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Cendakimab That Targets IL-13 Shows Promise in Eosinophilic Esophagitis
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM UEG 2024
Acid Blockers Appear Superior to PPIs in Erosive Esophagitis
TOPLINE:
, a meta-analysis suggests.
METHODOLOGY:
- Researchers conducted a database search up to May 31, 2023, for randomized controlled trials of potassium-competitive acid blockers and PPIs for the treatment of erosive esophagitis. They included 34 trials in a systematic review and a network meta-analysis comparing the efficacy of the two medication classes in this patient population.
- The trials included 25,054 patients with erosive esophagitis, and the treatments involved were standard or double doses of potassium-competitive acid blockers (tegoprazan, vonoprazan, keverprazan, and fexuprazan), PPIs (esomeprazole, ilaprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole), or placebo.
- The researchers compared the healing rates at 4 and 8 weeks.
TAKEAWAY:
- The main analysis found that both potassium-competitive acid blockers and PPIs showed better healing rates at 4 and 8 weeks than placebo. This finding held up in a subgroup analysis of patients with and without severe erosive esophagitis at both time points.
- For most treatments, the pooled healing rates at 8 weeks were significantly higher than those at 4 weeks.
- In the main analysis, ilaprazole 10 mg once daily had the best healing rate (surface under the cumulative ranking curve [SUCRA], 89.3) at 4 weeks, followed by vonoprazan 40 mg once daily (SUCRA, 86.7). At 8 weeks, keverprazan 20 mg once daily ranked best (SUCRA, 84.7), followed by ilaprazole 10 mg once daily (SUCRA, 82.0).
- The subgroup analysis found that healing rates were higher with most potassium-competitive acid blockers than with PPIs, particularly for patients with severe erosive esophagitis. Keverprazan 20 mg daily was found to have the highest healing rate at 8 weeks for both severe and non-severe erosive esophagitis, and vonoprazan 40 mg daily had a relatively higher healing rate at 4 weeks.
IN PRACTICE:
The finding that most potassium-competitive acid blockers showed a higher healing rate than PPIs, particularly for patients with severe erosive esophagitis, “may help inform future directions of treatment,” the authors wrote. But high-quality randomized controlled trials are required to confirm potassium-competitive acid blockers’ healing effect in patients with erosive esophagitis, they added.
SOURCE:
The study, led by Yin Liu of the Henan Cancer Hospital (Affiliated Cancer Hospital of Zhengzhou University), Zhengzhou, and Zhifeng Gao of the Department of Gastroenterology, The First People’s Hospital of Xuzhou, Xuzhou, China, was published online in Therapeutic Advances in Gastroenterology.
LIMITATIONS:
The limitations of the study included heterogeneity and bias across included studies, a lack of head-to-head trials for all included treatments, and insufficient reporting on outcomes based on the severity of erosive esophagitis.
DISCLOSURES:
The authors received no financial support for the study. There were no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
, a meta-analysis suggests.
METHODOLOGY:
- Researchers conducted a database search up to May 31, 2023, for randomized controlled trials of potassium-competitive acid blockers and PPIs for the treatment of erosive esophagitis. They included 34 trials in a systematic review and a network meta-analysis comparing the efficacy of the two medication classes in this patient population.
- The trials included 25,054 patients with erosive esophagitis, and the treatments involved were standard or double doses of potassium-competitive acid blockers (tegoprazan, vonoprazan, keverprazan, and fexuprazan), PPIs (esomeprazole, ilaprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole), or placebo.
- The researchers compared the healing rates at 4 and 8 weeks.
TAKEAWAY:
- The main analysis found that both potassium-competitive acid blockers and PPIs showed better healing rates at 4 and 8 weeks than placebo. This finding held up in a subgroup analysis of patients with and without severe erosive esophagitis at both time points.
- For most treatments, the pooled healing rates at 8 weeks were significantly higher than those at 4 weeks.
- In the main analysis, ilaprazole 10 mg once daily had the best healing rate (surface under the cumulative ranking curve [SUCRA], 89.3) at 4 weeks, followed by vonoprazan 40 mg once daily (SUCRA, 86.7). At 8 weeks, keverprazan 20 mg once daily ranked best (SUCRA, 84.7), followed by ilaprazole 10 mg once daily (SUCRA, 82.0).
- The subgroup analysis found that healing rates were higher with most potassium-competitive acid blockers than with PPIs, particularly for patients with severe erosive esophagitis. Keverprazan 20 mg daily was found to have the highest healing rate at 8 weeks for both severe and non-severe erosive esophagitis, and vonoprazan 40 mg daily had a relatively higher healing rate at 4 weeks.
IN PRACTICE:
The finding that most potassium-competitive acid blockers showed a higher healing rate than PPIs, particularly for patients with severe erosive esophagitis, “may help inform future directions of treatment,” the authors wrote. But high-quality randomized controlled trials are required to confirm potassium-competitive acid blockers’ healing effect in patients with erosive esophagitis, they added.
SOURCE:
The study, led by Yin Liu of the Henan Cancer Hospital (Affiliated Cancer Hospital of Zhengzhou University), Zhengzhou, and Zhifeng Gao of the Department of Gastroenterology, The First People’s Hospital of Xuzhou, Xuzhou, China, was published online in Therapeutic Advances in Gastroenterology.
LIMITATIONS:
The limitations of the study included heterogeneity and bias across included studies, a lack of head-to-head trials for all included treatments, and insufficient reporting on outcomes based on the severity of erosive esophagitis.
DISCLOSURES:
The authors received no financial support for the study. There were no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
, a meta-analysis suggests.
METHODOLOGY:
- Researchers conducted a database search up to May 31, 2023, for randomized controlled trials of potassium-competitive acid blockers and PPIs for the treatment of erosive esophagitis. They included 34 trials in a systematic review and a network meta-analysis comparing the efficacy of the two medication classes in this patient population.
- The trials included 25,054 patients with erosive esophagitis, and the treatments involved were standard or double doses of potassium-competitive acid blockers (tegoprazan, vonoprazan, keverprazan, and fexuprazan), PPIs (esomeprazole, ilaprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole), or placebo.
- The researchers compared the healing rates at 4 and 8 weeks.
TAKEAWAY:
- The main analysis found that both potassium-competitive acid blockers and PPIs showed better healing rates at 4 and 8 weeks than placebo. This finding held up in a subgroup analysis of patients with and without severe erosive esophagitis at both time points.
- For most treatments, the pooled healing rates at 8 weeks were significantly higher than those at 4 weeks.
- In the main analysis, ilaprazole 10 mg once daily had the best healing rate (surface under the cumulative ranking curve [SUCRA], 89.3) at 4 weeks, followed by vonoprazan 40 mg once daily (SUCRA, 86.7). At 8 weeks, keverprazan 20 mg once daily ranked best (SUCRA, 84.7), followed by ilaprazole 10 mg once daily (SUCRA, 82.0).
- The subgroup analysis found that healing rates were higher with most potassium-competitive acid blockers than with PPIs, particularly for patients with severe erosive esophagitis. Keverprazan 20 mg daily was found to have the highest healing rate at 8 weeks for both severe and non-severe erosive esophagitis, and vonoprazan 40 mg daily had a relatively higher healing rate at 4 weeks.
IN PRACTICE:
The finding that most potassium-competitive acid blockers showed a higher healing rate than PPIs, particularly for patients with severe erosive esophagitis, “may help inform future directions of treatment,” the authors wrote. But high-quality randomized controlled trials are required to confirm potassium-competitive acid blockers’ healing effect in patients with erosive esophagitis, they added.
SOURCE:
The study, led by Yin Liu of the Henan Cancer Hospital (Affiliated Cancer Hospital of Zhengzhou University), Zhengzhou, and Zhifeng Gao of the Department of Gastroenterology, The First People’s Hospital of Xuzhou, Xuzhou, China, was published online in Therapeutic Advances in Gastroenterology.
LIMITATIONS:
The limitations of the study included heterogeneity and bias across included studies, a lack of head-to-head trials for all included treatments, and insufficient reporting on outcomes based on the severity of erosive esophagitis.
DISCLOSURES:
The authors received no financial support for the study. There were no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
FDA OKs Voquezna for Heartburn Relief in Nonerosive Gastroesophageal Reflux Disease
It represents the third indication for the potassium-competitive acid blocker, which is already approved to treat all severities of erosive esophagitis and to eradicate Helicobacter pylori infection in combination with antibiotics.
The approval in nonerosive GERD was supported by results of the PHALCON-nonerosive GERD-301 study, a phase 3 randomized, placebo-controlled, double-blind, multicenter study evaluating the safety and efficacy of once-daily Voquezna in more than 700 adults with nonerosive GERD experiencing at least 4 days of heartburn per week.
“Vonoprazan was efficacious in reducing heartburn symptoms in patients with [nonerosive GERD], with the benefit appearing to begin as early as the first day of therapy. This treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period,” the study team wrote in a paper published online in Clinical Gastroenterology and Hepatology , and reported on by this news organization.
Voquezna “provides physicians with a novel, first-in-class treatment that can quickly and significantly reduce heartburn for many adult patients” with nonerosive GERD, Colin W. Howden, MD, AGAF, professor emeritus, University of Tennessee College of Medicine in Memphis, said in a news release. 
The most common adverse events reported in patients treated with Voquezna during the 4-week placebo-controlled period were abdominal pain, constipation, diarrhea, nausea, and urinary tract infection.
Upper respiratory tract infection and sinusitis were also reported in patients who taking Voquezna in the 20-week extension phase of the trial.
Full prescribing information is available online.
