Digestive Disease Week (DDW)

SAN DIEGO – Endorectal balloons appeared to protect against rectal complications from prostate cancer radiation in a small randomized trial from Australia.

The balloons have been around for years, but the Australian study is likely the first randomized trial of long-term clinical outcomes. The balloons are inserted and inflated during radiation treatments, which in the study were daily for 6-7 weeks. They distend the rectum, reducing radiation exposure, and also stabilize the prostate. The investigators used the RectalPro balloon from Qlrad.

M. Alexander Otto/Frontline Medical News

The 40 men were all undergoing image-guided radiation therapy; 20 got the balloon, 20 did not. At 2 years, four balloon patients (25%) had rectal bleeding, versus 10 (50%) of the controls (P less than .001). Balloon patients also had fewer bowel symptoms, less rectal hypersensitivity, and less reduction in internal anal sphincter thickness. Three (15%), versus six controls (30%), reported declines in physical function from their preradiation baseline, and one balloon patient (5%), versus three controls (15%) reported declines in role functioning (P less than .05 for both).

Rectal pain, however, was more common with the balloon at 2 years (six patients [30%] versus two [10%], P less than .001), and balloon patients had reduced anal squeeze pressures (P less than .05). They also reported a higher prevalence of urinary symptoms.

Further follow-up is needed to determine if benefits outweigh risks; if they do, then the balloon “will become standard procedure in our hospital,” said investigator Rochelle Botten, a research scientist in the department of radiation oncology at the Royal Adelaide Hospital.

Given the study’s small numbers, it’s unclear if urinary problems – for instance, incontinence, pain, frequency – are truly associated with the balloon, but it’s “something we’ve got to look at. We are going to study” the men “again at 3 years to see if they’ve resolved, and we’ll have more patients for 2-year follow-up. If we are pressing everything towards the bladder, it [could make] sense that the bladder is getting more radiation.

“We are hoping as the numbers increase, we’ll be able to look at how much of the bladder and how much of the rectum are actually irradiated, and if there’s a difference with the balloon,” she said at the annual Digestive Disease Week meeting.

Ms. Botten had no disclosures.

[email protected]

SAN DIEGO – Endorectal balloons appeared to protect against rectal complications from prostate cancer radiation in a small randomized trial from Australia.

The balloons have been around for years, but the Australian study is likely the first randomized trial of long-term clinical outcomes. The balloons are inserted and inflated during radiation treatments, which in the study were daily for 6-7 weeks. They distend the rectum, reducing radiation exposure, and also stabilize the prostate. The investigators used the RectalPro balloon from Qlrad.

M. Alexander Otto/Frontline Medical News

The 40 men were all undergoing image-guided radiation therapy; 20 got the balloon, 20 did not. At 2 years, four balloon patients (25%) had rectal bleeding, versus 10 (50%) of the controls (P less than .001). Balloon patients also had fewer bowel symptoms, less rectal hypersensitivity, and less reduction in internal anal sphincter thickness. Three (15%), versus six controls (30%), reported declines in physical function from their preradiation baseline, and one balloon patient (5%), versus three controls (15%) reported declines in role functioning (P less than .05 for both).

Rectal pain, however, was more common with the balloon at 2 years (six patients [30%] versus two [10%], P less than .001), and balloon patients had reduced anal squeeze pressures (P less than .05). They also reported a higher prevalence of urinary symptoms.

Further follow-up is needed to determine if benefits outweigh risks; if they do, then the balloon “will become standard procedure in our hospital,” said investigator Rochelle Botten, a research scientist in the department of radiation oncology at the Royal Adelaide Hospital.

Given the study’s small numbers, it’s unclear if urinary problems – for instance, incontinence, pain, frequency – are truly associated with the balloon, but it’s “something we’ve got to look at. We are going to study” the men “again at 3 years to see if they’ve resolved, and we’ll have more patients for 2-year follow-up. If we are pressing everything towards the bladder, it [could make] sense that the bladder is getting more radiation.

“We are hoping as the numbers increase, we’ll be able to look at how much of the bladder and how much of the rectum are actually irradiated, and if there’s a difference with the balloon,” she said at the annual Digestive Disease Week meeting.

Ms. Botten had no disclosures.

[email protected]

SAN DIEGO – Endorectal balloons appeared to protect against rectal complications from prostate cancer radiation in a small randomized trial from Australia.

The balloons have been around for years, but the Australian study is likely the first randomized trial of long-term clinical outcomes. The balloons are inserted and inflated during radiation treatments, which in the study were daily for 6-7 weeks. They distend the rectum, reducing radiation exposure, and also stabilize the prostate. The investigators used the RectalPro balloon from Qlrad.

M. Alexander Otto/Frontline Medical News

The 40 men were all undergoing image-guided radiation therapy; 20 got the balloon, 20 did not. At 2 years, four balloon patients (25%) had rectal bleeding, versus 10 (50%) of the controls (P less than .001). Balloon patients also had fewer bowel symptoms, less rectal hypersensitivity, and less reduction in internal anal sphincter thickness. Three (15%), versus six controls (30%), reported declines in physical function from their preradiation baseline, and one balloon patient (5%), versus three controls (15%) reported declines in role functioning (P less than .05 for both).

Rectal pain, however, was more common with the balloon at 2 years (six patients [30%] versus two [10%], P less than .001), and balloon patients had reduced anal squeeze pressures (P less than .05). They also reported a higher prevalence of urinary symptoms.

Further follow-up is needed to determine if benefits outweigh risks; if they do, then the balloon “will become standard procedure in our hospital,” said investigator Rochelle Botten, a research scientist in the department of radiation oncology at the Royal Adelaide Hospital.

Given the study’s small numbers, it’s unclear if urinary problems – for instance, incontinence, pain, frequency – are truly associated with the balloon, but it’s “something we’ve got to look at. We are going to study” the men “again at 3 years to see if they’ve resolved, and we’ll have more patients for 2-year follow-up. If we are pressing everything towards the bladder, it [could make] sense that the bladder is getting more radiation.

“We are hoping as the numbers increase, we’ll be able to look at how much of the bladder and how much of the rectum are actually irradiated, and if there’s a difference with the balloon,” she said at the annual Digestive Disease Week meeting.

Ms. Botten had no disclosures.

[email protected]

SAN DIEGO – Embryo transfers are less likely to result in live births when women with ulcerative colitis (UC) have fertility treatments, and the risk of preterm birth is higher, at least for twins, according to a 20-year nationwide cohort study from Denmark. On a brighter note, UC did not increase the risk of low birth weight or birth defects, and prior UC surgeries did not diminish success.

The take home conclusions from the study are that “women with ulcerative colitis may [want] to initiate ART [assisted reproductive technology] treatment” sooner than other women because “they cannot expect the same success per embryo transfer.” The greater risk of preterm birth means that “increased prenatal observation in UC pregnancies after ART should be considered,” but “women with UC should be reassured that surgery before ART treatment does not impact the chance of live birth per embryo transfer,” said senior investigator Dr. Sonia Friedman, a gastroenterologist at Brigham and Women’s Hospital in Boston.

Although it’s known that UC diminishes fertility in general, it hasn’t been known until now how it affects assisted reproduction. The investigators turned to Denmark to find out because Denmark has one of the highest incidence rates of UC worldwide, especially among women and men 15-29 years old, and the country captures virtually every ART outcome in national databases.

The study included 1,360 embryo transfers in 432 women with UC and 149,094 in 52,661 women without UC from 1994 to 2013. Treatments included in vitro fertilization, intracytoplasmic sperm injection, and embryo transfers. Women in both groups were a median of 33 years old; women with UC had a median disease duration of 8 years.

The chance of live birth per embryo transfer was 22% less in women with UC (odds ratio, 0.78; 95% confidence interval, 0.67-0.91), after adjusting for age, infertility cause, body mass index (BMI), smoking, and other factors, including calendar year, to take into account changes in ART over the years.

The risk of preterm birth was five times higher when singletons and multiple births were considered together (adjusted OR, 5.29; 95% CI, 2.41-11.63), but not statistically elevated when singleton births were analyzed on their own (aOR, 1.80; 95% CI, 0.49-6.62).

About 35% of the women with UC had prior surgeries, most commonly total colon resections. There was no difference in odds of live birth per cycle versus women with UC and without surgery (OR, 0.97; 95% CI, 0.61-1.36) after adjusting for disease duration, comorbidities, year of treatment, and other factors.

