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FDA OKs subcutaneous vedolizumab for UC maintenance therapy
The Food and Drug Administration has approved the subcutaneous administration of vedolizumab (Entyvio SC, Takeda) for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) following induction therapy with intravenous administration of vedolizumab.
The FDA approved the intravenous formulation of the biologic in 2014 for patients with moderate to severe UC and Crohn’s disease who failed or cannot tolerate other therapies.
The approval of subcutaneous (SC) vedolizumab was based on results from the phase 3, randomized, double-blind, placebo-controlled VISIBLE 1 trial.
The trial assessed the safety and efficacy of maintenance therapy with SC vedolizumab in adult patients with moderately to severely active UC who achieved clinical response at week 6 following two doses of intravenous vedolizumab.
At week 6, 162 patients were randomly allocated (2:1) to vedolizumab or placebo by subcutaneous injection every 2 weeks. The primary endpoint was clinical remission at week 52, defined as a total Mayo score of 2 or less and no individual subscore greater than 1.
At week 52, nearly half (46%) of patients who received vedolizumab SC maintenance therapy achieved clinical remission, compared with 14% of those who received placebo SC (P < .001).
The safety profile of SC vedolizumab was “generally consistent” with that of intravenous vedolizumab, with the addition of injection-site reactions, the drugmaker, Takeda, said in a news release.
The most common adverse reactions with intravenous vedolizumab are nasopharyngitis, headache, arthralgia, nausea, pyrexia (fever), upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in the extremities.
SC vedolizumab “can provide physicians with an additional administration option for achieving remission in their moderate to severe ulcerative colitis patients,” according to Bruce E. Sands, MD, AGAF, chief of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York. He provided a statement in the Takeda news release.
“I appreciate now having a subcutaneous administration option that provides a clinical profile consistent with Entyvio intravenous while also giving me and my appropriate UC patients a choice of how they receive their maintenance therapy,” Dr. Sands said.
The FDA is currently reviewing Takeda’s biologics license application for subcutaneous administration of vedolizumab in the treatment of adults with moderately to severely active Crohn’s disease.
Dr. Sands is a paid consultant of Takeda.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the subcutaneous administration of vedolizumab (Entyvio SC, Takeda) for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) following induction therapy with intravenous administration of vedolizumab.
The FDA approved the intravenous formulation of the biologic in 2014 for patients with moderate to severe UC and Crohn’s disease who failed or cannot tolerate other therapies.
The approval of subcutaneous (SC) vedolizumab was based on results from the phase 3, randomized, double-blind, placebo-controlled VISIBLE 1 trial.
The trial assessed the safety and efficacy of maintenance therapy with SC vedolizumab in adult patients with moderately to severely active UC who achieved clinical response at week 6 following two doses of intravenous vedolizumab.
At week 6, 162 patients were randomly allocated (2:1) to vedolizumab or placebo by subcutaneous injection every 2 weeks. The primary endpoint was clinical remission at week 52, defined as a total Mayo score of 2 or less and no individual subscore greater than 1.
At week 52, nearly half (46%) of patients who received vedolizumab SC maintenance therapy achieved clinical remission, compared with 14% of those who received placebo SC (P < .001).
The safety profile of SC vedolizumab was “generally consistent” with that of intravenous vedolizumab, with the addition of injection-site reactions, the drugmaker, Takeda, said in a news release.
The most common adverse reactions with intravenous vedolizumab are nasopharyngitis, headache, arthralgia, nausea, pyrexia (fever), upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in the extremities.
SC vedolizumab “can provide physicians with an additional administration option for achieving remission in their moderate to severe ulcerative colitis patients,” according to Bruce E. Sands, MD, AGAF, chief of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York. He provided a statement in the Takeda news release.
“I appreciate now having a subcutaneous administration option that provides a clinical profile consistent with Entyvio intravenous while also giving me and my appropriate UC patients a choice of how they receive their maintenance therapy,” Dr. Sands said.
The FDA is currently reviewing Takeda’s biologics license application for subcutaneous administration of vedolizumab in the treatment of adults with moderately to severely active Crohn’s disease.
Dr. Sands is a paid consultant of Takeda.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the subcutaneous administration of vedolizumab (Entyvio SC, Takeda) for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) following induction therapy with intravenous administration of vedolizumab.
The FDA approved the intravenous formulation of the biologic in 2014 for patients with moderate to severe UC and Crohn’s disease who failed or cannot tolerate other therapies.
The approval of subcutaneous (SC) vedolizumab was based on results from the phase 3, randomized, double-blind, placebo-controlled VISIBLE 1 trial.
The trial assessed the safety and efficacy of maintenance therapy with SC vedolizumab in adult patients with moderately to severely active UC who achieved clinical response at week 6 following two doses of intravenous vedolizumab.
At week 6, 162 patients were randomly allocated (2:1) to vedolizumab or placebo by subcutaneous injection every 2 weeks. The primary endpoint was clinical remission at week 52, defined as a total Mayo score of 2 or less and no individual subscore greater than 1.
At week 52, nearly half (46%) of patients who received vedolizumab SC maintenance therapy achieved clinical remission, compared with 14% of those who received placebo SC (P < .001).
The safety profile of SC vedolizumab was “generally consistent” with that of intravenous vedolizumab, with the addition of injection-site reactions, the drugmaker, Takeda, said in a news release.
The most common adverse reactions with intravenous vedolizumab are nasopharyngitis, headache, arthralgia, nausea, pyrexia (fever), upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in the extremities.
SC vedolizumab “can provide physicians with an additional administration option for achieving remission in their moderate to severe ulcerative colitis patients,” according to Bruce E. Sands, MD, AGAF, chief of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York. He provided a statement in the Takeda news release.
“I appreciate now having a subcutaneous administration option that provides a clinical profile consistent with Entyvio intravenous while also giving me and my appropriate UC patients a choice of how they receive their maintenance therapy,” Dr. Sands said.
The FDA is currently reviewing Takeda’s biologics license application for subcutaneous administration of vedolizumab in the treatment of adults with moderately to severely active Crohn’s disease.
Dr. Sands is a paid consultant of Takeda.
A version of this article first appeared on Medscape.com.
ChatGPT may aid decision-making in the ED for acute ulcerative colitis
(UC).
In a small study, ChatGPT version 4 (GPT-4) accurately gauged disease severity and made decisions about the need for hospitalization that were largely in line with expert gastroenterologists.
“Our findings suggest that GPT-4 has potential as a clinical decision-support tool in assessing UC severity and recommending suitable settings for further treatment,” say the authors, led by Asaf Levartovsky, MD, department of gastroenterology, Sheba Medical Center, Tel Aviv University.
The study was published online in the American Journal of Gastroenterology.
Assessing its potential
UC is a chronic inflammatory bowel disease known for episodes of flare-ups and remissions. Flare-ups often result in a trip to the ED, where staff must rapidly assess disease severity and need for hospital admission.
Dr. Levartovsky and colleagues explored how helpful GPT-4 could be in 20 distinct presentations of acute UC in the ED. They assessed the chatbot’s ability to determine the severity of disease and whether a specific presentation warranted hospital admission for further treatment.
They fed GPT-4 case summaries that included crucial data such as symptoms, vital signs, and laboratory results. For each case, they asked the chatbot to assess disease severity based on established criteria and recommend hospital admission or outpatient care.
The GPT-4 answers were compared with assessments made by gastroenterologists and the actual decision regarding hospitalization made by the physician in the ED.
Overall, ChatGPT categorized acute UC as severe in 12 patients, as moderate in 7, and as mild in 1. In each case, the chatbot provided a detailed answer depicting severity of every variable of the criteria and an overall severity classification.
