People of color with epilepsy, including Black, Hispanic, and Native Hawaiian and other Pacific Islander patients, are significantly less likely to be prescribed the latest antiseizure medications (ASMs), compared with their White counterparts, new research shows.

Even after controlling for epilepsy severity, comorbid conditions, and other factors that might affect medication choice, researchers found that newer medication use was 29% less likely in Black patients, 23% less likely in Native Hawaiian and other Pacific Islander patients, and 7% less likely in Hispanic patients, compared with White individuals.

“I hope that clinicians will see from our findings that minoritized patients with epilepsy face a myriad of barriers in receiving the highest quality of care, including ASM use,” said lead investigator Wyatt P. Bensken, PhD, adjunct assistant professor of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland. “Considering your patients’ barriers, and how that influences their care – including ASM selection – will be critical to helping reduce these population-level inequities.”

A prompt for practice change

For the study, researchers used Medicaid claims for more than 78,000 people who had filled at least two prescriptions for an ASM between 2010 and 2014.

Most patients were White (53.4%); 22.6% were Black; 11.9% were Hispanic; 1.6% were Asian; 1.5% were Native Hawaiian or other Pacific Islander; 0.6% American Indian or Alaskan Native; and 8.3% were classified as “other.”

One-quarter of participants were taking an older ASM, such as carbamazepine, phenytoin, and valproate. About 65% were taking second-generation ASMs, including gabapentin, levetiracetam, and zonisamide. A little less than 10% were taking lacosamide, perampenel, or another third-generation ASM.

Compared with White patients, newer medication prescriptions were significantly less likely in Black individuals (adjusted odds ratio, 0.71; 95% confidence interval, 0.68-0.75), Native Hawaiian or other Pacific Islanders (aOR, 0.77; 95% CI, 0.67-0.88), and Hispanic patients (aOR, 0.93; 95% CI, 0.88-0.99).

Third-generation ASMs were used by 10.7% of White patients versus 6% of Black individuals and 5.1% of American Indian or Alaskan Native patients.

Researchers also found that taking a second-generation ASM was associated with better treatment adherence (aOR, 1.17; 95% CI, 1.11-1.23) and that patients on newer ASMs were more than three times as likely to be under the care of a neurologist (aOR, 3.26; 95% CI, 3.13-3.41).

The findings draw attention to racial inequities surrounding access to medication and specialists and subspecialists, Dr. Bensken said. Identifying specific barriers and developing solutions is the long-range goal, he added.

“In the interim, increasing the attention to these inequities will, we hope, prompt changes across practices,” Dr. Bensken said.
 

A ‘wake-up call’

Commenting on the findings, Joseph Sirven, MD, professor of neurology at the Mayo Clinic Florida, Jacksonville, said the results were “striking” because newer ASMs are generally the go-to for most physicians who treat epilepsy. 

“Use of first-generation ASMs is typically reserved [for] if one runs out of options,” Dr. Sirven said.

This study and others like it should serve as a “wake-up call” for clinicians, Dr. Sirven added.

“This study is important because it shows that whether we realize it or not, race and ethnicities are playing a role in ASM, and this is related to financial access to newer-generation drugs,” he said. “Similar findings are seen in impoverished countries where first-generation ASM drugs are routinely used because of drug pricing.”
 

More to explore

Also commenting on the study, Scott Mintzer, MD, a professor and director of the Epilepsy Monitoring Unit at Thomas Jefferson University, Philadelphia, said using first-generation ASMs as a proxy for quality of care is “a very innovative concept.”

“From that perspective, the finding that racial minority patients are more likely to be on a first-generation drug is not surprising. But after that it gets far more complicated to interpret,” he added.  

Neither adherence nor care by a neurologist was different in a consistent direction within the various minority populations, Dr. Mintzer noted. In addition, Black patients were as likely to see a neurologist as White patients but still more likely to be on a first-generation drug.

There are also a few caveats to the findings that should be considered, Dr. Mintzer added. First, the sample included only Medicaid recipients, nearly 35% of whom had a comorbid psychosis. Those and other characteristics of the study pool suggest participants aren’t representative of the United States population as a whole. Second, significant shifts in ASM use have occurred since the study data cutoff in 2014, none of which are reflected in these findings.

“So, I don’t think we can really say how to address this yet,” Dr. Mintzer said. “There’s a lot to explore about whether this is still occurring, how generalizable these findings are, and what they might be due to, as there are a host of potential explanations, which the authors themselves acknowledge.”

The study was funded by the U.S. Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities. Dr. Bensken has received support for this work from NIMHD and serves on the Editorial Board of the journal Neurology. Dr. Sirven and Mintzer report no relevant financial relationships.

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

People of color with epilepsy, including Black, Hispanic, and Native Hawaiian and other Pacific Islander patients, are significantly less likely to be prescribed the latest antiseizure medications (ASMs), compared with their White counterparts, new research shows.

Even after controlling for epilepsy severity, comorbid conditions, and other factors that might affect medication choice, researchers found that newer medication use was 29% less likely in Black patients, 23% less likely in Native Hawaiian and other Pacific Islander patients, and 7% less likely in Hispanic patients, compared with White individuals.

“I hope that clinicians will see from our findings that minoritized patients with epilepsy face a myriad of barriers in receiving the highest quality of care, including ASM use,” said lead investigator Wyatt P. Bensken, PhD, adjunct assistant professor of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland. “Considering your patients’ barriers, and how that influences their care – including ASM selection – will be critical to helping reduce these population-level inequities.”

A prompt for practice change

For the study, researchers used Medicaid claims for more than 78,000 people who had filled at least two prescriptions for an ASM between 2010 and 2014.

Most patients were White (53.4%); 22.6% were Black; 11.9% were Hispanic; 1.6% were Asian; 1.5% were Native Hawaiian or other Pacific Islander; 0.6% American Indian or Alaskan Native; and 8.3% were classified as “other.”

One-quarter of participants were taking an older ASM, such as carbamazepine, phenytoin, and valproate. About 65% were taking second-generation ASMs, including gabapentin, levetiracetam, and zonisamide. A little less than 10% were taking lacosamide, perampenel, or another third-generation ASM.

Compared with White patients, newer medication prescriptions were significantly less likely in Black individuals (adjusted odds ratio, 0.71; 95% confidence interval, 0.68-0.75), Native Hawaiian or other Pacific Islanders (aOR, 0.77; 95% CI, 0.67-0.88), and Hispanic patients (aOR, 0.93; 95% CI, 0.88-0.99).

Third-generation ASMs were used by 10.7% of White patients versus 6% of Black individuals and 5.1% of American Indian or Alaskan Native patients.

Researchers also found that taking a second-generation ASM was associated with better treatment adherence (aOR, 1.17; 95% CI, 1.11-1.23) and that patients on newer ASMs were more than three times as likely to be under the care of a neurologist (aOR, 3.26; 95% CI, 3.13-3.41).

The findings draw attention to racial inequities surrounding access to medication and specialists and subspecialists, Dr. Bensken said. Identifying specific barriers and developing solutions is the long-range goal, he added.

“In the interim, increasing the attention to these inequities will, we hope, prompt changes across practices,” Dr. Bensken said.
 

A ‘wake-up call’

Commenting on the findings, Joseph Sirven, MD, professor of neurology at the Mayo Clinic Florida, Jacksonville, said the results were “striking” because newer ASMs are generally the go-to for most physicians who treat epilepsy. 

“Use of first-generation ASMs is typically reserved [for] if one runs out of options,” Dr. Sirven said.

This study and others like it should serve as a “wake-up call” for clinicians, Dr. Sirven added.

“This study is important because it shows that whether we realize it or not, race and ethnicities are playing a role in ASM, and this is related to financial access to newer-generation drugs,” he said. “Similar findings are seen in impoverished countries where first-generation ASM drugs are routinely used because of drug pricing.”
 

More to explore

Also commenting on the study, Scott Mintzer, MD, a professor and director of the Epilepsy Monitoring Unit at Thomas Jefferson University, Philadelphia, said using first-generation ASMs as a proxy for quality of care is “a very innovative concept.”