The impact of UC is probably related to disease activity. “Even though gynecologists in Denmark tell us they really try to keep their patients in remission before ART, there is some disease activity,” Dr. Friedman said at the annual Digestive Disease Week.

Surgery for Crohn’s disease is known to reduce success in ART, so it was a bit surprising that it didn’t seem to do so in UC. Perhaps it’s because UC surgery is often curative, while Crohn’s operations often are not, so Crohn’s patients may be more likely to have continued disease activity during ART treatment, Dr. Friedman said.

The majority of women in both study groups were normal weight and didn’t smoke. Outside of UC, most were free of comorbidities. In the UC surgery group, about half the women had one procedure, and the rest two or three.

The work was funded by the Crohn’s and Colitis Foundation of America. Dr. Friedman has no disclosures.

[email protected]

SAN DIEGO – Embryo transfers are less likely to result in live births when women with ulcerative colitis (UC) have fertility treatments, and the risk of preterm birth is higher, at least for twins, according to a 20-year nationwide cohort study from Denmark. On a brighter note, UC did not increase the risk of low birth weight or birth defects, and prior UC surgeries did not diminish success.

The take home conclusions from the study are that “women with ulcerative colitis may [want] to initiate ART [assisted reproductive technology] treatment” sooner than other women because “they cannot expect the same success per embryo transfer.” The greater risk of preterm birth means that “increased prenatal observation in UC pregnancies after ART should be considered,” but “women with UC should be reassured that surgery before ART treatment does not impact the chance of live birth per embryo transfer,” said senior investigator Dr. Sonia Friedman, a gastroenterologist at Brigham and Women’s Hospital in Boston.

Although it’s known that UC diminishes fertility in general, it hasn’t been known until now how it affects assisted reproduction. The investigators turned to Denmark to find out because Denmark has one of the highest incidence rates of UC worldwide, especially among women and men 15-29 years old, and the country captures virtually every ART outcome in national databases.

The study included 1,360 embryo transfers in 432 women with UC and 149,094 in 52,661 women without UC from 1994 to 2013. Treatments included in vitro fertilization, intracytoplasmic sperm injection, and embryo transfers. Women in both groups were a median of 33 years old; women with UC had a median disease duration of 8 years.

The chance of live birth per embryo transfer was 22% less in women with UC (odds ratio, 0.78; 95% confidence interval, 0.67-0.91), after adjusting for age, infertility cause, body mass index (BMI), smoking, and other factors, including calendar year, to take into account changes in ART over the years.

The risk of preterm birth was five times higher when singletons and multiple births were considered together (adjusted OR, 5.29; 95% CI, 2.41-11.63), but not statistically elevated when singleton births were analyzed on their own (aOR, 1.80; 95% CI, 0.49-6.62).

About 35% of the women with UC had prior surgeries, most commonly total colon resections. There was no difference in odds of live birth per cycle versus women with UC and without surgery (OR, 0.97; 95% CI, 0.61-1.36) after adjusting for disease duration, comorbidities, year of treatment, and other factors.

The impact of UC is probably related to disease activity. “Even though gynecologists in Denmark tell us they really try to keep their patients in remission before ART, there is some disease activity,” Dr. Friedman said at the annual Digestive Disease Week.

Surgery for Crohn’s disease is known to reduce success in ART, so it was a bit surprising that it didn’t seem to do so in UC. Perhaps it’s because UC surgery is often curative, while Crohn’s operations often are not, so Crohn’s patients may be more likely to have continued disease activity during ART treatment, Dr. Friedman said.

The majority of women in both study groups were normal weight and didn’t smoke. Outside of UC, most were free of comorbidities. In the UC surgery group, about half the women had one procedure, and the rest two or three.

The work was funded by the Crohn’s and Colitis Foundation of America. Dr. Friedman has no disclosures.

[email protected]

SAN DIEGO – Embryo transfers are less likely to result in live births when women with ulcerative colitis (UC) have fertility treatments, and the risk of preterm birth is higher, at least for twins, according to a 20-year nationwide cohort study from Denmark. On a brighter note, UC did not increase the risk of low birth weight or birth defects, and prior UC surgeries did not diminish success.

The take home conclusions from the study are that “women with ulcerative colitis may [want] to initiate ART [assisted reproductive technology] treatment” sooner than other women because “they cannot expect the same success per embryo transfer.” The greater risk of preterm birth means that “increased prenatal observation in UC pregnancies after ART should be considered,” but “women with UC should be reassured that surgery before ART treatment does not impact the chance of live birth per embryo transfer,” said senior investigator Dr. Sonia Friedman, a gastroenterologist at Brigham and Women’s Hospital in Boston.

Although it’s known that UC diminishes fertility in general, it hasn’t been known until now how it affects assisted reproduction. The investigators turned to Denmark to find out because Denmark has one of the highest incidence rates of UC worldwide, especially among women and men 15-29 years old, and the country captures virtually every ART outcome in national databases.

The study included 1,360 embryo transfers in 432 women with UC and 149,094 in 52,661 women without UC from 1994 to 2013. Treatments included in vitro fertilization, intracytoplasmic sperm injection, and embryo transfers. Women in both groups were a median of 33 years old; women with UC had a median disease duration of 8 years.

The chance of live birth per embryo transfer was 22% less in women with UC (odds ratio, 0.78; 95% confidence interval, 0.67-0.91), after adjusting for age, infertility cause, body mass index (BMI), smoking, and other factors, including calendar year, to take into account changes in ART over the years.

The risk of preterm birth was five times higher when singletons and multiple births were considered together (adjusted OR, 5.29; 95% CI, 2.41-11.63), but not statistically elevated when singleton births were analyzed on their own (aOR, 1.80; 95% CI, 0.49-6.62).

About 35% of the women with UC had prior surgeries, most commonly total colon resections. There was no difference in odds of live birth per cycle versus women with UC and without surgery (OR, 0.97; 95% CI, 0.61-1.36) after adjusting for disease duration, comorbidities, year of treatment, and other factors.

The impact of UC is probably related to disease activity. “Even though gynecologists in Denmark tell us they really try to keep their patients in remission before ART, there is some disease activity,” Dr. Friedman said at the annual Digestive Disease Week.

Surgery for Crohn’s disease is known to reduce success in ART, so it was a bit surprising that it didn’t seem to do so in UC. Perhaps it’s because UC surgery is often curative, while Crohn’s operations often are not, so Crohn’s patients may be more likely to have continued disease activity during ART treatment, Dr. Friedman said.

The majority of women in both study groups were normal weight and didn’t smoke. Outside of UC, most were free of comorbidities. In the UC surgery group, about half the women had one procedure, and the rest two or three.

The work was funded by the Crohn’s and Colitis Foundation of America. Dr. Friedman has no disclosures.

[email protected]

SAN DIEGO – Endoscopic and laparoscopic drainage worked about equally well for pancreatic pseudocysts and walled off necrosis in a small randomized trial from India, the first to compare the two options.

Both are in common use, but until now it wasn’t clear if one was better than the other. The findings mean that “in general, one could do either; the choice of treatment depends [largely] on the expertise available. As an endoscopist, I prefer endoscopic drainage,” said gastroenterologist Pramod Garg, of the All India Institute of Medical Sciences, New Delhi.

Laparoscopic drainage was a technical success in 23 of the 30 patients (76.6%) randomized to it, six of whom (20%) had symptomatic pseudocysts larger than 6 cm for more than 6 weeks; the rest had walled off necrosis (WON) containing less than 30% necrotic debris. Five of the other patients were converted to open surgery, and two underwent percutaneous drainage. One of the 30 patients required endoscopic lavage and necrosectomy for secondary infection.

Endoscopic drainage, meanwhile, was technically successful in 22 of 30 patients (73.3%) with similar distributions of pseudocysts and WON. Most of the other patients needed subsequent endoscopic lavage and necrosectomy for secondary infection.

Clinical success – defined as resolution by week 4 – was 100% in the laparoscopic and 97% (29/30) in the endoscopic groups; one endoscopic patient had a splenic artery pseudoaneurysm that required further surgery. The differences in technical and clinical success rates were not statistically significant. There were no recurrences and no deaths in either group after an average follow-up of 22 months.