ChatGPT’s assessments were consistent with gastroenterologists’ assessments 80% of the time, with a “high degree of reliability” between the two assessments, the study team reports.
The average correlation between ChatGPT and physician ratings was 0.839 (P < .001). Inconsistencies in four cases stemmed largely from inaccurate cut-off values for systemic variables (such as hemoglobin and tachycardia).
Following severity assessment, ChatGPT leaned toward hospital admission for 16 patients, whereas in actual clinical practice, only 12 patients were hospitalized. In one patient with moderate UC who was discharged, ChatGPT was in favor of hospitalization, based on the patient’s age and comorbid conditions. For two moderate UC cases, the chatbot recommended consultation with a health care professional for further evaluation and management, which the researchers deemed to be an indecisive response.
Based on their findings, the researchers say ChatGPT could serve as a real-time decision support tool – one that is not meant to replace physicians but rather enhance human decision-making.
They note that the small sample size is a limitation and that ChatGPT’s accuracy rate requires further validation across larger samples and diverse clinical scenarios.
The study had no specific funding. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(UC).
In a small study, ChatGPT version 4 (GPT-4) accurately gauged disease severity and made decisions about the need for hospitalization that were largely in line with expert gastroenterologists.
“Our findings suggest that GPT-4 has potential as a clinical decision-support tool in assessing UC severity and recommending suitable settings for further treatment,” say the authors, led by Asaf Levartovsky, MD, department of gastroenterology, Sheba Medical Center, Tel Aviv University.
The study was published online in the American Journal of Gastroenterology.
Assessing its potential
UC is a chronic inflammatory bowel disease known for episodes of flare-ups and remissions. Flare-ups often result in a trip to the ED, where staff must rapidly assess disease severity and need for hospital admission.
Dr. Levartovsky and colleagues explored how helpful GPT-4 could be in 20 distinct presentations of acute UC in the ED. They assessed the chatbot’s ability to determine the severity of disease and whether a specific presentation warranted hospital admission for further treatment.
They fed GPT-4 case summaries that included crucial data such as symptoms, vital signs, and laboratory results. For each case, they asked the chatbot to assess disease severity based on established criteria and recommend hospital admission or outpatient care.
The GPT-4 answers were compared with assessments made by gastroenterologists and the actual decision regarding hospitalization made by the physician in the ED.
Overall, ChatGPT categorized acute UC as severe in 12 patients, as moderate in 7, and as mild in 1. In each case, the chatbot provided a detailed answer depicting severity of every variable of the criteria and an overall severity classification.
ChatGPT’s assessments were consistent with gastroenterologists’ assessments 80% of the time, with a “high degree of reliability” between the two assessments, the study team reports.
The average correlation between ChatGPT and physician ratings was 0.839 (P < .001). Inconsistencies in four cases stemmed largely from inaccurate cut-off values for systemic variables (such as hemoglobin and tachycardia).
Following severity assessment, ChatGPT leaned toward hospital admission for 16 patients, whereas in actual clinical practice, only 12 patients were hospitalized. In one patient with moderate UC who was discharged, ChatGPT was in favor of hospitalization, based on the patient’s age and comorbid conditions. For two moderate UC cases, the chatbot recommended consultation with a health care professional for further evaluation and management, which the researchers deemed to be an indecisive response.
Based on their findings, the researchers say ChatGPT could serve as a real-time decision support tool – one that is not meant to replace physicians but rather enhance human decision-making.
They note that the small sample size is a limitation and that ChatGPT’s accuracy rate requires further validation across larger samples and diverse clinical scenarios.
The study had no specific funding. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(UC).
In a small study, ChatGPT version 4 (GPT-4) accurately gauged disease severity and made decisions about the need for hospitalization that were largely in line with expert gastroenterologists.
“Our findings suggest that GPT-4 has potential as a clinical decision-support tool in assessing UC severity and recommending suitable settings for further treatment,” say the authors, led by Asaf Levartovsky, MD, department of gastroenterology, Sheba Medical Center, Tel Aviv University.
The study was published online in the American Journal of Gastroenterology.
Assessing its potential
UC is a chronic inflammatory bowel disease known for episodes of flare-ups and remissions. Flare-ups often result in a trip to the ED, where staff must rapidly assess disease severity and need for hospital admission.
Dr. Levartovsky and colleagues explored how helpful GPT-4 could be in 20 distinct presentations of acute UC in the ED. They assessed the chatbot’s ability to determine the severity of disease and whether a specific presentation warranted hospital admission for further treatment.
They fed GPT-4 case summaries that included crucial data such as symptoms, vital signs, and laboratory results. For each case, they asked the chatbot to assess disease severity based on established criteria and recommend hospital admission or outpatient care.
The GPT-4 answers were compared with assessments made by gastroenterologists and the actual decision regarding hospitalization made by the physician in the ED.
Overall, ChatGPT categorized acute UC as severe in 12 patients, as moderate in 7, and as mild in 1. In each case, the chatbot provided a detailed answer depicting severity of every variable of the criteria and an overall severity classification.
ChatGPT’s assessments were consistent with gastroenterologists’ assessments 80% of the time, with a “high degree of reliability” between the two assessments, the study team reports.
The average correlation between ChatGPT and physician ratings was 0.839 (P < .001). Inconsistencies in four cases stemmed largely from inaccurate cut-off values for systemic variables (such as hemoglobin and tachycardia).
Following severity assessment, ChatGPT leaned toward hospital admission for 16 patients, whereas in actual clinical practice, only 12 patients were hospitalized. In one patient with moderate UC who was discharged, ChatGPT was in favor of hospitalization, based on the patient’s age and comorbid conditions. For two moderate UC cases, the chatbot recommended consultation with a health care professional for further evaluation and management, which the researchers deemed to be an indecisive response.
Based on their findings, the researchers say ChatGPT could serve as a real-time decision support tool – one that is not meant to replace physicians but rather enhance human decision-making.
They note that the small sample size is a limitation and that ChatGPT’s accuracy rate requires further validation across larger samples and diverse clinical scenarios.
The study had no specific funding. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Real-world data confirm efficacy of dupilumab in severe EoE
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Many young people stop ulcerative colitis maintenance treatment, risking relapse
, new research from the United Kingdom indicates.
“This is concerning as they are at risk of their condition returning and further complications. It can also lead to severe complications such as surgery to remove part of the gut,” Sonia Saxena, MBBS, director, Imperial Child Health Unit, School of Public Health, Imperial College London, said in a news release.
The study “highlights the importance of counseling and education of patients at diagnosis as this is a critical window that influences long-term health behavior,” Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist with Massachusetts General Hospital and Harvard Medical School, both in Boston, said in an interview.
“It has not been my experience in U.S.-based practice that the rates of discontinuation are that high, but it would be important to examine this in different locations,” added Dr. Ananthakrishnan, who wasn’t involved with the study.
The study was published online in the British Journal of General Practice.
Cases on the rise
Globally, the incidence of UC is increasing fastest in younger populations. It’s estimated that up to 30% of individuals with UC are diagnosed in childhood or young adulthood, and these individuals are more likely to have a severe disease course and years living with disability, compared with peers diagnosed later in life. This makes achieving disease control and maintaining remission “paramount” for those diagnosed in early life, Dr. Saxena and colleagues write.
International UC guidelines recommend starting therapy with 5-ASA, also known as mesalamine, soon after diagnosis and continuing it long term to maintain remission. However, some prior evidence suggests that adherence to UC medication may be less optimal in younger people – findings supported by the U.K. study.
Leveraging data from the UK Clinical Practice Research Datalink, Dr. Saxena and colleagues analyzed data for 607 children and young adults aged 10-24 years starting oral 5-ASA maintenance therapy for UC.