“From that perspective, the finding that racial minority patients are more likely to be on a first-generation drug is not surprising. But after that it gets far more complicated to interpret,” he added.  

Neither adherence nor care by a neurologist was different in a consistent direction within the various minority populations, Dr. Mintzer noted. In addition, Black patients were as likely to see a neurologist as White patients but still more likely to be on a first-generation drug.

There are also a few caveats to the findings that should be considered, Dr. Mintzer added. First, the sample included only Medicaid recipients, nearly 35% of whom had a comorbid psychosis. Those and other characteristics of the study pool suggest participants aren’t representative of the United States population as a whole. Second, significant shifts in ASM use have occurred since the study data cutoff in 2014, none of which are reflected in these findings.

“So, I don’t think we can really say how to address this yet,” Dr. Mintzer said. “There’s a lot to explore about whether this is still occurring, how generalizable these findings are, and what they might be due to, as there are a host of potential explanations, which the authors themselves acknowledge.”

The study was funded by the U.S. Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities. Dr. Bensken has received support for this work from NIMHD and serves on the Editorial Board of the journal Neurology. Dr. Sirven and Mintzer report no relevant financial relationships.

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

People of color with epilepsy, including Black, Hispanic, and Native Hawaiian and other Pacific Islander patients, are significantly less likely to be prescribed the latest antiseizure medications (ASMs), compared with their White counterparts, new research shows.

Even after controlling for epilepsy severity, comorbid conditions, and other factors that might affect medication choice, researchers found that newer medication use was 29% less likely in Black patients, 23% less likely in Native Hawaiian and other Pacific Islander patients, and 7% less likely in Hispanic patients, compared with White individuals.

“I hope that clinicians will see from our findings that minoritized patients with epilepsy face a myriad of barriers in receiving the highest quality of care, including ASM use,” said lead investigator Wyatt P. Bensken, PhD, adjunct assistant professor of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland. “Considering your patients’ barriers, and how that influences their care – including ASM selection – will be critical to helping reduce these population-level inequities.”

A prompt for practice change

For the study, researchers used Medicaid claims for more than 78,000 people who had filled at least two prescriptions for an ASM between 2010 and 2014.

Most patients were White (53.4%); 22.6% were Black; 11.9% were Hispanic; 1.6% were Asian; 1.5% were Native Hawaiian or other Pacific Islander; 0.6% American Indian or Alaskan Native; and 8.3% were classified as “other.”

One-quarter of participants were taking an older ASM, such as carbamazepine, phenytoin, and valproate. About 65% were taking second-generation ASMs, including gabapentin, levetiracetam, and zonisamide. A little less than 10% were taking lacosamide, perampenel, or another third-generation ASM.

Compared with White patients, newer medication prescriptions were significantly less likely in Black individuals (adjusted odds ratio, 0.71; 95% confidence interval, 0.68-0.75), Native Hawaiian or other Pacific Islanders (aOR, 0.77; 95% CI, 0.67-0.88), and Hispanic patients (aOR, 0.93; 95% CI, 0.88-0.99).

Third-generation ASMs were used by 10.7% of White patients versus 6% of Black individuals and 5.1% of American Indian or Alaskan Native patients.

Researchers also found that taking a second-generation ASM was associated with better treatment adherence (aOR, 1.17; 95% CI, 1.11-1.23) and that patients on newer ASMs were more than three times as likely to be under the care of a neurologist (aOR, 3.26; 95% CI, 3.13-3.41).

The findings draw attention to racial inequities surrounding access to medication and specialists and subspecialists, Dr. Bensken said. Identifying specific barriers and developing solutions is the long-range goal, he added.

“In the interim, increasing the attention to these inequities will, we hope, prompt changes across practices,” Dr. Bensken said.
 

A ‘wake-up call’

Commenting on the findings, Joseph Sirven, MD, professor of neurology at the Mayo Clinic Florida, Jacksonville, said the results were “striking” because newer ASMs are generally the go-to for most physicians who treat epilepsy. 

“Use of first-generation ASMs is typically reserved [for] if one runs out of options,” Dr. Sirven said.

This study and others like it should serve as a “wake-up call” for clinicians, Dr. Sirven added.

“This study is important because it shows that whether we realize it or not, race and ethnicities are playing a role in ASM, and this is related to financial access to newer-generation drugs,” he said. “Similar findings are seen in impoverished countries where first-generation ASM drugs are routinely used because of drug pricing.”
 

More to explore

Also commenting on the study, Scott Mintzer, MD, a professor and director of the Epilepsy Monitoring Unit at Thomas Jefferson University, Philadelphia, said using first-generation ASMs as a proxy for quality of care is “a very innovative concept.”

“From that perspective, the finding that racial minority patients are more likely to be on a first-generation drug is not surprising. But after that it gets far more complicated to interpret,” he added.  

Neither adherence nor care by a neurologist was different in a consistent direction within the various minority populations, Dr. Mintzer noted. In addition, Black patients were as likely to see a neurologist as White patients but still more likely to be on a first-generation drug.

There are also a few caveats to the findings that should be considered, Dr. Mintzer added. First, the sample included only Medicaid recipients, nearly 35% of whom had a comorbid psychosis. Those and other characteristics of the study pool suggest participants aren’t representative of the United States population as a whole. Second, significant shifts in ASM use have occurred since the study data cutoff in 2014, none of which are reflected in these findings.

“So, I don’t think we can really say how to address this yet,” Dr. Mintzer said. “There’s a lot to explore about whether this is still occurring, how generalizable these findings are, and what they might be due to, as there are a host of potential explanations, which the authors themselves acknowledge.”

The study was funded by the U.S. Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities. Dr. Bensken has received support for this work from NIMHD and serves on the Editorial Board of the journal Neurology. Dr. Sirven and Mintzer report no relevant financial relationships.

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

Key clinical point: Ustekinumab and tumor necrosis factor inhibitors (TNFi) demonstrated similar efficacy and persistence and were well tolerated as first-line to third-line biologic treatment for psoriatic arthritis (PsA).

Major finding: Over 3 years, treatment with ustekinumab vs TNFi resulted in comparable odds of attaining clinical Disease Activity Index for PsA low disease activity (adjusted odds ratio [aOR] 0.89; 95% CI 0.63-1.26) and remission (aOR 0.72; 95% CI 0.50-1.05), similar risk for stopping/switching treatment (adjusted hazard ratio 0.87; 95% CI 0.68-1.11), and no clinically relevant difference in serious adverse event rates (6.3% vs 7.2%).

Study details: The data come from an analysis of 895 patients with PsA from PsABio, a prospective observational study, who were prescribed first-line to third-line ustekinumab or a TNFi.

Disclosures: This study was sponsored by Janssen. Two authors declared being current or former employees of or owning stocks in Johnson & Johnson or Janssen. Several authors reported receiving personal fees, consulting fees, grants, payments, or honoraria from Janssen and various other sources.

Source: Gossec L et al. Long-term effectiveness and persistence of ustekinumab and TNF inhibitors in patients with psoriatic arthritis: Final 3-year results from the PsABio real-world study. Ann Rheum Dis. 2022 (Dec 13). Doi: 10.1136/ard-2022-222879

Key clinical point: Ustekinumab and tumor necrosis factor inhibitors (TNFi) demonstrated similar efficacy and persistence and were well tolerated as first-line to third-line biologic treatment for psoriatic arthritis (PsA).

Major finding: Over 3 years, treatment with ustekinumab vs TNFi resulted in comparable odds of attaining clinical Disease Activity Index for PsA low disease activity (adjusted odds ratio [aOR] 0.89; 95% CI 0.63-1.26) and remission (aOR 0.72; 95% CI 0.50-1.05), similar risk for stopping/switching treatment (adjusted hazard ratio 0.87; 95% CI 0.68-1.11), and no clinically relevant difference in serious adverse event rates (6.3% vs 7.2%).

Study details: The data come from an analysis of 895 patients with PsA from PsABio, a prospective observational study, who were prescribed first-line to third-line ustekinumab or a TNFi.

Disclosures: This study was sponsored by Janssen. Two authors declared being current or former employees of or owning stocks in Johnson & Johnson or Janssen. Several authors reported receiving personal fees, consulting fees, grants, payments, or honoraria from Janssen and various other sources.

Source: Gossec L et al. Long-term effectiveness and persistence of ustekinumab and TNF inhibitors in patients with psoriatic arthritis: Final 3-year results from the PsABio real-world study. Ann Rheum Dis. 2022 (Dec 13). Doi: 10.1136/ard-2022-222879

Key clinical point: Ustekinumab and tumor necrosis factor inhibitors (TNFi) demonstrated similar efficacy and persistence and were well tolerated as first-line to third-line biologic treatment for psoriatic arthritis (PsA).

Major finding: Over 3 years, treatment with ustekinumab vs TNFi resulted in comparable odds of attaining clinical Disease Activity Index for PsA low disease activity (adjusted odds ratio [aOR] 0.89; 95% CI 0.63-1.26) and remission (aOR 0.72; 95% CI 0.50-1.05), similar risk for stopping/switching treatment (adjusted hazard ratio 0.87; 95% CI 0.68-1.11), and no clinically relevant difference in serious adverse event rates (6.3% vs 7.2%).

Study details: The data come from an analysis of 895 patients with PsA from PsABio, a prospective observational study, who were prescribed first-line to third-line ustekinumab or a TNFi.

Disclosures: This study was sponsored by Janssen. Two authors declared being current or former employees of or owning stocks in Johnson & Johnson or Janssen. Several authors reported receiving personal fees, consulting fees, grants, payments, or honoraria from Janssen and various other sources.

Source: Gossec L et al. Long-term effectiveness and persistence of ustekinumab and TNF inhibitors in patients with psoriatic arthritis: Final 3-year results from the PsABio real-world study. Ann Rheum Dis. 2022 (Dec 13). Doi: 10.1136/ard-2022-222879

Key clinical point: Fluorescence-optical imaging (FOI) successfully detected the early signs of musculoskeletal inflammation in hands and predicted transition from psoriasis to psoriatic arthritis (PsA) at initial stages in patients with psoriasis at risk for PsA.

Major finding: PsA diagnosis was confirmed by clinical evaluations (CE) in 50% of patients with psoriasis at risk for PsA and an additional 30% of patients who were positive on FOI. Compared with previously published annual incidence rates, the incidence rate of PsA was higher among patients positive on FOI but negative on CE (11.8%).

Study details: This was an investigator-initiated prospective two-part observational cohort study including 389 patients with plaque psoriasis who were at risk for PsA.

Disclosures: This study was sponsored by Fraunhofer ITMP and supported by a research grant from Pfizer Germany. Five authors declared being supported by Fraunhofer ITMP. Several authors reported ties with various sources, including Pfizer. GR Burmester reported being on the editorial board of RMD Open.

Source: Koehm M et al. Fluorescence-optical imaging as a promising easy-to-use imaging biomarker to increase early psoriatic arthritis detection in patients with psoriasis: A cross-sectional cohort study with follow-up. RMD Open. 2022;8(2):e002682 (Dec 6). Doi: 10.1136/rmdopen-2022-002682

Key clinical point: Fluorescence-optical imaging (FOI) successfully detected the early signs of musculoskeletal inflammation in hands and predicted transition from psoriasis to psoriatic arthritis (PsA) at initial stages in patients with psoriasis at risk for PsA.

Major finding: PsA diagnosis was confirmed by clinical evaluations (CE) in 50% of patients with psoriasis at risk for PsA and an additional 30% of patients who were positive on FOI. Compared with previously published annual incidence rates, the incidence rate of PsA was higher among patients positive on FOI but negative on CE (11.8%).

Study details: This was an investigator-initiated prospective two-part observational cohort study including 389 patients with plaque psoriasis who were at risk for PsA.

Disclosures: This study was sponsored by Fraunhofer ITMP and supported by a research grant from Pfizer Germany. Five authors declared being supported by Fraunhofer ITMP. Several authors reported ties with various sources, including Pfizer. GR Burmester reported being on the editorial board of RMD Open.

Source: Koehm M et al. Fluorescence-optical imaging as a promising easy-to-use imaging biomarker to increase early psoriatic arthritis detection in patients with psoriasis: A cross-sectional cohort study with follow-up. RMD Open. 2022;8(2):e002682 (Dec 6). Doi: 10.1136/rmdopen-2022-002682

Key clinical point: Fluorescence-optical imaging (FOI) successfully detected the early signs of musculoskeletal inflammation in hands and predicted transition from psoriasis to psoriatic arthritis (PsA) at initial stages in patients with psoriasis at risk for PsA.

Major finding: PsA diagnosis was confirmed by clinical evaluations (CE) in 50% of patients with psoriasis at risk for PsA and an additional 30% of patients who were positive on FOI. Compared with previously published annual incidence rates, the incidence rate of PsA was higher among patients positive on FOI but negative on CE (11.8%).

Study details: This was an investigator-initiated prospective two-part observational cohort study including 389 patients with plaque psoriasis who were at risk for PsA.

Disclosures: This study was sponsored by Fraunhofer ITMP and supported by a research grant from Pfizer Germany. Five authors declared being supported by Fraunhofer ITMP. Several authors reported ties with various sources, including Pfizer. GR Burmester reported being on the editorial board of RMD Open.

Source: Koehm M et al. Fluorescence-optical imaging as a promising easy-to-use imaging biomarker to increase early psoriatic arthritis detection in patients with psoriasis: A cross-sectional cohort study with follow-up. RMD Open. 2022;8(2):e002682 (Dec 6). Doi: 10.1136/rmdopen-2022-002682

Key clinical point: Patient-reported flares occurred more frequently than physician-reported flares and demonstrated moderate agreement with worsening of disease activity in psoriatic arthritis (DAPSA), with patients with psoriatic arthritis (PsA) who reported flares having a significantly more active disease.

Major finding: Overall, 27.0% and 17.6% of patients had patient-reported and physician-reported flares, respectively, with patient-reported flare demonstrating 69.8% crude agreement with DAPSA (prevalence adjusted bias adjusted kappa  =  0.40) and patients reporting vs not reporting disease flare indicating a significantly more active disease for all outcomes (P < .001) except skin lesions (P  =  .01).

Study details: This was a longitudinal observational study including 222 patients with PsA.

Disclosures: This study was supported by unrestricted investigator-initiated research grant from Pfizer. Three authors declared receiving funds, research grants, or support from the US National Institutes of Health and other sources.

Source: Sousa M et al. Patient-defined flares and disease activity worsening in 222 patients with psoriatic arthritis from 14 countries. Joint Bone Spine. 2022;90(3):105511 (Dec 15). Doi: 10.1016/j.jbspin.2022.105511

Key clinical point: Patient-reported flares occurred more frequently than physician-reported flares and demonstrated moderate agreement with worsening of disease activity in psoriatic arthritis (DAPSA), with patients with psoriatic arthritis (PsA) who reported flares having a significantly more active disease.

Major finding: Overall, 27.0% and 17.6% of patients had patient-reported and physician-reported flares, respectively, with patient-reported flare demonstrating 69.8% crude agreement with DAPSA (prevalence adjusted bias adjusted kappa  =  0.40) and patients reporting vs not reporting disease flare indicating a significantly more active disease for all outcomes (P < .001) except skin lesions (P  =  .01).

Study details: This was a longitudinal observational study including 222 patients with PsA.

Disclosures: This study was supported by unrestricted investigator-initiated research grant from Pfizer. Three authors declared receiving funds, research grants, or support from the US National Institutes of Health and other sources.

Source: Sousa M et al. Patient-defined flares and disease activity worsening in 222 patients with psoriatic arthritis from 14 countries. Joint Bone Spine. 2022;90(3):105511 (Dec 15). Doi: 10.1016/j.jbspin.2022.105511

Key clinical point: Patient-reported flares occurred more frequently than physician-reported flares and demonstrated moderate agreement with worsening of disease activity in psoriatic arthritis (DAPSA), with patients with psoriatic arthritis (PsA) who reported flares having a significantly more active disease.

Major finding: Overall, 27.0% and 17.6% of patients had patient-reported and physician-reported flares, respectively, with patient-reported flare demonstrating 69.8% crude agreement with DAPSA (prevalence adjusted bias adjusted kappa  =  0.40) and patients reporting vs not reporting disease flare indicating a significantly more active disease for all outcomes (P < .001) except skin lesions (P  =  .01).

Study details: This was a longitudinal observational study including 222 patients with PsA.

Disclosures: This study was supported by unrestricted investigator-initiated research grant from Pfizer. Three authors declared receiving funds, research grants, or support from the US National Institutes of Health and other sources.

Source: Sousa M et al. Patient-defined flares and disease activity worsening in 222 patients with psoriatic arthritis from 14 countries. Joint Bone Spine. 2022;90(3):105511 (Dec 15). Doi: 10.1016/j.jbspin.2022.105511

Key clinical point: Ultrasound-detected residual inflammation in peripheral articular structures may be present even in patients with psoriatic arthritis (PsA) who have achieved stable minimal disease activity (MDA), with residual inflammation being more prevalent in patients with shorter duration of MDA.

Major finding: Despite stable MDA, 54.2% of patients had ≥1 positive Power Doppler (PD) signal in examined tissues, with 19.4% and 23.6% of patients showing ≥1 joint and enthesis with a positive PD signal, respectively. A higher proportion of patients with ≤12 vs >12 months of sustained MDA had ≥1 ultrasound detected PD lesion (55% vs 41%; P  =  .024).

Study details: This cross-sectional study included 72 patients with PsA who were on biologic or conventional synthetic disease-modifying antirheumatic drugs for ≥12 months and in continuous MDA for ≥6 months.

Disclosures: This study did not declare the source of funding. The authors declared no conflicts of interest.

Source: Macchioni P et al. Residual inflammation in psoriatic arthritis patients in stable minimal disease activity. Front Med. 2022;9:1096547 (Dec 20). Doi: 10.3389/fmed.2022.1096547

Key clinical point: Ultrasound-detected residual inflammation in peripheral articular structures may be present even in patients with psoriatic arthritis (PsA) who have achieved stable minimal disease activity (MDA), with residual inflammation being more prevalent in patients with shorter duration of MDA.

Major finding: Despite stable MDA, 54.2% of patients had ≥1 positive Power Doppler (PD) signal in examined tissues, with 19.4% and 23.6% of patients showing ≥1 joint and enthesis with a positive PD signal, respectively. A higher proportion of patients with ≤12 vs >12 months of sustained MDA had ≥1 ultrasound detected PD lesion (55% vs 41%; P  =  .024).

Study details: This cross-sectional study included 72 patients with PsA who were on biologic or conventional synthetic disease-modifying antirheumatic drugs for ≥12 months and in continuous MDA for ≥6 months.

Disclosures: This study did not declare the source of funding. The authors declared no conflicts of interest.

Source: Macchioni P et al. Residual inflammation in psoriatic arthritis patients in stable minimal disease activity. Front Med. 2022;9:1096547 (Dec 20). Doi: 10.3389/fmed.2022.1096547

Key clinical point: Ultrasound-detected residual inflammation in peripheral articular structures may be present even in patients with psoriatic arthritis (PsA) who have achieved stable minimal disease activity (MDA), with residual inflammation being more prevalent in patients with shorter duration of MDA.

Major finding: Despite stable MDA, 54.2% of patients had ≥1 positive Power Doppler (PD) signal in examined tissues, with 19.4% and 23.6% of patients showing ≥1 joint and enthesis with a positive PD signal, respectively. A higher proportion of patients with ≤12 vs >12 months of sustained MDA had ≥1 ultrasound detected PD lesion (55% vs 41%; P  =  .024).

Study details: This cross-sectional study included 72 patients with PsA who were on biologic or conventional synthetic disease-modifying antirheumatic drugs for ≥12 months and in continuous MDA for ≥6 months.

Disclosures: This study did not declare the source of funding. The authors declared no conflicts of interest.

Source: Macchioni P et al. Residual inflammation in psoriatic arthritis patients in stable minimal disease activity. Front Med. 2022;9:1096547 (Dec 20). Doi: 10.3389/fmed.2022.1096547

Key clinical point: The overall incidence of hematologic malignancies was not higher among patients with psoriatic arthritis (PsA) receiving treatment with tumor necrosis factor inhibitors (TNFi) compared with those who were biological disease-modifying antirheumatic drug (bDMARD) naive or individuals from the general population.

Major finding: Overall, the incidence rate of hematologic malignancies was similar among patients treated with TNFi vs those who were bDMARD naive (incidence rate ratio [IRR] 0.96; 95% CI 0.68-1.35) or individuals in the general population (IRR 1.35; 95% CI 0.98-1.86).

Study details: Findings are from a cohort study including patients with PsA who either initiated first TNFi (n = 10,621) or were bDMARD-naive (n = 18,387) and matched comparators from the general population.

Disclosures: This study was supported by NordForsk and FOREUM. B Delcoigne declared being partly employed by ARTIS/Swedish Biologics Register. Several authors reported receiving grants or research support or serving as consultants for or on speaker’s bureaus of various sources.

Source: Cordtz RL et al. Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors: A Nordic cohort study. RMD Open. 2022;8(2):e002776 (Dec 23). Doi: 10.1136/rmdopen-2022-002776

Key clinical point: The overall incidence of hematologic malignancies was not higher among patients with psoriatic arthritis (PsA) receiving treatment with tumor necrosis factor inhibitors (TNFi) compared with those who were biological disease-modifying antirheumatic drug (bDMARD) naive or individuals from the general population.

Major finding: Overall, the incidence rate of hematologic malignancies was similar among patients treated with TNFi vs those who were bDMARD naive (incidence rate ratio [IRR] 0.96; 95% CI 0.68-1.35) or individuals in the general population (IRR 1.35; 95% CI 0.98-1.86).

Study details: Findings are from a cohort study including patients with PsA who either initiated first TNFi (n = 10,621) or were bDMARD-naive (n = 18,387) and matched comparators from the general population.

Disclosures: This study was supported by NordForsk and FOREUM. B Delcoigne declared being partly employed by ARTIS/Swedish Biologics Register. Several authors reported receiving grants or research support or serving as consultants for or on speaker’s bureaus of various sources.

Source: Cordtz RL et al. Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors: A Nordic cohort study. RMD Open. 2022;8(2):e002776 (Dec 23). Doi: 10.1136/rmdopen-2022-002776

Key clinical point: The overall incidence of hematologic malignancies was not higher among patients with psoriatic arthritis (PsA) receiving treatment with tumor necrosis factor inhibitors (TNFi) compared with those who were biological disease-modifying antirheumatic drug (bDMARD) naive or individuals from the general population.

Major finding: Overall, the incidence rate of hematologic malignancies was similar among patients treated with TNFi vs those who were bDMARD naive (incidence rate ratio [IRR] 0.96; 95% CI 0.68-1.35) or individuals in the general population (IRR 1.35; 95% CI 0.98-1.86).

Study details: Findings are from a cohort study including patients with PsA who either initiated first TNFi (n = 10,621) or were bDMARD-naive (n = 18,387) and matched comparators from the general population.

Disclosures: This study was supported by NordForsk and FOREUM. B Delcoigne declared being partly employed by ARTIS/Swedish Biologics Register. Several authors reported receiving grants or research support or serving as consultants for or on speaker’s bureaus of various sources.

Source: Cordtz RL et al. Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors: A Nordic cohort study. RMD Open. 2022;8(2):e002776 (Dec 23). Doi: 10.1136/rmdopen-2022-002776

Key clinical point: The failure to achieve minimal disease activity (MDA) in the first year after the diagnosis of psoriatic arthritis (PsA) was associated with worse health-related quality of life and health status, functional impairment, fatigue, pain, and higher anxiety and depression.

Major finding: Compared with patients who achieved sustained MDA in the first year after diagnosis, those who did not achieve MDA had higher scores for pain (estimated mean difference [β] 35.38), fatigue (β 17.88), and functional ability (β 0.81; all P < .001) and higher anxiety and depression (both P < .001) during follow-up, which persisted despite treatment intensification.

Study details: This prospective cohort study included 240 patients with newly diagnosed PsA with oligoarthritis or polyarthritis  who were disease-modifying antirheumatic drug naive.

Disclosures: This study was sponsored by UCB Pharma. S Welby and AR Prickett declared being stockholders of UCB.

Source: Snoeck Henkemans SVJ et al. Importance of quick attainment of minimal disease activity for a positive impact on lives of patients with psoriatic arthritis. RMD Open. 2022;8(2):e002706 (Dec 7). Doi: 10.1136/rmdopen-2022-002706

Key clinical point: The failure to achieve minimal disease activity (MDA) in the first year after the diagnosis of psoriatic arthritis (PsA) was associated with worse health-related quality of life and health status, functional impairment, fatigue, pain, and higher anxiety and depression.

Major finding: Compared with patients who achieved sustained MDA in the first year after diagnosis, those who did not achieve MDA had higher scores for pain (estimated mean difference [β] 35.38), fatigue (β 17.88), and functional ability (β 0.81; all P < .001) and higher anxiety and depression (both P < .001) during follow-up, which persisted despite treatment intensification.

Study details: This prospective cohort study included 240 patients with newly diagnosed PsA with oligoarthritis or polyarthritis  who were disease-modifying antirheumatic drug naive.

Disclosures: This study was sponsored by UCB Pharma. S Welby and AR Prickett declared being stockholders of UCB.

Source: Snoeck Henkemans SVJ et al. Importance of quick attainment of minimal disease activity for a positive impact on lives of patients with psoriatic arthritis. RMD Open. 2022;8(2):e002706 (Dec 7). Doi: 10.1136/rmdopen-2022-002706

Key clinical point: The failure to achieve minimal disease activity (MDA) in the first year after the diagnosis of psoriatic arthritis (PsA) was associated with worse health-related quality of life and health status, functional impairment, fatigue, pain, and higher anxiety and depression.

Major finding: Compared with patients who achieved sustained MDA in the first year after diagnosis, those who did not achieve MDA had higher scores for pain (estimated mean difference [β] 35.38), fatigue (β 17.88), and functional ability (β 0.81; all P < .001) and higher anxiety and depression (both P < .001) during follow-up, which persisted despite treatment intensification.

Study details: This prospective cohort study included 240 patients with newly diagnosed PsA with oligoarthritis or polyarthritis  who were disease-modifying antirheumatic drug naive.

Disclosures: This study was sponsored by UCB Pharma. S Welby and AR Prickett declared being stockholders of UCB.

Source: Snoeck Henkemans SVJ et al. Importance of quick attainment of minimal disease activity for a positive impact on lives of patients with psoriatic arthritis. RMD Open. 2022;8(2):e002706 (Dec 7). Doi: 10.1136/rmdopen-2022-002706

Key clinical point: The addition of methotrexate or maintenance of ongoing methotrexate did not significantly enhance the efficacy of ustekinumab in patients with active psoriatic arthritis (PsA), suggesting ustekinumab as an effective therapy for PsA independent of methotrexate.

Major finding: Ustekinumab monotherapy demonstrated non-inferiority over ustekinumab+methotrexate with a comparable Disease Activity Score in 28 joints (DAS28) at week 24 (mean 2.9 vs 3.1; Mann-Whitney estimator 0.5426) and at week 52 (mean 2.8 vs 3.1; Mann-Whitney estimator 0.5461). Overall, serious adverse events occurred in 9% of patients in both treatment groups, but no deaths were reported.

Study details: Findings are from MUST, a phase 3b trial including 173 ustekinumab-naive patients with active PsA who were randomly assigned to receive ustekinumab+methotrexate or ustekinumab+placebo.

Disclosures: This study was supported by Janssen Cilag. Several authors reported receiving grants, contracts, travel support, or honoraria or fees for serving as speakers, consultants, or advisory board members for various sources.

Source: Koehm M et al. Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): A randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial. Lancet Rheumatol. 2023;5(1):E14-E23 (Jan 1). Doi: 10.1016/S2665-9913(22)00329-0

Key clinical point: The addition of methotrexate or maintenance of ongoing methotrexate did not significantly enhance the efficacy of ustekinumab in patients with active psoriatic arthritis (PsA), suggesting ustekinumab as an effective therapy for PsA independent of methotrexate.

Major finding: Ustekinumab monotherapy demonstrated non-inferiority over ustekinumab+methotrexate with a comparable Disease Activity Score in 28 joints (DAS28) at week 24 (mean 2.9 vs 3.1; Mann-Whitney estimator 0.5426) and at week 52 (mean 2.8 vs 3.1; Mann-Whitney estimator 0.5461). Overall, serious adverse events occurred in 9% of patients in both treatment groups, but no deaths were reported.

Study details: Findings are from MUST, a phase 3b trial including 173 ustekinumab-naive patients with active PsA who were randomly assigned to receive ustekinumab+methotrexate or ustekinumab+placebo.

Disclosures: This study was supported by Janssen Cilag. Several authors reported receiving grants, contracts, travel support, or honoraria or fees for serving as speakers, consultants, or advisory board members for various sources.

Source: Koehm M et al. Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): A randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial. Lancet Rheumatol. 2023;5(1):E14-E23 (Jan 1). Doi: 10.1016/S2665-9913(22)00329-0

Key clinical point: The addition of methotrexate or maintenance of ongoing methotrexate did not significantly enhance the efficacy of ustekinumab in patients with active psoriatic arthritis (PsA), suggesting ustekinumab as an effective therapy for PsA independent of methotrexate.

Major finding: Ustekinumab monotherapy demonstrated non-inferiority over ustekinumab+methotrexate with a comparable Disease Activity Score in 28 joints (DAS28) at week 24 (mean 2.9 vs 3.1; Mann-Whitney estimator 0.5426) and at week 52 (mean 2.8 vs 3.1; Mann-Whitney estimator 0.5461). Overall, serious adverse events occurred in 9% of patients in both treatment groups, but no deaths were reported.

Study details: Findings are from MUST, a phase 3b trial including 173 ustekinumab-naive patients with active PsA who were randomly assigned to receive ustekinumab+methotrexate or ustekinumab+placebo.

Disclosures: This study was supported by Janssen Cilag. Several authors reported receiving grants, contracts, travel support, or honoraria or fees for serving as speakers, consultants, or advisory board members for various sources.

Source: Koehm M et al. Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): A randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial. Lancet Rheumatol. 2023;5(1):E14-E23 (Jan 1). Doi: 10.1016/S2665-9913(22)00329-0

AURORA, COLO. – Dietary additives lurking in processed foods may contribute to the development or exacerbation of inflammatory bowel disease (IBD), a leading gastroenterologist contends.

At the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association, James D. Lewis, MD, MSCE, AGAF, of the University of Pennsylvania in Philadelphia, highlighted research from both animal and human studies pointing to certain widely used food additives such as carboxymethycellulose (CMC), polysorbate 80, and carrageenan as potential instigators in gastrointestinal inflammation.

“Extrapolating from mice to men, I think we can say that dietary additives may contribute to the etiology or perpetuation of IBD, but not all additives are the same,” he said.

Neil Osterweil/MDedge News

Some additives appear to have deleterious effects on intestinal microbiota, while others may exert their baleful influence through mechanisms such as endoplasmic stress.

“It looks like some people might be a little more sensitive to additives than others, and if you were going to use any of this [research] to try and give some advice, maybe we would say that patients or first-degree relatives of people with IBD may want to avoid foods that contain high levels of additives, and if for no other reason, mothers or people with a family history of IBD might be encouraged to breastfeed to avoid early exposure to additives that are in infant formulas,” he advised.
 

Processed foods defined

The typical American diet may include a large proportion of processed foods, defined as “foods that have undergone biological, chemical, or physical process to improve texture, taste, or shelf life.”

Processed foods tend to be higher in fats, added sugars, and salts, and lower in fiber and intrinsic vitamins than minimally processed foods.

There is also a category of “ultraprocessed” foods, which contain little or no whole foods but are high in energy density. Many of these super(bad) foods are staples of the American diet, such as chips, hot dogs, chicken nuggets, breakfast cereal, soda, candy, and margarine. These and similar foods contribute from 25% to 50% of daily energy intake in the United States and Canada, Dr. Lewis said.

And North America is not alone, he added, pointing to a 2015 study showing that the consumption of ultraprocessed foods in Sweden increased “dramatically” from 1960 through 2010, and that this increase mirrored an increase in obesity prevalence in that nation.
 

Emulsifiers and thickeners

Dr. Lewis focused on emulsifiers and thickeners that are commonly added to processed foods and are, according to the Food and Drug Administration, “generally recognized as safe.”

Emulsifiers are “detergent-like molecules that stabilize mixtures of immiscible [nonhomegenous] liquids.”

Thickeners are additives that increase the viscosity of liquids without otherwise substantially changing their other properties.

In addition to the aforementioned products, other common additives include xanthan gum (a polysaccharide used as an emulsifier in salad dressings, baked goods, ice cream, and gluten-free products), maltodextrin (a sugar substitute marketed as “Splenda”), and soy lecithin (a soy derivative used as an emulsifier, stabilizer, and wetting agent).
 

Evidence of harm

Dr. Lewis noted that in 2013, investigators at the University of Liverpool, England, published a hypothesis suggesting that consumption of emulsifiers in processed foods may promote Crohn’s disease by increasing bacterial translocation. Their hypothesis was based in part on evidence that “very small concentrations of the emulsifier polysorbate 80 enhance bacterial translocation across intestinal epithelia. Undigested emulsifiers may increase bacterial translocation, particularly in the small intestine where the mucus layer is discontinuous. “

The authors also suggested that their hypothesis could be tested in clinical trials comparing enteral feeding with and without emulsifiers.

Other suggestive if not definitive evidence of a potential link between additives and IBD are data showing that IBD is very rare in young children.

“In your early stages of your life, you’re not consuming a lot of ultraprocessed foods. Indeed, the rate of intake of at least fast foods, which you can think of almost as a surrogate for ultraprocessed foods, goes up dramatically when people get to their teens, and this is the same time as we see, really, the big uptick in the incidence of IBD,” Dr. Lewis said.

A link between ultraprocessed food consumption and later development of IBD, primarily Crohn’s disease, is also suggested by data from the Nurses Health Study I and II and Health Professionals Follow-Up study. Among 245,112 participants with about 5.5 million person-years of follow-up, the highest vs. lowest quartile of consumption of ultraprocessed foods was associated with a 70% increase in risk for developing Crohn’s (hazard ratio 1.70, P = .0008).
 

Animal studies

Evidence for a possible mechanism whereby emulsifiers and thickeners cause intestinal changes comes from a study published in Nature in 2015 showing that adding CMC and PS80 to the drinking water of mice resulted in major shifts in the gut microbiota in both wild-type and interleukin 10 knockout mice, a model for IBD.

When the additives were put into the water the mice had a thinning of the mucus layer, allowing bacteria in closer proximity to the epithelium.

“When you put these into the drinking water of IL-10 knockout mice that are already predisposed to developing colitis, they were far more likely to go on to develop colitis over the course of 3 months,” Dr. Lewis said.
 

From mouse to man

Dr. Lewis briefly summarized results of the FRESH study that he and colleagues recently published in Gastronterology. In this trial, 16 healthy adult volunteers who agreed to stay and eat all meals at the research center were randomized to receive either an emulsifier-free diet or the identical diet enriched with 15 g of CMC daily for 11 days.

“I will comment that that’s a lot of carboxymethycellulose,” Dr. Lewis said.

The volunteers fed the CMC-enriched diet had a slight increase in abdominal discomfort after eating and a reduction in species diversity in the gut microbiota. In addition, these participants had reductions in levels of short-chain fatty acids and free amino acids, both of which are signs of a health gut environment.

“Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition,” the investigators wrote.

Dr. Lewis cited a separate small study by investigators at the University of Illinois at Chicago and the University of Chicago. These investigators randomized patients with UC in remission to take supplements containing carrageenan – a seaweed-derived food additive that has been shown to cause inflammation in both in vitro and animal models – or placebo . The amount of carrageenan in the capsules was less than that found in an average daily Western diet, the authors noted.

The participants were followed with telephone calls every 2 weeks or until relapse, which was defined as an increase of 2 or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for UC.

Of the 12 patients who completed the study, 3 in the carrageenan group experienced relapses, compared with none of the patients in the placebo group (P = .046). The relapse occurred at 5, 32, and 42 weeks of follow-up.
 

Exceptions to the rule

“It’s not clear that all additives are harmful,” Dr. Lewis said, pointing to a placebo-controlled study suggesting a beneficial effect of soy lecithin in patients with UC. The additive is composed of at least 30% of phosphatidycholine, a component of intestinal mucus.

He also noted that there is an ongoing randomized, placebo-controlled trial comparing a low-additive diet to a habitual diet in 154 patients with mildly active, stable Crohn’s disease.

Session moderator Michael J. Rosen, MD, MSCI, a pediatric gastroenterologist at Stanford University Medical Center in Palo Alto, Calif., told this news organization that dietary components do appear to have an influence on the disease course in patients with IBD.

“I do think there are patients with IBD who are maybe genetically predisposed to being sensitive to certain components of diet,” he said in an interview seeking objective commentary.

“Particularly in pediatrics there are lines of evidence of diets maybe having some efficacy in treatment. It needs further study, but one commonality about those diets is that they tend to eliminate processed foods and focus on whole foods,” he said.

Dr. Lewis’ work is supported by grants from the National Institutes of Health, and from AbbVie, Takeda, Janssen, and Nestlé Health Science. He has served as a consultant to and data safety monitoring board member for several entitities. Dr. Rosen reported no conflicts of interest to disclose.

AURORA, COLO. – Dietary additives lurking in processed foods may contribute to the development or exacerbation of inflammatory bowel disease (IBD), a leading gastroenterologist contends.

At the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association, James D. Lewis, MD, MSCE, AGAF, of the University of Pennsylvania in Philadelphia, highlighted research from both animal and human studies pointing to certain widely used food additives such as carboxymethycellulose (CMC), polysorbate 80, and carrageenan as potential instigators in gastrointestinal inflammation.

“Extrapolating from mice to men, I think we can say that dietary additives may contribute to the etiology or perpetuation of IBD, but not all additives are the same,” he said.

Neil Osterweil/MDedge News

Some additives appear to have deleterious effects on intestinal microbiota, while others may exert their baleful influence through mechanisms such as endoplasmic stress.

“It looks like some people might be a little more sensitive to additives than others, and if you were going to use any of this [research] to try and give some advice, maybe we would say that patients or first-degree relatives of people with IBD may want to avoid foods that contain high levels of additives, and if for no other reason, mothers or people with a family history of IBD might be encouraged to breastfeed to avoid early exposure to additives that are in infant formulas,” he advised.
 

Processed foods defined

The typical American diet may include a large proportion of processed foods, defined as “foods that have undergone biological, chemical, or physical process to improve texture, taste, or shelf life.”

Processed foods tend to be higher in fats, added sugars, and salts, and lower in fiber and intrinsic vitamins than minimally processed foods.

There is also a category of “ultraprocessed” foods, which contain little or no whole foods but are high in energy density. Many of these super(bad) foods are staples of the American diet, such as chips, hot dogs, chicken nuggets, breakfast cereal, soda, candy, and margarine. These and similar foods contribute from 25% to 50% of daily energy intake in the United States and Canada, Dr. Lewis said.

And North America is not alone, he added, pointing to a 2015 study showing that the consumption of ultraprocessed foods in Sweden increased “dramatically” from 1960 through 2010, and that this increase mirrored an increase in obesity prevalence in that nation.
 

Emulsifiers and thickeners

Dr. Lewis focused on emulsifiers and thickeners that are commonly added to processed foods and are, according to the Food and Drug Administration, “generally recognized as safe.”

Emulsifiers are “detergent-like molecules that stabilize mixtures of immiscible [nonhomegenous] liquids.”

Thickeners are additives that increase the viscosity of liquids without otherwise substantially changing their other properties.

In addition to the aforementioned products, other common additives include xanthan gum (a polysaccharide used as an emulsifier in salad dressings, baked goods, ice cream, and gluten-free products), maltodextrin (a sugar substitute marketed as “Splenda”), and soy lecithin (a soy derivative used as an emulsifier, stabilizer, and wetting agent).
 

Evidence of harm

Dr. Lewis noted that in 2013, investigators at the University of Liverpool, England, published a hypothesis suggesting that consumption of emulsifiers in processed foods may promote Crohn’s disease by increasing bacterial translocation. Their hypothesis was based in part on evidence that “very small concentrations of the emulsifier polysorbate 80 enhance bacterial translocation across intestinal epithelia. Undigested emulsifiers may increase bacterial translocation, particularly in the small intestine where the mucus layer is discontinuous. “

The authors also suggested that their hypothesis could be tested in clinical trials comparing enteral feeding with and without emulsifiers.

Other suggestive if not definitive evidence of a potential link between additives and IBD are data showing that IBD is very rare in young children.

“In your early stages of your life, you’re not consuming a lot of ultraprocessed foods. Indeed, the rate of intake of at least fast foods, which you can think of almost as a surrogate for ultraprocessed foods, goes up dramatically when people get to their teens, and this is the same time as we see, really, the big uptick in the incidence of IBD,” Dr. Lewis said.

A link between ultraprocessed food consumption and later development of IBD, primarily Crohn’s disease, is also suggested by data from the Nurses Health Study I and II and Health Professionals Follow-Up study. Among 245,112 participants with about 5.5 million person-years of follow-up, the highest vs. lowest quartile of consumption of ultraprocessed foods was associated with a 70% increase in risk for developing Crohn’s (hazard ratio 1.70, P = .0008).
 

Animal studies

Evidence for a possible mechanism whereby emulsifiers and thickeners cause intestinal changes comes from a study published in Nature in 2015 showing that adding CMC and PS80 to the drinking water of mice resulted in major shifts in the gut microbiota in both wild-type and interleukin 10 knockout mice, a model for IBD.

When the additives were put into the water the mice had a thinning of the mucus layer, allowing bacteria in closer proximity to the epithelium.

“When you put these into the drinking water of IL-10 knockout mice that are already predisposed to developing colitis, they were far more likely to go on to develop colitis over the course of 3 months,” Dr. Lewis said.
 

From mouse to man

Dr. Lewis briefly summarized results of the FRESH study that he and colleagues recently published in Gastronterology. In this trial, 16 healthy adult volunteers who agreed to stay and eat all meals at the research center were randomized to receive either an emulsifier-free diet or the identical diet enriched with 15 g of CMC daily for 11 days.

“I will comment that that’s a lot of carboxymethycellulose,” Dr. Lewis said.

The volunteers fed the CMC-enriched diet had a slight increase in abdominal discomfort after eating and a reduction in species diversity in the gut microbiota. In addition, these participants had reductions in levels of short-chain fatty acids and free amino acids, both of which are signs of a health gut environment.

“Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition,” the investigators wrote.

Dr. Lewis cited a separate small study by investigators at the University of Illinois at Chicago and the University of Chicago. These investigators randomized patients with UC in remission to take supplements containing carrageenan – a seaweed-derived food additive that has been shown to cause inflammation in both in vitro and animal models – or placebo . The amount of carrageenan in the capsules was less than that found in an average daily Western diet, the authors noted.

The participants were followed with telephone calls every 2 weeks or until relapse, which was defined as an increase of 2 or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for UC.

Of the 12 patients who completed the study, 3 in the carrageenan group experienced relapses, compared with none of the patients in the placebo group (P = .046). The relapse occurred at 5, 32, and 42 weeks of follow-up.
 

Exceptions to the rule

“It’s not clear that all additives are harmful,” Dr. Lewis said, pointing to a placebo-controlled study suggesting a beneficial effect of soy lecithin in patients with UC. The additive is composed of at least 30% of phosphatidycholine, a component of intestinal mucus.

He also noted that there is an ongoing randomized, placebo-controlled trial comparing a low-additive diet to a habitual diet in 154 patients with mildly active, stable Crohn’s disease.

Session moderator Michael J. Rosen, MD, MSCI, a pediatric gastroenterologist at Stanford University Medical Center in Palo Alto, Calif., told this news organization that dietary components do appear to have an influence on the disease course in patients with IBD.

“I do think there are patients with IBD who are maybe genetically predisposed to being sensitive to certain components of diet,” he said in an interview seeking objective commentary.

“Particularly in pediatrics there are lines of evidence of diets maybe having some efficacy in treatment. It needs further study, but one commonality about those diets is that they tend to eliminate processed foods and focus on whole foods,” he said.

Dr. Lewis’ work is supported by grants from the National Institutes of Health, and from AbbVie, Takeda, Janssen, and Nestlé Health Science. He has served as a consultant to and data safety monitoring board member for several entitities. Dr. Rosen reported no conflicts of interest to disclose.

AURORA, COLO. – Dietary additives lurking in processed foods may contribute to the development or exacerbation of inflammatory bowel disease (IBD), a leading gastroenterologist contends.

At the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association, James D. Lewis, MD, MSCE, AGAF, of the University of Pennsylvania in Philadelphia, highlighted research from both animal and human studies pointing to certain widely used food additives such as carboxymethycellulose (CMC), polysorbate 80, and carrageenan as potential instigators in gastrointestinal inflammation.

“Extrapolating from mice to men, I think we can say that dietary additives may contribute to the etiology or perpetuation of IBD, but not all additives are the same,” he said.

Neil Osterweil/MDedge News

Some additives appear to have deleterious effects on intestinal microbiota, while others may exert their baleful influence through mechanisms such as endoplasmic stress.

“It looks like some people might be a little more sensitive to additives than others, and if you were going to use any of this [research] to try and give some advice, maybe we would say that patients or first-degree relatives of people with IBD may want to avoid foods that contain high levels of additives, and if for no other reason, mothers or people with a family history of IBD might be encouraged to breastfeed to avoid early exposure to additives that are in infant formulas,” he advised.
 

Processed foods defined

The typical American diet may include a large proportion of processed foods, defined as “foods that have undergone biological, chemical, or physical process to improve texture, taste, or shelf life.”

Processed foods tend to be higher in fats, added sugars, and salts, and lower in fiber and intrinsic vitamins than minimally processed foods.

There is also a category of “ultraprocessed” foods, which contain little or no whole foods but are high in energy density. Many of these super(bad) foods are staples of the American diet, such as chips, hot dogs, chicken nuggets, breakfast cereal, soda, candy, and margarine. These and similar foods contribute from 25% to 50% of daily energy intake in the United States and Canada, Dr. Lewis said.

And North America is not alone, he added, pointing to a 2015 study showing that the consumption of ultraprocessed foods in Sweden increased “dramatically” from 1960 through 2010, and that this increase mirrored an increase in obesity prevalence in that nation.
 

Emulsifiers and thickeners

Dr. Lewis focused on emulsifiers and thickeners that are commonly added to processed foods and are, according to the Food and Drug Administration, “generally recognized as safe.”

Emulsifiers are “detergent-like molecules that stabilize mixtures of immiscible [nonhomegenous] liquids.”

Thickeners are additives that increase the viscosity of liquids without otherwise substantially changing their other properties.

In addition to the aforementioned products, other common additives include xanthan gum (a polysaccharide used as an emulsifier in salad dressings, baked goods, ice cream, and gluten-free products), maltodextrin (a sugar substitute marketed as “Splenda”), and soy lecithin (a soy derivative used as an emulsifier, stabilizer, and wetting agent).
 

Evidence of harm

Dr. Lewis noted that in 2013, investigators at the University of Liverpool, England, published a hypothesis suggesting that consumption of emulsifiers in processed foods may promote Crohn’s disease by increasing bacterial translocation. Their hypothesis was based in part on evidence that “very small concentrations of the emulsifier polysorbate 80 enhance bacterial translocation across intestinal epithelia. Undigested emulsifiers may increase bacterial translocation, particularly in the small intestine where the mucus layer is discontinuous. “

The authors also suggested that their hypothesis could be tested in clinical trials comparing enteral feeding with and without emulsifiers.

Other suggestive if not definitive evidence of a potential link between additives and IBD are data showing that IBD is very rare in young children.

“In your early stages of your life, you’re not consuming a lot of ultraprocessed foods. Indeed, the rate of intake of at least fast foods, which you can think of almost as a surrogate for ultraprocessed foods, goes up dramatically when people get to their teens, and this is the same time as we see, really, the big uptick in the incidence of IBD,” Dr. Lewis said.

A link between ultraprocessed food consumption and later development of IBD, primarily Crohn’s disease, is also suggested by data from the Nurses Health Study I and II and Health Professionals Follow-Up study. Among 245,112 participants with about 5.5 million person-years of follow-up, the highest vs. lowest quartile of consumption of ultraprocessed foods was associated with a 70% increase in risk for developing Crohn’s (hazard ratio 1.70, P = .0008).
 

Animal studies

Evidence for a possible mechanism whereby emulsifiers and thickeners cause intestinal changes comes from a study published in Nature in 2015 showing that adding CMC and PS80 to the drinking water of mice resulted in major shifts in the gut microbiota in both wild-type and interleukin 10 knockout mice, a model for IBD.

When the additives were put into the water the mice had a thinning of the mucus layer, allowing bacteria in closer proximity to the epithelium.

“When you put these into the drinking water of IL-10 knockout mice that are already predisposed to developing colitis, they were far more likely to go on to develop colitis over the course of 3 months,” Dr. Lewis said.
 

From mouse to man

Dr. Lewis briefly summarized results of the FRESH study that he and colleagues recently published in Gastronterology. In this trial, 16 healthy adult volunteers who agreed to stay and eat all meals at the research center were randomized to receive either an emulsifier-free diet or the identical diet enriched with 15 g of CMC daily for 11 days.

“I will comment that that’s a lot of carboxymethycellulose,” Dr. Lewis said.

The volunteers fed the CMC-enriched diet had a slight increase in abdominal discomfort after eating and a reduction in species diversity in the gut microbiota. In addition, these participants had reductions in levels of short-chain fatty acids and free amino acids, both of which are signs of a health gut environment.

“Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition,” the investigators wrote.

Dr. Lewis cited a separate small study by investigators at the University of Illinois at Chicago and the University of Chicago. These investigators randomized patients with UC in remission to take supplements containing carrageenan – a seaweed-derived food additive that has been shown to cause inflammation in both in vitro and animal models – or placebo . The amount of carrageenan in the capsules was less than that found in an average daily Western diet, the authors noted.

The participants were followed with telephone calls every 2 weeks or until relapse, which was defined as an increase of 2 or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for UC.

Of the 12 patients who completed the study, 3 in the carrageenan group experienced relapses, compared with none of the patients in the placebo group (P = .046). The relapse occurred at 5, 32, and 42 weeks of follow-up.
 

Exceptions to the rule

“It’s not clear that all additives are harmful,” Dr. Lewis said, pointing to a placebo-controlled study suggesting a beneficial effect of soy lecithin in patients with UC. The additive is composed of at least 30% of phosphatidycholine, a component of intestinal mucus.

He also noted that there is an ongoing randomized, placebo-controlled trial comparing a low-additive diet to a habitual diet in 154 patients with mildly active, stable Crohn’s disease.

Session moderator Michael J. Rosen, MD, MSCI, a pediatric gastroenterologist at Stanford University Medical Center in Palo Alto, Calif., told this news organization that dietary components do appear to have an influence on the disease course in patients with IBD.

“I do think there are patients with IBD who are maybe genetically predisposed to being sensitive to certain components of diet,” he said in an interview seeking objective commentary.

“Particularly in pediatrics there are lines of evidence of diets maybe having some efficacy in treatment. It needs further study, but one commonality about those diets is that they tend to eliminate processed foods and focus on whole foods,” he said.

Dr. Lewis’ work is supported by grants from the National Institutes of Health, and from AbbVie, Takeda, Janssen, and Nestlé Health Science. He has served as a consultant to and data safety monitoring board member for several entitities. Dr. Rosen reported no conflicts of interest to disclose.

Key clinical point: Addition of metformin to the neoadjuvant docetaxel, epirubicin, and cyclophosphamide (TEC) regimen did not improve disease outcomes in patients with breast cancer (BC) and metabolic abnormalities.

Major finding: The total pathological complete response was achieved by a similar proportion of patients receiving TEC vs TEC+metformin (12.5% vs 14.6%; P  =  .777). Neutropenia and leucopenia, the most common grade ≥3 adverse events, were reported by 42.5% and 55.0% of patients in the TEC arm and 22.9% and 45.8% of patients in the TEC+metformin arm, respectively.

Study details: Findings are from the phase 2 NeoMET study including 92 patients with stage IIB/III BC and ≥1 metabolic syndrome component who were randomly assigned to receive six cycles of TEC or TEC+metformin.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Huang J, Tong Y et al. Neoadjuvant docetaxel, epirubicin, and cyclophosphamide with or without metformin in breast cancer patients with metabolic abnormality: Results from the randomized phase II NeoMET trial. Breast Cancer Res Treat. 2022 (Dec 16). Doi: 10.1007/s10549-022-06821-y

Key clinical point: Addition of metformin to the neoadjuvant docetaxel, epirubicin, and cyclophosphamide (TEC) regimen did not improve disease outcomes in patients with breast cancer (BC) and metabolic abnormalities.

Major finding: The total pathological complete response was achieved by a similar proportion of patients receiving TEC vs TEC+metformin (12.5% vs 14.6%; P  =  .777). Neutropenia and leucopenia, the most common grade ≥3 adverse events, were reported by 42.5% and 55.0% of patients in the TEC arm and 22.9% and 45.8% of patients in the TEC+metformin arm, respectively.

Study details: Findings are from the phase 2 NeoMET study including 92 patients with stage IIB/III BC and ≥1 metabolic syndrome component who were randomly assigned to receive six cycles of TEC or TEC+metformin.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Huang J, Tong Y et al. Neoadjuvant docetaxel, epirubicin, and cyclophosphamide with or without metformin in breast cancer patients with metabolic abnormality: Results from the randomized phase II NeoMET trial. Breast Cancer Res Treat. 2022 (Dec 16). Doi: 10.1007/s10549-022-06821-y

Key clinical point: Addition of metformin to the neoadjuvant docetaxel, epirubicin, and cyclophosphamide (TEC) regimen did not improve disease outcomes in patients with breast cancer (BC) and metabolic abnormalities.

Major finding: The total pathological complete response was achieved by a similar proportion of patients receiving TEC vs TEC+metformin (12.5% vs 14.6%; P  =  .777). Neutropenia and leucopenia, the most common grade ≥3 adverse events, were reported by 42.5% and 55.0% of patients in the TEC arm and 22.9% and 45.8% of patients in the TEC+metformin arm, respectively.

Study details: Findings are from the phase 2 NeoMET study including 92 patients with stage IIB/III BC and ≥1 metabolic syndrome component who were randomly assigned to receive six cycles of TEC or TEC+metformin.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Huang J, Tong Y et al. Neoadjuvant docetaxel, epirubicin, and cyclophosphamide with or without metformin in breast cancer patients with metabolic abnormality: Results from the randomized phase II NeoMET trial. Breast Cancer Res Treat. 2022 (Dec 16). Doi: 10.1007/s10549-022-06821-y