A version of this article appeared on Medscape.com.
It represents the third indication for the potassium-competitive acid blocker, which is already approved to treat all severities of erosive esophagitis and to eradicate Helicobacter pylori infection in combination with antibiotics.
The approval in nonerosive GERD was supported by results of the PHALCON-nonerosive GERD-301 study, a phase 3 randomized, placebo-controlled, double-blind, multicenter study evaluating the safety and efficacy of once-daily Voquezna in more than 700 adults with nonerosive GERD experiencing at least 4 days of heartburn per week.
“Vonoprazan was efficacious in reducing heartburn symptoms in patients with [nonerosive GERD], with the benefit appearing to begin as early as the first day of therapy. This treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period,” the study team wrote in a paper published online in Clinical Gastroenterology and Hepatology , and reported on by this news organization.
Voquezna “provides physicians with a novel, first-in-class treatment that can quickly and significantly reduce heartburn for many adult patients” with nonerosive GERD, Colin W. Howden, MD, AGAF, professor emeritus, University of Tennessee College of Medicine in Memphis, said in a news release.
The most common adverse events reported in patients treated with Voquezna during the 4-week placebo-controlled period were abdominal pain, constipation, diarrhea, nausea, and urinary tract infection.
Upper respiratory tract infection and sinusitis were also reported in patients who taking Voquezna in the 20-week extension phase of the trial.
Full prescribing information is available online.
A version of this article appeared on Medscape.com.
It represents the third indication for the potassium-competitive acid blocker, which is already approved to treat all severities of erosive esophagitis and to eradicate Helicobacter pylori infection in combination with antibiotics.
The approval in nonerosive GERD was supported by results of the PHALCON-nonerosive GERD-301 study, a phase 3 randomized, placebo-controlled, double-blind, multicenter study evaluating the safety and efficacy of once-daily Voquezna in more than 700 adults with nonerosive GERD experiencing at least 4 days of heartburn per week.
“Vonoprazan was efficacious in reducing heartburn symptoms in patients with [nonerosive GERD], with the benefit appearing to begin as early as the first day of therapy. This treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period,” the study team wrote in a paper published online in Clinical Gastroenterology and Hepatology , and reported on by this news organization.
Voquezna “provides physicians with a novel, first-in-class treatment that can quickly and significantly reduce heartburn for many adult patients” with nonerosive GERD, Colin W. Howden, MD, AGAF, professor emeritus, University of Tennessee College of Medicine in Memphis, said in a news release.
The most common adverse events reported in patients treated with Voquezna during the 4-week placebo-controlled period were abdominal pain, constipation, diarrhea, nausea, and urinary tract infection.
Upper respiratory tract infection and sinusitis were also reported in patients who taking Voquezna in the 20-week extension phase of the trial.
Full prescribing information is available online.
A version of this article appeared on Medscape.com.
Gene Tests Could Predict if a Drug Will Work for a Patient
What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?
That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.
“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.
Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.
Dr. Cicali said.
Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.
Why PGx Tests Can Have a Big Impact
These tests work by looking for genes that control drug metabolism.
“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”
While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.
Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)
“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”
What the Research Shows
When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.
The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.
When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.
The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.
“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”
Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.
By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:
- In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
- In a 2023 from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
- In a University of Pennsylvania of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.
PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.
The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.
Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.
“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”
When, Why, and How to Test
“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.
You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.
Here’s how four PGx experts suggest consumers and physicians approach this option.
Find a Test
More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)
Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.
The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.
For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.
Consider Cost
The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.
In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.
Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.
Understand the Results
As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.
In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.
Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.
Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).
Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.
Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.
Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.
A version of this article appeared on Medscape.com.
What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?
That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.
“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.
Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.
Dr. Cicali said.
Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.
Why PGx Tests Can Have a Big Impact
These tests work by looking for genes that control drug metabolism.
“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”
While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.
Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)
“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”
What the Research Shows
When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.
The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.
When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.
The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.
“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”
Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.
By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:
- In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
- In a 2023 from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
- In a University of Pennsylvania of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.
PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.
The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.
Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.
“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”
When, Why, and How to Test
“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.
You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.
Here’s how four PGx experts suggest consumers and physicians approach this option.
Find a Test
More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)
Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.
The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.
For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.
Consider Cost
The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.
In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.
Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.
Understand the Results
As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.
In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.
Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.
Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).
Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.
Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.
Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.
A version of this article appeared on Medscape.com.
What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?
That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.
“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.
Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.
Dr. Cicali said.
Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.
Why PGx Tests Can Have a Big Impact
These tests work by looking for genes that control drug metabolism.
“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”
While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.
Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)
“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”
What the Research Shows
When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.
The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.
When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.
The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.
“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”
Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.
By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:
- In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
- In a 2023 from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
- In a University of Pennsylvania of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.
PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.
The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.
Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.
“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”
When, Why, and How to Test
“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.
You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.
Here’s how four PGx experts suggest consumers and physicians approach this option.
Find a Test
More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)
Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.
The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.
For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.
Consider Cost
The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.
In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.
Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.
Understand the Results
As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.
In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.
Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.
Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).
Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.
Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.
Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.
A version of this article appeared on Medscape.com.
Menopause, RSV, and More: 4 New Meds to Know
BOSTON — The US Food and Drug Administration (FDA) approved 55 new medications in 2023 and 11 more in 2024 to date.
A New First-Line for GERD?
Vonoprazan, an oral potassium-competitive acid blocker — which received FDA approval in November 2023 — may be a good alternative for patients whose symptoms continue to linger despite taking medications designated to treat gastroesophageal reflux disease (GERD).
GERD is the most common gastrointestinal symptom encountered by primary care physicians. Proton-pump inhibitors (PPIs) are the first-line treatment for the condition but can have long-term side effects such as Clostridioides difficile infection and kidney lesions.
“We know that not all patients are going to have symptom relief with H2 blockers and PPIs, so there’s an opportunity for patients who don’t get full symptom relief,” Dr. Smetana told attendees.
Vonoprazan blocks potassium binding to ATPase proton pumps and inhibits the secretion of gastric acid.
The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study, a randomized, double-blind, multicenter study that found the drug to be more effective than lansoprazole in treating erosive esophagitis.
Vonoprazan “has more rapid absorption than PPIs [and a] longer half-life and is more potent than PPIs, so theoretically it could be more effective in certain settings,” Dr. Smetana said.
Vonoprazan is FDA approved for only 6 months of use. Despite its efficacy, cost may be a barrier to many patients. H2 blockers generally cost patients less than $10 for 1 month’s supply, whereas vonoprazan can cost up to $650.
Nonhormonal Drug for Menopause
Fezolinetant, the first neurokinin receptor antagonist to receive approval from the FDA to treat vasomotor symptoms, may be an option for women concerned about hormone-based therapy for menopausal hot flashes.
“[Fezolinetant] specifically works in the area of the brain that’s involved in body temperature regulation and sweating,” Dr. Smetana said.
Results from the SKYLIGHT 1 randomized controlled trial of fezolinetant found the medication reduced the frequency and severity of hot flashes. Some of the side effects include abdominal pain, diarrhea, and insomnia.
Other nonestrogen treatments, including selective serotonin reuptake inhibitors (SSRIs), gabapentin, cognitive-behavioral therapy, and hypnosis, are modestly effective, according to the North American Menopause Society.
“[Fezolinetant] offers a different option that physicians may be more comfortable prescribing,” Dr. Smetana said. “And I think this will be an important addition to nonhormonal therapy.”
RSV Vaccine for Everyone
Once considered an illness that is more prevalent in young children, respiratory syncytial virus (RSV) has become more prevalent and severe among older adults. Between 60,000 and 120,000 older adults are hospitalized and 6000-10,000 die of RSV infection each year, according to the US Centers for Disease Control and Prevention.
The FDA has approved two RSV vaccines approved for older adults, but clinicians may find it challenging to get older patients vaccinated for this and other preventable illnesses.
Patients who received the RSV vaccine had an 83% relative risk reduction for the illness, according to a recent study, and an overall lower risk for hospitalization.
Moderna is developing an mRNA vaccine for RSV that is similar to many COVID-19 vaccines. A study published in 2023 in The New England Journal of Medicine found no cases of neuroinflammatory disorders among patients who received the mRNA RSV vaccine, with a median follow-up of 112 days.
“This is important given ongoing concerns of neurological safety,” among older adults who receive the RSV vaccine, Dr. Smetana said.
As of March 2024, the CDC recommends shared decision-making for adults older than 60 years and for healthcare providers to “consider” rather than “recommend” the vaccine for their patients. The agency’s Adult RSV Work Group plans to meet at June 2024 to reconsider whether shared clinical decision-making remains the preferred policy option.
New Antidepressants
A medication thrice rejected by the FDA is now heading a new class of drugs to treat major depressive disorder.
Gepirone, a 5-HT1A receptor agonist, has a different mechanism of action from that of SSRIs, which are currently considered the first-line treatment for depression.
Gepirone was rejected by the FDA in 2002, 2004, and 2007, with concerns that the efficacy studies were too small. In 2015, an FDA advisory committee agreed that the evidence to date did not support approval of an extended-release form of the drug. But the agency decided to approve the medication in September 2023.
“So why is this medication worth discussing now?” Dr. Smetana said. “It’s because the side effect profile is different from existing antidepressants.”
Many patients may stop using SSRIs because of side effects such as insomnia and loss of libido, Dr. Smetana said. Gepirone has the potential to avoid activation of other 5-HT receptors that mediate side effects, he said.