They found that 152 individuals (25%) stopped 5-ASA treatment after 1 month, and 419 (69%) discontinued it within 1 year of starting treatment. The median time to stopping the anti-inflammatory drug was 162 days.
Discontinuation rates were highest in young adults aged 18-24 years (74%). The transition to adult care and loss of support from caregivers who encourage adherence in adolescents and provide financial and practical support could be one explanation for this, the researchers write.
After accounting for other factors, young adults aged 18-24 years starting 5-ASA were 43% more likely to discontinue it in the first year than adolescents aged 10-14 years.
Individuals living in socioeconomically deprived areas were 46% more likely to stop treatment, compared with those living in more affluent areas, a finding that suggests the need to address socioeconomic disparities that could drive discontinuation, the authors say.
They also found that early corticosteroid use for an acute UC flare was associated with a 32% lower likelihood of stopping 5-ASA therapy.
Adherence falls short
In terms of adherence, defined as the proportion of days covered by 5-ASA medication, the mean was 72%, equivalent to just under 9 months. Adherence fell with older age at initiation of therapy. Adherence was 80% among those 10-14 years, 78% among those 15-17 years, and 69% among those 18-24 years. Prior research has shown that nonadherence to UC medication – defined as proportion of days covered less than 80% – has been associated with a five-fold risk of disease, compared with adherence above 80%, the investigators note.
“If clinicians are unaware of suboptimal adherence to first-line medication, they may incorrectly assume therapy has failed, which may lead to unnecessary escalation in treatment and avoidable steroid use that remains high in UC,” the researchers write.
Psychiatric comorbidity (depression, anxiety, or antidepressant use) was not associated with discontinuation or adherence to treatment.
“As doctors, this study shows we need to be keeping a close eye on patients, particularly within that first year of starting medication,” Dr. Saxena said in the release.
“We should check if these patients are getting their medications and whether they have difficulty paying for them. We should also use the opportunity to talk through any recurring symptoms and how to access advice from providers such as a nurse specialist,” Dr. Saxena said.
Effectiveness of therapy in young adults
Reached for comment, Michael Dolinger, MD, assistant professor of pediatric gastroenterology, Icahn School of Medicine and Mount Sinai Kravis Children’s Hospital, both in New York, said he has seen 5-ASA stoppage among his younger patients.
“Generally, what we see is that the majority of patients over time are not able to be sustained on oral mesalamine treatment, and they need a more advanced therapy,” Dr. Dolinger said in an interview.
And while the U.K. study did not delve into the reasons for discontinuation, ineffectiveness of therapy is likely a main cause, Dr. Dolinger said.
“We especially see this in our younger adolescent and young adult patients. In these younger patients, the immune system is potentially driving inflammation a bit more than in older patients, often going beyond the inner lining of the colon to the entire bowel wall, even in ulcerative colitis, and therefore mesalamine may be ineffective over the first year,” Dr. Dolinger explained.
When choosing a more advanced therapy, Dr. Dolinger said, “it’s all about having that conversation in a shared decision-making process about what may be the most effective short- and long-term treatment options with the best safety for that patient. It’s a very individualized discussion.”
“One of the main things we preach and talk about is control of inflammation, getting into early deep remission, because the longer you have inflammation, even if it’s just smoldering, the harder it is to get into deep remission,” Dr. Dolinger added.
The study had no commercial funding. Dr. Saxena, Dr. Ananthakrishnan, and Dr. Dolinger have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research from the United Kingdom indicates.
“This is concerning as they are at risk of their condition returning and further complications. It can also lead to severe complications such as surgery to remove part of the gut,” Sonia Saxena, MBBS, director, Imperial Child Health Unit, School of Public Health, Imperial College London, said in a news release.
The study “highlights the importance of counseling and education of patients at diagnosis as this is a critical window that influences long-term health behavior,” Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist with Massachusetts General Hospital and Harvard Medical School, both in Boston, said in an interview.
“It has not been my experience in U.S.-based practice that the rates of discontinuation are that high, but it would be important to examine this in different locations,” added Dr. Ananthakrishnan, who wasn’t involved with the study.
The study was published online in the British Journal of General Practice.
Cases on the rise
Globally, the incidence of UC is increasing fastest in younger populations. It’s estimated that up to 30% of individuals with UC are diagnosed in childhood or young adulthood, and these individuals are more likely to have a severe disease course and years living with disability, compared with peers diagnosed later in life. This makes achieving disease control and maintaining remission “paramount” for those diagnosed in early life, Dr. Saxena and colleagues write.
International UC guidelines recommend starting therapy with 5-ASA, also known as mesalamine, soon after diagnosis and continuing it long term to maintain remission. However, some prior evidence suggests that adherence to UC medication may be less optimal in younger people – findings supported by the U.K. study.
Leveraging data from the UK Clinical Practice Research Datalink, Dr. Saxena and colleagues analyzed data for 607 children and young adults aged 10-24 years starting oral 5-ASA maintenance therapy for UC.
They found that 152 individuals (25%) stopped 5-ASA treatment after 1 month, and 419 (69%) discontinued it within 1 year of starting treatment. The median time to stopping the anti-inflammatory drug was 162 days.
Discontinuation rates were highest in young adults aged 18-24 years (74%). The transition to adult care and loss of support from caregivers who encourage adherence in adolescents and provide financial and practical support could be one explanation for this, the researchers write.
After accounting for other factors, young adults aged 18-24 years starting 5-ASA were 43% more likely to discontinue it in the first year than adolescents aged 10-14 years.
Individuals living in socioeconomically deprived areas were 46% more likely to stop treatment, compared with those living in more affluent areas, a finding that suggests the need to address socioeconomic disparities that could drive discontinuation, the authors say.
They also found that early corticosteroid use for an acute UC flare was associated with a 32% lower likelihood of stopping 5-ASA therapy.
Adherence falls short
In terms of adherence, defined as the proportion of days covered by 5-ASA medication, the mean was 72%, equivalent to just under 9 months. Adherence fell with older age at initiation of therapy. Adherence was 80% among those 10-14 years, 78% among those 15-17 years, and 69% among those 18-24 years. Prior research has shown that nonadherence to UC medication – defined as proportion of days covered less than 80% – has been associated with a five-fold risk of disease, compared with adherence above 80%, the investigators note.
“If clinicians are unaware of suboptimal adherence to first-line medication, they may incorrectly assume therapy has failed, which may lead to unnecessary escalation in treatment and avoidable steroid use that remains high in UC,” the researchers write.
Psychiatric comorbidity (depression, anxiety, or antidepressant use) was not associated with discontinuation or adherence to treatment.
“As doctors, this study shows we need to be keeping a close eye on patients, particularly within that first year of starting medication,” Dr. Saxena said in the release.
“We should check if these patients are getting their medications and whether they have difficulty paying for them. We should also use the opportunity to talk through any recurring symptoms and how to access advice from providers such as a nurse specialist,” Dr. Saxena said.
Effectiveness of therapy in young adults
Reached for comment, Michael Dolinger, MD, assistant professor of pediatric gastroenterology, Icahn School of Medicine and Mount Sinai Kravis Children’s Hospital, both in New York, said he has seen 5-ASA stoppage among his younger patients.
“Generally, what we see is that the majority of patients over time are not able to be sustained on oral mesalamine treatment, and they need a more advanced therapy,” Dr. Dolinger said in an interview.
And while the U.K. study did not delve into the reasons for discontinuation, ineffectiveness of therapy is likely a main cause, Dr. Dolinger said.
“We especially see this in our younger adolescent and young adult patients. In these younger patients, the immune system is potentially driving inflammation a bit more than in older patients, often going beyond the inner lining of the colon to the entire bowel wall, even in ulcerative colitis, and therefore mesalamine may be ineffective over the first year,” Dr. Dolinger explained.
