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SAN DIEGO – Electrical stimulation therapy of the lower esophageal sphincter is effective for treating refractory gastroesophageal reflux disease, according to interim results from a trial presented at the annual meeting of the American College of Gastroenterology.
A total of 32 patients underwent implantation of a pair of electrodes in the muscular layer of the gastroesophageal junction. The electrodes were connected to a pulse generator in the abdomen that delivered intermittent stimulation.
Six months later, the patients had a sustained, more than one-half reduction from baseline in exposure of the esophagus to acid and a two-thirds reduction in symptoms, reported first author Dr. Edy E. Soffer at the meeting.
Additionally, whereas most of the patients had been taking proton pump inhibitors (PPIs) at baseline, only about 1 in 10 were doing so at 6 months. None experienced any device-related adverse events.
The findings support the effectiveness and safety of electrical stimulation therapy in this population, according to Dr. Soffer, who is a professor in the gastroenterology division, Keck School of Medicine, University of Southern California, Los Angeles.
"Currently, there are ongoing studies, and there will be future sham-controlled studies that should clarify further the role of this intervention in the treatment of GERD [gastroesophageal reflux disease] and its mechanism of action," he noted.
Session attendee Dr. Marcelo Vela of the Baylor Clinic, Houston, noted that earlier studies have shown that this therapy increases basal pressure of the lower esophageal sphincter (LES). "Because the main mechanism for reflux is transient LES relaxations [TLESRs], particularly with small hernias as in your patients, do you have any data on TLESRs?" he asked.
"No, LES pressure was not an endpoint in these studies," Dr. Soffer replied. "Initially, we thought that this [basal pressure] is the main mechanism; as we are learning more, it is probably not going to be the main mechanism. We are looking at others, including TLESRs. ... We don’t have data yet."
Dr. Joel Richter, of the University of South Florida, Tampa, wondered whether patients experienced any of the oft-feared complications of antireflux surgery, such as bloating, diarrhea, and dysphagia.
"There were only two cases of dysphagia, and they basically resolved on their own," Dr. Soffer replied. "We didn’t see any of the symptoms that you see with postsurgical therapy. ... The intervention really should not result in the symptoms that come after standard surgical care."
Dr. Richter also requested more information on hiatal hernia repairs undertaken in some patients. "If you had a hernia repair, how do you know what part of the success was related to the hernia repair versus the stimulation?" he asked.
Thirteen patients had a hernia repair, with technique left up to the treating physician, Dr. Soffer replied. "We will look separately, when we complete that phase, at those that had the hernia repair versus those that did not."
"Was there a bit of a trend toward any improvement depending on your hernia size?" Dr. Richard McCallam of Texas Tech University in El Paso asked, while also noting that patients with hernias measuring 3 cm or more were excluded.
There were too few patients to assess trends, according to Dr. Soffer. "We tried not to take patients who had particularly severe disease at the beginning," he added. "The 3-cm hernia repair will be the one perhaps that will need to be looked at more carefully. This is a more sustained hernia situation as compared to the 1- and 2-cm [ones]."
The investigators enrolled GERD patients in the study who had a GERD health-related quality of life score of 20 or higher when not taking PPIs, and who had at least a partial response to these agents. They were required to have a basal LES end-expiratory pressure of at least 5 mm Hg, and to have a pH below 4.0 for more than 5% of the time on 24-hour esophageal pH monitoring.
The patients’ mean age was 50 years, and 18 of them were male, according to Dr. Soffer.
The main results showed a sustained reduction in esophageal acid exposure; the percentage of time at pH less than 4.0 was 10.3% at baseline, compared with 3.7% at 3 months (P less than .01), and 4.6% at 6 months (P less than .01).
There was also a sustained improvement in symptoms as assessed from GERD health-related quality of life; the score was 15 at baseline on PPIs and 31 at baseline off PPIs. These figures compared with a score of 4 at 3 months and 5 at 6 months.
Large proportions of patients met criteria for successful treatment at 6 months: 65% had control of esophageal acid exposure (either normalization or a greater than one-half reduction), 86% had control of GERD symptoms compared with level without medical therapy (a greater than 50% improvement versus baseline level not on PPIs), and 76% had control of GERD symptoms compared with level with medical therapy (any improvement of symptoms versus baseline level on PPIs).
Quality of life as assessed with the Short Form-12 showed improvement at 6 months in physical health scores compared with those measured at baseline while off PPIs.
Patients also had significant reductions from the level at baseline off PPIs at both 3 and 6 months in the median percentages of daily diary days with heartburn and with regurgitation symptoms.
Analyses of daytime versus nighttime symptoms are still ongoing, according to Dr. Soffer.
Stimulation therapy was also associated with a dramatic reduction in PPI use. Whereas only 10% of patients did not use any of these agents at baseline, 89% were not using any at 6 months.
There were just two serious adverse events: a procedure-related trocar perforation of the small bowel during laparoscopy (the stimulation device was prophylactically removed and there was resolution after surgical repair) and atrioventricular nodal reentrant tachycardia unrelated to the device or procedure.
There were no device-related serious adverse events. There were 35 nonserious events possibly or probably related to the device or procedure.
Dr. Soffer is a consultant for and shareholder in EndoStim*. The study was supported by EndoStim.
*Correction, 2/4/2014: An earlier version of the story misstated Dr. Soffer's conflicts of interest.
Electrical stimulation of the lower esophageal sphincter (LES) to compensate for sphincter incompetence seems a rather direct approach to treating GERD, and the data presented by Dr. Soffer seem to indicate that this can work. Most convincing is the reduction in esophageal acid exposure from a mean of 10.3% at baseline to a mean of 3.7% after implantation. True, there is the variable of surgical correction of hiatal hernia done in 13 of the 32 implanted patients to deal with, but nonetheless, these are very encouraging proof-of-concept data.
 |
| Dr. Peter J. Kahrilas |
So now the more difficult questions: Who needs this therapy, and how should its efficacy be further evaluated? With regard to who needs this therapy, I would argue against it being a mainstream approach. PPIs are simply too good, too inexpensive, and too safe to compete with. However, there are a number of intriguing niche applications for which the EndoStim device might be suitable, for example, patients with poor peristalsis or obesity for whom the conventional surgical approaches are not advised, lung transplant or bariatric surgery patients, or patients with excessive regurgitation after gastrostomy placement. In these situations, conventional approaches of PPIs or Nissen fundoplication are either ineffective or ill-advised. A true unmet need exists.
The other question that arises is how to further test the device. The issue raised by Dr. Richter of discriminating between the benefits from hiatus hernia repair and from the stimulator itself needs to be resolved. Certainly, a subgroup analysis of the stimulator-only population is in order, as is a future study of the device in hernia patients without adding a hernia repair. Another interesting potential with this device is that it can serve as its own control in future trials, assuming that the implanter can resist the temptation to attempt an anatomical correction at the time of implantation and presuming that the stimulator can be switched on and off. Then, as in the studies done with gastric pacing, patients could be studied physiologically or symptomatically with the device on or off in a blinded fashion. I look forward to hearing more on the development of the LES stimulator.
Dr. Peter J. Kahrilas is the Gilbert H. Marquardt Professor of Medicine at the Feinberg School of Medicine, Northwestern University, Chicago. He is a consultant for AstraZeneca, GlaxoSmithKline, Pfizer, Torax, and Reckitt Benckiser.
Electrical stimulation of the lower esophageal sphincter (LES) to compensate for sphincter incompetence seems a rather direct approach to treating GERD, and the data presented by Dr. Soffer seem to indicate that this can work. Most convincing is the reduction in esophageal acid exposure from a mean of 10.3% at baseline to a mean of 3.7% after implantation. True, there is the variable of surgical correction of hiatal hernia done in 13 of the 32 implanted patients to deal with, but nonetheless, these are very encouraging proof-of-concept data.
|
| Dr. Peter J. Kahrilas |
So now the more difficult questions: Who needs this therapy, and how should its efficacy be further evaluated? With regard to who needs this therapy, I would argue against it being a mainstream approach. PPIs are simply too good, too inexpensive, and too safe to compete with. However, there are a number of intriguing niche applications for which the EndoStim device might be suitable, for example, patients with poor peristalsis or obesity for whom the conventional surgical approaches are not advised, lung transplant or bariatric surgery patients, or patients with excessive regurgitation after gastrostomy placement. In these situations, conventional approaches of PPIs or Nissen fundoplication are either ineffective or ill-advised. A true unmet need exists.
The other question that arises is how to further test the device. The issue raised by Dr. Richter of discriminating between the benefits from hiatus hernia repair and from the stimulator itself needs to be resolved. Certainly, a subgroup analysis of the stimulator-only population is in order, as is a future study of the device in hernia patients without adding a hernia repair. Another interesting potential with this device is that it can serve as its own control in future trials, assuming that the implanter can resist the temptation to attempt an anatomical correction at the time of implantation and presuming that the stimulator can be switched on and off. Then, as in the studies done with gastric pacing, patients could be studied physiologically or symptomatically with the device on or off in a blinded fashion. I look forward to hearing more on the development of the LES stimulator.
Dr. Peter J. Kahrilas is the Gilbert H. Marquardt Professor of Medicine at the Feinberg School of Medicine, Northwestern University, Chicago. He is a consultant for AstraZeneca, GlaxoSmithKline, Pfizer, Torax, and Reckitt Benckiser.
Electrical stimulation of the lower esophageal sphincter (LES) to compensate for sphincter incompetence seems a rather direct approach to treating GERD, and the data presented by Dr. Soffer seem to indicate that this can work. Most convincing is the reduction in esophageal acid exposure from a mean of 10.3% at baseline to a mean of 3.7% after implantation. True, there is the variable of surgical correction of hiatal hernia done in 13 of the 32 implanted patients to deal with, but nonetheless, these are very encouraging proof-of-concept data.
|
| Dr. Peter J. Kahrilas |
So now the more difficult questions: Who needs this therapy, and how should its efficacy be further evaluated? With regard to who needs this therapy, I would argue against it being a mainstream approach. PPIs are simply too good, too inexpensive, and too safe to compete with. However, there are a number of intriguing niche applications for which the EndoStim device might be suitable, for example, patients with poor peristalsis or obesity for whom the conventional surgical approaches are not advised, lung transplant or bariatric surgery patients, or patients with excessive regurgitation after gastrostomy placement. In these situations, conventional approaches of PPIs or Nissen fundoplication are either ineffective or ill-advised. A true unmet need exists.
The other question that arises is how to further test the device. The issue raised by Dr. Richter of discriminating between the benefits from hiatus hernia repair and from the stimulator itself needs to be resolved. Certainly, a subgroup analysis of the stimulator-only population is in order, as is a future study of the device in hernia patients without adding a hernia repair. Another interesting potential with this device is that it can serve as its own control in future trials, assuming that the implanter can resist the temptation to attempt an anatomical correction at the time of implantation and presuming that the stimulator can be switched on and off. Then, as in the studies done with gastric pacing, patients could be studied physiologically or symptomatically with the device on or off in a blinded fashion. I look forward to hearing more on the development of the LES stimulator.
Dr. Peter J. Kahrilas is the Gilbert H. Marquardt Professor of Medicine at the Feinberg School of Medicine, Northwestern University, Chicago. He is a consultant for AstraZeneca, GlaxoSmithKline, Pfizer, Torax, and Reckitt Benckiser.
SAN DIEGO – Electrical stimulation therapy of the lower esophageal sphincter is effective for treating refractory gastroesophageal reflux disease, according to interim results from a trial presented at the annual meeting of the American College of Gastroenterology.
A total of 32 patients underwent implantation of a pair of electrodes in the muscular layer of the gastroesophageal junction. The electrodes were connected to a pulse generator in the abdomen that delivered intermittent stimulation.
Six months later, the patients had a sustained, more than one-half reduction from baseline in exposure of the esophagus to acid and a two-thirds reduction in symptoms, reported first author Dr. Edy E. Soffer at the meeting.
Additionally, whereas most of the patients had been taking proton pump inhibitors (PPIs) at baseline, only about 1 in 10 were doing so at 6 months. None experienced any device-related adverse events.
The findings support the effectiveness and safety of electrical stimulation therapy in this population, according to Dr. Soffer, who is a professor in the gastroenterology division, Keck School of Medicine, University of Southern California, Los Angeles.
"Currently, there are ongoing studies, and there will be future sham-controlled studies that should clarify further the role of this intervention in the treatment of GERD [gastroesophageal reflux disease] and its mechanism of action," he noted.
Session attendee Dr. Marcelo Vela of the Baylor Clinic, Houston, noted that earlier studies have shown that this therapy increases basal pressure of the lower esophageal sphincter (LES). "Because the main mechanism for reflux is transient LES relaxations [TLESRs], particularly with small hernias as in your patients, do you have any data on TLESRs?" he asked.
"No, LES pressure was not an endpoint in these studies," Dr. Soffer replied. "Initially, we thought that this [basal pressure] is the main mechanism; as we are learning more, it is probably not going to be the main mechanism. We are looking at others, including TLESRs. ... We don’t have data yet."
Dr. Joel Richter, of the University of South Florida, Tampa, wondered whether patients experienced any of the oft-feared complications of antireflux surgery, such as bloating, diarrhea, and dysphagia.
"There were only two cases of dysphagia, and they basically resolved on their own," Dr. Soffer replied. "We didn’t see any of the symptoms that you see with postsurgical therapy. ... The intervention really should not result in the symptoms that come after standard surgical care."
Dr. Richter also requested more information on hiatal hernia repairs undertaken in some patients. "If you had a hernia repair, how do you know what part of the success was related to the hernia repair versus the stimulation?" he asked.
Thirteen patients had a hernia repair, with technique left up to the treating physician, Dr. Soffer replied. "We will look separately, when we complete that phase, at those that had the hernia repair versus those that did not."
"Was there a bit of a trend toward any improvement depending on your hernia size?" Dr. Richard McCallam of Texas Tech University in El Paso asked, while also noting that patients with hernias measuring 3 cm or more were excluded.
There were too few patients to assess trends, according to Dr. Soffer. "We tried not to take patients who had particularly severe disease at the beginning," he added. "The 3-cm hernia repair will be the one perhaps that will need to be looked at more carefully. This is a more sustained hernia situation as compared to the 1- and 2-cm [ones]."
The investigators enrolled GERD patients in the study who had a GERD health-related quality of life score of 20 or higher when not taking PPIs, and who had at least a partial response to these agents. They were required to have a basal LES end-expiratory pressure of at least 5 mm Hg, and to have a pH below 4.0 for more than 5% of the time on 24-hour esophageal pH monitoring.
The patients’ mean age was 50 years, and 18 of them were male, according to Dr. Soffer.
The main results showed a sustained reduction in esophageal acid exposure; the percentage of time at pH less than 4.0 was 10.3% at baseline, compared with 3.7% at 3 months (P less than .01), and 4.6% at 6 months (P less than .01).
There was also a sustained improvement in symptoms as assessed from GERD health-related quality of life; the score was 15 at baseline on PPIs and 31 at baseline off PPIs. These figures compared with a score of 4 at 3 months and 5 at 6 months.
Large proportions of patients met criteria for successful treatment at 6 months: 65% had control of esophageal acid exposure (either normalization or a greater than one-half reduction), 86% had control of GERD symptoms compared with level without medical therapy (a greater than 50% improvement versus baseline level not on PPIs), and 76% had control of GERD symptoms compared with level with medical therapy (any improvement of symptoms versus baseline level on PPIs).
Quality of life as assessed with the Short Form-12 showed improvement at 6 months in physical health scores compared with those measured at baseline while off PPIs.
Patients also had significant reductions from the level at baseline off PPIs at both 3 and 6 months in the median percentages of daily diary days with heartburn and with regurgitation symptoms.
Analyses of daytime versus nighttime symptoms are still ongoing, according to Dr. Soffer.
Stimulation therapy was also associated with a dramatic reduction in PPI use. Whereas only 10% of patients did not use any of these agents at baseline, 89% were not using any at 6 months.
There were just two serious adverse events: a procedure-related trocar perforation of the small bowel during laparoscopy (the stimulation device was prophylactically removed and there was resolution after surgical repair) and atrioventricular nodal reentrant tachycardia unrelated to the device or procedure.
There were no device-related serious adverse events. There were 35 nonserious events possibly or probably related to the device or procedure.
Dr. Soffer is a consultant for and shareholder in EndoStim*. The study was supported by EndoStim.
*Correction, 2/4/2014: An earlier version of the story misstated Dr. Soffer's conflicts of interest.
SAN DIEGO – Electrical stimulation therapy of the lower esophageal sphincter is effective for treating refractory gastroesophageal reflux disease, according to interim results from a trial presented at the annual meeting of the American College of Gastroenterology.
A total of 32 patients underwent implantation of a pair of electrodes in the muscular layer of the gastroesophageal junction. The electrodes were connected to a pulse generator in the abdomen that delivered intermittent stimulation.
Six months later, the patients had a sustained, more than one-half reduction from baseline in exposure of the esophagus to acid and a two-thirds reduction in symptoms, reported first author Dr. Edy E. Soffer at the meeting.
Additionally, whereas most of the patients had been taking proton pump inhibitors (PPIs) at baseline, only about 1 in 10 were doing so at 6 months. None experienced any device-related adverse events.
The findings support the effectiveness and safety of electrical stimulation therapy in this population, according to Dr. Soffer, who is a professor in the gastroenterology division, Keck School of Medicine, University of Southern California, Los Angeles.
"Currently, there are ongoing studies, and there will be future sham-controlled studies that should clarify further the role of this intervention in the treatment of GERD [gastroesophageal reflux disease] and its mechanism of action," he noted.
Session attendee Dr. Marcelo Vela of the Baylor Clinic, Houston, noted that earlier studies have shown that this therapy increases basal pressure of the lower esophageal sphincter (LES). "Because the main mechanism for reflux is transient LES relaxations [TLESRs], particularly with small hernias as in your patients, do you have any data on TLESRs?" he asked.
"No, LES pressure was not an endpoint in these studies," Dr. Soffer replied. "Initially, we thought that this [basal pressure] is the main mechanism; as we are learning more, it is probably not going to be the main mechanism. We are looking at others, including TLESRs. ... We don’t have data yet."
Dr. Joel Richter, of the University of South Florida, Tampa, wondered whether patients experienced any of the oft-feared complications of antireflux surgery, such as bloating, diarrhea, and dysphagia.
"There were only two cases of dysphagia, and they basically resolved on their own," Dr. Soffer replied. "We didn’t see any of the symptoms that you see with postsurgical therapy. ... The intervention really should not result in the symptoms that come after standard surgical care."
Dr. Richter also requested more information on hiatal hernia repairs undertaken in some patients. "If you had a hernia repair, how do you know what part of the success was related to the hernia repair versus the stimulation?" he asked.
Thirteen patients had a hernia repair, with technique left up to the treating physician, Dr. Soffer replied. "We will look separately, when we complete that phase, at those that had the hernia repair versus those that did not."
"Was there a bit of a trend toward any improvement depending on your hernia size?" Dr. Richard McCallam of Texas Tech University in El Paso asked, while also noting that patients with hernias measuring 3 cm or more were excluded.
There were too few patients to assess trends, according to Dr. Soffer. "We tried not to take patients who had particularly severe disease at the beginning," he added. "The 3-cm hernia repair will be the one perhaps that will need to be looked at more carefully. This is a more sustained hernia situation as compared to the 1- and 2-cm [ones]."
The investigators enrolled GERD patients in the study who had a GERD health-related quality of life score of 20 or higher when not taking PPIs, and who had at least a partial response to these agents. They were required to have a basal LES end-expiratory pressure of at least 5 mm Hg, and to have a pH below 4.0 for more than 5% of the time on 24-hour esophageal pH monitoring.
The patients’ mean age was 50 years, and 18 of them were male, according to Dr. Soffer.
The main results showed a sustained reduction in esophageal acid exposure; the percentage of time at pH less than 4.0 was 10.3% at baseline, compared with 3.7% at 3 months (P less than .01), and 4.6% at 6 months (P less than .01).
There was also a sustained improvement in symptoms as assessed from GERD health-related quality of life; the score was 15 at baseline on PPIs and 31 at baseline off PPIs. These figures compared with a score of 4 at 3 months and 5 at 6 months.
Large proportions of patients met criteria for successful treatment at 6 months: 65% had control of esophageal acid exposure (either normalization or a greater than one-half reduction), 86% had control of GERD symptoms compared with level without medical therapy (a greater than 50% improvement versus baseline level not on PPIs), and 76% had control of GERD symptoms compared with level with medical therapy (any improvement of symptoms versus baseline level on PPIs).
Quality of life as assessed with the Short Form-12 showed improvement at 6 months in physical health scores compared with those measured at baseline while off PPIs.
Patients also had significant reductions from the level at baseline off PPIs at both 3 and 6 months in the median percentages of daily diary days with heartburn and with regurgitation symptoms.
Analyses of daytime versus nighttime symptoms are still ongoing, according to Dr. Soffer.
Stimulation therapy was also associated with a dramatic reduction in PPI use. Whereas only 10% of patients did not use any of these agents at baseline, 89% were not using any at 6 months.
There were just two serious adverse events: a procedure-related trocar perforation of the small bowel during laparoscopy (the stimulation device was prophylactically removed and there was resolution after surgical repair) and atrioventricular nodal reentrant tachycardia unrelated to the device or procedure.
There were no device-related serious adverse events. There were 35 nonserious events possibly or probably related to the device or procedure.
Dr. Soffer is a consultant for and shareholder in EndoStim*. The study was supported by EndoStim.
*Correction, 2/4/2014: An earlier version of the story misstated Dr. Soffer's conflicts of interest.
AT THE ACG ANNUAL MEETING
Major finding: At 6 months, there was a sustained, more than one-half reduction from baseline in esophageal acid exposure and a two-thirds reduction in GERD symptoms; 89% of patients were not taking any PPIs, up from 10% at baseline.
Data source: An interim analysis of an open-label trial in 32 patients with refractory GERD.
Disclosures: Dr. Soffer is a consultant for and shareholder in EndoStim*. The study was supported by EndoStim.