Studies suggest that gepirone reduces both anxiety and depression scores on the Hamilton Depression Rating Scale in patients who have both conditions and decreases rates of depression relapse compared with placebo through at least 48 weeks. The drug also may be less likely than SSRIs to cause sexual dysfunction in men, Dr. Smetana said.
Gepirone will be available to prescribe to patients in fall 2024.
Dr. Smetana reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
BOSTON — The US Food and Drug Administration (FDA) approved 55 new medications in 2023 and 11 more in 2024 to date.
A New First-Line for GERD?
Vonoprazan, an oral potassium-competitive acid blocker — which received FDA approval in November 2023 — may be a good alternative for patients whose symptoms continue to linger despite taking medications designated to treat gastroesophageal reflux disease (GERD).
GERD is the most common gastrointestinal symptom encountered by primary care physicians. Proton-pump inhibitors (PPIs) are the first-line treatment for the condition but can have long-term side effects such as Clostridioides difficile infection and kidney lesions.
“We know that not all patients are going to have symptom relief with H2 blockers and PPIs, so there’s an opportunity for patients who don’t get full symptom relief,” Dr. Smetana told attendees.
Vonoprazan blocks potassium binding to ATPase proton pumps and inhibits the secretion of gastric acid.
The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study, a randomized, double-blind, multicenter study that found the drug to be more effective than lansoprazole in treating erosive esophagitis.
Vonoprazan “has more rapid absorption than PPIs [and a] longer half-life and is more potent than PPIs, so theoretically it could be more effective in certain settings,” Dr. Smetana said.
Vonoprazan is FDA approved for only 6 months of use. Despite its efficacy, cost may be a barrier to many patients. H2 blockers generally cost patients less than $10 for 1 month’s supply, whereas vonoprazan can cost up to $650.
Nonhormonal Drug for Menopause
Fezolinetant, the first neurokinin receptor antagonist to receive approval from the FDA to treat vasomotor symptoms, may be an option for women concerned about hormone-based therapy for menopausal hot flashes.
“[Fezolinetant] specifically works in the area of the brain that’s involved in body temperature regulation and sweating,” Dr. Smetana said.
Results from the SKYLIGHT 1 randomized controlled trial of fezolinetant found the medication reduced the frequency and severity of hot flashes. Some of the side effects include abdominal pain, diarrhea, and insomnia.
Other nonestrogen treatments, including selective serotonin reuptake inhibitors (SSRIs), gabapentin, cognitive-behavioral therapy, and hypnosis, are modestly effective, according to the North American Menopause Society.
“[Fezolinetant] offers a different option that physicians may be more comfortable prescribing,” Dr. Smetana said. “And I think this will be an important addition to nonhormonal therapy.”
RSV Vaccine for Everyone
Once considered an illness that is more prevalent in young children, respiratory syncytial virus (RSV) has become more prevalent and severe among older adults. Between 60,000 and 120,000 older adults are hospitalized and 6000-10,000 die of RSV infection each year, according to the US Centers for Disease Control and Prevention.
The FDA has approved two RSV vaccines approved for older adults, but clinicians may find it challenging to get older patients vaccinated for this and other preventable illnesses.
Patients who received the RSV vaccine had an 83% relative risk reduction for the illness, according to a recent study, and an overall lower risk for hospitalization.
Moderna is developing an mRNA vaccine for RSV that is similar to many COVID-19 vaccines. A study published in 2023 in The New England Journal of Medicine found no cases of neuroinflammatory disorders among patients who received the mRNA RSV vaccine, with a median follow-up of 112 days.
“This is important given ongoing concerns of neurological safety,” among older adults who receive the RSV vaccine, Dr. Smetana said.
As of March 2024, the CDC recommends shared decision-making for adults older than 60 years and for healthcare providers to “consider” rather than “recommend” the vaccine for their patients. The agency’s Adult RSV Work Group plans to meet at June 2024 to reconsider whether shared clinical decision-making remains the preferred policy option.
New Antidepressants
A medication thrice rejected by the FDA is now heading a new class of drugs to treat major depressive disorder.
Gepirone, a 5-HT1A receptor agonist, has a different mechanism of action from that of SSRIs, which are currently considered the first-line treatment for depression.
Gepirone was rejected by the FDA in 2002, 2004, and 2007, with concerns that the efficacy studies were too small. In 2015, an FDA advisory committee agreed that the evidence to date did not support approval of an extended-release form of the drug. But the agency decided to approve the medication in September 2023.
“So why is this medication worth discussing now?” Dr. Smetana said. “It’s because the side effect profile is different from existing antidepressants.”
Many patients may stop using SSRIs because of side effects such as insomnia and loss of libido, Dr. Smetana said. Gepirone has the potential to avoid activation of other 5-HT receptors that mediate side effects, he said.
Studies suggest that gepirone reduces both anxiety and depression scores on the Hamilton Depression Rating Scale in patients who have both conditions and decreases rates of depression relapse compared with placebo through at least 48 weeks. The drug also may be less likely than SSRIs to cause sexual dysfunction in men, Dr. Smetana said.
Gepirone will be available to prescribe to patients in fall 2024.
Dr. Smetana reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
BOSTON — The US Food and Drug Administration (FDA) approved 55 new medications in 2023 and 11 more in 2024 to date.
A New First-Line for GERD?
Vonoprazan, an oral potassium-competitive acid blocker — which received FDA approval in November 2023 — may be a good alternative for patients whose symptoms continue to linger despite taking medications designated to treat gastroesophageal reflux disease (GERD).
GERD is the most common gastrointestinal symptom encountered by primary care physicians. Proton-pump inhibitors (PPIs) are the first-line treatment for the condition but can have long-term side effects such as Clostridioides difficile infection and kidney lesions.
“We know that not all patients are going to have symptom relief with H2 blockers and PPIs, so there’s an opportunity for patients who don’t get full symptom relief,” Dr. Smetana told attendees.
Vonoprazan blocks potassium binding to ATPase proton pumps and inhibits the secretion of gastric acid.
The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study, a randomized, double-blind, multicenter study that found the drug to be more effective than lansoprazole in treating erosive esophagitis.
Vonoprazan “has more rapid absorption than PPIs [and a] longer half-life and is more potent than PPIs, so theoretically it could be more effective in certain settings,” Dr. Smetana said.
Vonoprazan is FDA approved for only 6 months of use. Despite its efficacy, cost may be a barrier to many patients. H2 blockers generally cost patients less than $10 for 1 month’s supply, whereas vonoprazan can cost up to $650.
Nonhormonal Drug for Menopause
Fezolinetant, the first neurokinin receptor antagonist to receive approval from the FDA to treat vasomotor symptoms, may be an option for women concerned about hormone-based therapy for menopausal hot flashes.
“[Fezolinetant] specifically works in the area of the brain that’s involved in body temperature regulation and sweating,” Dr. Smetana said.
Results from the SKYLIGHT 1 randomized controlled trial of fezolinetant found the medication reduced the frequency and severity of hot flashes. Some of the side effects include abdominal pain, diarrhea, and insomnia.
Other nonestrogen treatments, including selective serotonin reuptake inhibitors (SSRIs), gabapentin, cognitive-behavioral therapy, and hypnosis, are modestly effective, according to the North American Menopause Society.
“[Fezolinetant] offers a different option that physicians may be more comfortable prescribing,” Dr. Smetana said. “And I think this will be an important addition to nonhormonal therapy.”
RSV Vaccine for Everyone
Once considered an illness that is more prevalent in young children, respiratory syncytial virus (RSV) has become more prevalent and severe among older adults. Between 60,000 and 120,000 older adults are hospitalized and 6000-10,000 die of RSV infection each year, according to the US Centers for Disease Control and Prevention.
The FDA has approved two RSV vaccines approved for older adults, but clinicians may find it challenging to get older patients vaccinated for this and other preventable illnesses.
Patients who received the RSV vaccine had an 83% relative risk reduction for the illness, according to a recent study, and an overall lower risk for hospitalization.
Moderna is developing an mRNA vaccine for RSV that is similar to many COVID-19 vaccines. A study published in 2023 in The New England Journal of Medicine found no cases of neuroinflammatory disorders among patients who received the mRNA RSV vaccine, with a median follow-up of 112 days.
“This is important given ongoing concerns of neurological safety,” among older adults who receive the RSV vaccine, Dr. Smetana said.
As of March 2024, the CDC recommends shared decision-making for adults older than 60 years and for healthcare providers to “consider” rather than “recommend” the vaccine for their patients. The agency’s Adult RSV Work Group plans to meet at June 2024 to reconsider whether shared clinical decision-making remains the preferred policy option.
New Antidepressants
A medication thrice rejected by the FDA is now heading a new class of drugs to treat major depressive disorder.
Gepirone, a 5-HT1A receptor agonist, has a different mechanism of action from that of SSRIs, which are currently considered the first-line treatment for depression.
Gepirone was rejected by the FDA in 2002, 2004, and 2007, with concerns that the efficacy studies were too small. In 2015, an FDA advisory committee agreed that the evidence to date did not support approval of an extended-release form of the drug. But the agency decided to approve the medication in September 2023.
“So why is this medication worth discussing now?” Dr. Smetana said. “It’s because the side effect profile is different from existing antidepressants.”
Many patients may stop using SSRIs because of side effects such as insomnia and loss of libido, Dr. Smetana said. Gepirone has the potential to avoid activation of other 5-HT receptors that mediate side effects, he said.
Studies suggest that gepirone reduces both anxiety and depression scores on the Hamilton Depression Rating Scale in patients who have both conditions and decreases rates of depression relapse compared with placebo through at least 48 weeks. The drug also may be less likely than SSRIs to cause sexual dysfunction in men, Dr. Smetana said.