When choosing a more advanced therapy, Dr. Dolinger said, “it’s all about having that conversation in a shared decision-making process about what may be the most effective short- and long-term treatment options with the best safety for that patient. It’s a very individualized discussion.”
“One of the main things we preach and talk about is control of inflammation, getting into early deep remission, because the longer you have inflammation, even if it’s just smoldering, the harder it is to get into deep remission,” Dr. Dolinger added.
The study had no commercial funding. Dr. Saxena, Dr. Ananthakrishnan, and Dr. Dolinger have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research from the United Kingdom indicates.
“This is concerning as they are at risk of their condition returning and further complications. It can also lead to severe complications such as surgery to remove part of the gut,” Sonia Saxena, MBBS, director, Imperial Child Health Unit, School of Public Health, Imperial College London, said in a news release.
The study “highlights the importance of counseling and education of patients at diagnosis as this is a critical window that influences long-term health behavior,” Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist with Massachusetts General Hospital and Harvard Medical School, both in Boston, said in an interview.
“It has not been my experience in U.S.-based practice that the rates of discontinuation are that high, but it would be important to examine this in different locations,” added Dr. Ananthakrishnan, who wasn’t involved with the study.
The study was published online in the British Journal of General Practice.
Cases on the rise
Globally, the incidence of UC is increasing fastest in younger populations. It’s estimated that up to 30% of individuals with UC are diagnosed in childhood or young adulthood, and these individuals are more likely to have a severe disease course and years living with disability, compared with peers diagnosed later in life. This makes achieving disease control and maintaining remission “paramount” for those diagnosed in early life, Dr. Saxena and colleagues write.
International UC guidelines recommend starting therapy with 5-ASA, also known as mesalamine, soon after diagnosis and continuing it long term to maintain remission. However, some prior evidence suggests that adherence to UC medication may be less optimal in younger people – findings supported by the U.K. study.
Leveraging data from the UK Clinical Practice Research Datalink, Dr. Saxena and colleagues analyzed data for 607 children and young adults aged 10-24 years starting oral 5-ASA maintenance therapy for UC.
They found that 152 individuals (25%) stopped 5-ASA treatment after 1 month, and 419 (69%) discontinued it within 1 year of starting treatment. The median time to stopping the anti-inflammatory drug was 162 days.
Discontinuation rates were highest in young adults aged 18-24 years (74%). The transition to adult care and loss of support from caregivers who encourage adherence in adolescents and provide financial and practical support could be one explanation for this, the researchers write.
After accounting for other factors, young adults aged 18-24 years starting 5-ASA were 43% more likely to discontinue it in the first year than adolescents aged 10-14 years.
Individuals living in socioeconomically deprived areas were 46% more likely to stop treatment, compared with those living in more affluent areas, a finding that suggests the need to address socioeconomic disparities that could drive discontinuation, the authors say.
They also found that early corticosteroid use for an acute UC flare was associated with a 32% lower likelihood of stopping 5-ASA therapy.
Adherence falls short
In terms of adherence, defined as the proportion of days covered by 5-ASA medication, the mean was 72%, equivalent to just under 9 months. Adherence fell with older age at initiation of therapy. Adherence was 80% among those 10-14 years, 78% among those 15-17 years, and 69% among those 18-24 years. Prior research has shown that nonadherence to UC medication – defined as proportion of days covered less than 80% – has been associated with a five-fold risk of disease, compared with adherence above 80%, the investigators note.
“If clinicians are unaware of suboptimal adherence to first-line medication, they may incorrectly assume therapy has failed, which may lead to unnecessary escalation in treatment and avoidable steroid use that remains high in UC,” the researchers write.
Psychiatric comorbidity (depression, anxiety, or antidepressant use) was not associated with discontinuation or adherence to treatment.
“As doctors, this study shows we need to be keeping a close eye on patients, particularly within that first year of starting medication,” Dr. Saxena said in the release.
“We should check if these patients are getting their medications and whether they have difficulty paying for them. We should also use the opportunity to talk through any recurring symptoms and how to access advice from providers such as a nurse specialist,” Dr. Saxena said.
Effectiveness of therapy in young adults
Reached for comment, Michael Dolinger, MD, assistant professor of pediatric gastroenterology, Icahn School of Medicine and Mount Sinai Kravis Children’s Hospital, both in New York, said he has seen 5-ASA stoppage among his younger patients.
“Generally, what we see is that the majority of patients over time are not able to be sustained on oral mesalamine treatment, and they need a more advanced therapy,” Dr. Dolinger said in an interview.
And while the U.K. study did not delve into the reasons for discontinuation, ineffectiveness of therapy is likely a main cause, Dr. Dolinger said.
“We especially see this in our younger adolescent and young adult patients. In these younger patients, the immune system is potentially driving inflammation a bit more than in older patients, often going beyond the inner lining of the colon to the entire bowel wall, even in ulcerative colitis, and therefore mesalamine may be ineffective over the first year,” Dr. Dolinger explained.
When choosing a more advanced therapy, Dr. Dolinger said, “it’s all about having that conversation in a shared decision-making process about what may be the most effective short- and long-term treatment options with the best safety for that patient. It’s a very individualized discussion.”
“One of the main things we preach and talk about is control of inflammation, getting into early deep remission, because the longer you have inflammation, even if it’s just smoldering, the harder it is to get into deep remission,” Dr. Dolinger added.
The study had no commercial funding. Dr. Saxena, Dr. Ananthakrishnan, and Dr. Dolinger have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF GENERAL PRACTICE
Omitting sentinel lymph node biopsy safe for some early breast cancers
TOPLINE:
Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.
METHODOLOGY:
- In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
- The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
- Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
- Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.
TAKEAWAY:
- Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
- Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
- Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
- The authors reported no significant differences in adjuvant treatment recommendations between the two groups.
IN PRACTICE:
“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.
In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”
SOURCE:
The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.
LIMITATIONS:
The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.
DISCLOSURES:
The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.
METHODOLOGY:
- In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
- The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
- Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
- Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.
TAKEAWAY:
- Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
- Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
- Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
- The authors reported no significant differences in adjuvant treatment recommendations between the two groups.
IN PRACTICE:
“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.
In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”
SOURCE:
The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.
LIMITATIONS:
The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.
DISCLOSURES:
The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.
METHODOLOGY:
- In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
- The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
- Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
- Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.
TAKEAWAY:
- Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
- Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
- Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
- The authors reported no significant differences in adjuvant treatment recommendations between the two groups.
IN PRACTICE:
“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.
In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”
SOURCE:
The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.
LIMITATIONS:
The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.
DISCLOSURES:
The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.
A version of this article appeared on Medscape.com.
FROM JAMA ONCOLOGY
High-risk colon polyps detected at screening colonoscopy linked to liver cancer death
TOPLINE:
METHODOLOGY:
- Researchers conducted a retrospective analysis of 343,838 screening colonoscopies performed in Austria from 2007 to 2020. National death registry data were used to identify deaths from gastrointestinal cancers among patients in the cohort.
- Risk for hepatobiliary cancer death by colon polyp risk profile was assessed.
- A cause-specific Cox regression model was used to estimate the association of time to death with polyp risk group at screening colonoscopy.
TAKEAWAY:
- Of the screening colonoscopies, 17,678 (5.1%) revealed high-risk polyps: that is, polyps of at least 10 mm, adenomas with high-grade dysplasia, serrated polyps with dysplasia, or five or more adenomas.
- The cumulative incidence of hepatobiliary cancer death was 0.19% at 6 years and 0.44% at 12 years in the high-risk polyp group versus 0.07% and 0.18%, respectively, in the negative colonoscopy group.
