval would improve access to the drug for patients who need it and provide an alternative for patients who may not be good candidates for omalizumab,” he added. However, more research is needed to define optimal management of patients with CSU with inadequate response to omalizumab.

“The LIBERTY-CSU CUPID Study B showed a small improvement in itch severity and urticaria activity among such patients receiving dupilumab,” he noted. “Future work should aim to identify biomarkers and other features predictive of response to various therapies.” 

Study B involved patients with CSU who were uncontrolled on standard-of-care antihistamines and refractory or intolerant to omalizumab, according to Regeneron. 

On November 15, after the ACAAI meeting had ended, the company announced that the FDA had accepted the resubmission of an application for approval of dupilumab for the treatment of CSU in adults and pediatric patients aged 12 years or older not adequately controlled with H1-antihistamines.

The study was supported and sponsored by Sanofi and Regeneron Pharmaceuticals. Casale disclosed serving as a consultant for ALK, ARS Pharma, AstraZeneca, Bryn Pharma, Celgene, Eli Lilly, Genentech, GSK, Jasper, Novartis, Regeneron, and Sanofi and as a speaker for Genentech and Regeneron. Micheletti had no relevant financial conflicts to disclose.

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

A simple, single-question hearing screening administered by medical assistants could effectively identify older adults with untreated hearing loss, according to a study presented at the Gerontological Society of America (GSA) 2024 Annual Scientific Meeting.

The study, conducted by researchers at the University of Massachusetts Amherst, involved 49 participants aged between 56 and 90 years who attended a health clinic with a Program for All-Inclusive Care for the Elderly (PACE). Most of the participants who are in PACE are dually eligible for both Medicare and Medicaid.

Medical assistants were trained to incorporate the following single-question hearing screener during health clinic appointments: “Do you have any difficulty with your hearing (without hearing aids)?” The screening offered a Likert-scale option of responses.

“A single-question hearing screener requires no equipment,” said study author Sara Mamo, AuD, PhD, and associate professor of Speech, Language, and Hearing Sciences at the University of Massachusetts Amherst. “It simply requires a systemic belief that addressing hearing loss matters.”

Following these screenings, the research team conducted on-site hearing threshold testing to evaluate the effectiveness of the method.

Mamo and her research team found that nearly three quarters of the participants had some degree of hearing loss, with 24 individuals showing mild hearing loss and 11 exhibiting moderate or worse hearing loss.

None of the participants were current users of hearing aids, which underscores the widespread issue of untreated hearing loss in older adults, according to Mamo.

“One benefit of screening by asking a question is that the patient who says ‘yes’ to having difficulty is more likely to accept support to address the difficulty,” said Mamo. “A medical provider asking about hearing loss is an important cue to action.”

The results showed a sensitivity of 71.4% and a specificity of 42.9%, suggesting that this simple screening can help identify individuals with untreated hearing loss during routine health visits.

Despite known links between age-related hearing loss and increased risks for dementia, depression, and loneliness, the US Preventive Services Task Force does not currently recommend routine hearing loss screening for adults.

“With minimal burden, we can identify individuals with untreated hearing loss during routine health appointments,” she said.

Carla Perissinotto, MD, MHS, professor in the Division of Geriatrics at the University of California, San Francisco, agreed.

“We do not screen enough for hearing loss,” said Perissinotto, who was not involved in the study.

The researchers also provide practical communication tips for healthcare providers working with patients with untreated hearing loss. These include speaking face-to-face, speaking slowly, and using personal sound amplifiers.

Perissinotto added that integrating an individual’s hearing status into their medical records could enhance overall care and any future communication strategies.

“Writing hearing status [into medical records] prominently could be very important, as I have had patients inappropriately labeled as having dementia when it was a hearing issue,” said Perissinotto.

Mamo and Perissinotto had no conflicts of interest.

 

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

A simple, single-question hearing screening administered by medical assistants could effectively identify older adults with untreated hearing loss, according to a study presented at the Gerontological Society of America (GSA) 2024 Annual Scientific Meeting.