Gepirone will be available to prescribe to patients in fall 2024.
Dr. Smetana reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Erosive Esophagitis: 5 Things to Know
Erosive esophagitis (EE) is erosion of the esophageal epithelium due to chronic irritation. It can be caused by a number of factors but is primarily a result of gastroesophageal reflux disease (GERD). The main symptoms of EE are heartburn and regurgitation; other symptoms can include epigastric pain, odynophagia, dysphagia, nausea, chronic cough, dental erosion, laryngitis, and asthma. , including nonerosive esophagitis and Barrett esophagus (BE). EE occurs in approximately 30% of cases of GERD, and EE may evolve to BE in 1%-13% of cases.
Long-term management of EE focuses on relieving symptoms to allow the esophageal lining to heal, thereby reducing both acute symptoms and the risk for other complications. Management plans may incorporate lifestyle changes, such as dietary modifications and weight loss, alongside pharmacologic therapy. In extreme cases, surgery may be considered to repair a damaged esophagus and/or to prevent ongoing acid reflux. If left untreated, EE may progress, potentially leading to more serious conditions.
Here are five things to know about EE.
1. GERD is the main risk factor for EE, but not the only risk factor.
An estimated 1% of the population has EE. Risk factors other than GERD include:
Radiation therapy toxicity can cause acute or chronic EE. For individuals undergoing radiotherapy, radiation esophagitis is a relatively frequent complication. Acute esophagitis generally occurs in all patients taking radiation doses of 6000 cGy given in fractions of 1000 cGy per week. The risk is lower among patients on longer schedules and lower doses of radiotherapy.
Bacterial, viral, and fungal infections can cause EE. These include herpes, CMV, HIV, Helicobacter pylori, and Candida.
Food allergies, asthma, and eczema are associated with eosinophilic esophagitis, which disproportionately affects young men and has an estimated prevalence of 55 cases per 100,000 population.
Oral medication in pill form causes esophagitis at an estimated rate of 3.9 cases per 100,000 population per year. The mean age at diagnosis is 41.5 years. Oral bisphosphonates such as alendronate are the most common agents, along with antibiotics such as tetracycline, doxycycline, and clindamycin. There have also been reports of pill-induced esophagitis with NSAIDs, aspirin, ferrous sulfate, potassium chloride, and mexiletine.
Excessive vomiting can, in rare cases, cause esophagitis.
Certain autoimmune diseases can manifest as EE.
2. Proton pump inhibitors (PPIs) remain the preferred treatment for EE.
Several over-the-counter and prescription medications can be used to manage the symptoms of EE. PPIs are the preferred treatment both in the acute setting and for maintenance therapy. PPIs help to alleviate symptoms and promote healing of the esophageal lining by reducing the production of stomach acid. Options include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. Many patients with EE require a dose that exceeds the FDA-approved dose for GERD. For instance, a 40-mg/d dosage of omeprazole is recommended in the latest guidelines, although the FDA-approved dosage is 20 mg/d.
H2-receptor antagonists, including famotidine, cimetidine, and nizatidine, may also be prescribed to reduce stomach acid production and promote healing in patients with EE due to GERD, but these agents are considered less efficacious than PPIs for either acute or maintenance therapy.
The potassium-competitive acid blocker (PCAB) vonoprazan is the latest agent to be indicated for EE and may provide more potent acid suppression for patients. A randomized comparative trial showed noninferiority compared with lansoprazole for healing and maintenance of healing of EE. In another randomized comparative study, the investigational PCAP fexuprazan was shown to be noninferior to the PPI esomeprazole in treating EE.
Mild GERD symptoms can be controlled by traditional antacids taken after each meal and at bedtime or with short-term use of prokinetic agents, which can help reduce acid reflux by improving esophageal and stomach motility and by increasing pressure to the lower esophageal sphincter. Gastric emptying is also accelerated by prokinetic agents. Long-term use is discouraged, as it may cause serious or life-threatening complications.
In patients who do not fully respond to PPI therapy, surgical therapy may be considered. Other candidates for surgery include younger patients, those who have difficulty adhering to treatment, postmenopausal women with osteoporosis, patients with cardiac conduction defects, and those for whom the cost of treatment is prohibitive. Surgery may also be warranted if there are extraesophageal manifestations of GERD, such as enamel erosion; respiratory issues (eg, coughing, wheezing, aspiration); or ear, nose, and throat manifestations (eg, hoarseness, sore throat, otitis media). For those who have progressed to BE, surgical intervention is also indicated.
The types of surgery for patients with EE have evolved to include both transthoracic and transabdominal fundoplication. Usually, a 360° transabdominal fundoplication is performed. General anesthesia is required for laparoscopic fundoplication, in which five small incisions are used to create a new valve at the level of the esophagogastric junction by wrapping the fundus of the stomach around the esophagus.
Laparoscopic insertion of a small band known as the LINX Reflux Management System is FDA approved to augment the lower esophageal sphincter. The system creates a natural barrier to reflux by placing a band consisting of titanium beads with magnetic cores around the esophagus just above the stomach. The magnetic bond is temporarily disrupted by swallowing, allowing food and liquid to pass.
Endoscopic therapies are another treatment option for certain patients who are not considered candidates for surgery or long-term therapy. Among the types of endoscopic procedures are radiofrequency therapy, suturing/plication, and mucosal ablation/resection techniques at the gastroesophageal junction. Full-thickness endoscopic suturing is an area of interest because this technique offers significant durability of the recreated lower esophageal sphincter.
3. PPI therapy for GERD should be stopped before endoscopy is performed to confirm a diagnosis of EE.
A clinical diagnosis of GERD can be made if the presenting symptoms are heartburn and regurgitation, without chest pain or alarm symptoms such as dysphagia, weight loss, or gastrointestinal bleeding. In this setting, once-daily PPIs are generally prescribed for 8 weeks to see if symptoms resolve. If symptoms have not resolved, a twice-daily PPI regimen may be prescribed. In patients who do not respond to PPIs, or for whom GERD returns after stopping therapy, an upper endoscopy with biopsy is recommended after 2-4 weeks off therapy to rule out other causes. Endoscopy should be the first step in diagnosis for individuals experiencing chest pain without heartburn; those in whom heart disease has been ruled out; individuals experiencing dysphagia, weight loss, or gastrointestinal bleeding; or those who have multiple risk factors for BE.
4. The most serious complication of EE is BE, which can lead to esophageal cancer.
Several complications can arise from EE. The most serious of these is BE, which can lead to esophageal adenocarcinoma. BE is characterized by the conversion of normal distal squamous esophageal epithelium to columnar epithelium. It has the potential to become malignant if it exhibits intestinal-type metaplasia. In the industrialized world, adenocarcinoma currently represents more than half of all esophageal cancers. The most common symptom of esophageal cancer is dysphagia. Other signs and symptoms include weight loss, hoarseness, chronic or intractable cough, bleeding, epigastric or retrosternal pain, frequent pneumonia, and, if metastatic, bone pain.
5. Lifestyle modifications can help control the symptoms of EE.
Guidelines recommend a number of lifestyle modification strategies to help control the symptoms of EE. Smoking cessation and weight loss are two evidence-based strategies for relieving symptoms of GERD and, ultimately, lowering the risk for esophageal cancer. One large prospective Norwegian cohort study (N = 29,610) found that stopping smoking improved GERD symptoms, but only in those with normal body mass index. In a smaller Japanese study (N = 191) specifically surveying people attempting smoking cessation, individuals who successfully stopped smoking had a 44% improvement in GERD symptoms at 1 year, vs an 18% improvement in those who continued to smoke, with no statistical difference between the success and failure groups based on patient body mass index (P = .60).
Other recommended strategies for nonpharmacologic management of EE symptoms include elevation of the head when lying down in bed and avoidance of lying down after eating, cessation of alcohol consumption, avoidance of food close to bedtime, and avoidance of trigger foods that can incite or worsen symptoms of acid reflux. Such trigger foods vary among individuals, but they often include fatty foods, coffee, chocolate, carbonated beverages, spicy foods, citrus fruits, and tomatoes.
Dr. Puerta has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Erosive esophagitis (EE) is erosion of the esophageal epithelium due to chronic irritation. It can be caused by a number of factors but is primarily a result of gastroesophageal reflux disease (GERD). The main symptoms of EE are heartburn and regurgitation; other symptoms can include epigastric pain, odynophagia, dysphagia, nausea, chronic cough, dental erosion, laryngitis, and asthma. , including nonerosive esophagitis and Barrett esophagus (BE). EE occurs in approximately 30% of cases of GERD, and EE may evolve to BE in 1%-13% of cases.
Long-term management of EE focuses on relieving symptoms to allow the esophageal lining to heal, thereby reducing both acute symptoms and the risk for other complications. Management plans may incorporate lifestyle changes, such as dietary modifications and weight loss, alongside pharmacologic therapy. In extreme cases, surgery may be considered to repair a damaged esophagus and/or to prevent ongoing acid reflux. If left untreated, EE may progress, potentially leading to more serious conditions.
Here are five things to know about EE.
1. GERD is the main risk factor for EE, but not the only risk factor.
An estimated 1% of the population has EE. Risk factors other than GERD include:
Radiation therapy toxicity can cause acute or chronic EE. For individuals undergoing radiotherapy, radiation esophagitis is a relatively frequent complication. Acute esophagitis generally occurs in all patients taking radiation doses of 6000 cGy given in fractions of 1000 cGy per week. The risk is lower among patients on longer schedules and lower doses of radiotherapy.