Although it seems okay to opt for either approach, “it’s very important for us to assess the amount of necrotic debris. If the amount is sizable, say 50% or more of the volume, one should hesitate before doing purely endoscopic drainage.” As seen in the study, “the chances of developing an infection are pretty high, especially if,” like the investigators, “you place only a plastic stent,” Dr. Garg said at the annual Digestive Disease Week.

Laparoscopic drainage would probably be better when there’s a lot of necrotic tissue, and certainly so if patients need their gallbladder removed, because it can be taken out at the same time. If endoscopy is still the choice, “you should be prepared to do repeat procedures for endoscopic lavage and necrosectomy. The chance of infection may be less if you use a metal stent with a wide diameter,” Dr. Garg said. Before tackling WON with endoscopy, he suggested getting input from a radiologist and surgeon.

Laparoscopic cystogastrostomy was done in the usual manner, with an endostapler to create a wide cystogastrostomy, necrotic debris suction, and concomitant cholecystectomies as needed.

Endoscopic drainage was performed under endosonographic guidance in the 13 patients without bulging cysts, and directly in the 17 patients whose cysts bulged. A balloon was used to dilate the cystogastrostomy tract to 12-15 mm, and a 10 F double pigtail plastic stent placed to keep it open.

Patients in both groups received perioperative antibiotics. The demographic, clinical, and laboratory parameters and etiology of acute pancreatitis were comparable between the two groups. Patients tended to be in their mid-30s, and about 75% in both groups were women. Over a third in each group had gallstone disease. The median hospital stay in both groups was about a week. Fever was more common following endoscopic drainage, probably because of the higher incidence of secondary infection.

Patients with complicated pseudocysts, coagulopathies, or organ failure were excluded from the investigation, as well as those otherwise unfit for surgery.

There was no industry funding for the work, and Dr. Garg had no disclosures.

[email protected]

SAN DIEGO – Endoscopic and laparoscopic drainage worked about equally well for pancreatic pseudocysts and walled off necrosis in a small randomized trial from India, the first to compare the two options.

Both are in common use, but until now it wasn’t clear if one was better than the other. The findings mean that “in general, one could do either; the choice of treatment depends [largely] on the expertise available. As an endoscopist, I prefer endoscopic drainage,” said gastroenterologist Pramod Garg, of the All India Institute of Medical Sciences, New Delhi.

Laparoscopic drainage was a technical success in 23 of the 30 patients (76.6%) randomized to it, six of whom (20%) had symptomatic pseudocysts larger than 6 cm for more than 6 weeks; the rest had walled off necrosis (WON) containing less than 30% necrotic debris. Five of the other patients were converted to open surgery, and two underwent percutaneous drainage. One of the 30 patients required endoscopic lavage and necrosectomy for secondary infection.

Endoscopic drainage, meanwhile, was technically successful in 22 of 30 patients (73.3%) with similar distributions of pseudocysts and WON. Most of the other patients needed subsequent endoscopic lavage and necrosectomy for secondary infection.

Clinical success – defined as resolution by week 4 – was 100% in the laparoscopic and 97% (29/30) in the endoscopic groups; one endoscopic patient had a splenic artery pseudoaneurysm that required further surgery. The differences in technical and clinical success rates were not statistically significant. There were no recurrences and no deaths in either group after an average follow-up of 22 months.

Although it seems okay to opt for either approach, “it’s very important for us to assess the amount of necrotic debris. If the amount is sizable, say 50% or more of the volume, one should hesitate before doing purely endoscopic drainage.” As seen in the study, “the chances of developing an infection are pretty high, especially if,” like the investigators, “you place only a plastic stent,” Dr. Garg said at the annual Digestive Disease Week.

Laparoscopic drainage would probably be better when there’s a lot of necrotic tissue, and certainly so if patients need their gallbladder removed, because it can be taken out at the same time. If endoscopy is still the choice, “you should be prepared to do repeat procedures for endoscopic lavage and necrosectomy. The chance of infection may be less if you use a metal stent with a wide diameter,” Dr. Garg said. Before tackling WON with endoscopy, he suggested getting input from a radiologist and surgeon.

Laparoscopic cystogastrostomy was done in the usual manner, with an endostapler to create a wide cystogastrostomy, necrotic debris suction, and concomitant cholecystectomies as needed.

Endoscopic drainage was performed under endosonographic guidance in the 13 patients without bulging cysts, and directly in the 17 patients whose cysts bulged. A balloon was used to dilate the cystogastrostomy tract to 12-15 mm, and a 10 F double pigtail plastic stent placed to keep it open.

Patients in both groups received perioperative antibiotics. The demographic, clinical, and laboratory parameters and etiology of acute pancreatitis were comparable between the two groups. Patients tended to be in their mid-30s, and about 75% in both groups were women. Over a third in each group had gallstone disease. The median hospital stay in both groups was about a week. Fever was more common following endoscopic drainage, probably because of the higher incidence of secondary infection.

Patients with complicated pseudocysts, coagulopathies, or organ failure were excluded from the investigation, as well as those otherwise unfit for surgery.

There was no industry funding for the work, and Dr. Garg had no disclosures.

[email protected]

SAN DIEGO – Endoscopic and laparoscopic drainage worked about equally well for pancreatic pseudocysts and walled off necrosis in a small randomized trial from India, the first to compare the two options.

Both are in common use, but until now it wasn’t clear if one was better than the other. The findings mean that “in general, one could do either; the choice of treatment depends [largely] on the expertise available. As an endoscopist, I prefer endoscopic drainage,” said gastroenterologist Pramod Garg, of the All India Institute of Medical Sciences, New Delhi.

Laparoscopic drainage was a technical success in 23 of the 30 patients (76.6%) randomized to it, six of whom (20%) had symptomatic pseudocysts larger than 6 cm for more than 6 weeks; the rest had walled off necrosis (WON) containing less than 30% necrotic debris. Five of the other patients were converted to open surgery, and two underwent percutaneous drainage. One of the 30 patients required endoscopic lavage and necrosectomy for secondary infection.

Endoscopic drainage, meanwhile, was technically successful in 22 of 30 patients (73.3%) with similar distributions of pseudocysts and WON. Most of the other patients needed subsequent endoscopic lavage and necrosectomy for secondary infection.

Clinical success – defined as resolution by week 4 – was 100% in the laparoscopic and 97% (29/30) in the endoscopic groups; one endoscopic patient had a splenic artery pseudoaneurysm that required further surgery. The differences in technical and clinical success rates were not statistically significant. There were no recurrences and no deaths in either group after an average follow-up of 22 months.

Although it seems okay to opt for either approach, “it’s very important for us to assess the amount of necrotic debris. If the amount is sizable, say 50% or more of the volume, one should hesitate before doing purely endoscopic drainage.” As seen in the study, “the chances of developing an infection are pretty high, especially if,” like the investigators, “you place only a plastic stent,” Dr. Garg said at the annual Digestive Disease Week.

Laparoscopic drainage would probably be better when there’s a lot of necrotic tissue, and certainly so if patients need their gallbladder removed, because it can be taken out at the same time. If endoscopy is still the choice, “you should be prepared to do repeat procedures for endoscopic lavage and necrosectomy. The chance of infection may be less if you use a metal stent with a wide diameter,” Dr. Garg said. Before tackling WON with endoscopy, he suggested getting input from a radiologist and surgeon.

Laparoscopic cystogastrostomy was done in the usual manner, with an endostapler to create a wide cystogastrostomy, necrotic debris suction, and concomitant cholecystectomies as needed.

Endoscopic drainage was performed under endosonographic guidance in the 13 patients without bulging cysts, and directly in the 17 patients whose cysts bulged. A balloon was used to dilate the cystogastrostomy tract to 12-15 mm, and a 10 F double pigtail plastic stent placed to keep it open.

Patients in both groups received perioperative antibiotics. The demographic, clinical, and laboratory parameters and etiology of acute pancreatitis were comparable between the two groups. Patients tended to be in their mid-30s, and about 75% in both groups were women. Over a third in each group had gallstone disease. The median hospital stay in both groups was about a week. Fever was more common following endoscopic drainage, probably because of the higher incidence of secondary infection.

Patients with complicated pseudocysts, coagulopathies, or organ failure were excluded from the investigation, as well as those otherwise unfit for surgery.

There was no industry funding for the work, and Dr. Garg had no disclosures.

[email protected]

SAN DIEGO – Phentermine-topiramate was the most effective long-term weight loss drug, based on findings from a network meta-analysis from the University of California, San Diego.