- Overall hepatobiliary cancer mortality was more than twice as high in patients with high-risk polyps compared with peers who had negative colonoscopy (cumulative incidence, 0.39% vs 0.17%).
- After adjustment for age and sex, the presence of high-risk polyps at screening colonoscopy was significantly associated with death from any hepatobiliary cancer (hazard ratio [HR], 1.83); the HRs for death from hepatocellular carcinoma (HCC) and non-HCC hepatobiliary cancer were 1.79 and 1.88, respectively.
- There was no significant association of low-risk polyps with hepatobiliary cancer death (HR, 1.23).
IN PRACTICE:
“Hepatobiliary cancers share risk factors with colorectal cancer, but there are no combined screening programs for these conditions,” the researchers write. “Our findings imply that risk stratification at colonoscopy might be helping to identify patients at need for liver cancer surveillance. However, further studies will be needed to address whether a targeted surveillance of these patients will be cost effective.”
SOURCE:
The study, with first author Jasmin Zessner-Spitzenberg, MD, of the Medical University of Vienna, was published online in Digestive and Liver Disease.
LIMITATIONS:
Some liver cancer deaths might have been falsely classified as other hepatic cancers. The authors lacked information on modifiable cancer risk factors. The generalizability of the findings outside of the screening setting is limited.
DISCLOSURES:
Support for data collection was provided by the Main Association of Statutory Insurance Institutions, the Austrian Society for Gastroenterology and Hepatology, and Austrian Cancer Aid. One author reported relationships with various pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a retrospective analysis of 343,838 screening colonoscopies performed in Austria from 2007 to 2020. National death registry data were used to identify deaths from gastrointestinal cancers among patients in the cohort.
- Risk for hepatobiliary cancer death by colon polyp risk profile was assessed.
- A cause-specific Cox regression model was used to estimate the association of time to death with polyp risk group at screening colonoscopy.
TAKEAWAY:
- Of the screening colonoscopies, 17,678 (5.1%) revealed high-risk polyps: that is, polyps of at least 10 mm, adenomas with high-grade dysplasia, serrated polyps with dysplasia, or five or more adenomas.
- The cumulative incidence of hepatobiliary cancer death was 0.19% at 6 years and 0.44% at 12 years in the high-risk polyp group versus 0.07% and 0.18%, respectively, in the negative colonoscopy group.
- Overall hepatobiliary cancer mortality was more than twice as high in patients with high-risk polyps compared with peers who had negative colonoscopy (cumulative incidence, 0.39% vs 0.17%).
- After adjustment for age and sex, the presence of high-risk polyps at screening colonoscopy was significantly associated with death from any hepatobiliary cancer (hazard ratio [HR], 1.83); the HRs for death from hepatocellular carcinoma (HCC) and non-HCC hepatobiliary cancer were 1.79 and 1.88, respectively.
- There was no significant association of low-risk polyps with hepatobiliary cancer death (HR, 1.23).
IN PRACTICE:
“Hepatobiliary cancers share risk factors with colorectal cancer, but there are no combined screening programs for these conditions,” the researchers write. “Our findings imply that risk stratification at colonoscopy might be helping to identify patients at need for liver cancer surveillance. However, further studies will be needed to address whether a targeted surveillance of these patients will be cost effective.”
SOURCE:
The study, with first author Jasmin Zessner-Spitzenberg, MD, of the Medical University of Vienna, was published online in Digestive and Liver Disease.
LIMITATIONS:
Some liver cancer deaths might have been falsely classified as other hepatic cancers. The authors lacked information on modifiable cancer risk factors. The generalizability of the findings outside of the screening setting is limited.
DISCLOSURES:
Support for data collection was provided by the Main Association of Statutory Insurance Institutions, the Austrian Society for Gastroenterology and Hepatology, and Austrian Cancer Aid. One author reported relationships with various pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a retrospective analysis of 343,838 screening colonoscopies performed in Austria from 2007 to 2020. National death registry data were used to identify deaths from gastrointestinal cancers among patients in the cohort.
- Risk for hepatobiliary cancer death by colon polyp risk profile was assessed.
- A cause-specific Cox regression model was used to estimate the association of time to death with polyp risk group at screening colonoscopy.
TAKEAWAY:
- Of the screening colonoscopies, 17,678 (5.1%) revealed high-risk polyps: that is, polyps of at least 10 mm, adenomas with high-grade dysplasia, serrated polyps with dysplasia, or five or more adenomas.
- The cumulative incidence of hepatobiliary cancer death was 0.19% at 6 years and 0.44% at 12 years in the high-risk polyp group versus 0.07% and 0.18%, respectively, in the negative colonoscopy group.
- Overall hepatobiliary cancer mortality was more than twice as high in patients with high-risk polyps compared with peers who had negative colonoscopy (cumulative incidence, 0.39% vs 0.17%).
- After adjustment for age and sex, the presence of high-risk polyps at screening colonoscopy was significantly associated with death from any hepatobiliary cancer (hazard ratio [HR], 1.83); the HRs for death from hepatocellular carcinoma (HCC) and non-HCC hepatobiliary cancer were 1.79 and 1.88, respectively.
- There was no significant association of low-risk polyps with hepatobiliary cancer death (HR, 1.23).
IN PRACTICE:
“Hepatobiliary cancers share risk factors with colorectal cancer, but there are no combined screening programs for these conditions,” the researchers write. “Our findings imply that risk stratification at colonoscopy might be helping to identify patients at need for liver cancer surveillance. However, further studies will be needed to address whether a targeted surveillance of these patients will be cost effective.”
SOURCE:
The study, with first author Jasmin Zessner-Spitzenberg, MD, of the Medical University of Vienna, was published online in Digestive and Liver Disease.
LIMITATIONS:
Some liver cancer deaths might have been falsely classified as other hepatic cancers. The authors lacked information on modifiable cancer risk factors. The generalizability of the findings outside of the screening setting is limited.
DISCLOSURES:
Support for data collection was provided by the Main Association of Statutory Insurance Institutions, the Austrian Society for Gastroenterology and Hepatology, and Austrian Cancer Aid. One author reported relationships with various pharmaceutical companies.
A version of this article appeared on Medscape.com.
FROM DIGESTIVE AND LIVER DISEASE
Artificial sweeteners in processed foods tied to increased depression risk
new data from the Nurses Health Study II (NHS II) suggest.
Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.
However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.
“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.
“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.
The study was published online in JAMA Network Open.
Multiple potential mechanisms
The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.
Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.
During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.
Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.
This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).
“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.
In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.
Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.
In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.
“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.
For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.
There is also a link between UPF and disruption of the gut microbiome.
“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
Association, not causation
Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.
“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.
What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.
“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.
“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.
Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”
Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.
“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.
Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.
“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.
The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.
A version of this article first appeared on Medscape.com.
new data from the Nurses Health Study II (NHS II) suggest.
Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.
However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.
“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.
“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.
The study was published online in JAMA Network Open.
Multiple potential mechanisms
The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.
Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.
During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.
Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.
This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).
“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.
In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.
Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.
In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.
“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.
For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.
There is also a link between UPF and disruption of the gut microbiome.
“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
Association, not causation
Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.
“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.
What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.
“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.
“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.
Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”
Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.
“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.
Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.
“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.
The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.
A version of this article first appeared on Medscape.com.
new data from the Nurses Health Study II (NHS II) suggest.
Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.
However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.
“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.
“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.
The study was published online in JAMA Network Open.
Multiple potential mechanisms
The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.
Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.
During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.
Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.
This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).
“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.
In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.
Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.
In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.
“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.
For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.
There is also a link between UPF and disruption of the gut microbiome.
“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
Association, not causation
Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.
“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.
What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.
“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.
“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.
Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”
Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.
“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.
Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.
“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.