Bacterial, viral, and fungal infections can cause EE. These include herpes, CMV, HIV, Helicobacter pylori, and Candida.
Food allergies, asthma, and eczema are associated with eosinophilic esophagitis, which disproportionately affects young men and has an estimated prevalence of 55 cases per 100,000 population.
Oral medication in pill form causes esophagitis at an estimated rate of 3.9 cases per 100,000 population per year. The mean age at diagnosis is 41.5 years. Oral bisphosphonates such as alendronate are the most common agents, along with antibiotics such as tetracycline, doxycycline, and clindamycin. There have also been reports of pill-induced esophagitis with NSAIDs, aspirin, ferrous sulfate, potassium chloride, and mexiletine.
Excessive vomiting can, in rare cases, cause esophagitis.
Certain autoimmune diseases can manifest as EE.
2. Proton pump inhibitors (PPIs) remain the preferred treatment for EE.
Several over-the-counter and prescription medications can be used to manage the symptoms of EE. PPIs are the preferred treatment both in the acute setting and for maintenance therapy. PPIs help to alleviate symptoms and promote healing of the esophageal lining by reducing the production of stomach acid. Options include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. Many patients with EE require a dose that exceeds the FDA-approved dose for GERD. For instance, a 40-mg/d dosage of omeprazole is recommended in the latest guidelines, although the FDA-approved dosage is 20 mg/d.
H2-receptor antagonists, including famotidine, cimetidine, and nizatidine, may also be prescribed to reduce stomach acid production and promote healing in patients with EE due to GERD, but these agents are considered less efficacious than PPIs for either acute or maintenance therapy.
The potassium-competitive acid blocker (PCAB) vonoprazan is the latest agent to be indicated for EE and may provide more potent acid suppression for patients. A randomized comparative trial showed noninferiority compared with lansoprazole for healing and maintenance of healing of EE. In another randomized comparative study, the investigational PCAP fexuprazan was shown to be noninferior to the PPI esomeprazole in treating EE.
Mild GERD symptoms can be controlled by traditional antacids taken after each meal and at bedtime or with short-term use of prokinetic agents, which can help reduce acid reflux by improving esophageal and stomach motility and by increasing pressure to the lower esophageal sphincter. Gastric emptying is also accelerated by prokinetic agents. Long-term use is discouraged, as it may cause serious or life-threatening complications.
In patients who do not fully respond to PPI therapy, surgical therapy may be considered. Other candidates for surgery include younger patients, those who have difficulty adhering to treatment, postmenopausal women with osteoporosis, patients with cardiac conduction defects, and those for whom the cost of treatment is prohibitive. Surgery may also be warranted if there are extraesophageal manifestations of GERD, such as enamel erosion; respiratory issues (eg, coughing, wheezing, aspiration); or ear, nose, and throat manifestations (eg, hoarseness, sore throat, otitis media). For those who have progressed to BE, surgical intervention is also indicated.
The types of surgery for patients with EE have evolved to include both transthoracic and transabdominal fundoplication. Usually, a 360° transabdominal fundoplication is performed. General anesthesia is required for laparoscopic fundoplication, in which five small incisions are used to create a new valve at the level of the esophagogastric junction by wrapping the fundus of the stomach around the esophagus.
Laparoscopic insertion of a small band known as the LINX Reflux Management System is FDA approved to augment the lower esophageal sphincter. The system creates a natural barrier to reflux by placing a band consisting of titanium beads with magnetic cores around the esophagus just above the stomach. The magnetic bond is temporarily disrupted by swallowing, allowing food and liquid to pass.
Endoscopic therapies are another treatment option for certain patients who are not considered candidates for surgery or long-term therapy. Among the types of endoscopic procedures are radiofrequency therapy, suturing/plication, and mucosal ablation/resection techniques at the gastroesophageal junction. Full-thickness endoscopic suturing is an area of interest because this technique offers significant durability of the recreated lower esophageal sphincter.
3. PPI therapy for GERD should be stopped before endoscopy is performed to confirm a diagnosis of EE.
A clinical diagnosis of GERD can be made if the presenting symptoms are heartburn and regurgitation, without chest pain or alarm symptoms such as dysphagia, weight loss, or gastrointestinal bleeding. In this setting, once-daily PPIs are generally prescribed for 8 weeks to see if symptoms resolve. If symptoms have not resolved, a twice-daily PPI regimen may be prescribed. In patients who do not respond to PPIs, or for whom GERD returns after stopping therapy, an upper endoscopy with biopsy is recommended after 2-4 weeks off therapy to rule out other causes. Endoscopy should be the first step in diagnosis for individuals experiencing chest pain without heartburn; those in whom heart disease has been ruled out; individuals experiencing dysphagia, weight loss, or gastrointestinal bleeding; or those who have multiple risk factors for BE.
4. The most serious complication of EE is BE, which can lead to esophageal cancer.
Several complications can arise from EE. The most serious of these is BE, which can lead to esophageal adenocarcinoma. BE is characterized by the conversion of normal distal squamous esophageal epithelium to columnar epithelium. It has the potential to become malignant if it exhibits intestinal-type metaplasia. In the industrialized world, adenocarcinoma currently represents more than half of all esophageal cancers. The most common symptom of esophageal cancer is dysphagia. Other signs and symptoms include weight loss, hoarseness, chronic or intractable cough, bleeding, epigastric or retrosternal pain, frequent pneumonia, and, if metastatic, bone pain.
5. Lifestyle modifications can help control the symptoms of EE.
Guidelines recommend a number of lifestyle modification strategies to help control the symptoms of EE. Smoking cessation and weight loss are two evidence-based strategies for relieving symptoms of GERD and, ultimately, lowering the risk for esophageal cancer. One large prospective Norwegian cohort study (N = 29,610) found that stopping smoking improved GERD symptoms, but only in those with normal body mass index. In a smaller Japanese study (N = 191) specifically surveying people attempting smoking cessation, individuals who successfully stopped smoking had a 44% improvement in GERD symptoms at 1 year, vs an 18% improvement in those who continued to smoke, with no statistical difference between the success and failure groups based on patient body mass index (P = .60).
Other recommended strategies for nonpharmacologic management of EE symptoms include elevation of the head when lying down in bed and avoidance of lying down after eating, cessation of alcohol consumption, avoidance of food close to bedtime, and avoidance of trigger foods that can incite or worsen symptoms of acid reflux. Such trigger foods vary among individuals, but they often include fatty foods, coffee, chocolate, carbonated beverages, spicy foods, citrus fruits, and tomatoes.
Dr. Puerta has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Erosive esophagitis (EE) is erosion of the esophageal epithelium due to chronic irritation. It can be caused by a number of factors but is primarily a result of gastroesophageal reflux disease (GERD). The main symptoms of EE are heartburn and regurgitation; other symptoms can include epigastric pain, odynophagia, dysphagia, nausea, chronic cough, dental erosion, laryngitis, and asthma. , including nonerosive esophagitis and Barrett esophagus (BE). EE occurs in approximately 30% of cases of GERD, and EE may evolve to BE in 1%-13% of cases.
Long-term management of EE focuses on relieving symptoms to allow the esophageal lining to heal, thereby reducing both acute symptoms and the risk for other complications. Management plans may incorporate lifestyle changes, such as dietary modifications and weight loss, alongside pharmacologic therapy. In extreme cases, surgery may be considered to repair a damaged esophagus and/or to prevent ongoing acid reflux. If left untreated, EE may progress, potentially leading to more serious conditions.
Here are five things to know about EE.
1. GERD is the main risk factor for EE, but not the only risk factor.
An estimated 1% of the population has EE. Risk factors other than GERD include:
Radiation therapy toxicity can cause acute or chronic EE. For individuals undergoing radiotherapy, radiation esophagitis is a relatively frequent complication. Acute esophagitis generally occurs in all patients taking radiation doses of 6000 cGy given in fractions of 1000 cGy per week. The risk is lower among patients on longer schedules and lower doses of radiotherapy.
Bacterial, viral, and fungal infections can cause EE. These include herpes, CMV, HIV, Helicobacter pylori, and Candida.
Food allergies, asthma, and eczema are associated with eosinophilic esophagitis, which disproportionately affects young men and has an estimated prevalence of 55 cases per 100,000 population.
Oral medication in pill form causes esophagitis at an estimated rate of 3.9 cases per 100,000 population per year. The mean age at diagnosis is 41.5 years. Oral bisphosphonates such as alendronate are the most common agents, along with antibiotics such as tetracycline, doxycycline, and clindamycin. There have also been reports of pill-induced esophagitis with NSAIDs, aspirin, ferrous sulfate, potassium chloride, and mexiletine.
Excessive vomiting can, in rare cases, cause esophagitis.
Certain autoimmune diseases can manifest as EE.
2. Proton pump inhibitors (PPIs) remain the preferred treatment for EE.
Several over-the-counter and prescription medications can be used to manage the symptoms of EE. PPIs are the preferred treatment both in the acute setting and for maintenance therapy. PPIs help to alleviate symptoms and promote healing of the esophageal lining by reducing the production of stomach acid. Options include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. Many patients with EE require a dose that exceeds the FDA-approved dose for GERD. For instance, a 40-mg/d dosage of omeprazole is recommended in the latest guidelines, although the FDA-approved dosage is 20 mg/d.
H2-receptor antagonists, including famotidine, cimetidine, and nizatidine, may also be prescribed to reduce stomach acid production and promote healing in patients with EE due to GERD, but these agents are considered less efficacious than PPIs for either acute or maintenance therapy.