The investigators pooled data from 28 studies of phentermine-topiramate (Qsymia) and four other drugs: orlistat (Xenical, Alli), lorcaserin (Belviq), naltrexone-bupropion (Contrave), and liraglutide (Victoza, Saxenda). The most commonly prescribed weight loss drug in the United States – generic phentermine – was not included because it’s not indicated for long-term use.

“It’s good to have a problem of plenty,” said Dr. Siddharth Singh, but it also makes it hard to figure out which drug to prescribe, especially given the lack of head-to-head studies. He said he hopes the results will help. However, the 30%-45% attrition rate across the studies means that the results have to be interpreted cautiously, said Dr. Singh, who is in the division of gastroenterology in the department of internal medicine, UCSD.

Most of the studies were company-funded phase III trials of weight loss drugs vs. placebo; the trials all were at least 1 year long and included more than 29,000 overweight or obese adults. The analysis was limited to patients on the maximum recommended dose of each drug.

All the drugs were more effective than placebo, but phentermine-topiramate was the most effective, with about 75% of patients losing at least 5% of their weight at 1 year and more than half losing at least 10%, with an average weight loss above placebo of 9 kg. Phentermine-topiramate patients were 10 times more likely than patients on placebo to hit the 5% mark at 1 year; liraglutide patients were 5.5 times more likely to do so; naltrexone-bupropion patients were 4 times more likely; lorcaserin patients, 3.1 times more likely; and orlistat patients, 2.7 times more likely to hit the 5% mark. The spread was similar for weight loss of 10% or more at 1 year vs. placebo.

Phentermine-topiramate’s tolerability profile was acceptable, with 10% of patients quitting the drug by 1 year because of adverse events. The best tolerated was lorcaserin, with a discontinuation rate of 6%, and the least tolerated was liraglutide, with a 13% discontinuation rate. Patients were more likely to quit active drug than placebo in all the studies.

Of course, there are other considerations, especially comorbidities; liraglutide might be the best choice in diabetics, for instance, and patients with psychiatric issues might want to avoid naltrexone-bupropion and lorcaserin, Dr. Singh said.

Subjects were a median of 46 years old, and 74% were women. The median body mass index was 36 kg/m². All the patients had lifestyle and nutrition counseling along with their study medications.

The investigators next plan to compare the drugs’ safety and efficacy in real world settings.

There was no industry funding for the work, and Dr. Singh had no relevant financial disclosures.

[email protected]

SAN DIEGO – Phentermine-topiramate was the most effective long-term weight loss drug, based on findings from a network meta-analysis from the University of California, San Diego.

The investigators pooled data from 28 studies of phentermine-topiramate (Qsymia) and four other drugs: orlistat (Xenical, Alli), lorcaserin (Belviq), naltrexone-bupropion (Contrave), and liraglutide (Victoza, Saxenda). The most commonly prescribed weight loss drug in the United States – generic phentermine – was not included because it’s not indicated for long-term use.

“It’s good to have a problem of plenty,” said Dr. Siddharth Singh, but it also makes it hard to figure out which drug to prescribe, especially given the lack of head-to-head studies. He said he hopes the results will help. However, the 30%-45% attrition rate across the studies means that the results have to be interpreted cautiously, said Dr. Singh, who is in the division of gastroenterology in the department of internal medicine, UCSD.

Most of the studies were company-funded phase III trials of weight loss drugs vs. placebo; the trials all were at least 1 year long and included more than 29,000 overweight or obese adults. The analysis was limited to patients on the maximum recommended dose of each drug.

All the drugs were more effective than placebo, but phentermine-topiramate was the most effective, with about 75% of patients losing at least 5% of their weight at 1 year and more than half losing at least 10%, with an average weight loss above placebo of 9 kg. Phentermine-topiramate patients were 10 times more likely than patients on placebo to hit the 5% mark at 1 year; liraglutide patients were 5.5 times more likely to do so; naltrexone-bupropion patients were 4 times more likely; lorcaserin patients, 3.1 times more likely; and orlistat patients, 2.7 times more likely to hit the 5% mark. The spread was similar for weight loss of 10% or more at 1 year vs. placebo.

Phentermine-topiramate’s tolerability profile was acceptable, with 10% of patients quitting the drug by 1 year because of adverse events. The best tolerated was lorcaserin, with a discontinuation rate of 6%, and the least tolerated was liraglutide, with a 13% discontinuation rate. Patients were more likely to quit active drug than placebo in all the studies.

Of course, there are other considerations, especially comorbidities; liraglutide might be the best choice in diabetics, for instance, and patients with psychiatric issues might want to avoid naltrexone-bupropion and lorcaserin, Dr. Singh said.

Subjects were a median of 46 years old, and 74% were women. The median body mass index was 36 kg/m². All the patients had lifestyle and nutrition counseling along with their study medications.

The investigators next plan to compare the drugs’ safety and efficacy in real world settings.

There was no industry funding for the work, and Dr. Singh had no relevant financial disclosures.

[email protected]

SAN DIEGO – Phentermine-topiramate was the most effective long-term weight loss drug, based on findings from a network meta-analysis from the University of California, San Diego.

The investigators pooled data from 28 studies of phentermine-topiramate (Qsymia) and four other drugs: orlistat (Xenical, Alli), lorcaserin (Belviq), naltrexone-bupropion (Contrave), and liraglutide (Victoza, Saxenda). The most commonly prescribed weight loss drug in the United States – generic phentermine – was not included because it’s not indicated for long-term use.

“It’s good to have a problem of plenty,” said Dr. Siddharth Singh, but it also makes it hard to figure out which drug to prescribe, especially given the lack of head-to-head studies. He said he hopes the results will help. However, the 30%-45% attrition rate across the studies means that the results have to be interpreted cautiously, said Dr. Singh, who is in the division of gastroenterology in the department of internal medicine, UCSD.

Most of the studies were company-funded phase III trials of weight loss drugs vs. placebo; the trials all were at least 1 year long and included more than 29,000 overweight or obese adults. The analysis was limited to patients on the maximum recommended dose of each drug.

All the drugs were more effective than placebo, but phentermine-topiramate was the most effective, with about 75% of patients losing at least 5% of their weight at 1 year and more than half losing at least 10%, with an average weight loss above placebo of 9 kg. Phentermine-topiramate patients were 10 times more likely than patients on placebo to hit the 5% mark at 1 year; liraglutide patients were 5.5 times more likely to do so; naltrexone-bupropion patients were 4 times more likely; lorcaserin patients, 3.1 times more likely; and orlistat patients, 2.7 times more likely to hit the 5% mark. The spread was similar for weight loss of 10% or more at 1 year vs. placebo.

Phentermine-topiramate’s tolerability profile was acceptable, with 10% of patients quitting the drug by 1 year because of adverse events. The best tolerated was lorcaserin, with a discontinuation rate of 6%, and the least tolerated was liraglutide, with a 13% discontinuation rate. Patients were more likely to quit active drug than placebo in all the studies.

Of course, there are other considerations, especially comorbidities; liraglutide might be the best choice in diabetics, for instance, and patients with psychiatric issues might want to avoid naltrexone-bupropion and lorcaserin, Dr. Singh said.

Subjects were a median of 46 years old, and 74% were women. The median body mass index was 36 kg/m². All the patients had lifestyle and nutrition counseling along with their study medications.

The investigators next plan to compare the drugs’ safety and efficacy in real world settings.

There was no industry funding for the work, and Dr. Singh had no relevant financial disclosures.

[email protected]

SAN DIEGO – Patients with hepatitis C virus (HCV) infections had distinct duodenal mucosal microbiomes and greater intestinal permeability, compared with healthy controls and patients with other chronic liver diseases, Dr. Ashok Raj reported.

The findings might one day lead to therapies that aim to restore or normalize the microbiomes of patients with HCV, Dr. Raj said in an interview at the annual Digestive Disease Week.

Amy Karon/Frontline Medical News

Chronic liver disease (CLD) has been linked to dysbiosis, or abnormal shifts of the microbiome. But most studies have focused on fecal specimens, and “recent evidence suggests that the mucosal microbiota differ from fecal microbiota,” said Dr. Raj, a gastroenterologist and hepatologist at Princess Alexandra Hospital in Brisbane, Australia, and a PhD candidate at the University of Queensland at Brisbane.