The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Surgery approach may improve survival in advanced ovarian cancer
TOPLINE:
Neoadjuvant chemotherapy followed by interval cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves progression-free survival (PFS) and overall survival, compared with interval cytoreductive surgery alone, in patients with advanced ovarian cancer, new research shows.
METHODOLOGY:
- Several randomized controlled trials have shown survival benefits with HIPEC followed by interval cytoreductive surgery in advanced ovarian cancer. Despite the data, the use of HIPEC in clinical practice remains limited.
- Potential downsides of HIPEC include longer operative time and treatment-related complications.
- This prospective, multicenter, comparative effectiveness study evaluated the safety and effectiveness of interval cytoreductive surgery with HIPEC versus the surgery alone.
- The study, conducted at seven Korean Gynecologic Oncology Group institutions, included 196 patients (mean age, 58 years) with stage III or IV ovarian cancer who had received at least three cycles of neoadjuvant chemotherapy followed by interval cytoreductive surgery with HIPEC (n = 109) or without HIPEC (n = 87).
- The researchers reported progression-free survival as well as overall survival and treatment-related toxic effects.
TAKEAWAY:
- During a median follow-up of 28.2 months, 128 patients (65%) had a recurrence and 30 died (15.3%) – 8.3% in the HIPEC group and 24.1% in the non-HIPEC group.
- Compared with no HIPEC, interval cytoreductive surgery with HIPEC led to a significant improvement in median PFS (22.9 months vs. 14.2 months; P = .005) and median overall survival (not reached vs. 53 months; P = .002).
- The frequency of grade 3 or 4 postoperative complications was similar in both groups: 2.8% with HIPEC versus 3.4% without HIPEC.
- Among patients with recurrence, the frequency of peritoneal recurrence was significantly lower among those who received HIPEC (32.8% vs. 64.1% without HIPEC; P = .001).
IN PRACTICE:
“We observed a significantly superior survival benefit associated with [interval cytoreductive surgery] with HIPEC, without higher rates of postoperative complications,” the authors concluded, adding that “the survival benefit remained consistent, irrespective of maintenance therapy.”
SOURCE:
The study, led by Jung-Yun Lee, MD, PhD, Yonsei University College of Medicine, Seoul, Korea, was published online in JAMA Surgery.
LIMITATIONS:
The patients were not randomly assigned and the decision to give HIPEC was at the clinician’s discretion, introducing the possibility of selection and treatment bias. The different types of drugs used in HIPEC could result in bias in data interpretation.
DISCLOSURES:
The authors reported no conflicts of interest. The study had no specific funding.
A version of this article first appeared on Medscape.com.
TOPLINE:
Neoadjuvant chemotherapy followed by interval cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves progression-free survival (PFS) and overall survival, compared with interval cytoreductive surgery alone, in patients with advanced ovarian cancer, new research shows.
METHODOLOGY:
- Several randomized controlled trials have shown survival benefits with HIPEC followed by interval cytoreductive surgery in advanced ovarian cancer. Despite the data, the use of HIPEC in clinical practice remains limited.
- Potential downsides of HIPEC include longer operative time and treatment-related complications.
- This prospective, multicenter, comparative effectiveness study evaluated the safety and effectiveness of interval cytoreductive surgery with HIPEC versus the surgery alone.
- The study, conducted at seven Korean Gynecologic Oncology Group institutions, included 196 patients (mean age, 58 years) with stage III or IV ovarian cancer who had received at least three cycles of neoadjuvant chemotherapy followed by interval cytoreductive surgery with HIPEC (n = 109) or without HIPEC (n = 87).
- The researchers reported progression-free survival as well as overall survival and treatment-related toxic effects.
TAKEAWAY:
- During a median follow-up of 28.2 months, 128 patients (65%) had a recurrence and 30 died (15.3%) – 8.3% in the HIPEC group and 24.1% in the non-HIPEC group.
- Compared with no HIPEC, interval cytoreductive surgery with HIPEC led to a significant improvement in median PFS (22.9 months vs. 14.2 months; P = .005) and median overall survival (not reached vs. 53 months; P = .002).
- The frequency of grade 3 or 4 postoperative complications was similar in both groups: 2.8% with HIPEC versus 3.4% without HIPEC.
- Among patients with recurrence, the frequency of peritoneal recurrence was significantly lower among those who received HIPEC (32.8% vs. 64.1% without HIPEC; P = .001).
IN PRACTICE:
“We observed a significantly superior survival benefit associated with [interval cytoreductive surgery] with HIPEC, without higher rates of postoperative complications,” the authors concluded, adding that “the survival benefit remained consistent, irrespective of maintenance therapy.”
SOURCE:
The study, led by Jung-Yun Lee, MD, PhD, Yonsei University College of Medicine, Seoul, Korea, was published online in JAMA Surgery.
LIMITATIONS:
The patients were not randomly assigned and the decision to give HIPEC was at the clinician’s discretion, introducing the possibility of selection and treatment bias. The different types of drugs used in HIPEC could result in bias in data interpretation.
DISCLOSURES:
The authors reported no conflicts of interest. The study had no specific funding.
A version of this article first appeared on Medscape.com.
TOPLINE:
Neoadjuvant chemotherapy followed by interval cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves progression-free survival (PFS) and overall survival, compared with interval cytoreductive surgery alone, in patients with advanced ovarian cancer, new research shows.
METHODOLOGY:
- Several randomized controlled trials have shown survival benefits with HIPEC followed by interval cytoreductive surgery in advanced ovarian cancer. Despite the data, the use of HIPEC in clinical practice remains limited.
- Potential downsides of HIPEC include longer operative time and treatment-related complications.
- This prospective, multicenter, comparative effectiveness study evaluated the safety and effectiveness of interval cytoreductive surgery with HIPEC versus the surgery alone.
- The study, conducted at seven Korean Gynecologic Oncology Group institutions, included 196 patients (mean age, 58 years) with stage III or IV ovarian cancer who had received at least three cycles of neoadjuvant chemotherapy followed by interval cytoreductive surgery with HIPEC (n = 109) or without HIPEC (n = 87).
- The researchers reported progression-free survival as well as overall survival and treatment-related toxic effects.
TAKEAWAY:
- During a median follow-up of 28.2 months, 128 patients (65%) had a recurrence and 30 died (15.3%) – 8.3% in the HIPEC group and 24.1% in the non-HIPEC group.
- Compared with no HIPEC, interval cytoreductive surgery with HIPEC led to a significant improvement in median PFS (22.9 months vs. 14.2 months; P = .005) and median overall survival (not reached vs. 53 months; P = .002).
- The frequency of grade 3 or 4 postoperative complications was similar in both groups: 2.8% with HIPEC versus 3.4% without HIPEC.
- Among patients with recurrence, the frequency of peritoneal recurrence was significantly lower among those who received HIPEC (32.8% vs. 64.1% without HIPEC; P = .001).
IN PRACTICE:
“We observed a significantly superior survival benefit associated with [interval cytoreductive surgery] with HIPEC, without higher rates of postoperative complications,” the authors concluded, adding that “the survival benefit remained consistent, irrespective of maintenance therapy.”
SOURCE:
The study, led by Jung-Yun Lee, MD, PhD, Yonsei University College of Medicine, Seoul, Korea, was published online in JAMA Surgery.
LIMITATIONS:
The patients were not randomly assigned and the decision to give HIPEC was at the clinician’s discretion, introducing the possibility of selection and treatment bias. The different types of drugs used in HIPEC could result in bias in data interpretation.
DISCLOSURES:
The authors reported no conflicts of interest. The study had no specific funding.
A version of this article first appeared on Medscape.com.