The potassium-competitive acid blocker (PCAB) vonoprazan is the latest agent to be indicated for EE and may provide more potent acid suppression for patients. A randomized comparative trial showed noninferiority compared with lansoprazole for healing and maintenance of healing of EE. In another randomized comparative study, the investigational PCAP fexuprazan was shown to be noninferior to the PPI esomeprazole in treating EE.
Mild GERD symptoms can be controlled by traditional antacids taken after each meal and at bedtime or with short-term use of prokinetic agents, which can help reduce acid reflux by improving esophageal and stomach motility and by increasing pressure to the lower esophageal sphincter. Gastric emptying is also accelerated by prokinetic agents. Long-term use is discouraged, as it may cause serious or life-threatening complications.
In patients who do not fully respond to PPI therapy, surgical therapy may be considered. Other candidates for surgery include younger patients, those who have difficulty adhering to treatment, postmenopausal women with osteoporosis, patients with cardiac conduction defects, and those for whom the cost of treatment is prohibitive. Surgery may also be warranted if there are extraesophageal manifestations of GERD, such as enamel erosion; respiratory issues (eg, coughing, wheezing, aspiration); or ear, nose, and throat manifestations (eg, hoarseness, sore throat, otitis media). For those who have progressed to BE, surgical intervention is also indicated.
The types of surgery for patients with EE have evolved to include both transthoracic and transabdominal fundoplication. Usually, a 360° transabdominal fundoplication is performed. General anesthesia is required for laparoscopic fundoplication, in which five small incisions are used to create a new valve at the level of the esophagogastric junction by wrapping the fundus of the stomach around the esophagus.
Laparoscopic insertion of a small band known as the LINX Reflux Management System is FDA approved to augment the lower esophageal sphincter. The system creates a natural barrier to reflux by placing a band consisting of titanium beads with magnetic cores around the esophagus just above the stomach. The magnetic bond is temporarily disrupted by swallowing, allowing food and liquid to pass.
Endoscopic therapies are another treatment option for certain patients who are not considered candidates for surgery or long-term therapy. Among the types of endoscopic procedures are radiofrequency therapy, suturing/plication, and mucosal ablation/resection techniques at the gastroesophageal junction. Full-thickness endoscopic suturing is an area of interest because this technique offers significant durability of the recreated lower esophageal sphincter.
3. PPI therapy for GERD should be stopped before endoscopy is performed to confirm a diagnosis of EE.
A clinical diagnosis of GERD can be made if the presenting symptoms are heartburn and regurgitation, without chest pain or alarm symptoms such as dysphagia, weight loss, or gastrointestinal bleeding. In this setting, once-daily PPIs are generally prescribed for 8 weeks to see if symptoms resolve. If symptoms have not resolved, a twice-daily PPI regimen may be prescribed. In patients who do not respond to PPIs, or for whom GERD returns after stopping therapy, an upper endoscopy with biopsy is recommended after 2-4 weeks off therapy to rule out other causes. Endoscopy should be the first step in diagnosis for individuals experiencing chest pain without heartburn; those in whom heart disease has been ruled out; individuals experiencing dysphagia, weight loss, or gastrointestinal bleeding; or those who have multiple risk factors for BE.
4. The most serious complication of EE is BE, which can lead to esophageal cancer.
Several complications can arise from EE. The most serious of these is BE, which can lead to esophageal adenocarcinoma. BE is characterized by the conversion of normal distal squamous esophageal epithelium to columnar epithelium. It has the potential to become malignant if it exhibits intestinal-type metaplasia. In the industrialized world, adenocarcinoma currently represents more than half of all esophageal cancers. The most common symptom of esophageal cancer is dysphagia. Other signs and symptoms include weight loss, hoarseness, chronic or intractable cough, bleeding, epigastric or retrosternal pain, frequent pneumonia, and, if metastatic, bone pain.
5. Lifestyle modifications can help control the symptoms of EE.
Guidelines recommend a number of lifestyle modification strategies to help control the symptoms of EE. Smoking cessation and weight loss are two evidence-based strategies for relieving symptoms of GERD and, ultimately, lowering the risk for esophageal cancer. One large prospective Norwegian cohort study (N = 29,610) found that stopping smoking improved GERD symptoms, but only in those with normal body mass index. In a smaller Japanese study (N = 191) specifically surveying people attempting smoking cessation, individuals who successfully stopped smoking had a 44% improvement in GERD symptoms at 1 year, vs an 18% improvement in those who continued to smoke, with no statistical difference between the success and failure groups based on patient body mass index (P = .60).
Other recommended strategies for nonpharmacologic management of EE symptoms include elevation of the head when lying down in bed and avoidance of lying down after eating, cessation of alcohol consumption, avoidance of food close to bedtime, and avoidance of trigger foods that can incite or worsen symptoms of acid reflux. Such trigger foods vary among individuals, but they often include fatty foods, coffee, chocolate, carbonated beverages, spicy foods, citrus fruits, and tomatoes.
Dr. Puerta has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
How Does Diet Affect Gastroesophageal Reflux Disease?
What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.
In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.
Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.
“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.
Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
Caloric Intake and Lipid Content
Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.
A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.
Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
The Role of Carbohydrates
While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.
Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.
A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.
A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.
Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
Questionable Studies
Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.
Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.
Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.
Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.
Dr. Zerbib reported no relevant financial conflicts related to his presentation.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.
In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.
Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.
“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.
Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
Caloric Intake and Lipid Content
Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.
A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.
Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
The Role of Carbohydrates
While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.
Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.
A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.
A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.
Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
Questionable Studies
Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.
Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.
Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.
Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.
Dr. Zerbib reported no relevant financial conflicts related to his presentation.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.
In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.
Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.
“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.
Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
Caloric Intake and Lipid Content
Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.
A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.
Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
The Role of Carbohydrates
While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.
Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.
A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.
A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.
Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
Questionable Studies
Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.
Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.
Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.
Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.
Dr. Zerbib reported no relevant financial conflicts related to his presentation.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Swallow this: Tiny tech tracks your gut in real time
From heartburn to hemorrhoids and everything in between, gastrointestinal troubles affect 60 million to 70 million Americans. Part of what makes them so frustrating – besides the frequent flights to the bathroom – are the invasive and uncomfortable tests one must endure for diagnosis, such as endoscopy (feeding a flexible tube into a person’s digestive tract) or x-rays that can involve higher radiation exposure.
But a revolutionary new option promising greater comfort and convenience could become available within the next few years.
The technology is described in Nature Electronics, along with the results of in vitro and animal testing of how well it works.
“You can think of this like a GPS that you can see on your phone as your Lyft or Uber driver is moving around,” says study author Azita Emami, PhD, a professor of electrical engineering and medical engineering at the California Institute of Technology, Pasadena. “You can see the driver coming through the streets, and you can track it in real time, but imagine you can do that with much higher precision for a much smaller device inside the body.”
It’s not the first option for GI testing that can be swallowed. A “capsule endoscopy” camera can take pictures of the digestive tract. And a “wireless motility capsule” uses sensors to measure pH, temperature, and pressure. But these technologies may not work for the entire time it takes to pass through the gut, usually about 1-3 days. And while they gather information, you can’t track their location in the GI tract in real time. Your doctor can learn a lot from this level of detail.
“If a patient has motility problems in their GI tract, it can actually tell the [doctor] where the motility problem is happening, where the slowdown is happening, which is much more informative,” says Dr. Emami. Such slowdowns are common in notoriously frustrating GI issues like irritable bowel syndrome, or IBS, and inflammatory bowel disease, or IBD.
To develop this technology, the research team drew inspiration from magnetic resonance imaging, or MRI. Magnetic fields transmit data from the Bluetooth-enabled device to a smartphone. An external component, a magnetic field generator that looks like a flat mat, powers the device and is small enough to be carried in a backpack – or placed under a bed, attached to a jacket, or mounted to a toilet seat. The part that can be swallowed has tiny chips embedded in a capsulelike package.
Before this technology can go to market, more testing is needed, including clinical trials in humans, says Dr. Emami. That will likely take a few years.
The team also aims to make the device even smaller (it now measures about 1 cm wide and 2 cm long) and less expensive, and they want it to do more things, such as sending medicines to the GI tract. Those innovations could take a few more years.
A version of this article first appeared on WebMD.com.
From heartburn to hemorrhoids and everything in between, gastrointestinal troubles affect 60 million to 70 million Americans. Part of what makes them so frustrating – besides the frequent flights to the bathroom – are the invasive and uncomfortable tests one must endure for diagnosis, such as endoscopy (feeding a flexible tube into a person’s digestive tract) or x-rays that can involve higher radiation exposure.
But a revolutionary new option promising greater comfort and convenience could become available within the next few years.
The technology is described in Nature Electronics, along with the results of in vitro and animal testing of how well it works.
“You can think of this like a GPS that you can see on your phone as your Lyft or Uber driver is moving around,” says study author Azita Emami, PhD, a professor of electrical engineering and medical engineering at the California Institute of Technology, Pasadena. “You can see the driver coming through the streets, and you can track it in real time, but imagine you can do that with much higher precision for a much smaller device inside the body.”
It’s not the first option for GI testing that can be swallowed. A “capsule endoscopy” camera can take pictures of the digestive tract. And a “wireless motility capsule” uses sensors to measure pH, temperature, and pressure. But these technologies may not work for the entire time it takes to pass through the gut, usually about 1-3 days. And while they gather information, you can’t track their location in the GI tract in real time. Your doctor can learn a lot from this level of detail.
“If a patient has motility problems in their GI tract, it can actually tell the [doctor] where the motility problem is happening, where the slowdown is happening, which is much more informative,” says Dr. Emami. Such slowdowns are common in notoriously frustrating GI issues like irritable bowel syndrome, or IBS, and inflammatory bowel disease, or IBD.