“The small-intestinal mucosal microbiota are of particular interest to us,” Dr. Raj explained. “Anatomically, all the blood from this region of the gut drains into the portal vein and flows directly to the liver. Because of small-intestinal permeability, either bacteria or their products could travel to the liver and contribute to disease. But very little is known about this microbiota in CLD.”

Therefore, Dr. Raj and his associates sequenced bacterial DNA from mucosal biopsies of the second part of the duodenum from 38 prospectively recruited endoscopy patients with CLD and 13 healthy controls. The researchers also evaluated dietary habits, intestinal permeability, hepatic stiffness based on transient elastography, and the presence of metabolic syndrome, as measured by the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute 2009 Consensus criteria. The CLD group included 28 men and 10 women aged 36-82 years, including 16 patients with HCV, 10 patients with nonalcoholic fatty liver disease, 7 patients with fatty liver disease, 3 patients with autoimmune hepatitis, and 2 patients with hepatitis B virus infection. The controls were between 24 and 73 years old, and 70% were women.

Sequencing of bacteria DNA revealed significant differences between patients and controls, particularly among patients with HCV, Dr. Raj said. The HCV patients not only had significantly less microbial diversity (P less than .02), but the overall changes in their microbiota were significant enough for them to cluster separately from controls and from patients with other types of CLD (P less than .01 for both comparisons). Furthermore, HCV patients had significantly greater small-intestinal permeability (mean ± SD log lactulose to rhamnose ratio, 1.57 ± 0.27) than controls (1.21 ± 0.25; P less than .01) or patients with other CLDs (1.24 ± 0.39; P = .01).

“Additionally, for the HCV patients, dietary fat intake showed a moderately strong positive correlation with intestinal permeability,” Dr. Raj said (r = 0.58; P = .03). “These findings are in keeping with animal models, which have shown that dietary fat can change the microbiota and also increase intestinal permeability.” However, the multivariate analysis found no links between microbial characteristics and hepatic stiffness or metabolic syndrome – perhaps because most patients were “at the cirrhotic end of the spectrum, reflecting their indication for endoscopy,” or because “these relationships are subtler and require larger sample numbers,” he said.

“Patients with HCV may have a unique small-intestinal microbiome,” Dr. Raj concluded. “These patients had higher intestinal permeability, and it is possible that the microbiota have a part to play in that.” Exactly how microbiota and gut permeability contribute to disease remains unclear, but pathology in the small intestine could help explain some features of the HCV trajectory, such as extrahepatic manifestations or variations in disease progression, he added. “Future studies may lead to targeting the small-intestinal gut microbiome to modulate and even treat HCV.”

The study was funded by a postgraduate award from the government of Australia and by the Princess Alexandra Hospital Research Foundation. Dr. Raj had no disclosures.

SAN DIEGO – Patients with hepatitis C virus (HCV) infections had distinct duodenal mucosal microbiomes and greater intestinal permeability, compared with healthy controls and patients with other chronic liver diseases, Dr. Ashok Raj reported.

The findings might one day lead to therapies that aim to restore or normalize the microbiomes of patients with HCV, Dr. Raj said in an interview at the annual Digestive Disease Week.

Amy Karon/Frontline Medical News

Chronic liver disease (CLD) has been linked to dysbiosis, or abnormal shifts of the microbiome. But most studies have focused on fecal specimens, and “recent evidence suggests that the mucosal microbiota differ from fecal microbiota,” said Dr. Raj, a gastroenterologist and hepatologist at Princess Alexandra Hospital in Brisbane, Australia, and a PhD candidate at the University of Queensland at Brisbane.

“The small-intestinal mucosal microbiota are of particular interest to us,” Dr. Raj explained. “Anatomically, all the blood from this region of the gut drains into the portal vein and flows directly to the liver. Because of small-intestinal permeability, either bacteria or their products could travel to the liver and contribute to disease. But very little is known about this microbiota in CLD.”

Therefore, Dr. Raj and his associates sequenced bacterial DNA from mucosal biopsies of the second part of the duodenum from 38 prospectively recruited endoscopy patients with CLD and 13 healthy controls. The researchers also evaluated dietary habits, intestinal permeability, hepatic stiffness based on transient elastography, and the presence of metabolic syndrome, as measured by the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute 2009 Consensus criteria. The CLD group included 28 men and 10 women aged 36-82 years, including 16 patients with HCV, 10 patients with nonalcoholic fatty liver disease, 7 patients with fatty liver disease, 3 patients with autoimmune hepatitis, and 2 patients with hepatitis B virus infection. The controls were between 24 and 73 years old, and 70% were women.

Sequencing of bacteria DNA revealed significant differences between patients and controls, particularly among patients with HCV, Dr. Raj said. The HCV patients not only had significantly less microbial diversity (P less than .02), but the overall changes in their microbiota were significant enough for them to cluster separately from controls and from patients with other types of CLD (P less than .01 for both comparisons). Furthermore, HCV patients had significantly greater small-intestinal permeability (mean ± SD log lactulose to rhamnose ratio, 1.57 ± 0.27) than controls (1.21 ± 0.25; P less than .01) or patients with other CLDs (1.24 ± 0.39; P = .01).

“Additionally, for the HCV patients, dietary fat intake showed a moderately strong positive correlation with intestinal permeability,” Dr. Raj said (r = 0.58; P = .03). “These findings are in keeping with animal models, which have shown that dietary fat can change the microbiota and also increase intestinal permeability.” However, the multivariate analysis found no links between microbial characteristics and hepatic stiffness or metabolic syndrome – perhaps because most patients were “at the cirrhotic end of the spectrum, reflecting their indication for endoscopy,” or because “these relationships are subtler and require larger sample numbers,” he said.

“Patients with HCV may have a unique small-intestinal microbiome,” Dr. Raj concluded. “These patients had higher intestinal permeability, and it is possible that the microbiota have a part to play in that.” Exactly how microbiota and gut permeability contribute to disease remains unclear, but pathology in the small intestine could help explain some features of the HCV trajectory, such as extrahepatic manifestations or variations in disease progression, he added. “Future studies may lead to targeting the small-intestinal gut microbiome to modulate and even treat HCV.”

The study was funded by a postgraduate award from the government of Australia and by the Princess Alexandra Hospital Research Foundation. Dr. Raj had no disclosures.

SAN DIEGO – Patients with hepatitis C virus (HCV) infections had distinct duodenal mucosal microbiomes and greater intestinal permeability, compared with healthy controls and patients with other chronic liver diseases, Dr. Ashok Raj reported.

The findings might one day lead to therapies that aim to restore or normalize the microbiomes of patients with HCV, Dr. Raj said in an interview at the annual Digestive Disease Week.

Amy Karon/Frontline Medical News

Chronic liver disease (CLD) has been linked to dysbiosis, or abnormal shifts of the microbiome. But most studies have focused on fecal specimens, and “recent evidence suggests that the mucosal microbiota differ from fecal microbiota,” said Dr. Raj, a gastroenterologist and hepatologist at Princess Alexandra Hospital in Brisbane, Australia, and a PhD candidate at the University of Queensland at Brisbane.

“The small-intestinal mucosal microbiota are of particular interest to us,” Dr. Raj explained. “Anatomically, all the blood from this region of the gut drains into the portal vein and flows directly to the liver. Because of small-intestinal permeability, either bacteria or their products could travel to the liver and contribute to disease. But very little is known about this microbiota in CLD.”

Therefore, Dr. Raj and his associates sequenced bacterial DNA from mucosal biopsies of the second part of the duodenum from 38 prospectively recruited endoscopy patients with CLD and 13 healthy controls. The researchers also evaluated dietary habits, intestinal permeability, hepatic stiffness based on transient elastography, and the presence of metabolic syndrome, as measured by the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute 2009 Consensus criteria. The CLD group included 28 men and 10 women aged 36-82 years, including 16 patients with HCV, 10 patients with nonalcoholic fatty liver disease, 7 patients with fatty liver disease, 3 patients with autoimmune hepatitis, and 2 patients with hepatitis B virus infection. The controls were between 24 and 73 years old, and 70% were women.

Sequencing of bacteria DNA revealed significant differences between patients and controls, particularly among patients with HCV, Dr. Raj said. The HCV patients not only had significantly less microbial diversity (P less than .02), but the overall changes in their microbiota were significant enough for them to cluster separately from controls and from patients with other types of CLD (P less than .01 for both comparisons). Furthermore, HCV patients had significantly greater small-intestinal permeability (mean ± SD log lactulose to rhamnose ratio, 1.57 ± 0.27) than controls (1.21 ± 0.25; P less than .01) or patients with other CLDs (1.24 ± 0.39; P = .01).

“Additionally, for the HCV patients, dietary fat intake showed a moderately strong positive correlation with intestinal permeability,” Dr. Raj said (r = 0.58; P = .03). “These findings are in keeping with animal models, which have shown that dietary fat can change the microbiota and also increase intestinal permeability.” However, the multivariate analysis found no links between microbial characteristics and hepatic stiffness or metabolic syndrome – perhaps because most patients were “at the cirrhotic end of the spectrum, reflecting their indication for endoscopy,” or because “these relationships are subtler and require larger sample numbers,” he said.

“Patients with HCV may have a unique small-intestinal microbiome,” Dr. Raj concluded. “These patients had higher intestinal permeability, and it is possible that the microbiota have a part to play in that.” Exactly how microbiota and gut permeability contribute to disease remains unclear, but pathology in the small intestine could help explain some features of the HCV trajectory, such as extrahepatic manifestations or variations in disease progression, he added. “Future studies may lead to targeting the small-intestinal gut microbiome to modulate and even treat HCV.”

The study was funded by a postgraduate award from the government of Australia and by the Princess Alexandra Hospital Research Foundation. Dr. Raj had no disclosures.

SAN DIEGO – About 90% of patients reported improvement in symptoms of irritable bowel syndrome after avoiding type 4 food allergens identified by skin patch testing, according to an uncontrolled study.

Furthermore, 69% of patients reported at least moderate improvement after eliminating foods to which they reacted, said Dr. Michael Stierstorfer, a dermatologist at East Penn Dermatology in North Wales, Pa., who partnered with gastroenterologists at Temple University to conduct the study. “This raises questions about a possible overlap between IBS and allergic contact enteritis,” the researchers stated in a poster presented at the annual Digestive Disease Week.

Amy Karon/Frontline Medical News

Irritable bowel syndrome is often treatment refractory and tends to elude conventional diagnostics. That was the case for Dr. Stierstorfer, who several years ago developed symptoms of IBS with constipation (IBS-C) that eventually affected him about half the time, he said in an interview. A hydrogen breath test, upper endoscopy, colonoscopy, abdominal/pelvic CT, and tests for gluten-sensitive enteropathy and parasites revealed no abnormalities except decreased small intestinal motility, he said.

But after “flaring badly” twice when he ate Indian food, he began to suspect a cause. “I stopped eating garlic and within a day, I was absolutely fine,” Dr. Stierstorfer said. “The symptoms recurred only if I accidentally ate garlic again.”

Studies had refuted links between IBS and type 1 hypersensitivity but had not explored the role of type 4 (delayed) hypersensitivity in the disorder, Dr. Stierstorfer discovered. “Dermatologists do patch testing all the time for patients with refractory eczema to search for type 4 allergic contact factors that might be causing their rash,” he said. “I performed a patch test of garlic on myself to look for a type 4 allergy, and it was strongly positive. I thought I probably wasn’t the only person walking around with symptoms that mimicked IBS but were really from a type 4 food allergy.”

He tested that idea by skin patch testing 50 patients with IBS symptoms whom he recruited through his dermatology practice. In all, 30 (60%) patients reacted to at least one food allergen, of whom 14 (46%) reported symptomatic improvement after eliminating the suspected triggers from their diets. The findings appeared in the March 2013 Journal of the American Academy of Dermatology (68:377-84).

Next, Dr. Stierstorfer partnered with Dr. Grace Shin, a 3rd-year gastroenterology fellow at Temple University, Philadelphia, and her colleagues. Together, they tested 57 patients with physician-diagnosed IBS with diarrhea (about 43% of patients), IBS with constipation (16%), mixed IBS (30%), or unsubtyped IBS (11%). Patients averaged 41 years of age (standard deviation, 15 years) and 77% were female. Each patient had between 118 and 122 individual allergen patches placed on his or her back. Two days later, the patches were removed and the skin evaluated for macular erythema consistent with a type 4 hypersensitivity reaction. The patients were checked again a day or 2 later to catch any highly delayed reactions.

In all, 56 patients (98%) showed evidence of at least one hypersensitivity, and most reacted to between two and three allergens, Dr. Stierstorfer said. The most commonly identified triggers were cinnamon bark (35 patients; 61%) and sodium bisulfite (26 patients; 46%). At baseline, patients rated their abdominal pain or discomfort at an average of 6.7 on a 10-point severity scale (SD, 2.3 points). After 2-4 weeks of avoiding allergens to which they developed macular edema, they reported a mean 4.4-point improvement in their abdominal symptoms (SD, 2.7 points; P less than .001).

The patients also reported an average 5.8-point improvement on a 10-point scale of global IBS symptom severity (SD, 3.2 points; P less than .001). Overall, 91% of patients reported at least partial relief of abdominal symptoms, while 89% of patients reported at least partial relief of global symptoms, the investigators reported.

Based on these results, “food-related type 4 hypersensitivity reactions may contribute to the pathogenesis of IBS and IBS-like symptoms,” Dr. Shin said in an interview. “The idea of allergic contact enteritis intrigued me, because it made me think that some patients diagnosed with IBS, especially IBS with diarrhea, might benefit from allergy testing when the standard approaches don’t work.”

Another dietary intervention for IBS, the low-FODMAP diet, can help relieve symptoms, “but it’s a hard diet to follow,” Dr. Shin added. “Being able to focus on eliminating one or two things would be easier than eliminating multiple classes of foods that are so common to an American diet.”

Next, the team is planning a controlled trial of the skin patch test. “There is still more validation work to do,” said Dr. Stierstorfer. “But I think this shows that looking at something from a unique perspective – in this case, a dermatologic perspective for a GI problem – can result in a new approach, and potentially an advance in medicine.”

Dr. Shin had no disclosures. Dr. Stierstorfer disclosed financial ties to IBS Centers for Advanced Food Allergy Testing.

SAN DIEGO – About 90% of patients reported improvement in symptoms of irritable bowel syndrome after avoiding type 4 food allergens identified by skin patch testing, according to an uncontrolled study.

Furthermore, 69% of patients reported at least moderate improvement after eliminating foods to which they reacted, said Dr. Michael Stierstorfer, a dermatologist at East Penn Dermatology in North Wales, Pa., who partnered with gastroenterologists at Temple University to conduct the study. “This raises questions about a possible overlap between IBS and allergic contact enteritis,” the researchers stated in a poster presented at the annual Digestive Disease Week.

Amy Karon/Frontline Medical News

Irritable bowel syndrome is often treatment refractory and tends to elude conventional diagnostics. That was the case for Dr. Stierstorfer, who several years ago developed symptoms of IBS with constipation (IBS-C) that eventually affected him about half the time, he said in an interview. A hydrogen breath test, upper endoscopy, colonoscopy, abdominal/pelvic CT, and tests for gluten-sensitive enteropathy and parasites revealed no abnormalities except decreased small intestinal motility, he said.

But after “flaring badly” twice when he ate Indian food, he began to suspect a cause. “I stopped eating garlic and within a day, I was absolutely fine,” Dr. Stierstorfer said. “The symptoms recurred only if I accidentally ate garlic again.”

Studies had refuted links between IBS and type 1 hypersensitivity but had not explored the role of type 4 (delayed) hypersensitivity in the disorder, Dr. Stierstorfer discovered. “Dermatologists do patch testing all the time for patients with refractory eczema to search for type 4 allergic contact factors that might be causing their rash,” he said. “I performed a patch test of garlic on myself to look for a type 4 allergy, and it was strongly positive. I thought I probably wasn’t the only person walking around with symptoms that mimicked IBS but were really from a type 4 food allergy.”

He tested that idea by skin patch testing 50 patients with IBS symptoms whom he recruited through his dermatology practice. In all, 30 (60%) patients reacted to at least one food allergen, of whom 14 (46%) reported symptomatic improvement after eliminating the suspected triggers from their diets. The findings appeared in the March 2013 Journal of the American Academy of Dermatology (68:377-84).