FROM JAMA SURGERY
More data needed on stopping GLP-1 use prior to endoscopy
In a new statement, five professional gastroenterology organizations caution that there are currently no data to support stopping glucagonlike peptide 1 (GLP-1) receptor agonists prior to elective endoscopy
The medications, which include semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro), and liraglutide (Saxenda), among others, are used for the treatment of diabetes or for weight loss and may be associated with delayed gastric emptying.
Patients taking GLP-1 receptor agonists for diabetes management “need to be cautious about withholding these medications because doing so can adversely impact blood glucose control,” said Octavia Pickett-Blakely, MD, a gastroenterologist with University of Pennsylvania in Philadelphia and spokesperson for the American Gastroenterological Association (AGA). “In patients undergoing endoscopic procedures, poorly controlled blood glucose could raise the risk of complications.”
In a commentary on Medscape, David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, urges clinicians to learn about the topic and inform patients when prescribing GLP-1 receptor agonists.
“These are new and changing issues. In our world as gastroenterologists, we should be considering – very strongly – mitigating strategies to protect the patients on this wonderful class of therapy,” he says. “Sometimes these drugs can have significant side effects that we need to at least be aware of. Nothing is perfect, but let us be better informed.”
“We really don’t know what the risks are yet. With endoscopy, they could be significant, but perhaps they’re not,” Jonathan Leighton, MD, a gastroenterologist with Mayo Clinic Arizona in Phoenix and president-elect of the American College of Gastroenterology (ACG), told this news organization. “There are a lot of factors that go into this, and we just want to proceed cautiously and carefully until we know more.”
The ACG, AGA, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition released the statement on Aug. 11.
It was issued in response to recent guidance on the preoperative management of adults and children on GLP-1 receptor agonists put forth by the American Society of Anesthesiologists.
In a separate statement, the AGA stated that there is little, or no data on complications from aspiration.
“While there is anecdotal experience that increased gastroparesis risk may be dose dependent or related to whether it is being used for diabetes control versus weight loss, we also acknowledge that there is little, or no data related to the relative risk of complications from aspiration. As a result, the impact associated with stopping these therapies prior to undergoing upper GI endoscopy (EGD) or other moderate to deep sedated procedures is unknown at this time.
“As clinical gastroenterologists and hepatologists, we are very familiar with safety issues regarding the performance of endoscopy in our patients suffering from gastroparesis as well as unexplained nausea, vomiting, and epigastric pain, particularly in emergency situations. As patient safety will always be paramount, and in the absence of actionable data, we encourage our members to exercise best practices when performing endoscopy on these patients who are taking GLP-1 receptor agonists. More data are needed to understand if and when these medications should be held prior to elective endoscopy. Given the need for further data regarding the emerging use of these novel compounds, we encourage our anesthesiology, endocrinology, and industry partners to work collaboratively with our members to develop the necessary evidence to appropriately inform medication adjustments prior to elective endoscopy.”
ASA recommendations
The ASA Task Force on Preoperative Fasting reviewed the available literature on GLP-1 receptor agonists and associated gastrointestinal adverse effects, including the consequences of delayed gastric emptying.
The task force acknowledges that the evidence to provide guidance for preoperative management of these drugs to prevent regurgitation and pulmonary aspiration of gastric contents is “sparse, limited only to several case reports.”
Nevertheless, given the concerns of GLP-1 receptor agonist–induced delayed gastric emptying and associated high risk for regurgitation and aspiration of gastric contents, the task force made these recommendations for elective procedures.
The day before the procedure
For patients on daily dosing, consider holding GLP-1 agonists on the day of the procedure/surgery. For patients on weekly dosing, consider holding GLP-1 agonists a week prior to the procedure/surgery.
This suggestion is irrespective of the indication (type 2 diabetes or weight loss), dose, or the type of procedure/surgery.
If GLP-1 agonists prescribed for diabetes are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycemia.
The day of the procedure
If GI symptoms such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain are present, consider delaying the elective procedure and discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
If the patient has no GI symptoms and the GLP-1 agonists have been held as advised, proceed as usual.
If the patient has no GI symptoms but the GLP-1 agonists were not held as advised, proceed with “full stomach” precautions or consider evaluating gastric volume by ultrasound, if possible and if proficient with the technique. If the stomach is empty, proceed as usual. If the stomach is full or if gastric ultrasound is inconclusive or not possible, consider delaying the procedure or treat the patient as “full stomach” and manage accordingly. Discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
There is no evidence to suggest the optimal duration of fasting for patients on GLP-1 agonists. Therefore, until we have adequate evidence, we suggest following the current ASA fasting guidelines.
For patients on GLP-1 receptor agonists who need urgent or emergent procedures, the ASA advises proceeding and treating the patient as “full stomach” and managing accordingly.
Dr. Leighton has financial relationships with Olympus and Pfizer. Dr. Pickett-Blakely has no relevant disclosures. Dr. Johnson is an adviser to ISOTHRIVE and Johnson & Johnson.
This story was adapted for GI&Hepatology News from Medscape.
In a new statement, five professional gastroenterology organizations caution that there are currently no data to support stopping glucagonlike peptide 1 (GLP-1) receptor agonists prior to elective endoscopy
The medications, which include semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro), and liraglutide (Saxenda), among others, are used for the treatment of diabetes or for weight loss and may be associated with delayed gastric emptying.
Patients taking GLP-1 receptor agonists for diabetes management “need to be cautious about withholding these medications because doing so can adversely impact blood glucose control,” said Octavia Pickett-Blakely, MD, a gastroenterologist with University of Pennsylvania in Philadelphia and spokesperson for the American Gastroenterological Association (AGA). “In patients undergoing endoscopic procedures, poorly controlled blood glucose could raise the risk of complications.”
In a commentary on Medscape, David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, urges clinicians to learn about the topic and inform patients when prescribing GLP-1 receptor agonists.
“These are new and changing issues. In our world as gastroenterologists, we should be considering – very strongly – mitigating strategies to protect the patients on this wonderful class of therapy,” he says. “Sometimes these drugs can have significant side effects that we need to at least be aware of. Nothing is perfect, but let us be better informed.”
“We really don’t know what the risks are yet. With endoscopy, they could be significant, but perhaps they’re not,” Jonathan Leighton, MD, a gastroenterologist with Mayo Clinic Arizona in Phoenix and president-elect of the American College of Gastroenterology (ACG), told this news organization. “There are a lot of factors that go into this, and we just want to proceed cautiously and carefully until we know more.”
The ACG, AGA, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition released the statement on Aug. 11.
It was issued in response to recent guidance on the preoperative management of adults and children on GLP-1 receptor agonists put forth by the American Society of Anesthesiologists.
In a separate statement, the AGA stated that there is little, or no data on complications from aspiration.
“While there is anecdotal experience that increased gastroparesis risk may be dose dependent or related to whether it is being used for diabetes control versus weight loss, we also acknowledge that there is little, or no data related to the relative risk of complications from aspiration. As a result, the impact associated with stopping these therapies prior to undergoing upper GI endoscopy (EGD) or other moderate to deep sedated procedures is unknown at this time.
“As clinical gastroenterologists and hepatologists, we are very familiar with safety issues regarding the performance of endoscopy in our patients suffering from gastroparesis as well as unexplained nausea, vomiting, and epigastric pain, particularly in emergency situations. As patient safety will always be paramount, and in the absence of actionable data, we encourage our members to exercise best practices when performing endoscopy on these patients who are taking GLP-1 receptor agonists. More data are needed to understand if and when these medications should be held prior to elective endoscopy. Given the need for further data regarding the emerging use of these novel compounds, we encourage our anesthesiology, endocrinology, and industry partners to work collaboratively with our members to develop the necessary evidence to appropriately inform medication adjustments prior to elective endoscopy.”