The study, conducted by researchers at the University of Massachusetts Amherst, involved 49 participants aged between 56 and 90 years who attended a health clinic with a Program for All-Inclusive Care for the Elderly (PACE). Most of the participants who are in PACE are dually eligible for both Medicare and Medicaid.

Medical assistants were trained to incorporate the following single-question hearing screener during health clinic appointments: “Do you have any difficulty with your hearing (without hearing aids)?” The screening offered a Likert-scale option of responses.

“A single-question hearing screener requires no equipment,” said study author Sara Mamo, AuD, PhD, and associate professor of Speech, Language, and Hearing Sciences at the University of Massachusetts Amherst. “It simply requires a systemic belief that addressing hearing loss matters.”

Following these screenings, the research team conducted on-site hearing threshold testing to evaluate the effectiveness of the method.

Mamo and her research team found that nearly three quarters of the participants had some degree of hearing loss, with 24 individuals showing mild hearing loss and 11 exhibiting moderate or worse hearing loss.

None of the participants were current users of hearing aids, which underscores the widespread issue of untreated hearing loss in older adults, according to Mamo.

“One benefit of screening by asking a question is that the patient who says ‘yes’ to having difficulty is more likely to accept support to address the difficulty,” said Mamo. “A medical provider asking about hearing loss is an important cue to action.”

The results showed a sensitivity of 71.4% and a specificity of 42.9%, suggesting that this simple screening can help identify individuals with untreated hearing loss during routine health visits.

Despite known links between age-related hearing loss and increased risks for dementia, depression, and loneliness, the US Preventive Services Task Force does not currently recommend routine hearing loss screening for adults.

“With minimal burden, we can identify individuals with untreated hearing loss during routine health appointments,” she said.

Carla Perissinotto, MD, MHS, professor in the Division of Geriatrics at the University of California, San Francisco, agreed.

“We do not screen enough for hearing loss,” said Perissinotto, who was not involved in the study.

The researchers also provide practical communication tips for healthcare providers working with patients with untreated hearing loss. These include speaking face-to-face, speaking slowly, and using personal sound amplifiers.

Perissinotto added that integrating an individual’s hearing status into their medical records could enhance overall care and any future communication strategies.

“Writing hearing status [into medical records] prominently could be very important, as I have had patients inappropriately labeled as having dementia when it was a hearing issue,” said Perissinotto.

Mamo and Perissinotto had no conflicts of interest.

 

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

A simple, single-question hearing screening administered by medical assistants could effectively identify older adults with untreated hearing loss, according to a study presented at the Gerontological Society of America (GSA) 2024 Annual Scientific Meeting.

The study, conducted by researchers at the University of Massachusetts Amherst, involved 49 participants aged between 56 and 90 years who attended a health clinic with a Program for All-Inclusive Care for the Elderly (PACE). Most of the participants who are in PACE are dually eligible for both Medicare and Medicaid.

Medical assistants were trained to incorporate the following single-question hearing screener during health clinic appointments: “Do you have any difficulty with your hearing (without hearing aids)?” The screening offered a Likert-scale option of responses.

“A single-question hearing screener requires no equipment,” said study author Sara Mamo, AuD, PhD, and associate professor of Speech, Language, and Hearing Sciences at the University of Massachusetts Amherst. “It simply requires a systemic belief that addressing hearing loss matters.”

Following these screenings, the research team conducted on-site hearing threshold testing to evaluate the effectiveness of the method.

Mamo and her research team found that nearly three quarters of the participants had some degree of hearing loss, with 24 individuals showing mild hearing loss and 11 exhibiting moderate or worse hearing loss.

None of the participants were current users of hearing aids, which underscores the widespread issue of untreated hearing loss in older adults, according to Mamo.

“One benefit of screening by asking a question is that the patient who says ‘yes’ to having difficulty is more likely to accept support to address the difficulty,” said Mamo. “A medical provider asking about hearing loss is an important cue to action.”

The results showed a sensitivity of 71.4% and a specificity of 42.9%, suggesting that this simple screening can help identify individuals with untreated hearing loss during routine health visits.

Despite known links between age-related hearing loss and increased risks for dementia, depression, and loneliness, the US Preventive Services Task Force does not currently recommend routine hearing loss screening for adults.

“With minimal burden, we can identify individuals with untreated hearing loss during routine health appointments,” she said.

Carla Perissinotto, MD, MHS, professor in the Division of Geriatrics at the University of California, San Francisco, agreed.

“We do not screen enough for hearing loss,” said Perissinotto, who was not involved in the study.

The researchers also provide practical communication tips for healthcare providers working with patients with untreated hearing loss. These include speaking face-to-face, speaking slowly, and using personal sound amplifiers.

Perissinotto added that integrating an individual’s hearing status into their medical records could enhance overall care and any future communication strategies.

“Writing hearing status [into medical records] prominently could be very important, as I have had patients inappropriately labeled as having dementia when it was a hearing issue,” said Perissinotto.

Mamo and Perissinotto had no conflicts of interest.

 

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

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

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

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

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

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

SEATTLE — A novel, quick, and low-cost dementia screening test could significantly improve early detection of Alzheimer’s disease in primary care settings, according to research presented at the Gerontological Society of America (GSA) 2024 Annual Scientific Meeting.

The test, called qBEANS — short for Quick Behavioral Exam to Advance Neuropsychological Screening — involves patients spooning raw kidney beans into small plastic cups in a specific sequence to assess motor learning, visuospatial memory, and executive function. It requires no technology or wearable sensors, making it accessible and easy to implement.

Previous research has shown qBEANS to be sensitive and specific to Alzheimer’s disease pathology, as well as predictive of cognitive and functional decline, the researchers said.

However, the current version of the test takes around 7 minutes to administer, which is too long for use in primary care, according to study author Sydney Schaefer, PhD, associate professor in the School of Biological and Health Systems Engineering at Arizona State University, Tempe, Arizona.

“The purpose of this study was to identify the minimum number of trials needed for reliability relative to the original longer version,” said Schaefer.

The study involved 48 participants without dementia, 77% of whom were women, and an average age of 75.4 years.

The researchers found that the shortened version of the qBEANS test takes only about 3.85 minutes on average — nearly 48% faster than the original version — while still maintaining high reliability (intraclass correlation of 0.85).

With its brevity and simplicity, the test could be easily administered by medical assistants during patient check-in, potentially increasing early dementia detection rates in primary care, said Schaefer.

While the shortened qBEANS test shows promise, further research is needed to assess its acceptability in primary care settings.

“The findings also warrant further development of the BEAN as a direct-to-consumer product, given its low cost and ease of administration,” said Schaefer.

However, Carla Perissinotto, MD, MHS, professor in the Division of Geriatrics at the University of California, San Francisco, cautioned that direct-to-consumer plans “could lead to participants not knowing what to do with the results out of context and without clinical input.”

“I’m not sure that we need to have a new evaluation tool, but instead, greater adoption of known and existing tools,” said Perissinotto, who was not involved in the study.

According to Perissinotto, existing cognitive screening tools Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are more commonly used to evaluate cognition and are also relatively quick to administer.

“If [qBEANS] is not benchmarked to other standard tools like the MMSE or MoCA, clinicians may have trouble interpreting results,” said Perissinotto.

Study co-authors Schaefer and Jill Love are co-founders and managing members of Neurosessments LLC, which developed the qBEANS test.

 

A version of this article appeared on Medscape.com.

SEATTLE — A novel, quick, and low-cost dementia screening test could significantly improve early detection of Alzheimer’s disease in primary care settings, according to research presented at the Gerontological Society of America (GSA) 2024 Annual Scientific Meeting.

The test, called qBEANS — short for Quick Behavioral Exam to Advance Neuropsychological Screening — involves patients spooning raw kidney beans into small plastic cups in a specific sequence to assess motor learning, visuospatial memory, and executive function. It requires no technology or wearable sensors, making it accessible and easy to implement.

Previous research has shown qBEANS to be sensitive and specific to Alzheimer’s disease pathology, as well as predictive of cognitive and functional decline, the researchers said.

However, the current version of the test takes around 7 minutes to administer, which is too long for use in primary care, according to study author Sydney Schaefer, PhD, associate professor in the School of Biological and Health Systems Engineering at Arizona State University, Tempe, Arizona.