To develop this technology, the research team drew inspiration from magnetic resonance imaging, or MRI. Magnetic fields transmit data from the Bluetooth-enabled device to a smartphone. An external component, a magnetic field generator that looks like a flat mat, powers the device and is small enough to be carried in a backpack – or placed under a bed, attached to a jacket, or mounted to a toilet seat. The part that can be swallowed has tiny chips embedded in a capsulelike package.
Before this technology can go to market, more testing is needed, including clinical trials in humans, says Dr. Emami. That will likely take a few years.
The team also aims to make the device even smaller (it now measures about 1 cm wide and 2 cm long) and less expensive, and they want it to do more things, such as sending medicines to the GI tract. Those innovations could take a few more years.
A version of this article first appeared on WebMD.com.
From heartburn to hemorrhoids and everything in between, gastrointestinal troubles affect 60 million to 70 million Americans. Part of what makes them so frustrating – besides the frequent flights to the bathroom – are the invasive and uncomfortable tests one must endure for diagnosis, such as endoscopy (feeding a flexible tube into a person’s digestive tract) or x-rays that can involve higher radiation exposure.
But a revolutionary new option promising greater comfort and convenience could become available within the next few years.
The technology is described in Nature Electronics, along with the results of in vitro and animal testing of how well it works.
“You can think of this like a GPS that you can see on your phone as your Lyft or Uber driver is moving around,” says study author Azita Emami, PhD, a professor of electrical engineering and medical engineering at the California Institute of Technology, Pasadena. “You can see the driver coming through the streets, and you can track it in real time, but imagine you can do that with much higher precision for a much smaller device inside the body.”
It’s not the first option for GI testing that can be swallowed. A “capsule endoscopy” camera can take pictures of the digestive tract. And a “wireless motility capsule” uses sensors to measure pH, temperature, and pressure. But these technologies may not work for the entire time it takes to pass through the gut, usually about 1-3 days. And while they gather information, you can’t track their location in the GI tract in real time. Your doctor can learn a lot from this level of detail.
“If a patient has motility problems in their GI tract, it can actually tell the [doctor] where the motility problem is happening, where the slowdown is happening, which is much more informative,” says Dr. Emami. Such slowdowns are common in notoriously frustrating GI issues like irritable bowel syndrome, or IBS, and inflammatory bowel disease, or IBD.
To develop this technology, the research team drew inspiration from magnetic resonance imaging, or MRI. Magnetic fields transmit data from the Bluetooth-enabled device to a smartphone. An external component, a magnetic field generator that looks like a flat mat, powers the device and is small enough to be carried in a backpack – or placed under a bed, attached to a jacket, or mounted to a toilet seat. The part that can be swallowed has tiny chips embedded in a capsulelike package.
Before this technology can go to market, more testing is needed, including clinical trials in humans, says Dr. Emami. That will likely take a few years.
The team also aims to make the device even smaller (it now measures about 1 cm wide and 2 cm long) and less expensive, and they want it to do more things, such as sending medicines to the GI tract. Those innovations could take a few more years.
A version of this article first appeared on WebMD.com.
FROM NATURE ELECTRONICS
PPI use in type 2 diabetes links with cardiovascular events
Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.
During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.
The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.
PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).
The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
Prior observational reports
For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)
And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.
However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.
U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
Long-term PPI use threatens harm
“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”
The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.
The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine2 receptor antagonists, a drug class with indications similar to those for PPIs.
The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.
The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.
During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.
The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.
PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).
The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
Prior observational reports
For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)
And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.
However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.
U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
Long-term PPI use threatens harm
“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”
The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.
The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine2 receptor antagonists, a drug class with indications similar to those for PPIs.
The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.
The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.
During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.
The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.
PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).
The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
Prior observational reports
For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)
And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.
However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.
U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
Long-term PPI use threatens harm
“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”
The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.
The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine2 receptor antagonists, a drug class with indications similar to those for PPIs.
The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.
The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
How can clinicians distinguish food allergy and GERD in young kids?
The debate about a possible link between food allergy (FA) and pediatric gastroesophageal reflux disease (GERD) continues, and more, better-designed research is needed, a position paper by the European Academy of Allergy and Clinical Immunology reports.
The report offers consensus-based recommendations and a graphical decision pathway to guide providers through assessing and treating food allergy–related GERD. And the authors call for further, better-designed related research.
Food allergy and GERD are common in babies under 1 year of age and can lead to bothersome GERD, the authors write.
“An extensive literature search has found that whilst food proteins, in particular cow milk protein, can be a contributing factor to FA-associated” GERD, distinguishing between FA and non–FA-associated GERD is difficult, lead author Rosan Meyer, RD, PhD, senior lecturer at Imperial College London, and colleagues from the Academy task force on non-IgE mediated allergy, write in Pediatric Allergy and Immunology.
Consensus despite limited data
Dr. Meyer and colleagues developed clinical questions that addressed various aspects of the relationship between food allergy and GERD – pathophysiology, symptoms, diagnosis, dietary and medical management, prevalence, and impact on quality of life.
To address these issues, they systematically searched the literature for randomized controlled, observational, case-control, and retrospective studies of infants and children diagnosed with non-IgE gastrointestinal food allergies and GERD, published in English until February 2021.
Because of limited data in many of these areas, they used a modified Delphi method to reach consensus and provide practical advice on food allergy–associated GERD management.
The task force concludes:
- Food proteins, especially cow’s milk protein, can contribute to food allergy–associated GERD. The confirmation of food allergy is based on the elimination diet, always followed by reintroducing the offending allergen, and the diagnosis and treatment pathway should consider effects on quality of life.
- Breastfeeding should be supported in food allergy–associated GERD, and dietary advice should consider the potential nutritional impact on the breastfeeding mother. When breast milk is not available or is insufficient, formula and dietary advice to counteract the child’s nutrient deficiencies should be considered.
- Although some clarity exists about when GERD medications may be considered, they are often used inappropriately and may harm patients, especially infants.
Rigorous research needed
“Clinicians can use this algorithm to help them identify patients who may be affected by food allergy–related GERD,” Jonathan Tam, MD, medical director of the Gores Family Allergy Center at Children’s Hospital Los Angeles, told this news organization by email.
“Clinicians who suspect their patients may have food allergy–related GERD now have clearer guidance on how to systemically evaluate their patients,” added Dr. Tam, who was not involved in developing the report.
“Many allergists fear that patients may be labeled with a food allergy unnecessarily. Because no biomarkers or tests for food allergy–related GERD are available, elimination diets are a crucial part of the evaluation,” he said.
Dr. Tam added that the authors point out two key parts of a trial elimination: First, the trial should last at least 2 weeks, but full resolution may not occur until 6 weeks. Second, targeted elimination must be followed by reintroduction to confirm that the food was causing the symptoms, not that time itself may have been responsible for the clinical change.
“The authors’ note on allergy testing is important,” he said. “Allergy testing is not necessary when a clinician is concerned about food allergy–related GERD unless there are other associated atopic comorbidities, like eczema or IgE-mediated immediate food allergies.”
Jonathan M. Spergel, MD, PhD, chief of the allergy section at Children’s Hospital of Philadelphia, said in an email that families often ask whether food allergy is causing their child’s reflux.
“Both conditions are common and, in most cases, may not be related. As the report highlights, the risk of food allergy is increased if the patient has other atopic disease (atopic dermatitis), and standard allergy testing (skin testing, specific IgE) and IgG4 testing are not recommended,” he explained. “Food allergy in a patient with reflux can be considered if standard therapy is failing.”
Expert opinion on diagnosis and management
Dr. Spergel, also not involved in the report, joined the authors in advocating further, stronger studies. “While the expert opinion is a major strength,” he said, “with most available studies being neither randomized nor placebo-controlled, the true prevalence of food allergy reflux is unknown.”
Jay M. Portnoy, MD, specialist in pediatric allergy and immunology and medical director of telemedicine at Children’s Mercy Kansas City, said: “While most physicians believe that food allergy contributes to GERD, the evidence for the relationship is minimal. Reflux often occurs regardless of what food is eaten,” said Dr. Portnoy, who was not associated with the research.
Before removing a food from the diet, it’s important to determine whether that food is causing the problem, he urged.
“Blaming a food is easy. Food allergy is often suspected to cause symptoms it does not cause,” he said. “This unfounded blame can lead to unnecessary avoidance, reduce a family’s quality of life, and cause malnutrition.
“How a child is evaluated and treated depends as much on which physician they see as on whether the food is the culprit,” Dr. Portnoy said. “This report is an attempt to clarify the issues and to standardize an approach to the condition, so each provider evaluates and manages the condition in a consistent and evidence-based manner.
“It is important to see how well this report is incorporated into practice and whether following its guidance actually improves patient care,” Dr. Portnoy noted.
Funding information was not provided. Dr. Meyer and two coauthors report financial relationships with the nutritional health care industry. The full list can be found with the original article. The remaining authors and Dr. Tam, Dr. Spergel, and Dr. Portnoy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The debate about a possible link between food allergy (FA) and pediatric gastroesophageal reflux disease (GERD) continues, and more, better-designed research is needed, a position paper by the European Academy of Allergy and Clinical Immunology reports.
The report offers consensus-based recommendations and a graphical decision pathway to guide providers through assessing and treating food allergy–related GERD. And the authors call for further, better-designed related research.
Food allergy and GERD are common in babies under 1 year of age and can lead to bothersome GERD, the authors write.