ASA recommendations
The ASA Task Force on Preoperative Fasting reviewed the available literature on GLP-1 receptor agonists and associated gastrointestinal adverse effects, including the consequences of delayed gastric emptying.
The task force acknowledges that the evidence to provide guidance for preoperative management of these drugs to prevent regurgitation and pulmonary aspiration of gastric contents is “sparse, limited only to several case reports.”
Nevertheless, given the concerns of GLP-1 receptor agonist–induced delayed gastric emptying and associated high risk for regurgitation and aspiration of gastric contents, the task force made these recommendations for elective procedures.
The day before the procedure
For patients on daily dosing, consider holding GLP-1 agonists on the day of the procedure/surgery. For patients on weekly dosing, consider holding GLP-1 agonists a week prior to the procedure/surgery.
This suggestion is irrespective of the indication (type 2 diabetes or weight loss), dose, or the type of procedure/surgery.
If GLP-1 agonists prescribed for diabetes are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycemia.
The day of the procedure
If GI symptoms such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain are present, consider delaying the elective procedure and discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
If the patient has no GI symptoms and the GLP-1 agonists have been held as advised, proceed as usual.
If the patient has no GI symptoms but the GLP-1 agonists were not held as advised, proceed with “full stomach” precautions or consider evaluating gastric volume by ultrasound, if possible and if proficient with the technique. If the stomach is empty, proceed as usual. If the stomach is full or if gastric ultrasound is inconclusive or not possible, consider delaying the procedure or treat the patient as “full stomach” and manage accordingly. Discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
There is no evidence to suggest the optimal duration of fasting for patients on GLP-1 agonists. Therefore, until we have adequate evidence, we suggest following the current ASA fasting guidelines.
For patients on GLP-1 receptor agonists who need urgent or emergent procedures, the ASA advises proceeding and treating the patient as “full stomach” and managing accordingly.
Dr. Leighton has financial relationships with Olympus and Pfizer. Dr. Pickett-Blakely has no relevant disclosures. Dr. Johnson is an adviser to ISOTHRIVE and Johnson & Johnson.
This story was adapted for GI&Hepatology News from Medscape.
In a new statement, five professional gastroenterology organizations caution that there are currently no data to support stopping glucagonlike peptide 1 (GLP-1) receptor agonists prior to elective endoscopy
The medications, which include semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro), and liraglutide (Saxenda), among others, are used for the treatment of diabetes or for weight loss and may be associated with delayed gastric emptying.
Patients taking GLP-1 receptor agonists for diabetes management “need to be cautious about withholding these medications because doing so can adversely impact blood glucose control,” said Octavia Pickett-Blakely, MD, a gastroenterologist with University of Pennsylvania in Philadelphia and spokesperson for the American Gastroenterological Association (AGA). “In patients undergoing endoscopic procedures, poorly controlled blood glucose could raise the risk of complications.”
In a commentary on Medscape, David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, urges clinicians to learn about the topic and inform patients when prescribing GLP-1 receptor agonists.
“These are new and changing issues. In our world as gastroenterologists, we should be considering – very strongly – mitigating strategies to protect the patients on this wonderful class of therapy,” he says. “Sometimes these drugs can have significant side effects that we need to at least be aware of. Nothing is perfect, but let us be better informed.”
“We really don’t know what the risks are yet. With endoscopy, they could be significant, but perhaps they’re not,” Jonathan Leighton, MD, a gastroenterologist with Mayo Clinic Arizona in Phoenix and president-elect of the American College of Gastroenterology (ACG), told this news organization. “There are a lot of factors that go into this, and we just want to proceed cautiously and carefully until we know more.”
The ACG, AGA, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition released the statement on Aug. 11.
It was issued in response to recent guidance on the preoperative management of adults and children on GLP-1 receptor agonists put forth by the American Society of Anesthesiologists.
In a separate statement, the AGA stated that there is little, or no data on complications from aspiration.
“While there is anecdotal experience that increased gastroparesis risk may be dose dependent or related to whether it is being used for diabetes control versus weight loss, we also acknowledge that there is little, or no data related to the relative risk of complications from aspiration. As a result, the impact associated with stopping these therapies prior to undergoing upper GI endoscopy (EGD) or other moderate to deep sedated procedures is unknown at this time.
“As clinical gastroenterologists and hepatologists, we are very familiar with safety issues regarding the performance of endoscopy in our patients suffering from gastroparesis as well as unexplained nausea, vomiting, and epigastric pain, particularly in emergency situations. As patient safety will always be paramount, and in the absence of actionable data, we encourage our members to exercise best practices when performing endoscopy on these patients who are taking GLP-1 receptor agonists. More data are needed to understand if and when these medications should be held prior to elective endoscopy. Given the need for further data regarding the emerging use of these novel compounds, we encourage our anesthesiology, endocrinology, and industry partners to work collaboratively with our members to develop the necessary evidence to appropriately inform medication adjustments prior to elective endoscopy.”
ASA recommendations
The ASA Task Force on Preoperative Fasting reviewed the available literature on GLP-1 receptor agonists and associated gastrointestinal adverse effects, including the consequences of delayed gastric emptying.
The task force acknowledges that the evidence to provide guidance for preoperative management of these drugs to prevent regurgitation and pulmonary aspiration of gastric contents is “sparse, limited only to several case reports.”
Nevertheless, given the concerns of GLP-1 receptor agonist–induced delayed gastric emptying and associated high risk for regurgitation and aspiration of gastric contents, the task force made these recommendations for elective procedures.
The day before the procedure
For patients on daily dosing, consider holding GLP-1 agonists on the day of the procedure/surgery. For patients on weekly dosing, consider holding GLP-1 agonists a week prior to the procedure/surgery.
This suggestion is irrespective of the indication (type 2 diabetes or weight loss), dose, or the type of procedure/surgery.
If GLP-1 agonists prescribed for diabetes are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycemia.
The day of the procedure
If GI symptoms such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain are present, consider delaying the elective procedure and discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
If the patient has no GI symptoms and the GLP-1 agonists have been held as advised, proceed as usual.
If the patient has no GI symptoms but the GLP-1 agonists were not held as advised, proceed with “full stomach” precautions or consider evaluating gastric volume by ultrasound, if possible and if proficient with the technique. If the stomach is empty, proceed as usual. If the stomach is full or if gastric ultrasound is inconclusive or not possible, consider delaying the procedure or treat the patient as “full stomach” and manage accordingly. Discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
There is no evidence to suggest the optimal duration of fasting for patients on GLP-1 agonists. Therefore, until we have adequate evidence, we suggest following the current ASA fasting guidelines.
For patients on GLP-1 receptor agonists who need urgent or emergent procedures, the ASA advises proceeding and treating the patient as “full stomach” and managing accordingly.
Dr. Leighton has financial relationships with Olympus and Pfizer. Dr. Pickett-Blakely has no relevant disclosures. Dr. Johnson is an adviser to ISOTHRIVE and Johnson & Johnson.
This story was adapted for GI&Hepatology News from Medscape.
AHA reviews impact of aggressive LDL lowering on the brain
“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.
The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.
The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.
The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.
They reached four main conclusions:
- First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
- Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
- Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
- Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.
The research had no commercial funding. A list of disclosures for the writing group is available with the original article.
A version of this article appeared on Medscape.com.
“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.
The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.
The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.
The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.
They reached four main conclusions:
- First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
- Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
- Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
- Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.
The research had no commercial funding. A list of disclosures for the writing group is available with the original article.
A version of this article appeared on Medscape.com.
“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.
The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.
The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.
The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.
They reached four main conclusions:
- First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
- Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
- Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
- Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.
The research had no commercial funding. A list of disclosures for the writing group is available with the original article.
A version of this article appeared on Medscape.com.
FROM ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY