VIENNA — Guselkumab has been shown to be efficacious vs placebo in patients with moderately to severely active Crohn’s disease (CD), regardless of prior biologic therapy exposure, according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.

“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.

These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.

Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.

Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
 

GALAXI 2 and 3 Pooled Dataset

In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.

Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.

Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.

The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.

Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.

The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.

The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
 

Short- and Long-Term Endpoints in Both Subgroups

In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).

In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).

“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.

Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).

Sands noted that the drug has an excellent safety profile.

“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.

Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.

A version of this article appeared on Medscape.com.

VIENNA — Guselkumab has been shown to be efficacious vs placebo in patients with moderately to severely active Crohn’s disease (CD), regardless of prior biologic therapy exposure, according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.

“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.

These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.

Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.

Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
 

GALAXI 2 and 3 Pooled Dataset

In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.

Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.

Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.

The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.

Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.

The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.

The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
 

Short- and Long-Term Endpoints in Both Subgroups

In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).

In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).

“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.

Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).

Sands noted that the drug has an excellent safety profile.

“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.

Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.

A version of this article appeared on Medscape.com.

VIENNA — Guselkumab has been shown to be efficacious vs placebo in patients with moderately to severely active Crohn’s disease (CD), regardless of prior biologic therapy exposure, according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.

“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.

These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.

Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.

Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
 

GALAXI 2 and 3 Pooled Dataset

In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.

Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.

Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.

The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.

Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.

The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.

The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
 

Short- and Long-Term Endpoints in Both Subgroups

In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).

In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).

“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.

Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).

Sands noted that the drug has an excellent safety profile.

“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.

Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.

A version of this article appeared on Medscape.com.

VIENNA — Researchers have determined a bidirectional relationship between inflammatory bowel disease (IBD) and type 1 diabetes (T1D), using both a cohort and case-control approach to analysis.

Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.

Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.

“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.

Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.

Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
 

Exploring the Bidirectional Relationship 

Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.

These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.

In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors. 

The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).

The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.

The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.

Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.

In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.

In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.

Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.

That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.

“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”

Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”

“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.

Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.

Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.

A version of this article appeared on Medscape.com.

VIENNA — Researchers have determined a bidirectional relationship between inflammatory bowel disease (IBD) and type 1 diabetes (T1D), using both a cohort and case-control approach to analysis.

Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.

Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.

“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.

Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.

Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
 

Exploring the Bidirectional Relationship 

Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.

These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.

In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors. 

The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).

The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.

The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.

Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.

In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.

In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.

Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.

That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.

“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”

Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”

“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.

Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.

Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.

A version of this article appeared on Medscape.com.

VIENNA — Researchers have determined a bidirectional relationship between inflammatory bowel disease (IBD) and type 1 diabetes (T1D), using both a cohort and case-control approach to analysis.

Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.

Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.

“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.

Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.

Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
 

Exploring the Bidirectional Relationship 

Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.

These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.

In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors. 

The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).

The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.

The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.

Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.

In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.

In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.

Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.

That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.

“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”

Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”

“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.

Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.

Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.

A version of this article appeared on Medscape.com.

In a world that is more connected than ever, a silent epidemic is taking its toll. Overall, one in three US adults report chronic loneliness — a condition so detrimental that it rivals smoking and obesity with respect to its negative effect on health and well-being. From anxiety and depression to life-threatening conditions like cardiovascular disease, stroke, and Alzheimer’s and Parkinson’s diseases, loneliness is more than an emotion — it’s a serious threat to both the brain and body.

In 2023, a US Surgeon General advisory raised the alarm about the national problem of loneliness and isolation, describing it as an epidemic.

“Given the significant health consequences of loneliness and isolation, we must prioritize building social connection in the same way we have prioritized other critical public health issues such as tobacco, obesity, and substance use disorders. Together, we can build a country that’s healthier, more resilient, less lonely, and more connected,” the report concluded.

But how, exactly, does chronic loneliness affect the physiology and function of the brain? What does the latest research reveal about the link between loneliness and neurologic and psychiatric illness, and what can clinicians do to address the issue?

This news organization spoke to multiple experts in the field to explore these issues.
 

A Major Risk Factor

Anna Finley, PhD, assistant professor of psychology at North Dakota State University, Fargo, explained that loneliness and social isolation are different entities. Social isolation is an objective measure of the number of people someone interacts with on a regular basis, whereas loneliness is a subjective feeling that occurs when close connections are lacking.

“These two things are not actually as related as you think they would be. People can feel lonely in a crowd or feel well connected with only a few friendships. It’s more about the quality of the connection and the quality of your perception of it. So someone could be in some very supportive relationships but still feel that there’s something missing,” she said in an interview.

So what do we know about how loneliness affects health? Evidence supporting the hypothesis that loneliness is an emerging risk factor for many diseases is steadily building.

Recently, the American Heart Association published a statement summarizing the evidence for a direct association between social isolation and loneliness and coronary heart disease and stroke mortality.

In addition, many studies have shown that individuals experiencing social isolation or loneliness have an increased risk for anxiety and depression, dementia, infectious disease, hospitalization, and all-cause death, even after adjusting for age and many other traditional risk factors.

One study revealed that eliminating loneliness has the potential to prevent nearly 20% of cases of depression in adults aged 50 years or older.

Indu Subramanian, MD, professor of neurology at the University of California, Los Angeles, and colleagues conducted a study involving patients with Parkinson’s disease, which showed that the negative impact of loneliness on disease severity was as significant as the positive effects of 30 minutes of daily exercise.

“The importance of loneliness is under-recognized and undervalued, and it poses a major risk for health outcomes and quality of life,” said Subramanian.

Subramanian noted that loneliness is stigmatizing, causing people to feel unlikable and blame themselves, which prevents them from opening up to doctors or loved ones about their struggle. At the same time, healthcare providers may not think to ask about loneliness or know about potential interventions. She emphasized that much more work is needed to address this issue.
 

Early Mortality Risk

Julianne Holt-Lunstad, PhD, professor of psychology and neuroscience at Brigham Young University in Provo, Utah, is the author of two large meta-analyses that suggest loneliness, social isolation, or living alone are independent risk factors for early mortality, increasing this risk by about a third — the equivalent to the risk of smoking 15 cigarettes per day.

“We have quite robust evidence across a number of health outcomes implicating the harmful effects of loneliness and social isolation. While these are observational studies and show mainly associations, we do have evidence from longitudinal studies that show lacking social connection, whether that be loneliness or social isolation, predicts subsequent worse outcomes, and most of these studies have adjusted for alternative kinds of explanations, like age, initial health status, lifestyle factors,” Holt-Lunstad said.

There is some evidence to suggest that isolation is more predictive of physical health outcomes, whereas loneliness is more predictive of mental health outcomes. That said, both isolation and loneliness have significant effects on mental and physical health outcomes, she noted.

There is also the question of whether loneliness is causing poor health or whether people who are in poor health feel lonely because poor health can lead to social isolation.

Finley said there’s probably a bit of both going on, but longitudinal studies, where loneliness is measured at a fixed timepoint then health outcomes are reported a few years later, suggest that loneliness is contributing to these adverse outcomes.

She added that there is also some evidence in animal models to suggest that loneliness is a causal risk factor for adverse health outcomes. “But you can’t ask a mouse or rat how lonely they’re feeling. All you can do is house them individually — removing them from social connection. This isn’t necessarily the same thing as loneliness in humans.”

Finley is studying mechanisms in the brain that may be involved in mediating the adverse health consequences of loneliness.

“What I’ve been seeing in the data so far is that it tends to be the self-report of how lonely folks are feeling that has the associations with differences in the brain, as opposed to the number of social connections people have. It does seem to be the more subjective, emotional perception of loneliness that is important.”

In a review of potential mechanisms involved, she concluded that it is dysregulated emotions and altered perceptions of social interactions that has profound impacts on the brain, suggesting that people who are lonely may have a tendency to interpret social cues in a negative way, preventing them from forming productive positive relationships.
 

Lack of Trust

One researcher who has studied this phenomenon is Dirk Scheele, PhD, professor of social neuroscience at Ruhr University Bochum in Germany.

“We were interested to find out why people remained lonely,” he said in an interview. “Loneliness is an unpleasant experience, and there are so many opportunities for social contacts nowadays, it’s not really clear at first sight why people are chronically lonely.”

To examine this question, Scheele and his team conducted a study in which functional MRI was used to examine the brain in otherwise healthy individuals with high or low loneliness scores while they played a trust game.

They also simulated a positive social interaction between participants and researchers, in which they talked about plans for a fictitious lottery win, and about their hobbies and interests, during which mood was measured with questionnaires, and saliva samples were collected to measure hormone levels.

Results showed that the high-lonely individuals had reduced activation in the insula cortex during the trust decisions. “This area of the brain is involved in the processing of bodily signals, such as ‘gut feelings.’ So reduced activity here could be interpreted as fewer gut feelings on who can be trusted,” Scheele explained.

The high-lonely individuals also had reduced responsiveness to the positive social interaction with a lower release of oxytocin and a smaller elevation in mood compared with the control individuals.

Scheele pointed out that there is some evidence that oxytocin might increase trust, and there is reduced release of endogenous oxytocin in high loneliness.

“Our results are consistent with the idea that loneliness is associated with negative biases about other people. So if we expect negative things from other people — for instance, that they cannot be trusted — then that would hamper further social interactions and could lead to loneliness,” he added.
 

A Role for Oxytocin?

In another study, the same researchers tested short-term (five weekly sessions) group psychotherapy to reduce loneliness using established techniques to target these negative biases. They also investigated whether the effects of this group psychotherapy could be augmented by administering intranasal oxytocin (vs placebo) before the group psychotherapy sessions.

Results showed that the group psychotherapy intervention reduced trait loneliness (loneliness experienced over a prolonged period). The oxytocin did not show a significant effect on trait loneliness, but there was a suggestion that it may enhance the reduction in state loneliness (how someone is feeling at a specific time) brought about by the psychotherapy sessions.

“We found that bonding within the groups was experienced as more positive in the oxytocin treated groups. It is possible that a longer intervention would be helpful for longer-term results,” Scheele concluded. “It’s not going to be a quick fix for loneliness, but there may be a role for oxytocin as an adjunct to psychotherapy.”
 

A Basic Human Need

Another loneliness researcher, Livia Tomova, PhD, assistant professor of psychology at Cardiff University in Wales, has used social isolation to induce loneliness in young people and found that this intervention was linked to brain patterns similar to those associated with hunger.

“We know that the drive to eat food is a very basic human need. We know quite well how it is represented in the brain,” she explained.

The researchers tested how the brains of the participants responded to seeing pictures of social interactions after they underwent a prolonged period of social isolation. In a subsequent session, the same people were asked to undergo food fasting and then underwent brain scans when looking at pictures of food. Results showed that the neural patterns were similar in the two situations with increased activity in the substantia nigra area within the midbrain.

“This area of the brain processes rewards and motivation. It consists primarily of dopamine neurons and increased activity corresponds to a feeling of craving something. So this area of the brain that controls essential homeostatic needs is activated when people feel lonely, suggesting that our need for social contact with others is potentially a very basic need similar to eating,” Tomova said.
 

Lower Gray Matter Volumes in Key Brain Areas

And another group from Germany has found that higher loneliness scores are negatively associated with specific brain regions responsible for memory, emotion regulation, and social processing.

Sandra Düzel, PhD, and colleagues from the Max Planck Institute for Human Development and the Charité – Universitätsmedizin Berlin, both in Berlin, Germany, reported a study in which individuals who reported higher loneliness had smaller gray matter volumes in brain regions such as the left amygdala, anterior hippocampus, and cerebellum, regions which are crucial for both emotional regulation and higher-order cognitive processes, such as self-reflection and executive function.

Düzel believes that possible mechanisms behind the link between loneliness and brain volume differences could include stress-related damage, with prolonged loneliness associated with elevated levels of stress hormones, which can damage the hippocampus over time, and reduced cognitive and social stimulation, which may contribute to brain volume reductions in regions critical for memory and emotional processing.

“Loneliness is often characterized by reduced social and environmental diversity, leading to less engagement with novel experiences and potentially lower hippocampal-striatal connectivity.

Since novelty-seeking and environmental diversity are associated with positive emotional states, individuals experiencing loneliness might benefit from increased exposure to new environments which could stimulate the brain’s reward circuits, fostering positive affect and potentially mitigating the emotional burden of loneliness,” she said.
 

Is Social Prescribing the Answer?

So are there enough data now to act and attempt to develop interventions to reduce loneliness? Most of these researchers believe so.

“I think we have enough information to act on this now. There are a number of national academies consensus reports, which suggest that, while certainly there are still gaps in our evidence and more to be learned, there is sufficient evidence that a concerning portion of the population seems to lack connection, and that the consequences are serious enough that we need to do something about it,” said Holt-Lunstad.

Some countries have introduced social prescribing where doctors can prescribe a group activity or a regular visit or telephone conversation with a supportive person.

Subramanian pointed out that it’s easier to implement in countries with national health services and may be more difficult to embrace in the US healthcare system.

“We are not so encouraged from a financial perspective to think about preventive care in the US. We don’t have an easy way to recognize in any tangible way the downstream of such activities in terms of preventing future problems. That is something we need to work on,” she said.

Finley cautioned that to work well, social prescribing will require an understanding of each person’s individual situation.

“Some people may only receive benefit of interacting with others if they are also getting some sort of support to address the social and emotional concerns that are tagging along with loneliness. I’m not sure that just telling people to go join their local gardening club or whatever will be the correct answer for everyone.”

She pointed out that many people will have issues in their life that are making it hard for them to be social. These could be mobility or financial challenges, care responsibilities, or concerns about illnesses or life events. “We need to figure out what would have the most bang for the person’s buck, so to speak, as an intervention. That could mean connecting them to a group relevant to their individual situation.”
 

Opportunity to Connect Not Enough?

Tomova believes that training people in social skills may be a better option. “It appears that some people who are chronically lonely seem to struggle to make relationships with others. So just encouraging them to interact with others more will not necessarily help. We need to better understand the pathways involved and who are the people who become ill. We can then develop and target better interventions and teach people coping strategies for that situation.”

Scheele agreed. “While just giving people the opportunity to connect may work for some, others who are experiencing really chronic loneliness may not benefit very much from this unless their negative belief systems are addressed.” He suggested some sort of psychotherapy may be helpful in this situation.

But at least all seem to agree that healthcare providers need to be more aware of loneliness as a health risk factor, try to identify people at risk, and to think about how best to support them.

Holt-Lunstad noted that one of the recommendations in the US Surgeon General’s advisory was to increase the education, training, and resources on loneliness for healthcare providers.

“If we want this to be addressed, we need to give healthcare providers the time, resources, and training in order to do that, otherwise, we are adding one more thing to an already overburdened system. They need to understand how important it is, and how it might help them take care of the patient.”

“Our hope is that we can start to reverse some of the trends that we are seeing, both in terms of the prevalence rates of loneliness, but also that we could start seeing improvements in health and other kinds of outcomes,” she concluded.

Progress is being made in increasing awareness about the dangers of chronic loneliness. It’s now recognized as a serious health risk, but there are actionable steps that can help. Loneliness doesn’t have to be a permanent condition for anyone, said Scheele.

Holt-Lunstad served as an adviser for Foundation for Social Connection, Global Initiative on Loneliness and Connection, and Nextdoor Neighborhood Vitality Board and received research grants/income from Templeton Foundation, Eventbrite, Foundation for Social Connection, and Triple-S Foundation. Subramanian served as a speaker bureau for Acorda Pharma. The other researchers reported no disclosures.

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

In a world that is more connected than ever, a silent epidemic is taking its toll. Overall, one in three US adults report chronic loneliness — a condition so detrimental that it rivals smoking and obesity with respect to its negative effect on health and well-being. From anxiety and depression to life-threatening conditions like cardiovascular disease, stroke, and Alzheimer’s and Parkinson’s diseases, loneliness is more than an emotion — it’s a serious threat to both the brain and body.

In 2023, a US Surgeon General advisory raised the alarm about the national problem of loneliness and isolation, describing it as an epidemic.

“Given the significant health consequences of loneliness and isolation, we must prioritize building social connection in the same way we have prioritized other critical public health issues such as tobacco, obesity, and substance use disorders. Together, we can build a country that’s healthier, more resilient, less lonely, and more connected,” the report concluded.

But how, exactly, does chronic loneliness affect the physiology and function of the brain? What does the latest research reveal about the link between loneliness and neurologic and psychiatric illness, and what can clinicians do to address the issue?

This news organization spoke to multiple experts in the field to explore these issues.
 

A Major Risk Factor

Anna Finley, PhD, assistant professor of psychology at North Dakota State University, Fargo, explained that loneliness and social isolation are different entities. Social isolation is an objective measure of the number of people someone interacts with on a regular basis, whereas loneliness is a subjective feeling that occurs when close connections are lacking.

“These two things are not actually as related as you think they would be. People can feel lonely in a crowd or feel well connected with only a few friendships. It’s more about the quality of the connection and the quality of your perception of it. So someone could be in some very supportive relationships but still feel that there’s something missing,” she said in an interview.

So what do we know about how loneliness affects health? Evidence supporting the hypothesis that loneliness is an emerging risk factor for many diseases is steadily building.

Recently, the American Heart Association published a statement summarizing the evidence for a direct association between social isolation and loneliness and coronary heart disease and stroke mortality.

In addition, many studies have shown that individuals experiencing social isolation or loneliness have an increased risk for anxiety and depression, dementia, infectious disease, hospitalization, and all-cause death, even after adjusting for age and many other traditional risk factors.

One study revealed that eliminating loneliness has the potential to prevent nearly 20% of cases of depression in adults aged 50 years or older.

Indu Subramanian, MD, professor of neurology at the University of California, Los Angeles, and colleagues conducted a study involving patients with Parkinson’s disease, which showed that the negative impact of loneliness on disease severity was as significant as the positive effects of 30 minutes of daily exercise.

“The importance of loneliness is under-recognized and undervalued, and it poses a major risk for health outcomes and quality of life,” said Subramanian.

Subramanian noted that loneliness is stigmatizing, causing people to feel unlikable and blame themselves, which prevents them from opening up to doctors or loved ones about their struggle. At the same time, healthcare providers may not think to ask about loneliness or know about potential interventions. She emphasized that much more work is needed to address this issue.
 

Early Mortality Risk

Julianne Holt-Lunstad, PhD, professor of psychology and neuroscience at Brigham Young University in Provo, Utah, is the author of two large meta-analyses that suggest loneliness, social isolation, or living alone are independent risk factors for early mortality, increasing this risk by about a third — the equivalent to the risk of smoking 15 cigarettes per day.

“We have quite robust evidence across a number of health outcomes implicating the harmful effects of loneliness and social isolation. While these are observational studies and show mainly associations, we do have evidence from longitudinal studies that show lacking social connection, whether that be loneliness or social isolation, predicts subsequent worse outcomes, and most of these studies have adjusted for alternative kinds of explanations, like age, initial health status, lifestyle factors,” Holt-Lunstad said.

There is some evidence to suggest that isolation is more predictive of physical health outcomes, whereas loneliness is more predictive of mental health outcomes. That said, both isolation and loneliness have significant effects on mental and physical health outcomes, she noted.

There is also the question of whether loneliness is causing poor health or whether people who are in poor health feel lonely because poor health can lead to social isolation.

Finley said there’s probably a bit of both going on, but longitudinal studies, where loneliness is measured at a fixed timepoint then health outcomes are reported a few years later, suggest that loneliness is contributing to these adverse outcomes.

She added that there is also some evidence in animal models to suggest that loneliness is a causal risk factor for adverse health outcomes. “But you can’t ask a mouse or rat how lonely they’re feeling. All you can do is house them individually — removing them from social connection. This isn’t necessarily the same thing as loneliness in humans.”

Finley is studying mechanisms in the brain that may be involved in mediating the adverse health consequences of loneliness.

“What I’ve been seeing in the data so far is that it tends to be the self-report of how lonely folks are feeling that has the associations with differences in the brain, as opposed to the number of social connections people have. It does seem to be the more subjective, emotional perception of loneliness that is important.”

In a review of potential mechanisms involved, she concluded that it is dysregulated emotions and altered perceptions of social interactions that has profound impacts on the brain, suggesting that people who are lonely may have a tendency to interpret social cues in a negative way, preventing them from forming productive positive relationships.
 

Lack of Trust

One researcher who has studied this phenomenon is Dirk Scheele, PhD, professor of social neuroscience at Ruhr University Bochum in Germany.

“We were interested to find out why people remained lonely,” he said in an interview. “Loneliness is an unpleasant experience, and there are so many opportunities for social contacts nowadays, it’s not really clear at first sight why people are chronically lonely.”

To examine this question, Scheele and his team conducted a study in which functional MRI was used to examine the brain in otherwise healthy individuals with high or low loneliness scores while they played a trust game.

They also simulated a positive social interaction between participants and researchers, in which they talked about plans for a fictitious lottery win, and about their hobbies and interests, during which mood was measured with questionnaires, and saliva samples were collected to measure hormone levels.

Results showed that the high-lonely individuals had reduced activation in the insula cortex during the trust decisions. “This area of the brain is involved in the processing of bodily signals, such as ‘gut feelings.’ So reduced activity here could be interpreted as fewer gut feelings on who can be trusted,” Scheele explained.

The high-lonely individuals also had reduced responsiveness to the positive social interaction with a lower release of oxytocin and a smaller elevation in mood compared with the control individuals.

Scheele pointed out that there is some evidence that oxytocin might increase trust, and there is reduced release of endogenous oxytocin in high loneliness.

“Our results are consistent with the idea that loneliness is associated with negative biases about other people. So if we expect negative things from other people — for instance, that they cannot be trusted — then that would hamper further social interactions and could lead to loneliness,” he added.
 

A Role for Oxytocin?

In another study, the same researchers tested short-term (five weekly sessions) group psychotherapy to reduce loneliness using established techniques to target these negative biases. They also investigated whether the effects of this group psychotherapy could be augmented by administering intranasal oxytocin (vs placebo) before the group psychotherapy sessions.

Results showed that the group psychotherapy intervention reduced trait loneliness (loneliness experienced over a prolonged period). The oxytocin did not show a significant effect on trait loneliness, but there was a suggestion that it may enhance the reduction in state loneliness (how someone is feeling at a specific time) brought about by the psychotherapy sessions.

“We found that bonding within the groups was experienced as more positive in the oxytocin treated groups. It is possible that a longer intervention would be helpful for longer-term results,” Scheele concluded. “It’s not going to be a quick fix for loneliness, but there may be a role for oxytocin as an adjunct to psychotherapy.”
 

A Basic Human Need

Another loneliness researcher, Livia Tomova, PhD, assistant professor of psychology at Cardiff University in Wales, has used social isolation to induce loneliness in young people and found that this intervention was linked to brain patterns similar to those associated with hunger.

“We know that the drive to eat food is a very basic human need. We know quite well how it is represented in the brain,” she explained.

The researchers tested how the brains of the participants responded to seeing pictures of social interactions after they underwent a prolonged period of social isolation. In a subsequent session, the same people were asked to undergo food fasting and then underwent brain scans when looking at pictures of food. Results showed that the neural patterns were similar in the two situations with increased activity in the substantia nigra area within the midbrain.

“This area of the brain processes rewards and motivation. It consists primarily of dopamine neurons and increased activity corresponds to a feeling of craving something. So this area of the brain that controls essential homeostatic needs is activated when people feel lonely, suggesting that our need for social contact with others is potentially a very basic need similar to eating,” Tomova said.
 