“An extensive literature search has found that whilst food proteins, in particular cow milk protein, can be a contributing factor to FA-associated” GERD, distinguishing between FA and non–FA-associated GERD is difficult, lead author Rosan Meyer, RD, PhD, senior lecturer at Imperial College London, and colleagues from the Academy task force on non-IgE mediated allergy, write in Pediatric Allergy and Immunology.
Consensus despite limited data
Dr. Meyer and colleagues developed clinical questions that addressed various aspects of the relationship between food allergy and GERD – pathophysiology, symptoms, diagnosis, dietary and medical management, prevalence, and impact on quality of life.
To address these issues, they systematically searched the literature for randomized controlled, observational, case-control, and retrospective studies of infants and children diagnosed with non-IgE gastrointestinal food allergies and GERD, published in English until February 2021.
Because of limited data in many of these areas, they used a modified Delphi method to reach consensus and provide practical advice on food allergy–associated GERD management.
The task force concludes:
- Food proteins, especially cow’s milk protein, can contribute to food allergy–associated GERD. The confirmation of food allergy is based on the elimination diet, always followed by reintroducing the offending allergen, and the diagnosis and treatment pathway should consider effects on quality of life.
- Breastfeeding should be supported in food allergy–associated GERD, and dietary advice should consider the potential nutritional impact on the breastfeeding mother. When breast milk is not available or is insufficient, formula and dietary advice to counteract the child’s nutrient deficiencies should be considered.
- Although some clarity exists about when GERD medications may be considered, they are often used inappropriately and may harm patients, especially infants.
Rigorous research needed
“Clinicians can use this algorithm to help them identify patients who may be affected by food allergy–related GERD,” Jonathan Tam, MD, medical director of the Gores Family Allergy Center at Children’s Hospital Los Angeles, told this news organization by email.
“Clinicians who suspect their patients may have food allergy–related GERD now have clearer guidance on how to systemically evaluate their patients,” added Dr. Tam, who was not involved in developing the report.
“Many allergists fear that patients may be labeled with a food allergy unnecessarily. Because no biomarkers or tests for food allergy–related GERD are available, elimination diets are a crucial part of the evaluation,” he said.
Dr. Tam added that the authors point out two key parts of a trial elimination: First, the trial should last at least 2 weeks, but full resolution may not occur until 6 weeks. Second, targeted elimination must be followed by reintroduction to confirm that the food was causing the symptoms, not that time itself may have been responsible for the clinical change.
“The authors’ note on allergy testing is important,” he said. “Allergy testing is not necessary when a clinician is concerned about food allergy–related GERD unless there are other associated atopic comorbidities, like eczema or IgE-mediated immediate food allergies.”
Jonathan M. Spergel, MD, PhD, chief of the allergy section at Children’s Hospital of Philadelphia, said in an email that families often ask whether food allergy is causing their child’s reflux.
“Both conditions are common and, in most cases, may not be related. As the report highlights, the risk of food allergy is increased if the patient has other atopic disease (atopic dermatitis), and standard allergy testing (skin testing, specific IgE) and IgG4 testing are not recommended,” he explained. “Food allergy in a patient with reflux can be considered if standard therapy is failing.”
Expert opinion on diagnosis and management
Dr. Spergel, also not involved in the report, joined the authors in advocating further, stronger studies. “While the expert opinion is a major strength,” he said, “with most available studies being neither randomized nor placebo-controlled, the true prevalence of food allergy reflux is unknown.”
Jay M. Portnoy, MD, specialist in pediatric allergy and immunology and medical director of telemedicine at Children’s Mercy Kansas City, said: “While most physicians believe that food allergy contributes to GERD, the evidence for the relationship is minimal. Reflux often occurs regardless of what food is eaten,” said Dr. Portnoy, who was not associated with the research.
Before removing a food from the diet, it’s important to determine whether that food is causing the problem, he urged.
“Blaming a food is easy. Food allergy is often suspected to cause symptoms it does not cause,” he said. “This unfounded blame can lead to unnecessary avoidance, reduce a family’s quality of life, and cause malnutrition.
“How a child is evaluated and treated depends as much on which physician they see as on whether the food is the culprit,” Dr. Portnoy said. “This report is an attempt to clarify the issues and to standardize an approach to the condition, so each provider evaluates and manages the condition in a consistent and evidence-based manner.
“It is important to see how well this report is incorporated into practice and whether following its guidance actually improves patient care,” Dr. Portnoy noted.
Funding information was not provided. Dr. Meyer and two coauthors report financial relationships with the nutritional health care industry. The full list can be found with the original article. The remaining authors and Dr. Tam, Dr. Spergel, and Dr. Portnoy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The debate about a possible link between food allergy (FA) and pediatric gastroesophageal reflux disease (GERD) continues, and more, better-designed research is needed, a position paper by the European Academy of Allergy and Clinical Immunology reports.
The report offers consensus-based recommendations and a graphical decision pathway to guide providers through assessing and treating food allergy–related GERD. And the authors call for further, better-designed related research.
Food allergy and GERD are common in babies under 1 year of age and can lead to bothersome GERD, the authors write.
“An extensive literature search has found that whilst food proteins, in particular cow milk protein, can be a contributing factor to FA-associated” GERD, distinguishing between FA and non–FA-associated GERD is difficult, lead author Rosan Meyer, RD, PhD, senior lecturer at Imperial College London, and colleagues from the Academy task force on non-IgE mediated allergy, write in Pediatric Allergy and Immunology.
Consensus despite limited data
Dr. Meyer and colleagues developed clinical questions that addressed various aspects of the relationship between food allergy and GERD – pathophysiology, symptoms, diagnosis, dietary and medical management, prevalence, and impact on quality of life.
To address these issues, they systematically searched the literature for randomized controlled, observational, case-control, and retrospective studies of infants and children diagnosed with non-IgE gastrointestinal food allergies and GERD, published in English until February 2021.
Because of limited data in many of these areas, they used a modified Delphi method to reach consensus and provide practical advice on food allergy–associated GERD management.
The task force concludes:
- Food proteins, especially cow’s milk protein, can contribute to food allergy–associated GERD. The confirmation of food allergy is based on the elimination diet, always followed by reintroducing the offending allergen, and the diagnosis and treatment pathway should consider effects on quality of life.
- Breastfeeding should be supported in food allergy–associated GERD, and dietary advice should consider the potential nutritional impact on the breastfeeding mother. When breast milk is not available or is insufficient, formula and dietary advice to counteract the child’s nutrient deficiencies should be considered.
- Although some clarity exists about when GERD medications may be considered, they are often used inappropriately and may harm patients, especially infants.
Rigorous research needed
“Clinicians can use this algorithm to help them identify patients who may be affected by food allergy–related GERD,” Jonathan Tam, MD, medical director of the Gores Family Allergy Center at Children’s Hospital Los Angeles, told this news organization by email.
“Clinicians who suspect their patients may have food allergy–related GERD now have clearer guidance on how to systemically evaluate their patients,” added Dr. Tam, who was not involved in developing the report.
“Many allergists fear that patients may be labeled with a food allergy unnecessarily. Because no biomarkers or tests for food allergy–related GERD are available, elimination diets are a crucial part of the evaluation,” he said.
Dr. Tam added that the authors point out two key parts of a trial elimination: First, the trial should last at least 2 weeks, but full resolution may not occur until 6 weeks. Second, targeted elimination must be followed by reintroduction to confirm that the food was causing the symptoms, not that time itself may have been responsible for the clinical change.
“The authors’ note on allergy testing is important,” he said. “Allergy testing is not necessary when a clinician is concerned about food allergy–related GERD unless there are other associated atopic comorbidities, like eczema or IgE-mediated immediate food allergies.”
Jonathan M. Spergel, MD, PhD, chief of the allergy section at Children’s Hospital of Philadelphia, said in an email that families often ask whether food allergy is causing their child’s reflux.
“Both conditions are common and, in most cases, may not be related. As the report highlights, the risk of food allergy is increased if the patient has other atopic disease (atopic dermatitis), and standard allergy testing (skin testing, specific IgE) and IgG4 testing are not recommended,” he explained. “Food allergy in a patient with reflux can be considered if standard therapy is failing.”
Expert opinion on diagnosis and management
Dr. Spergel, also not involved in the report, joined the authors in advocating further, stronger studies. “While the expert opinion is a major strength,” he said, “with most available studies being neither randomized nor placebo-controlled, the true prevalence of food allergy reflux is unknown.”
Jay M. Portnoy, MD, specialist in pediatric allergy and immunology and medical director of telemedicine at Children’s Mercy Kansas City, said: “While most physicians believe that food allergy contributes to GERD, the evidence for the relationship is minimal. Reflux often occurs regardless of what food is eaten,” said Dr. Portnoy, who was not associated with the research.
Before removing a food from the diet, it’s important to determine whether that food is causing the problem, he urged.
“Blaming a food is easy. Food allergy is often suspected to cause symptoms it does not cause,” he said. “This unfounded blame can lead to unnecessary avoidance, reduce a family’s quality of life, and cause malnutrition.
“How a child is evaluated and treated depends as much on which physician they see as on whether the food is the culprit,” Dr. Portnoy said. “This report is an attempt to clarify the issues and to standardize an approach to the condition, so each provider evaluates and manages the condition in a consistent and evidence-based manner.
“It is important to see how well this report is incorporated into practice and whether following its guidance actually improves patient care,” Dr. Portnoy noted.
Funding information was not provided. Dr. Meyer and two coauthors report financial relationships with the nutritional health care industry. The full list can be found with the original article. The remaining authors and Dr. Tam, Dr. Spergel, and Dr. Portnoy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.