Next, Dr. Stierstorfer partnered with Dr. Grace Shin, a 3rd-year gastroenterology fellow at Temple University, Philadelphia, and her colleagues. Together, they tested 57 patients with physician-diagnosed IBS with diarrhea (about 43% of patients), IBS with constipation (16%), mixed IBS (30%), or unsubtyped IBS (11%). Patients averaged 41 years of age (standard deviation, 15 years) and 77% were female. Each patient had between 118 and 122 individual allergen patches placed on his or her back. Two days later, the patches were removed and the skin evaluated for macular erythema consistent with a type 4 hypersensitivity reaction. The patients were checked again a day or 2 later to catch any highly delayed reactions.

In all, 56 patients (98%) showed evidence of at least one hypersensitivity, and most reacted to between two and three allergens, Dr. Stierstorfer said. The most commonly identified triggers were cinnamon bark (35 patients; 61%) and sodium bisulfite (26 patients; 46%). At baseline, patients rated their abdominal pain or discomfort at an average of 6.7 on a 10-point severity scale (SD, 2.3 points). After 2-4 weeks of avoiding allergens to which they developed macular edema, they reported a mean 4.4-point improvement in their abdominal symptoms (SD, 2.7 points; P less than .001).

The patients also reported an average 5.8-point improvement on a 10-point scale of global IBS symptom severity (SD, 3.2 points; P less than .001). Overall, 91% of patients reported at least partial relief of abdominal symptoms, while 89% of patients reported at least partial relief of global symptoms, the investigators reported.

Based on these results, “food-related type 4 hypersensitivity reactions may contribute to the pathogenesis of IBS and IBS-like symptoms,” Dr. Shin said in an interview. “The idea of allergic contact enteritis intrigued me, because it made me think that some patients diagnosed with IBS, especially IBS with diarrhea, might benefit from allergy testing when the standard approaches don’t work.”

Another dietary intervention for IBS, the low-FODMAP diet, can help relieve symptoms, “but it’s a hard diet to follow,” Dr. Shin added. “Being able to focus on eliminating one or two things would be easier than eliminating multiple classes of foods that are so common to an American diet.”

Next, the team is planning a controlled trial of the skin patch test. “There is still more validation work to do,” said Dr. Stierstorfer. “But I think this shows that looking at something from a unique perspective – in this case, a dermatologic perspective for a GI problem – can result in a new approach, and potentially an advance in medicine.”

Dr. Shin had no disclosures. Dr. Stierstorfer disclosed financial ties to IBS Centers for Advanced Food Allergy Testing.

SAN DIEGO – About 90% of patients reported improvement in symptoms of irritable bowel syndrome after avoiding type 4 food allergens identified by skin patch testing, according to an uncontrolled study.

Furthermore, 69% of patients reported at least moderate improvement after eliminating foods to which they reacted, said Dr. Michael Stierstorfer, a dermatologist at East Penn Dermatology in North Wales, Pa., who partnered with gastroenterologists at Temple University to conduct the study. “This raises questions about a possible overlap between IBS and allergic contact enteritis,” the researchers stated in a poster presented at the annual Digestive Disease Week.

Amy Karon/Frontline Medical News

Irritable bowel syndrome is often treatment refractory and tends to elude conventional diagnostics. That was the case for Dr. Stierstorfer, who several years ago developed symptoms of IBS with constipation (IBS-C) that eventually affected him about half the time, he said in an interview. A hydrogen breath test, upper endoscopy, colonoscopy, abdominal/pelvic CT, and tests for gluten-sensitive enteropathy and parasites revealed no abnormalities except decreased small intestinal motility, he said.

But after “flaring badly” twice when he ate Indian food, he began to suspect a cause. “I stopped eating garlic and within a day, I was absolutely fine,” Dr. Stierstorfer said. “The symptoms recurred only if I accidentally ate garlic again.”

Studies had refuted links between IBS and type 1 hypersensitivity but had not explored the role of type 4 (delayed) hypersensitivity in the disorder, Dr. Stierstorfer discovered. “Dermatologists do patch testing all the time for patients with refractory eczema to search for type 4 allergic contact factors that might be causing their rash,” he said. “I performed a patch test of garlic on myself to look for a type 4 allergy, and it was strongly positive. I thought I probably wasn’t the only person walking around with symptoms that mimicked IBS but were really from a type 4 food allergy.”

He tested that idea by skin patch testing 50 patients with IBS symptoms whom he recruited through his dermatology practice. In all, 30 (60%) patients reacted to at least one food allergen, of whom 14 (46%) reported symptomatic improvement after eliminating the suspected triggers from their diets. The findings appeared in the March 2013 Journal of the American Academy of Dermatology (68:377-84).

Next, Dr. Stierstorfer partnered with Dr. Grace Shin, a 3rd-year gastroenterology fellow at Temple University, Philadelphia, and her colleagues. Together, they tested 57 patients with physician-diagnosed IBS with diarrhea (about 43% of patients), IBS with constipation (16%), mixed IBS (30%), or unsubtyped IBS (11%). Patients averaged 41 years of age (standard deviation, 15 years) and 77% were female. Each patient had between 118 and 122 individual allergen patches placed on his or her back. Two days later, the patches were removed and the skin evaluated for macular erythema consistent with a type 4 hypersensitivity reaction. The patients were checked again a day or 2 later to catch any highly delayed reactions.

In all, 56 patients (98%) showed evidence of at least one hypersensitivity, and most reacted to between two and three allergens, Dr. Stierstorfer said. The most commonly identified triggers were cinnamon bark (35 patients; 61%) and sodium bisulfite (26 patients; 46%). At baseline, patients rated their abdominal pain or discomfort at an average of 6.7 on a 10-point severity scale (SD, 2.3 points). After 2-4 weeks of avoiding allergens to which they developed macular edema, they reported a mean 4.4-point improvement in their abdominal symptoms (SD, 2.7 points; P less than .001).

The patients also reported an average 5.8-point improvement on a 10-point scale of global IBS symptom severity (SD, 3.2 points; P less than .001). Overall, 91% of patients reported at least partial relief of abdominal symptoms, while 89% of patients reported at least partial relief of global symptoms, the investigators reported.

Based on these results, “food-related type 4 hypersensitivity reactions may contribute to the pathogenesis of IBS and IBS-like symptoms,” Dr. Shin said in an interview. “The idea of allergic contact enteritis intrigued me, because it made me think that some patients diagnosed with IBS, especially IBS with diarrhea, might benefit from allergy testing when the standard approaches don’t work.”

Another dietary intervention for IBS, the low-FODMAP diet, can help relieve symptoms, “but it’s a hard diet to follow,” Dr. Shin added. “Being able to focus on eliminating one or two things would be easier than eliminating multiple classes of foods that are so common to an American diet.”

Next, the team is planning a controlled trial of the skin patch test. “There is still more validation work to do,” said Dr. Stierstorfer. “But I think this shows that looking at something from a unique perspective – in this case, a dermatologic perspective for a GI problem – can result in a new approach, and potentially an advance in medicine.”

Dr. Shin had no disclosures. Dr. Stierstorfer disclosed financial ties to IBS Centers for Advanced Food Allergy Testing.

SAN DIEGO – Tensions among academic investigators, industry sponsors, and the Food and Drug Administration can hinder new drug approvals and slow or block communication of important results, experts said at the annual Digestive Disease Week.

Relationships between investigators and industry have become especially strained, according to Dr. M. Scott Harris, cofounder of Lyric Pharmaceuticals in San Francisco. “I can tell you as a former investigator, and someone who speaks to investigators all the time, they feel disenfranchised,” he said.

Several steps can help. Industry should focus on empowering investigators, “not study sites,” said Dr. Harris. “Have protocol development meetings, not investigator meetings. Have open dialogue so that investigators can share in the excitement of the study, the results, and the science.”

Intellectual property is a particularly hot topic, acknowledged Dr. Harris, who started out in academic gastroenterology before making the jump to working for pharmaceutical and biotechnology companies. “Intellectual property is the lifeblood of a company – the only thing that generates the likelihood of a return on investment,” he emphasized. “Please do not push back if some information cannot be shared with you.” But within those constraints, industry should “force itself to be as patient as possible,” he said. “A balance has to be struck between the need for IP [intellectual property] and the need to share knowledge.”

Sharing knowledge also means that industry sponsors need to commit to a clear publication strategy, said Dr. Harris. “Investigators want the results of the studies to be communicated, including reasons for failure. We have failed at this as an industry, and this is not acceptable.”