Lower Gray Matter Volumes in Key Brain Areas

And another group from Germany has found that higher loneliness scores are negatively associated with specific brain regions responsible for memory, emotion regulation, and social processing.

Sandra Düzel, PhD, and colleagues from the Max Planck Institute for Human Development and the Charité – Universitätsmedizin Berlin, both in Berlin, Germany, reported a study in which individuals who reported higher loneliness had smaller gray matter volumes in brain regions such as the left amygdala, anterior hippocampus, and cerebellum, regions which are crucial for both emotional regulation and higher-order cognitive processes, such as self-reflection and executive function.

Düzel believes that possible mechanisms behind the link between loneliness and brain volume differences could include stress-related damage, with prolonged loneliness associated with elevated levels of stress hormones, which can damage the hippocampus over time, and reduced cognitive and social stimulation, which may contribute to brain volume reductions in regions critical for memory and emotional processing.

“Loneliness is often characterized by reduced social and environmental diversity, leading to less engagement with novel experiences and potentially lower hippocampal-striatal connectivity.

Since novelty-seeking and environmental diversity are associated with positive emotional states, individuals experiencing loneliness might benefit from increased exposure to new environments which could stimulate the brain’s reward circuits, fostering positive affect and potentially mitigating the emotional burden of loneliness,” she said.
 

Is Social Prescribing the Answer?

So are there enough data now to act and attempt to develop interventions to reduce loneliness? Most of these researchers believe so.

“I think we have enough information to act on this now. There are a number of national academies consensus reports, which suggest that, while certainly there are still gaps in our evidence and more to be learned, there is sufficient evidence that a concerning portion of the population seems to lack connection, and that the consequences are serious enough that we need to do something about it,” said Holt-Lunstad.

Some countries have introduced social prescribing where doctors can prescribe a group activity or a regular visit or telephone conversation with a supportive person.

Subramanian pointed out that it’s easier to implement in countries with national health services and may be more difficult to embrace in the US healthcare system.

“We are not so encouraged from a financial perspective to think about preventive care in the US. We don’t have an easy way to recognize in any tangible way the downstream of such activities in terms of preventing future problems. That is something we need to work on,” she said.

Finley cautioned that to work well, social prescribing will require an understanding of each person’s individual situation.

“Some people may only receive benefit of interacting with others if they are also getting some sort of support to address the social and emotional concerns that are tagging along with loneliness. I’m not sure that just telling people to go join their local gardening club or whatever will be the correct answer for everyone.”

She pointed out that many people will have issues in their life that are making it hard for them to be social. These could be mobility or financial challenges, care responsibilities, or concerns about illnesses or life events. “We need to figure out what would have the most bang for the person’s buck, so to speak, as an intervention. That could mean connecting them to a group relevant to their individual situation.”
 

Opportunity to Connect Not Enough?

Tomova believes that training people in social skills may be a better option. “It appears that some people who are chronically lonely seem to struggle to make relationships with others. So just encouraging them to interact with others more will not necessarily help. We need to better understand the pathways involved and who are the people who become ill. We can then develop and target better interventions and teach people coping strategies for that situation.”

Scheele agreed. “While just giving people the opportunity to connect may work for some, others who are experiencing really chronic loneliness may not benefit very much from this unless their negative belief systems are addressed.” He suggested some sort of psychotherapy may be helpful in this situation.

But at least all seem to agree that healthcare providers need to be more aware of loneliness as a health risk factor, try to identify people at risk, and to think about how best to support them.

Holt-Lunstad noted that one of the recommendations in the US Surgeon General’s advisory was to increase the education, training, and resources on loneliness for healthcare providers.

“If we want this to be addressed, we need to give healthcare providers the time, resources, and training in order to do that, otherwise, we are adding one more thing to an already overburdened system. They need to understand how important it is, and how it might help them take care of the patient.”

“Our hope is that we can start to reverse some of the trends that we are seeing, both in terms of the prevalence rates of loneliness, but also that we could start seeing improvements in health and other kinds of outcomes,” she concluded.

Progress is being made in increasing awareness about the dangers of chronic loneliness. It’s now recognized as a serious health risk, but there are actionable steps that can help. Loneliness doesn’t have to be a permanent condition for anyone, said Scheele.

Holt-Lunstad served as an adviser for Foundation for Social Connection, Global Initiative on Loneliness and Connection, and Nextdoor Neighborhood Vitality Board and received research grants/income from Templeton Foundation, Eventbrite, Foundation for Social Connection, and Triple-S Foundation. Subramanian served as a speaker bureau for Acorda Pharma. The other researchers reported no disclosures.

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

In a world that is more connected than ever, a silent epidemic is taking its toll. Overall, one in three US adults report chronic loneliness — a condition so detrimental that it rivals smoking and obesity with respect to its negative effect on health and well-being. From anxiety and depression to life-threatening conditions like cardiovascular disease, stroke, and Alzheimer’s and Parkinson’s diseases, loneliness is more than an emotion — it’s a serious threat to both the brain and body.

In 2023, a US Surgeon General advisory raised the alarm about the national problem of loneliness and isolation, describing it as an epidemic.

“Given the significant health consequences of loneliness and isolation, we must prioritize building social connection in the same way we have prioritized other critical public health issues such as tobacco, obesity, and substance use disorders. Together, we can build a country that’s healthier, more resilient, less lonely, and more connected,” the report concluded.

But how, exactly, does chronic loneliness affect the physiology and function of the brain? What does the latest research reveal about the link between loneliness and neurologic and psychiatric illness, and what can clinicians do to address the issue?

This news organization spoke to multiple experts in the field to explore these issues.
 

A Major Risk Factor

Anna Finley, PhD, assistant professor of psychology at North Dakota State University, Fargo, explained that loneliness and social isolation are different entities. Social isolation is an objective measure of the number of people someone interacts with on a regular basis, whereas loneliness is a subjective feeling that occurs when close connections are lacking.

“These two things are not actually as related as you think they would be. People can feel lonely in a crowd or feel well connected with only a few friendships. It’s more about the quality of the connection and the quality of your perception of it. So someone could be in some very supportive relationships but still feel that there’s something missing,” she said in an interview.

So what do we know about how loneliness affects health? Evidence supporting the hypothesis that loneliness is an emerging risk factor for many diseases is steadily building.

Recently, the American Heart Association published a statement summarizing the evidence for a direct association between social isolation and loneliness and coronary heart disease and stroke mortality.

In addition, many studies have shown that individuals experiencing social isolation or loneliness have an increased risk for anxiety and depression, dementia, infectious disease, hospitalization, and all-cause death, even after adjusting for age and many other traditional risk factors.

One study revealed that eliminating loneliness has the potential to prevent nearly 20% of cases of depression in adults aged 50 years or older.

Indu Subramanian, MD, professor of neurology at the University of California, Los Angeles, and colleagues conducted a study involving patients with Parkinson’s disease, which showed that the negative impact of loneliness on disease severity was as significant as the positive effects of 30 minutes of daily exercise.

“The importance of loneliness is under-recognized and undervalued, and it poses a major risk for health outcomes and quality of life,” said Subramanian.

Subramanian noted that loneliness is stigmatizing, causing people to feel unlikable and blame themselves, which prevents them from opening up to doctors or loved ones about their struggle. At the same time, healthcare providers may not think to ask about loneliness or know about potential interventions. She emphasized that much more work is needed to address this issue.
 

Early Mortality Risk

Julianne Holt-Lunstad, PhD, professor of psychology and neuroscience at Brigham Young University in Provo, Utah, is the author of two large meta-analyses that suggest loneliness, social isolation, or living alone are independent risk factors for early mortality, increasing this risk by about a third — the equivalent to the risk of smoking 15 cigarettes per day.

“We have quite robust evidence across a number of health outcomes implicating the harmful effects of loneliness and social isolation. While these are observational studies and show mainly associations, we do have evidence from longitudinal studies that show lacking social connection, whether that be loneliness or social isolation, predicts subsequent worse outcomes, and most of these studies have adjusted for alternative kinds of explanations, like age, initial health status, lifestyle factors,” Holt-Lunstad said.

There is some evidence to suggest that isolation is more predictive of physical health outcomes, whereas loneliness is more predictive of mental health outcomes. That said, both isolation and loneliness have significant effects on mental and physical health outcomes, she noted.

There is also the question of whether loneliness is causing poor health or whether people who are in poor health feel lonely because poor health can lead to social isolation.

Finley said there’s probably a bit of both going on, but longitudinal studies, where loneliness is measured at a fixed timepoint then health outcomes are reported a few years later, suggest that loneliness is contributing to these adverse outcomes.

She added that there is also some evidence in animal models to suggest that loneliness is a causal risk factor for adverse health outcomes. “But you can’t ask a mouse or rat how lonely they’re feeling. All you can do is house them individually — removing them from social connection. This isn’t necessarily the same thing as loneliness in humans.”

Finley is studying mechanisms in the brain that may be involved in mediating the adverse health consequences of loneliness.

“What I’ve been seeing in the data so far is that it tends to be the self-report of how lonely folks are feeling that has the associations with differences in the brain, as opposed to the number of social connections people have. It does seem to be the more subjective, emotional perception of loneliness that is important.”

In a review of potential mechanisms involved, she concluded that it is dysregulated emotions and altered perceptions of social interactions that has profound impacts on the brain, suggesting that people who are lonely may have a tendency to interpret social cues in a negative way, preventing them from forming productive positive relationships.
 

Lack of Trust

One researcher who has studied this phenomenon is Dirk Scheele, PhD, professor of social neuroscience at Ruhr University Bochum in Germany.

“We were interested to find out why people remained lonely,” he said in an interview. “Loneliness is an unpleasant experience, and there are so many opportunities for social contacts nowadays, it’s not really clear at first sight why people are chronically lonely.”

To examine this question, Scheele and his team conducted a study in which functional MRI was used to examine the brain in otherwise healthy individuals with high or low loneliness scores while they played a trust game.

They also simulated a positive social interaction between participants and researchers, in which they talked about plans for a fictitious lottery win, and about their hobbies and interests, during which mood was measured with questionnaires, and saliva samples were collected to measure hormone levels.

Results showed that the high-lonely individuals had reduced activation in the insula cortex during the trust decisions. “This area of the brain is involved in the processing of bodily signals, such as ‘gut feelings.’ So reduced activity here could be interpreted as fewer gut feelings on who can be trusted,” Scheele explained.

The high-lonely individuals also had reduced responsiveness to the positive social interaction with a lower release of oxytocin and a smaller elevation in mood compared with the control individuals.

Scheele pointed out that there is some evidence that oxytocin might increase trust, and there is reduced release of endogenous oxytocin in high loneliness.

“Our results are consistent with the idea that loneliness is associated with negative biases about other people. So if we expect negative things from other people — for instance, that they cannot be trusted — then that would hamper further social interactions and could lead to loneliness,” he added.
 

A Role for Oxytocin?

In another study, the same researchers tested short-term (five weekly sessions) group psychotherapy to reduce loneliness using established techniques to target these negative biases. They also investigated whether the effects of this group psychotherapy could be augmented by administering intranasal oxytocin (vs placebo) before the group psychotherapy sessions.

Results showed that the group psychotherapy intervention reduced trait loneliness (loneliness experienced over a prolonged period). The oxytocin did not show a significant effect on trait loneliness, but there was a suggestion that it may enhance the reduction in state loneliness (how someone is feeling at a specific time) brought about by the psychotherapy sessions.

“We found that bonding within the groups was experienced as more positive in the oxytocin treated groups. It is possible that a longer intervention would be helpful for longer-term results,” Scheele concluded. “It’s not going to be a quick fix for loneliness, but there may be a role for oxytocin as an adjunct to psychotherapy.”
 

A Basic Human Need

Another loneliness researcher, Livia Tomova, PhD, assistant professor of psychology at Cardiff University in Wales, has used social isolation to induce loneliness in young people and found that this intervention was linked to brain patterns similar to those associated with hunger.

“We know that the drive to eat food is a very basic human need. We know quite well how it is represented in the brain,” she explained.

The researchers tested how the brains of the participants responded to seeing pictures of social interactions after they underwent a prolonged period of social isolation. In a subsequent session, the same people were asked to undergo food fasting and then underwent brain scans when looking at pictures of food. Results showed that the neural patterns were similar in the two situations with increased activity in the substantia nigra area within the midbrain.

“This area of the brain processes rewards and motivation. It consists primarily of dopamine neurons and increased activity corresponds to a feeling of craving something. So this area of the brain that controls essential homeostatic needs is activated when people feel lonely, suggesting that our need for social contact with others is potentially a very basic need similar to eating,” Tomova said.
 

Lower Gray Matter Volumes in Key Brain Areas

And another group from Germany has found that higher loneliness scores are negatively associated with specific brain regions responsible for memory, emotion regulation, and social processing.

Sandra Düzel, PhD, and colleagues from the Max Planck Institute for Human Development and the Charité – Universitätsmedizin Berlin, both in Berlin, Germany, reported a study in which individuals who reported higher loneliness had smaller gray matter volumes in brain regions such as the left amygdala, anterior hippocampus, and cerebellum, regions which are crucial for both emotional regulation and higher-order cognitive processes, such as self-reflection and executive function.

Düzel believes that possible mechanisms behind the link between loneliness and brain volume differences could include stress-related damage, with prolonged loneliness associated with elevated levels of stress hormones, which can damage the hippocampus over time, and reduced cognitive and social stimulation, which may contribute to brain volume reductions in regions critical for memory and emotional processing.

“Loneliness is often characterized by reduced social and environmental diversity, leading to less engagement with novel experiences and potentially lower hippocampal-striatal connectivity.

Since novelty-seeking and environmental diversity are associated with positive emotional states, individuals experiencing loneliness might benefit from increased exposure to new environments which could stimulate the brain’s reward circuits, fostering positive affect and potentially mitigating the emotional burden of loneliness,” she said.
 

Is Social Prescribing the Answer?

So are there enough data now to act and attempt to develop interventions to reduce loneliness? Most of these researchers believe so.

“I think we have enough information to act on this now. There are a number of national academies consensus reports, which suggest that, while certainly there are still gaps in our evidence and more to be learned, there is sufficient evidence that a concerning portion of the population seems to lack connection, and that the consequences are serious enough that we need to do something about it,” said Holt-Lunstad.

Some countries have introduced social prescribing where doctors can prescribe a group activity or a regular visit or telephone conversation with a supportive person.

Subramanian pointed out that it’s easier to implement in countries with national health services and may be more difficult to embrace in the US healthcare system.

“We are not so encouraged from a financial perspective to think about preventive care in the US. We don’t have an easy way to recognize in any tangible way the downstream of such activities in terms of preventing future problems. That is something we need to work on,” she said.

Finley cautioned that to work well, social prescribing will require an understanding of each person’s individual situation.

“Some people may only receive benefit of interacting with others if they are also getting some sort of support to address the social and emotional concerns that are tagging along with loneliness. I’m not sure that just telling people to go join their local gardening club or whatever will be the correct answer for everyone.”

She pointed out that many people will have issues in their life that are making it hard for them to be social. These could be mobility or financial challenges, care responsibilities, or concerns about illnesses or life events. “We need to figure out what would have the most bang for the person’s buck, so to speak, as an intervention. That could mean connecting them to a group relevant to their individual situation.”
 

Opportunity to Connect Not Enough?

Tomova believes that training people in social skills may be a better option. “It appears that some people who are chronically lonely seem to struggle to make relationships with others. So just encouraging them to interact with others more will not necessarily help. We need to better understand the pathways involved and who are the people who become ill. We can then develop and target better interventions and teach people coping strategies for that situation.”

Scheele agreed. “While just giving people the opportunity to connect may work for some, others who are experiencing really chronic loneliness may not benefit very much from this unless their negative belief systems are addressed.” He suggested some sort of psychotherapy may be helpful in this situation.

But at least all seem to agree that healthcare providers need to be more aware of loneliness as a health risk factor, try to identify people at risk, and to think about how best to support them.

Holt-Lunstad noted that one of the recommendations in the US Surgeon General’s advisory was to increase the education, training, and resources on loneliness for healthcare providers.

“If we want this to be addressed, we need to give healthcare providers the time, resources, and training in order to do that, otherwise, we are adding one more thing to an already overburdened system. They need to understand how important it is, and how it might help them take care of the patient.”

“Our hope is that we can start to reverse some of the trends that we are seeing, both in terms of the prevalence rates of loneliness, but also that we could start seeing improvements in health and other kinds of outcomes,” she concluded.

Progress is being made in increasing awareness about the dangers of chronic loneliness. It’s now recognized as a serious health risk, but there are actionable steps that can help. Loneliness doesn’t have to be a permanent condition for anyone, said Scheele.

Holt-Lunstad served as an adviser for Foundation for Social Connection, Global Initiative on Loneliness and Connection, and Nextdoor Neighborhood Vitality Board and received research grants/income from Templeton Foundation, Eventbrite, Foundation for Social Connection, and Triple-S Foundation. Subramanian served as a speaker bureau for Acorda Pharma. The other researchers reported no disclosures.

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

AMSTERDAM — The monoclonal antibody bimekizumab (Bimzelx) achieves significant and clinically meaningful improvements in moderate to severe hidradenitis suppurativa (HS) that are maintained well beyond the initial 1-year clinical trial treatment period, according to new data from an open-label extension period.

“Efficacy and health-related quality-of-life outcomes were maintained through 2 years of treatment,” study presenter Christos C. Zouboulis, MD, professor of dermatology, venereology, and allergology, Brandenburg Medical School Theodor Fontane, Dessau, Germany, said at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“No new safety signals were observed,” he added. “These data highlight the durability and consistency of bimekizumab treatment in patients with moderate to severe hidradenitis suppurativa,” Zouboulis concluded.
 

Efficacy Maintained

“This is the type of long-term data that clinicians hope to see in large phase 3 trials for hidradenitis suppurativa medications,” commented Jennifer L. Hsiao, MD, clinical associate professor of dermatology, University of Southern California, Los Angeles, who was not involved in the study.

She told this news organization that, beyond maintained improvement of patient-reported quality of life, the results are “raising the bar in terms of measuring treatment success,” with over three quarters of patients achieving a high level of response on the Hidradenitis Suppurativa Clinical Response (HiSCR) scale at the final 96-week follow-up.

“Clinicians and patients have struggled with maintaining treatment efficacy over time with the first [Food and Drug Administration]–approved class of biologics for hidradenitis suppurativa — TNF [tumor necrosis factor]–alpha antagonists,” Hsiao said. She emphasized that sustained treatment efficacy will reduce the need for continued treatment switching and “hopefully improve treatment adherence.”

“It was also helpful to see that, consistent with studies of bimekizumab in psoriasis, rates of oral candidiasis appear to decrease with prolonged exposure over 2 years, though as with any open-label extension study, study dropout is a limitation,” she said.

“The availability of long-term efficacy and safety data, such as those shown in this study, will help guide shared decision-making discussions with our patients.” Overall, Hsiao believes there is “much to be excited about in the field of hidradenitis suppurativa, with a robust pipeline of potential treatments.”
 

One-Year Extension Study

HS is a “chronic and debilitating inflammatory skin disease,” Zouboulis told the audience. He noted that interleukin (IL)–17F and IL-17A are highly expressed in lesional skin and play a role in the disease immunopathogenesis.

Bimekizumab is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits both IL-17F and IL-17A. It has previously demonstrated clinically meaningful improvements in patients with moderate to severe HS in the phase 3 BE HEARD I and BE HEARD II trials evaluating several dosing regimens.

Zouboulis said the current analysis combines data from the two phase 3 studies with the BE HEARD EXT open-label extension study, in which patients from both trials were continued on bimekizumab 320 mg every 2 weeks.

Of the 1014 patients initially enrolled in the two trials, 556 continued into the open-label extension. Their average age was 36.6 years, and 53.8% were women. The majority (80.6%) were White. Of the 556 patients enrolled in the extension, 446 completed the 1-year extension study.

The average draining tunnel count at baseline was 3.8, and 54.5% had Hurley stage II disease; the remaining 45.5% had stage III disease. The mean total Dermatology Life Quality Index (DLQI) score at baseline was 11.0, indicating the HS was having a very large impact on the patients’ lives.

After the 16-week initial treatment period and the maintenance treatment period out to 48 weeks, 64.0% of patients achieved HiSCR75, indicating at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, rising to 77.1% at the end of the open-label extension, after a total follow-up of 96 weeks.

HiSCR100 scores, indicating a 100% reduction in total abscess and inflammatory nodule counts, were achieved by 30.2% of 556 patients after 48 weeks and 44.2% of 446 at the 96-week follow-up.

These findings were mirrored by substantial reductions on the International HS Severity Score System, with a 70.3% reduction over baseline at 48 weeks and a 79.8% reduction at the final follow-up.

There were also “clinically meaningful” reductions in the total draining tunnel count at 1 year that were further reduced at 2 years, Zouboulis reported, at a 57.5% reduction over baseline, increasing to 73.7% by 96 weeks. The mean draining tunnel count at the end of follow-up was 1.1.

Over the full 96 weeks, the mean DLQI score reduced from 11.0 to 4.7, with 33.9% of patients achieving a score of 0 or 1 on the scale, which he said is basically patients saying: “I don’t have disease now.”

Finally, the safety data showed that there were “no differences compared to what we knew before,” Zouboulis said, with the most common treatment-related adverse events being hidradenitis, coronavirus infection, and oral candidiasis. There were few serious and severe treatment-related adverse events, and few that led to treatment discontinuation.

The study was funded by UCB.Zouboulis declared relationships with AstraZeneca, Boehringer Ingelheim, Brandenburg Medical School Theodor Fontane, EAD, European Union, German Federal Ministry of Education and Research, GSK, InflaRx, MSD, Novartis, Relaxera, UCB, Almirall, Boehringer Ingelheim, Eli Lilly, Idorsia, Incyte, L’Oréal, NAOS-BIODERMA, Pfizer, PM, Sanofi. Hsiao is on the board of directors for the Hidradenitis Suppurativa Foundation and has declared relationships with AbbVie, Aclaris Therapeutics, Amgen, Boehringer Ingelheim, Incyte, Novartis, Sanofi-Regeneron, and UCB.

A version of this article appeared on Medscape.com.

AMSTERDAM — The monoclonal antibody bimekizumab (Bimzelx) achieves significant and clinically meaningful improvements in moderate to severe hidradenitis suppurativa (HS) that are maintained well beyond the initial 1-year clinical trial treatment period, according to new data from an open-label extension period.

“Efficacy and health-related quality-of-life outcomes were maintained through 2 years of treatment,” study presenter Christos C. Zouboulis, MD, professor of dermatology, venereology, and allergology, Brandenburg Medical School Theodor Fontane, Dessau, Germany, said at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“No new safety signals were observed,” he added. “These data highlight the durability and consistency of bimekizumab treatment in patients with moderate to severe hidradenitis suppurativa,” Zouboulis concluded.
 

Efficacy Maintained

“This is the type of long-term data that clinicians hope to see in large phase 3 trials for hidradenitis suppurativa medications,” commented Jennifer L. Hsiao, MD, clinical associate professor of dermatology, University of Southern California, Los Angeles, who was not involved in the study.

She told this news organization that, beyond maintained improvement of patient-reported quality of life, the results are “raising the bar in terms of measuring treatment success,” with over three quarters of patients achieving a high level of response on the Hidradenitis Suppurativa Clinical Response (HiSCR) scale at the final 96-week follow-up.

“Clinicians and patients have struggled with maintaining treatment efficacy over time with the first [Food and Drug Administration]–approved class of biologics for hidradenitis suppurativa — TNF [tumor necrosis factor]–alpha antagonists,” Hsiao said. She emphasized that sustained treatment efficacy will reduce the need for continued treatment switching and “hopefully improve treatment adherence.”

“It was also helpful to see that, consistent with studies of bimekizumab in psoriasis, rates of oral candidiasis appear to decrease with prolonged exposure over 2 years, though as with any open-label extension study, study dropout is a limitation,” she said.

“The availability of long-term efficacy and safety data, such as those shown in this study, will help guide shared decision-making discussions with our patients.” Overall, Hsiao believes there is “much to be excited about in the field of hidradenitis suppurativa, with a robust pipeline of potential treatments.”
 

One-Year Extension Study

HS is a “chronic and debilitating inflammatory skin disease,” Zouboulis told the audience. He noted that interleukin (IL)–17F and IL-17A are highly expressed in lesional skin and play a role in the disease immunopathogenesis.

Bimekizumab is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits both IL-17F and IL-17A. It has previously demonstrated clinically meaningful improvements in patients with moderate to severe HS in the phase 3 BE HEARD I and BE HEARD II trials evaluating several dosing regimens.

Zouboulis said the current analysis combines data from the two phase 3 studies with the BE HEARD EXT open-label extension study, in which patients from both trials were continued on bimekizumab 320 mg every 2 weeks.

Of the 1014 patients initially enrolled in the two trials, 556 continued into the open-label extension. Their average age was 36.6 years, and 53.8% were women. The majority (80.6%) were White. Of the 556 patients enrolled in the extension, 446 completed the 1-year extension study.

The average draining tunnel count at baseline was 3.8, and 54.5% had Hurley stage II disease; the remaining 45.5% had stage III disease. The mean total Dermatology Life Quality Index (DLQI) score at baseline was 11.0, indicating the HS was having a very large impact on the patients’ lives.

After the 16-week initial treatment period and the maintenance treatment period out to 48 weeks, 64.0% of patients achieved HiSCR75, indicating at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, rising to 77.1% at the end of the open-label extension, after a total follow-up of 96 weeks.

HiSCR100 scores, indicating a 100% reduction in total abscess and inflammatory nodule counts, were achieved by 30.2% of 556 patients after 48 weeks and 44.2% of 446 at the 96-week follow-up.

These findings were mirrored by substantial reductions on the International HS Severity Score System, with a 70.3% reduction over baseline at 48 weeks and a 79.8% reduction at the final follow-up.

There were also “clinically meaningful” reductions in the total draining tunnel count at 1 year that were further reduced at 2 years, Zouboulis reported, at a 57.5% reduction over baseline, increasing to 73.7% by 96 weeks. The mean draining tunnel count at the end of follow-up was 1.1.

Over the full 96 weeks, the mean DLQI score reduced from 11.0 to 4.7, with 33.9% of patients achieving a score of 0 or 1 on the scale, which he said is basically patients saying: “I don’t have disease now.”

Finally, the safety data showed that there were “no differences compared to what we knew before,” Zouboulis said, with the most common treatment-related adverse events being hidradenitis, coronavirus infection, and oral candidiasis. There were few serious and severe treatment-related adverse events, and few that led to treatment discontinuation.

The study was funded by UCB.Zouboulis declared relationships with AstraZeneca, Boehringer Ingelheim, Brandenburg Medical School Theodor Fontane, EAD, European Union, German Federal Ministry of Education and Research, GSK, InflaRx, MSD, Novartis, Relaxera, UCB, Almirall, Boehringer Ingelheim, Eli Lilly, Idorsia, Incyte, L’Oréal, NAOS-BIODERMA, Pfizer, PM, Sanofi. Hsiao is on the board of directors for the Hidradenitis Suppurativa Foundation and has declared relationships with AbbVie, Aclaris Therapeutics, Amgen, Boehringer Ingelheim, Incyte, Novartis, Sanofi-Regeneron, and UCB.

A version of this article appeared on Medscape.com.

AMSTERDAM — The monoclonal antibody bimekizumab (Bimzelx) achieves significant and clinically meaningful improvements in moderate to severe hidradenitis suppurativa (HS) that are maintained well beyond the initial 1-year clinical trial treatment period, according to new data from an open-label extension period.

“Efficacy and health-related quality-of-life outcomes were maintained through 2 years of treatment,” study presenter Christos C. Zouboulis, MD, professor of dermatology, venereology, and allergology, Brandenburg Medical School Theodor Fontane, Dessau, Germany, said at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“No new safety signals were observed,” he added. “These data highlight the durability and consistency of bimekizumab treatment in patients with moderate to severe hidradenitis suppurativa,” Zouboulis concluded.
 

Efficacy Maintained

“This is the type of long-term data that clinicians hope to see in large phase 3 trials for hidradenitis suppurativa medications,” commented Jennifer L. Hsiao, MD, clinical associate professor of dermatology, University of Southern California, Los Angeles, who was not involved in the study.

She told this news organization that, beyond maintained improvement of patient-reported quality of life, the results are “raising the bar in terms of measuring treatment success,” with over three quarters of patients achieving a high level of response on the Hidradenitis Suppurativa Clinical Response (HiSCR) scale at the final 96-week follow-up.

“Clinicians and patients have struggled with maintaining treatment efficacy over time with the first [Food and Drug Administration]–approved class of biologics for hidradenitis suppurativa — TNF [tumor necrosis factor]–alpha antagonists,” Hsiao said. She emphasized that sustained treatment efficacy will reduce the need for continued treatment switching and “hopefully improve treatment adherence.”

“It was also helpful to see that, consistent with studies of bimekizumab in psoriasis, rates of oral candidiasis appear to decrease with prolonged exposure over 2 years, though as with any open-label extension study, study dropout is a limitation,” she said.

“The availability of long-term efficacy and safety data, such as those shown in this study, will help guide shared decision-making discussions with our patients.” Overall, Hsiao believes there is “much to be excited about in the field of hidradenitis suppurativa, with a robust pipeline of potential treatments.”
 

One-Year Extension Study

HS is a “chronic and debilitating inflammatory skin disease,” Zouboulis told the audience. He noted that interleukin (IL)–17F and IL-17A are highly expressed in lesional skin and play a role in the disease immunopathogenesis.

Bimekizumab is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits both IL-17F and IL-17A. It has previously demonstrated clinically meaningful improvements in patients with moderate to severe HS in the phase 3 BE HEARD I and BE HEARD II trials evaluating several dosing regimens.

Zouboulis said the current analysis combines data from the two phase 3 studies with the BE HEARD EXT open-label extension study, in which patients from both trials were continued on bimekizumab 320 mg every 2 weeks.

Of the 1014 patients initially enrolled in the two trials, 556 continued into the open-label extension. Their average age was 36.6 years, and 53.8% were women. The majority (80.6%) were White. Of the 556 patients enrolled in the extension, 446 completed the 1-year extension study.

The average draining tunnel count at baseline was 3.8, and 54.5% had Hurley stage II disease; the remaining 45.5% had stage III disease. The mean total Dermatology Life Quality Index (DLQI) score at baseline was 11.0, indicating the HS was having a very large impact on the patients’ lives.

After the 16-week initial treatment period and the maintenance treatment period out to 48 weeks, 64.0% of patients achieved HiSCR75, indicating at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, rising to 77.1% at the end of the open-label extension, after a total follow-up of 96 weeks.

HiSCR100 scores, indicating a 100% reduction in total abscess and inflammatory nodule counts, were achieved by 30.2% of 556 patients after 48 weeks and 44.2% of 446 at the 96-week follow-up.

These findings were mirrored by substantial reductions on the International HS Severity Score System, with a 70.3% reduction over baseline at 48 weeks and a 79.8% reduction at the final follow-up.

There were also “clinically meaningful” reductions in the total draining tunnel count at 1 year that were further reduced at 2 years, Zouboulis reported, at a 57.5% reduction over baseline, increasing to 73.7% by 96 weeks. The mean draining tunnel count at the end of follow-up was 1.1.

Over the full 96 weeks, the mean DLQI score reduced from 11.0 to 4.7, with 33.9% of patients achieving a score of 0 or 1 on the scale, which he said is basically patients saying: “I don’t have disease now.”

Finally, the safety data showed that there were “no differences compared to what we knew before,” Zouboulis said, with the most common treatment-related adverse events being hidradenitis, coronavirus infection, and oral candidiasis. There were few serious and severe treatment-related adverse events, and few that led to treatment discontinuation.

The study was funded by UCB.Zouboulis declared relationships with AstraZeneca, Boehringer Ingelheim, Brandenburg Medical School Theodor Fontane, EAD, European Union, German Federal Ministry of Education and Research, GSK, InflaRx, MSD, Novartis, Relaxera, UCB, Almirall, Boehringer Ingelheim, Eli Lilly, Idorsia, Incyte, L’Oréal, NAOS-BIODERMA, Pfizer, PM, Sanofi. Hsiao is on the board of directors for the Hidradenitis Suppurativa Foundation and has declared relationships with AbbVie, Aclaris Therapeutics, Amgen, Boehringer Ingelheim, Incyte, Novartis, Sanofi-Regeneron, and UCB.

A version of this article appeared on Medscape.com.

Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.

Unfortunately, IBS is often misunderstood or minimized by some healthcare professionals, according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.

Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.

A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.

“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.

IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.

Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.

“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
 

Diagnostic Pathway

One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”

IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).

Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.

Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.

Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.

 

If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
 

New Understanding of IBS Etiology

Now, advances in the understanding of IBS are changing the approach to the disease.

“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”

Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.

Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.

The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.

CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.

This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”

Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.

“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.

Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.

“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”

The blood test also can identify IBS-M but not IBS-C.

Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
 

Diet as a Treatment Option

Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).

Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”

A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
 

Pharmacotherapy for IBS

Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.

Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.

Antidiarrheal agents include loperamide and diphenoxylate.

For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.

Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
 

Targeting the Gut-Brain Relationship

Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.

“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”

Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.

“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.

Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.

Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.

Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.

Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”

Finally, all the experts agree that more research is needed.

“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”

Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.

Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.

Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.

Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.

A version of this article appeared on Medscape.com.

Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.

Unfortunately, IBS is often misunderstood or minimized by some healthcare professionals, according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.

Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.

A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.

“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.

IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.

Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.

“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
 

Diagnostic Pathway

One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”

IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).

Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.

Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.

Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.

 

If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
 

New Understanding of IBS Etiology

Now, advances in the understanding of IBS are changing the approach to the disease.

“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”

Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.

Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.

The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.

CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.

This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”

Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.

“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.

Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.

“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”

The blood test also can identify IBS-M but not IBS-C.

Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
 

Diet as a Treatment Option

Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).

Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”

A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
 

Pharmacotherapy for IBS

Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.

Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.

Antidiarrheal agents include loperamide and diphenoxylate.

For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.

Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
 

Targeting the Gut-Brain Relationship

Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.

“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”

Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.

“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.

Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.

Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.

Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.

Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”

Finally, all the experts agree that more research is needed.

“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”

Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.

Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.

Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.

Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.

A version of this article appeared on Medscape.com.

Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.

Unfortunately, IBS is often misunderstood or minimized by some healthcare professionals, according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.

Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.

A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.

“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.

IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.

Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.

“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
 

Diagnostic Pathway

One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”

IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).

Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.

Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.

Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.

 

If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
 

New Understanding of IBS Etiology

Now, advances in the understanding of IBS are changing the approach to the disease.

“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”

Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.

Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.

The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.

CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.

This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”

Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.

“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.

Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.

“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”

The blood test also can identify IBS-M but not IBS-C.

Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
 

Diet as a Treatment Option

Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).

Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”

A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
 

Pharmacotherapy for IBS

Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.

Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.

Antidiarrheal agents include loperamide and diphenoxylate.

For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.

Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
 

Targeting the Gut-Brain Relationship

Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.

“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”

Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.

“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.

Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.

Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.

Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.

Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”

Finally, all the experts agree that more research is needed.

“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”

Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.

Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.

Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.

Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.

A version of this article appeared on Medscape.com.

SAN ANTONIO, TEXAS — An upcoming document will entirely reframe obesity as a “condition of excess adiposity” that constitutes a disease called “clinical obesity” when related tissue and organ abnormalities are present.

The authors of the new framework are a Lancet Commission of 56 of the world’s leading obesity experts, including academic clinicians, scientists, public health experts, patient representatives, and officers from the World Health Organization. Following peer review, it will be launched via livestream and published in Lancet Diabetes & Endocrinology in mid-January 2025, with formal endorsement from more than 75 medical societies and other relevant stakeholder organizations.

On November 4, 2024, at the Obesity Society’s Obesity Week meeting, the publication’s lead author, Francesco Rubino, MD, Chair of Bariatric and Metabolic Surgery at King’s College London in England, gave a preview. He began by noting that, despite the declaration of obesity as a chronic disease over a decade ago, the concept is still debated and not widely accepted by the public or even by all in the medical community.

“The idea of obesity as a disease remains highly controversial,” Rubino noted, adding that the current body mass index (BMI)–based definition contributes to this because it doesn’t distinguish between people whose excess adiposity place them at excess risk for disease but they’re currently healthy vs those who already have undergone bodily harm from that adiposity.

“Having a framework that distinguishes at an individual level when you are in a condition of risk and when you have a condition of disease is fundamentally important. You don’t want to blur the picture in either direction, because obviously the consequence would be quite significant. ... So, the commission focused exactly on that point,” he said.

The new paper will propose a two-part clinical approach: First, assess whether the patient has excess adiposity, with methods that will be outlined. Next, assess on an organ-by-organ basis for the presence of abnormalities related to excess adiposity, or “clinical obesity.” The document will also provide those specific criteria, Rubino said, noting that those details are under embargo until January.

However, he did say that “We are going to propose a pragmatic approach to say that BMI alone is not enough in the clinic. It’s okay as a screening tool, but when somebody potentially has obesity, then you have to add additional measures of adiposity that makes sure you decrease the level of risk… Once you have obesity, then you need to establish if it’s clinical or nonclinical.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, said in an interview, “I think it’ll help explain and move medicine as a whole in a direction to a greater understanding of obesity actually being a disease, how to define it, and how to identify it. And will, I think, lead to a greater understanding of the underlying disease.”

And, Clark said, it should also help target individuals with preventive vs therapeutic approaches. “I would describe it as matching the right tool to the right patient. If a person has clinical obesity, they likely can and would benefit from either different or additional tools, as opposed to otherwise healthy obesity.”

Rubino said he hopes the new framework will prompt improvements in reimbursement and public policy. “Policymakers scratch their heads when they have limited resources and you need to prioritize things. Having an obesity definition that is blurry doesn’t allow you to have a fair, human, and meaningful prioritization. ... Now that we have drugs that cannot be given to 100% of people, how do you decide who gets them first? I hope this will make it easier for people to access treatment. At the moment, it is not only difficult, but it’s also unfair. It’s random. Somebody gets access, while somebody else who is very, very sick has no access. I don’t think that’s what we want.”

A version of this article appeared on Medscape.com.

SAN ANTONIO, TEXAS — An upcoming document will entirely reframe obesity as a “condition of excess adiposity” that constitutes a disease called “clinical obesity” when related tissue and organ abnormalities are present.

The authors of the new framework are a Lancet Commission of 56 of the world’s leading obesity experts, including academic clinicians, scientists, public health experts, patient representatives, and officers from the World Health Organization. Following peer review, it will be launched via livestream and published in Lancet Diabetes & Endocrinology in mid-January 2025, with formal endorsement from more than 75 medical societies and other relevant stakeholder organizations.

On November 4, 2024, at the Obesity Society’s Obesity Week meeting, the publication’s lead author, Francesco Rubino, MD, Chair of Bariatric and Metabolic Surgery at King’s College London in England, gave a preview. He began by noting that, despite the declaration of obesity as a chronic disease over a decade ago, the concept is still debated and not widely accepted by the public or even by all in the medical community.

“The idea of obesity as a disease remains highly controversial,” Rubino noted, adding that the current body mass index (BMI)–based definition contributes to this because it doesn’t distinguish between people whose excess adiposity place them at excess risk for disease but they’re currently healthy vs those who already have undergone bodily harm from that adiposity.

“Having a framework that distinguishes at an individual level when you are in a condition of risk and when you have a condition of disease is fundamentally important. You don’t want to blur the picture in either direction, because obviously the consequence would be quite significant. ... So, the commission focused exactly on that point,” he said.

The new paper will propose a two-part clinical approach: First, assess whether the patient has excess adiposity, with methods that will be outlined. Next, assess on an organ-by-organ basis for the presence of abnormalities related to excess adiposity, or “clinical obesity.” The document will also provide those specific criteria, Rubino said, noting that those details are under embargo until January.

However, he did say that “We are going to propose a pragmatic approach to say that BMI alone is not enough in the clinic. It’s okay as a screening tool, but when somebody potentially has obesity, then you have to add additional measures of adiposity that makes sure you decrease the level of risk… Once you have obesity, then you need to establish if it’s clinical or nonclinical.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, said in an interview, “I think it’ll help explain and move medicine as a whole in a direction to a greater understanding of obesity actually being a disease, how to define it, and how to identify it. And will, I think, lead to a greater understanding of the underlying disease.”

And, Clark said, it should also help target individuals with preventive vs therapeutic approaches. “I would describe it as matching the right tool to the right patient. If a person has clinical obesity, they likely can and would benefit from either different or additional tools, as opposed to otherwise healthy obesity.”

Rubino said he hopes the new framework will prompt improvements in reimbursement and public policy. “Policymakers scratch their heads when they have limited resources and you need to prioritize things. Having an obesity definition that is blurry doesn’t allow you to have a fair, human, and meaningful prioritization. ... Now that we have drugs that cannot be given to 100% of people, how do you decide who gets them first? I hope this will make it easier for people to access treatment. At the moment, it is not only difficult, but it’s also unfair. It’s random. Somebody gets access, while somebody else who is very, very sick has no access. I don’t think that’s what we want.”

A version of this article appeared on Medscape.com.

SAN ANTONIO, TEXAS — An upcoming document will entirely reframe obesity as a “condition of excess adiposity” that constitutes a disease called “clinical obesity” when related tissue and organ abnormalities are present.

The authors of the new framework are a Lancet Commission of 56 of the world’s leading obesity experts, including academic clinicians, scientists, public health experts, patient representatives, and officers from the World Health Organization. Following peer review, it will be launched via livestream and published in Lancet Diabetes & Endocrinology in mid-January 2025, with formal endorsement from more than 75 medical societies and other relevant stakeholder organizations.

On November 4, 2024, at the Obesity Society’s Obesity Week meeting, the publication’s lead author, Francesco Rubino, MD, Chair of Bariatric and Metabolic Surgery at King’s College London in England, gave a preview. He began by noting that, despite the declaration of obesity as a chronic disease over a decade ago, the concept is still debated and not widely accepted by the public or even by all in the medical community.

“The idea of obesity as a disease remains highly controversial,” Rubino noted, adding that the current body mass index (BMI)–based definition contributes to this because it doesn’t distinguish between people whose excess adiposity place them at excess risk for disease but they’re currently healthy vs those who already have undergone bodily harm from that adiposity.

“Having a framework that distinguishes at an individual level when you are in a condition of risk and when you have a condition of disease is fundamentally important. You don’t want to blur the picture in either direction, because obviously the consequence would be quite significant. ... So, the commission focused exactly on that point,” he said.

The new paper will propose a two-part clinical approach: First, assess whether the patient has excess adiposity, with methods that will be outlined. Next, assess on an organ-by-organ basis for the presence of abnormalities related to excess adiposity, or “clinical obesity.” The document will also provide those specific criteria, Rubino said, noting that those details are under embargo until January.

However, he did say that “We are going to propose a pragmatic approach to say that BMI alone is not enough in the clinic. It’s okay as a screening tool, but when somebody potentially has obesity, then you have to add additional measures of adiposity that makes sure you decrease the level of risk… Once you have obesity, then you need to establish if it’s clinical or nonclinical.”

Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, said in an interview, “I think it’ll help explain and move medicine as a whole in a direction to a greater understanding of obesity actually being a disease, how to define it, and how to identify it. And will, I think, lead to a greater understanding of the underlying disease.”

And, Clark said, it should also help target individuals with preventive vs therapeutic approaches. “I would describe it as matching the right tool to the right patient. If a person has clinical obesity, they likely can and would benefit from either different or additional tools, as opposed to otherwise healthy obesity.”

Rubino said he hopes the new framework will prompt improvements in reimbursement and public policy. “Policymakers scratch their heads when they have limited resources and you need to prioritize things. Having an obesity definition that is blurry doesn’t allow you to have a fair, human, and meaningful prioritization. ... Now that we have drugs that cannot be given to 100% of people, how do you decide who gets them first? I hope this will make it easier for people to access treatment. At the moment, it is not only difficult, but it’s also unfair. It’s random. Somebody gets access, while somebody else who is very, very sick has no access. I don’t think that’s what we want.”

A version of this article appeared on Medscape.com.

Only 12% of the nurses providing patient care at hospitals and health clinics today are men. Although the percentage of nurses has increased — men made up just 2.7% of nurses in 1970 — nursing is still considered a “pink collar” profession, a female-dominated field.

“We’ve made strides over the last couple of decades, but [the number of men pursuing nursing careers] is leveling out,” said Jason Dunne, DNP, MSN, RN, chief academic officer at the Arizona College of Nursing, Phoenix. “There continues to be persistent gender stereotypes that [have] discouraged men from entering the profession.”

A nationwide nursing shortage has led to increased efforts to attract more men to the profession and ensure that men in nursing feel valued and supported and want to continue their careers long term.

“The nursing shortage is very real,” Dunne said. “We need to be highly focused on the shortage and look at opportunities to bring diversity into the profession, and one big way to solve it is bringing more men into nursing.”
 

Representation Matters

Colleges recognize the need to diversify their nursing student population and have turned their attention to increasing the number of men attending informational sessions and career days. Dunne believes, “There is a general lack of awareness of nursing as a career choice [for men].”

The Nursing Consortium of Florida hosts a “Day in the Life of a Nurse” program to introduce high school students to nursing careers, and the University of Virginia School of Nursing invites male nursing students to speak at educational events to promote workforce diversity.

“When I was growing up, the males wouldn’t have been included in those sessions,” said Melissa Gilbert Gomes, PhD, APRN, PMHNP-BC, FNAP, FAAN, associate dean for diversity, equity, and inclusion at the University of Virginia School of Nursing, Charlottesville, Virginia. “It was nice to see their interest and to have a male student there for them to ask questions and to help them see that this could be a place for them.”

Nursing schools have also engaged in other efforts to encourage more men to consider nursing careers, from highlighting male nurses in marketing materials and engaging with men at career fairs to updating course curriculum to include content on men’s health and connecting male nursing students with men in nursing faculty or clinical settings.

Focusing on nursing as a lucrative career choice could also attract more men to the profession. On average, male registered nurses (RNs) make $7300 per year more than their female counterparts due to the gender pay gap. The median wage for male RNs in acute care, cardiology, and perioperative specialties is $90,000 annually.

At the University of Virginia School of Nursing, which the American Association for Men in Nursing (AAMN) named “Best School for Men in Nursing” in 2023, 20% of nursing students are men.

The school has a Men Advancing Nursing club and is in the process of chartering a new AAMN chapter. The goal, according to Gomes, is to create an environment where male nursing students feel represented and supported.

“Valuing the perspective that men bring [to nursing] is important,” she said. “Coming together [and] having that camaraderie and intrinsic motivation to specifically speak to areas that impact men ... is important.”
 

Promoting Patient Care

Highlighting the diversity of career options within the nursing profession is also essential. RNs can pursue careers in specialties ranging from pediatrics, orthopedics, and occupational health to anesthesia, cardiology, and nephrology. The specialty with the highest number of male RNs tends to be acute care, which encompasses emergency/trauma and medical-surgical.

John Schmidt, DNP, MSN, BSN, faculty member and program lead for the acute care nurse practitioner program at Purdue Global School of Nursing, refers to these specialties as having a high excitement factor.

“Men gravitate to nursing to help people,” he said. “In critical care, there is instant gratification. You see patients get better. It’s the same in the [intensive care unit] and the emergency department. We take care of them and can see how we made a difference.”

When hospitals and health systems create environments that support men in nursing, patients also benefit. Research shows that patients often prefer nurses of the same gender, and a more diverse healthcare workforce has been linked to improved patient outcomes. Reducing gender inequities among nursing staff could also improve job satisfaction and retention rates for men in nursing.

“When you’re in a vulnerable space as a patient ... it’s important to know that your care provider understands you [and] having men as nurses is a part of that,” said Gomes. “Even though patients might not be used to having a male nurse at the bedside, once they have the experience, it challenges preconceived notions [and] that connection is important.”

Hospitals must proactively support men in nursing to achieve the benefits of greater gender diversity in the nursing workforce. Male nurses have fewer role models and report higher levels of loneliness, isolation, and role strain.

Groups such as NYC Men in Nursing and mentorship programs such as Men in Nursing at RUSH University College of Nursing and RUSH University Medical Center, and the North Carolina Healthcare Association Diverse Healthcare Leaders Mentorship Program were designed to provide coaching, education, and networking opportunities and connect men in nursing.

Male nurses, Dunne added, must be role models and must take the lead in changing the conversations about gender roles in nursing. Establishing support systems and mentorship opportunities is instrumental in inspiring men to pursue nursing careers and creating visibility into the profession and “would create a level of parity for men in the profession and encourage them to want to stay in nursing as a long-term career.”

He told this news organization that creating scholarships for men enrolled in nursing school, increasing the involvement of male nurse leaders in recruitment efforts, and updating curriculum to ensure men are reflected in the materials is also essential.

“We’ve got to be willing and open to having the conversations to end the stereotypes that have plagued the profession,” said Dunne. “And we’ve got to push men in nursing to be front and center so folks see that there are opportunities for men in nursing.”
 

A version of this article appeared on Medscape.com.

Only 12% of the nurses providing patient care at hospitals and health clinics today are men. Although the percentage of nurses has increased — men made up just 2.7% of nurses in 1970 — nursing is still considered a “pink collar” profession, a female-dominated field.

“We’ve made strides over the last couple of decades, but [the number of men pursuing nursing careers] is leveling out,” said Jason Dunne, DNP, MSN, RN, chief academic officer at the Arizona College of Nursing, Phoenix. “There continues to be persistent gender stereotypes that [have] discouraged men from entering the profession.”

A nationwide nursing shortage has led to increased efforts to attract more men to the profession and ensure that men in nursing feel valued and supported and want to continue their careers long term.

“The nursing shortage is very real,” Dunne said. “We need to be highly focused on the shortage and look at opportunities to bring diversity into the profession, and one big way to solve it is bringing more men into nursing.”
 

Representation Matters

Colleges recognize the need to diversify their nursing student population and have turned their attention to increasing the number of men attending informational sessions and career days. Dunne believes, “There is a general lack of awareness of nursing as a career choice [for men].”

The Nursing Consortium of Florida hosts a “Day in the Life of a Nurse” program to introduce high school students to nursing careers, and the University of Virginia School of Nursing invites male nursing students to speak at educational events to promote workforce diversity.

“When I was growing up, the males wouldn’t have been included in those sessions,” said Melissa Gilbert Gomes, PhD, APRN, PMHNP-BC, FNAP, FAAN, associate dean for diversity, equity, and inclusion at the University of Virginia School of Nursing, Charlottesville, Virginia. “It was nice to see their interest and to have a male student there for them to ask questions and to help them see that this could be a place for them.”

Nursing schools have also engaged in other efforts to encourage more men to consider nursing careers, from highlighting male nurses in marketing materials and engaging with men at career fairs to updating course curriculum to include content on men’s health and connecting male nursing students with men in nursing faculty or clinical settings.

Focusing on nursing as a lucrative career choice could also attract more men to the profession. On average, male registered nurses (RNs) make $7300 per year more than their female counterparts due to the gender pay gap. The median wage for male RNs in acute care, cardiology, and perioperative specialties is $90,000 annually.

At the University of Virginia School of Nursing, which the American Association for Men in Nursing (AAMN) named “Best School for Men in Nursing” in 2023, 20% of nursing students are men.

The school has a Men Advancing Nursing club and is in the process of chartering a new AAMN chapter. The goal, according to Gomes, is to create an environment where male nursing students feel represented and supported.

“Valuing the perspective that men bring [to nursing] is important,” she said. “Coming together [and] having that camaraderie and intrinsic motivation to specifically speak to areas that impact men ... is important.”
 

Promoting Patient Care

Highlighting the diversity of career options within the nursing profession is also essential. RNs can pursue careers in specialties ranging from pediatrics, orthopedics, and occupational health to anesthesia, cardiology, and nephrology. The specialty with the highest number of male RNs tends to be acute care, which encompasses emergency/trauma and medical-surgical.

John Schmidt, DNP, MSN, BSN, faculty member and program lead for the acute care nurse practitioner program at Purdue Global School of Nursing, refers to these specialties as having a high excitement factor.

“Men gravitate to nursing to help people,” he said. “In critical care, there is instant gratification. You see patients get better. It’s the same in the [intensive care unit] and the emergency department. We take care of them and can see how we made a difference.”

When hospitals and health systems create environments that support men in nursing, patients also benefit. Research shows that patients often prefer nurses of the same gender, and a more diverse healthcare workforce has been linked to improved patient outcomes. Reducing gender inequities among nursing staff could also improve job satisfaction and retention rates for men in nursing.

“When you’re in a vulnerable space as a patient ... it’s important to know that your care provider understands you [and] having men as nurses is a part of that,” said Gomes. “Even though patients might not be used to having a male nurse at the bedside, once they have the experience, it challenges preconceived notions [and] that connection is important.”

Hospitals must proactively support men in nursing to achieve the benefits of greater gender diversity in the nursing workforce. Male nurses have fewer role models and report higher levels of loneliness, isolation, and role strain.

Groups such as NYC Men in Nursing and mentorship programs such as Men in Nursing at RUSH University College of Nursing and RUSH University Medical Center, and the North Carolina Healthcare Association Diverse Healthcare Leaders Mentorship Program were designed to provide coaching, education, and networking opportunities and connect men in nursing.

Male nurses, Dunne added, must be role models and must take the lead in changing the conversations about gender roles in nursing. Establishing support systems and mentorship opportunities is instrumental in inspiring men to pursue nursing careers and creating visibility into the profession and “would create a level of parity for men in the profession and encourage them to want to stay in nursing as a long-term career.”

He told this news organization that creating scholarships for men enrolled in nursing school, increasing the involvement of male nurse leaders in recruitment efforts, and updating curriculum to ensure men are reflected in the materials is also essential.

“We’ve got to be willing and open to having the conversations to end the stereotypes that have plagued the profession,” said Dunne. “And we’ve got to push men in nursing to be front and center so folks see that there are opportunities for men in nursing.”
 

A version of this article appeared on Medscape.com.

Only 12% of the nurses providing patient care at hospitals and health clinics today are men. Although the percentage of nurses has increased — men made up just 2.7% of nurses in 1970 — nursing is still considered a “pink collar” profession, a female-dominated field.

“We’ve made strides over the last couple of decades, but [the number of men pursuing nursing careers] is leveling out,” said Jason Dunne, DNP, MSN, RN, chief academic officer at the Arizona College of Nursing, Phoenix. “There continues to be persistent gender stereotypes that [have] discouraged men from entering the profession.”

A nationwide nursing shortage has led to increased efforts to attract more men to the profession and ensure that men in nursing feel valued and supported and want to continue their careers long term.

“The nursing shortage is very real,” Dunne said. “We need to be highly focused on the shortage and look at opportunities to bring diversity into the profession, and one big way to solve it is bringing more men into nursing.”
 

Representation Matters

Colleges recognize the need to diversify their nursing student population and have turned their attention to increasing the number of men attending informational sessions and career days. Dunne believes, “There is a general lack of awareness of nursing as a career choice [for men].”

The Nursing Consortium of Florida hosts a “Day in the Life of a Nurse” program to introduce high school students to nursing careers, and the University of Virginia School of Nursing invites male nursing students to speak at educational events to promote workforce diversity.

“When I was growing up, the males wouldn’t have been included in those sessions,” said Melissa Gilbert Gomes, PhD, APRN, PMHNP-BC, FNAP, FAAN, associate dean for diversity, equity, and inclusion at the University of Virginia School of Nursing, Charlottesville, Virginia. “It was nice to see their interest and to have a male student there for them to ask questions and to help them see that this could be a place for them.”

Nursing schools have also engaged in other efforts to encourage more men to consider nursing careers, from highlighting male nurses in marketing materials and engaging with men at career fairs to updating course curriculum to include content on men’s health and connecting male nursing students with men in nursing faculty or clinical settings.

Focusing on nursing as a lucrative career choice could also attract more men to the profession. On average, male registered nurses (RNs) make $7300 per year more than their female counterparts due to the gender pay gap. The median wage for male RNs in acute care, cardiology, and perioperative specialties is $90,000 annually.

At the University of Virginia School of Nursing, which the American Association for Men in Nursing (AAMN) named “Best School for Men in Nursing” in 2023, 20% of nursing students are men.

The school has a Men Advancing Nursing club and is in the process of chartering a new AAMN chapter. The goal, according to Gomes, is to create an environment where male nursing students feel represented and supported.

“Valuing the perspective that men bring [to nursing] is important,” she said. “Coming together [and] having that camaraderie and intrinsic motivation to specifically speak to areas that impact men ... is important.”
 

Promoting Patient Care

Highlighting the diversity of career options within the nursing profession is also essential. RNs can pursue careers in specialties ranging from pediatrics, orthopedics, and occupational health to anesthesia, cardiology, and nephrology. The specialty with the highest number of male RNs tends to be acute care, which encompasses emergency/trauma and medical-surgical.

John Schmidt, DNP, MSN, BSN, faculty member and program lead for the acute care nurse practitioner program at Purdue Global School of Nursing, refers to these specialties as having a high excitement factor.

“Men gravitate to nursing to help people,” he said. “In critical care, there is instant gratification. You see patients get better. It’s the same in the [intensive care unit] and the emergency department. We take care of them and can see how we made a difference.”

When hospitals and health systems create environments that support men in nursing, patients also benefit. Research shows that patients often prefer nurses of the same gender, and a more diverse healthcare workforce has been linked to improved patient outcomes. Reducing gender inequities among nursing staff could also improve job satisfaction and retention rates for men in nursing.

“When you’re in a vulnerable space as a patient ... it’s important to know that your care provider understands you [and] having men as nurses is a part of that,” said Gomes. “Even though patients might not be used to having a male nurse at the bedside, once they have the experience, it challenges preconceived notions [and] that connection is important.”

Hospitals must proactively support men in nursing to achieve the benefits of greater gender diversity in the nursing workforce. Male nurses have fewer role models and report higher levels of loneliness, isolation, and role strain.

Groups such as NYC Men in Nursing and mentorship programs such as Men in Nursing at RUSH University College of Nursing and RUSH University Medical Center, and the North Carolina Healthcare Association Diverse Healthcare Leaders Mentorship Program were designed to provide coaching, education, and networking opportunities and connect men in nursing.

Male nurses, Dunne added, must be role models and must take the lead in changing the conversations about gender roles in nursing. Establishing support systems and mentorship opportunities is instrumental in inspiring men to pursue nursing careers and creating visibility into the profession and “would create a level of parity for men in the profession and encourage them to want to stay in nursing as a long-term career.”

He told this news organization that creating scholarships for men enrolled in nursing school, increasing the involvement of male nurse leaders in recruitment efforts, and updating curriculum to ensure men are reflected in the materials is also essential.

“We’ve got to be willing and open to having the conversations to end the stereotypes that have plagued the profession,” said Dunne. “And we’ve got to push men in nursing to be front and center so folks see that there are opportunities for men in nursing.”
 

A version of this article appeared on Medscape.com.

Federal lawmakers are rushing to soften the blow of Medicare’s 2025 effective pay cut for doctors in 2025, introducing a bill that could limit the cut. But they have little time to act.

In 2025, the conversion factor used to calculate payment to doctors and hospitals caring for Medicare patients will drop to $32.35, a nearly 3% decrease from the current level. 

Congress likely will act before the cuts take effect, said Rep. Larry Bucshon, MD (R-IN), who specialized in cardiothoracic surgery before joining Congress. Lawmakers in past years have typically tinkered with the Medicare physician fee schedule at the last minute, tucking in fixes to December legislative packages and spending bills. 

“I’m pretty optimistic that a good portion of the fee cuts will be mitigated and they won’t go through,” Bucshon told this news organization in an interview.

Bruce A. Scott, MD, president of the American Medical Association (AMA) said in a statement that CMS’ release of the final fee schedule on November 1 should trigger serious work on a change to the 2025 Medicare physician fee schedule.

“The fee schedule rule released [on November 1] starts the clock — with January 1 looming,” Scott said. “A legislative remedy will require hard work and compromise. The 66 million patients who rely on Medicare are counting on that.”

Both Bucshon and Scott also joined many lawmakers and medical associations in calling on Congress for a larger overhaul of the Medicare physician fee schedule, well beyond whatever temporary adjustment may be made in the months ahead to avoid or soften the 2025 cuts.

The physician fee schedule sets formulas and rules regarding how the largest US buyer of health services pays the almost 1.3 million clinicians who bill Medicare. Of these, 51% are physicians. The physician fee schedule also covers payments for nurse practitioners, physician assistants, physical therapists, and other health professionals.
 

Last Major Overhaul Unpopular

There’s broad dissatisfaction with Congress’ last major overhaul of the Medicare physician fee schedule. The 2015 Medicare Access and CHIP Reauthorization Act (MACRA) aimed to shift clinicians toward programs tying pay increases to quality measures. But the implementation of that aim through the Merit-based Incentive Payment System is widely considered a disappointment.

MACRA was intended to end the need for annual “doc fixes,” as Congress’ last-minute Medicare adjustments are known. Seventeen such tweaks passed before MACRA took effect. 

But MACRA did not include a broad-based inflation adjuster, and some clinicians’ incomes are lagging as inflation rates — and practice costs — have risen. Scott said the Medicare Economic Index, which is a measure used to gauge increases in practice costs for clinicians, is expected to rise by 3.5%.

“To put it bluntly, Medicare plans to pay us less while costs go up. You don’t have to be an economist to know that is an unsustainable trend, though one that has been going on for decades,” Scott said. “For physician practices operating on small margins already, this means it is harder to acquire new equipment, harder to retain staff, harder to take on new Medicare patients, and harder to keep the doors open, particularly in rural and underserved areas.”

In a statement, Jen Brull, MD, president of the American Academy of Family Physicians, noted that this likely will be the fifth year in a row that Congress will need to do a patch to prevent cuts in pay to clinicians. 

Bucshon, who will retire from the House in January, said he expects Congress to pass legislation tying Medicare payment rates to inflation — eventually.

“People want to find a way to fix this problem, but also do it in a way that does not cut benefits to anyone, and that’s the key,” Bucshon said. “We’re going to have to find a way to make sure that providers are properly reimbursed.”

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

Federal lawmakers are rushing to soften the blow of Medicare’s 2025 effective pay cut for doctors in 2025, introducing a bill that could limit the cut. But they have little time to act.

In 2025, the conversion factor used to calculate payment to doctors and hospitals caring for Medicare patients will drop to $32.35, a nearly 3% decrease from the current level. 

Congress likely will act before the cuts take effect, said Rep. Larry Bucshon, MD (R-IN), who specialized in cardiothoracic surgery before joining Congress. Lawmakers in past years have typically tinkered with the Medicare physician fee schedule at the last minute, tucking in fixes to December legislative packages and spending bills. 

“I’m pretty optimistic that a good portion of the fee cuts will be mitigated and they won’t go through,” Bucshon told this news organization in an interview.

Bruce A. Scott, MD, president of the American Medical Association (AMA) said in a statement that CMS’ release of the final fee schedule on November 1 should trigger serious work on a change to the 2025 Medicare physician fee schedule.

“The fee schedule rule released [on November 1] starts the clock — with January 1 looming,” Scott said. “A legislative remedy will require hard work and compromise. The 66 million patients who rely on Medicare are counting on that.”

Both Bucshon and Scott also joined many lawmakers and medical associations in calling on Congress for a larger overhaul of the Medicare physician fee schedule, well beyond whatever temporary adjustment may be made in the months ahead to avoid or soften the 2025 cuts.

The physician fee schedule sets formulas and rules regarding how the largest US buyer of health services pays the almost 1.3 million clinicians who bill Medicare. Of these, 51% are physicians. The physician fee schedule also covers payments for nurse practitioners, physician assistants, physical therapists, and other health professionals.
 

Last Major Overhaul Unpopular

There’s broad dissatisfaction with Congress’ last major overhaul of the Medicare physician fee schedule. The 2015 Medicare Access and CHIP Reauthorization Act (MACRA) aimed to shift clinicians toward programs tying pay increases to quality measures. But the implementation of that aim through the Merit-based Incentive Payment System is widely considered a disappointment.

MACRA was intended to end the need for annual “doc fixes,” as Congress’ last-minute Medicare adjustments are known. Seventeen such tweaks passed before MACRA took effect. 

But MACRA did not include a broad-based inflation adjuster, and some clinicians’ incomes are lagging as inflation rates — and practice costs — have risen. Scott said the Medicare Economic Index, which is a measure used to gauge increases in practice costs for clinicians, is expected to rise by 3.5%.

“To put it bluntly, Medicare plans to pay us less while costs go up. You don’t have to be an economist to know that is an unsustainable trend, though one that has been going on for decades,” Scott said. “For physician practices operating on small margins already, this means it is harder to acquire new equipment, harder to retain staff, harder to take on new Medicare patients, and harder to keep the doors open, particularly in rural and underserved areas.”

In a statement, Jen Brull, MD, president of the American Academy of Family Physicians, noted that this likely will be the fifth year in a row that Congress will need to do a patch to prevent cuts in pay to clinicians. 

Bucshon, who will retire from the House in January, said he expects Congress to pass legislation tying Medicare payment rates to inflation — eventually.

“People want to find a way to fix this problem, but also do it in a way that does not cut benefits to anyone, and that’s the key,” Bucshon said. “We’re going to have to find a way to make sure that providers are properly reimbursed.”

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

Federal lawmakers are rushing to soften the blow of Medicare’s 2025 effective pay cut for doctors in 2025, introducing a bill that could limit the cut. But they have little time to act.

In 2025, the conversion factor used to calculate payment to doctors and hospitals caring for Medicare patients will drop to $32.35, a nearly 3% decrease from the current level. 

Congress likely will act before the cuts take effect, said Rep. Larry Bucshon, MD (R-IN), who specialized in cardiothoracic surgery before joining Congress. Lawmakers in past years have typically tinkered with the Medicare physician fee schedule at the last minute, tucking in fixes to December legislative packages and spending bills. 

“I’m pretty optimistic that a good portion of the fee cuts will be mitigated and they won’t go through,” Bucshon told this news organization in an interview.

Bruce A. Scott, MD, president of the American Medical Association (AMA) said in a statement that CMS’ release of the final fee schedule on November 1 should trigger serious work on a change to the 2025 Medicare physician fee schedule.

“The fee schedule rule released [on November 1] starts the clock — with January 1 looming,” Scott said. “A legislative remedy will require hard work and compromise. The 66 million patients who rely on Medicare are counting on that.”

Both Bucshon and Scott also joined many lawmakers and medical associations in calling on Congress for a larger overhaul of the Medicare physician fee schedule, well beyond whatever temporary adjustment may be made in the months ahead to avoid or soften the 2025 cuts.

The physician fee schedule sets formulas and rules regarding how the largest US buyer of health services pays the almost 1.3 million clinicians who bill Medicare. Of these, 51% are physicians. The physician fee schedule also covers payments for nurse practitioners, physician assistants, physical therapists, and other health professionals.
 

Last Major Overhaul Unpopular

There’s broad dissatisfaction with Congress’ last major overhaul of the Medicare physician fee schedule. The 2015 Medicare Access and CHIP Reauthorization Act (MACRA) aimed to shift clinicians toward programs tying pay increases to quality measures. But the implementation of that aim through the Merit-based Incentive Payment System is widely considered a disappointment.

MACRA was intended to end the need for annual “doc fixes,” as Congress’ last-minute Medicare adjustments are known. Seventeen such tweaks passed before MACRA took effect. 

But MACRA did not include a broad-based inflation adjuster, and some clinicians’ incomes are lagging as inflation rates — and practice costs — have risen. Scott said the Medicare Economic Index, which is a measure used to gauge increases in practice costs for clinicians, is expected to rise by 3.5%.

“To put it bluntly, Medicare plans to pay us less while costs go up. You don’t have to be an economist to know that is an unsustainable trend, though one that has been going on for decades,” Scott said. “For physician practices operating on small margins already, this means it is harder to acquire new equipment, harder to retain staff, harder to take on new Medicare patients, and harder to keep the doors open, particularly in rural and underserved areas.”

In a statement, Jen Brull, MD, president of the American Academy of Family Physicians, noted that this likely will be the fifth year in a row that Congress will need to do a patch to prevent cuts in pay to clinicians. 

Bucshon, who will retire from the House in January, said he expects Congress to pass legislation tying Medicare payment rates to inflation — eventually.

“People want to find a way to fix this problem, but also do it in a way that does not cut benefits to anyone, and that’s the key,” Bucshon said. “We’re going to have to find a way to make sure that providers are properly reimbursed.”

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

TOPLINE:

Weekend exercise, involving one or two sessions per week, is associated with a similar reduction in risk for mild dementia as that reported with more frequent exercise, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.

METHODOLOGY:

• Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
• Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
• Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
• The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
• The mean follow-up duration was 16 years.

TAKEAWAY:

• When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
• When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
• Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
• The findings were consistent in men and women.

IN PRACTICE:

“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.

SOURCE:

The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.

LIMITATIONS:

The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.

DISCLOSURES:

The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Weekend exercise, involving one or two sessions per week, is associated with a similar reduction in risk for mild dementia as that reported with more frequent exercise, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.

METHODOLOGY:

• Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
• Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
• Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
• The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
• The mean follow-up duration was 16 years.

TAKEAWAY:

• When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
• When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
• Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
• The findings were consistent in men and women.

IN PRACTICE:

“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.

SOURCE:

The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.

LIMITATIONS:

The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.

DISCLOSURES:

The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Weekend exercise, involving one or two sessions per week, is associated with a similar reduction in risk for mild dementia as that reported with more frequent exercise, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.

METHODOLOGY:

• Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
• Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
• Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
• The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
• The mean follow-up duration was 16 years.

TAKEAWAY:

• When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
• When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
• Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
• The findings were consistent in men and women.

IN PRACTICE:

“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.

SOURCE:

The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.

LIMITATIONS:

The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.

DISCLOSURES:

The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.