“The purpose of this study was to identify the minimum number of trials needed for reliability relative to the original longer version,” said Schaefer.

The study involved 48 participants without dementia, 77% of whom were women, and an average age of 75.4 years.

The researchers found that the shortened version of the qBEANS test takes only about 3.85 minutes on average — nearly 48% faster than the original version — while still maintaining high reliability (intraclass correlation of 0.85).

With its brevity and simplicity, the test could be easily administered by medical assistants during patient check-in, potentially increasing early dementia detection rates in primary care, said Schaefer.

While the shortened qBEANS test shows promise, further research is needed to assess its acceptability in primary care settings.

“The findings also warrant further development of the BEAN as a direct-to-consumer product, given its low cost and ease of administration,” said Schaefer.

However, Carla Perissinotto, MD, MHS, professor in the Division of Geriatrics at the University of California, San Francisco, cautioned that direct-to-consumer plans “could lead to participants not knowing what to do with the results out of context and without clinical input.”

“I’m not sure that we need to have a new evaluation tool, but instead, greater adoption of known and existing tools,” said Perissinotto, who was not involved in the study.

According to Perissinotto, existing cognitive screening tools Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are more commonly used to evaluate cognition and are also relatively quick to administer.

“If [qBEANS] is not benchmarked to other standard tools like the MMSE or MoCA, clinicians may have trouble interpreting results,” said Perissinotto.

Study co-authors Schaefer and Jill Love are co-founders and managing members of Neurosessments LLC, which developed the qBEANS test.

 

A version of this article appeared on Medscape.com.

SEATTLE — A novel, quick, and low-cost dementia screening test could significantly improve early detection of Alzheimer’s disease in primary care settings, according to research presented at the Gerontological Society of America (GSA) 2024 Annual Scientific Meeting.

The test, called qBEANS — short for Quick Behavioral Exam to Advance Neuropsychological Screening — involves patients spooning raw kidney beans into small plastic cups in a specific sequence to assess motor learning, visuospatial memory, and executive function. It requires no technology or wearable sensors, making it accessible and easy to implement.

Previous research has shown qBEANS to be sensitive and specific to Alzheimer’s disease pathology, as well as predictive of cognitive and functional decline, the researchers said.

However, the current version of the test takes around 7 minutes to administer, which is too long for use in primary care, according to study author Sydney Schaefer, PhD, associate professor in the School of Biological and Health Systems Engineering at Arizona State University, Tempe, Arizona.

“The purpose of this study was to identify the minimum number of trials needed for reliability relative to the original longer version,” said Schaefer.

The study involved 48 participants without dementia, 77% of whom were women, and an average age of 75.4 years.

The researchers found that the shortened version of the qBEANS test takes only about 3.85 minutes on average — nearly 48% faster than the original version — while still maintaining high reliability (intraclass correlation of 0.85).

With its brevity and simplicity, the test could be easily administered by medical assistants during patient check-in, potentially increasing early dementia detection rates in primary care, said Schaefer.

While the shortened qBEANS test shows promise, further research is needed to assess its acceptability in primary care settings.

“The findings also warrant further development of the BEAN as a direct-to-consumer product, given its low cost and ease of administration,” said Schaefer.

However, Carla Perissinotto, MD, MHS, professor in the Division of Geriatrics at the University of California, San Francisco, cautioned that direct-to-consumer plans “could lead to participants not knowing what to do with the results out of context and without clinical input.”

“I’m not sure that we need to have a new evaluation tool, but instead, greater adoption of known and existing tools,” said Perissinotto, who was not involved in the study.

According to Perissinotto, existing cognitive screening tools Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are more commonly used to evaluate cognition and are also relatively quick to administer.

“If [qBEANS] is not benchmarked to other standard tools like the MMSE or MoCA, clinicians may have trouble interpreting results,” said Perissinotto.

Study co-authors Schaefer and Jill Love are co-founders and managing members of Neurosessments LLC, which developed the qBEANS test.

 

A version of this article appeared on Medscape.com.