But academic investigators need to make some changes, too. Successfully joining a trial means engaging actively with the sponsor and protocol, Dr. Harris emphasized. “Don’t tell your staff you’re too busy to talk to me when I call. Focus on ethical study conduct, good clinical practice, training, data quality, and meeting timelines.”

Dr. Gary Lichtenstein agreed. A gastroenterologist at the University of Pennsylvania, Philadelphia, with more than 30 years of experience in clinical trials, he knows that successful academic study sites have “efficient and businesslike operations,” a proven internal audit system, and solid, reasonable budgeting for staff time, overhead, equipment, and storage. In particular, academic investigators should double-check training requirements, the qualifications of the study coordinator, and who will handle regulatory, legal, and budgeting concerns, he said.

Vetting a potential industry sponsor is just as important. Ask “if they have the staff, time, equipment, and space to do the study,” Dr. Lichtenstein stressed. “Communicate expectations in writing back and forth to avoid misunderstandings. An indemnification clause is also very important to hold the consultant harmless from and against any claim, loss, or damage whatsoever.”

The FDA, for its part, needs to respond faster to meeting requests and offer clearer guidance about appropriate study designs and outcome measures, both experts emphasized. The median time for FDA to approve a drug application is about 180 days, while approving new gastroenterology agents takes nearly twice as long, according to Dr. Lichtenstein. “There is clearly a discrepancy, and it would be nice if we moved the bar closer. As an investigator, I need to know which trials are acceptable in design, and what endpoints are clearly defined, with examples,” he said. “If I have a question, I need a point of contact to call to get an answer in rapid time, instead of having to wait for months, and I need to know which biomarkers are appropriate to use.”

Dr. Harris agreed. “There should be tension between FDA and industry – that is part of the process,” he said. “But open communication and rapid response to meeting requests are crucial.”

Timeliness and transparency are especially important as FDA transitions “from being a classic regulator to a proactive partner in drug development,” Dr. Harris said. “What industry needs and expects from FDA is greater certainty on the path. Companies may or may not like a particular FDA guidance document, but they greatly appreciate the clarity that guidance documents provide.”

Dr. Lichtenstein disclosed ties to AbbVie, Hospira, Pfizer, and numerous other pharmaceutical companies. Dr. Harris is employed by Lyric Pharmaceuticals and disclosed relationships with several other biopharmaceutical companies.

SAN DIEGO – Tensions among academic investigators, industry sponsors, and the Food and Drug Administration can hinder new drug approvals and slow or block communication of important results, experts said at the annual Digestive Disease Week.

Relationships between investigators and industry have become especially strained, according to Dr. M. Scott Harris, cofounder of Lyric Pharmaceuticals in San Francisco. “I can tell you as a former investigator, and someone who speaks to investigators all the time, they feel disenfranchised,” he said.

Several steps can help. Industry should focus on empowering investigators, “not study sites,” said Dr. Harris. “Have protocol development meetings, not investigator meetings. Have open dialogue so that investigators can share in the excitement of the study, the results, and the science.”

Intellectual property is a particularly hot topic, acknowledged Dr. Harris, who started out in academic gastroenterology before making the jump to working for pharmaceutical and biotechnology companies. “Intellectual property is the lifeblood of a company – the only thing that generates the likelihood of a return on investment,” he emphasized. “Please do not push back if some information cannot be shared with you.” But within those constraints, industry should “force itself to be as patient as possible,” he said. “A balance has to be struck between the need for IP [intellectual property] and the need to share knowledge.”

Sharing knowledge also means that industry sponsors need to commit to a clear publication strategy, said Dr. Harris. “Investigators want the results of the studies to be communicated, including reasons for failure. We have failed at this as an industry, and this is not acceptable.”

But academic investigators need to make some changes, too. Successfully joining a trial means engaging actively with the sponsor and protocol, Dr. Harris emphasized. “Don’t tell your staff you’re too busy to talk to me when I call. Focus on ethical study conduct, good clinical practice, training, data quality, and meeting timelines.”

Dr. Gary Lichtenstein agreed. A gastroenterologist at the University of Pennsylvania, Philadelphia, with more than 30 years of experience in clinical trials, he knows that successful academic study sites have “efficient and businesslike operations,” a proven internal audit system, and solid, reasonable budgeting for staff time, overhead, equipment, and storage. In particular, academic investigators should double-check training requirements, the qualifications of the study coordinator, and who will handle regulatory, legal, and budgeting concerns, he said.

Vetting a potential industry sponsor is just as important. Ask “if they have the staff, time, equipment, and space to do the study,” Dr. Lichtenstein stressed. “Communicate expectations in writing back and forth to avoid misunderstandings. An indemnification clause is also very important to hold the consultant harmless from and against any claim, loss, or damage whatsoever.”

The FDA, for its part, needs to respond faster to meeting requests and offer clearer guidance about appropriate study designs and outcome measures, both experts emphasized. The median time for FDA to approve a drug application is about 180 days, while approving new gastroenterology agents takes nearly twice as long, according to Dr. Lichtenstein. “There is clearly a discrepancy, and it would be nice if we moved the bar closer. As an investigator, I need to know which trials are acceptable in design, and what endpoints are clearly defined, with examples,” he said. “If I have a question, I need a point of contact to call to get an answer in rapid time, instead of having to wait for months, and I need to know which biomarkers are appropriate to use.”

Dr. Harris agreed. “There should be tension between FDA and industry – that is part of the process,” he said. “But open communication and rapid response to meeting requests are crucial.”

Timeliness and transparency are especially important as FDA transitions “from being a classic regulator to a proactive partner in drug development,” Dr. Harris said. “What industry needs and expects from FDA is greater certainty on the path. Companies may or may not like a particular FDA guidance document, but they greatly appreciate the clarity that guidance documents provide.”

Dr. Lichtenstein disclosed ties to AbbVie, Hospira, Pfizer, and numerous other pharmaceutical companies. Dr. Harris is employed by Lyric Pharmaceuticals and disclosed relationships with several other biopharmaceutical companies.

SAN DIEGO – Tensions among academic investigators, industry sponsors, and the Food and Drug Administration can hinder new drug approvals and slow or block communication of important results, experts said at the annual Digestive Disease Week.

Relationships between investigators and industry have become especially strained, according to Dr. M. Scott Harris, cofounder of Lyric Pharmaceuticals in San Francisco. “I can tell you as a former investigator, and someone who speaks to investigators all the time, they feel disenfranchised,” he said.

Several steps can help. Industry should focus on empowering investigators, “not study sites,” said Dr. Harris. “Have protocol development meetings, not investigator meetings. Have open dialogue so that investigators can share in the excitement of the study, the results, and the science.”

Intellectual property is a particularly hot topic, acknowledged Dr. Harris, who started out in academic gastroenterology before making the jump to working for pharmaceutical and biotechnology companies. “Intellectual property is the lifeblood of a company – the only thing that generates the likelihood of a return on investment,” he emphasized. “Please do not push back if some information cannot be shared with you.” But within those constraints, industry should “force itself to be as patient as possible,” he said. “A balance has to be struck between the need for IP [intellectual property] and the need to share knowledge.”

Sharing knowledge also means that industry sponsors need to commit to a clear publication strategy, said Dr. Harris. “Investigators want the results of the studies to be communicated, including reasons for failure. We have failed at this as an industry, and this is not acceptable.”

But academic investigators need to make some changes, too. Successfully joining a trial means engaging actively with the sponsor and protocol, Dr. Harris emphasized. “Don’t tell your staff you’re too busy to talk to me when I call. Focus on ethical study conduct, good clinical practice, training, data quality, and meeting timelines.”

Dr. Gary Lichtenstein agreed. A gastroenterologist at the University of Pennsylvania, Philadelphia, with more than 30 years of experience in clinical trials, he knows that successful academic study sites have “efficient and businesslike operations,” a proven internal audit system, and solid, reasonable budgeting for staff time, overhead, equipment, and storage. In particular, academic investigators should double-check training requirements, the qualifications of the study coordinator, and who will handle regulatory, legal, and budgeting concerns, he said.

Vetting a potential industry sponsor is just as important. Ask “if they have the staff, time, equipment, and space to do the study,” Dr. Lichtenstein stressed. “Communicate expectations in writing back and forth to avoid misunderstandings. An indemnification clause is also very important to hold the consultant harmless from and against any claim, loss, or damage whatsoever.”

The FDA, for its part, needs to respond faster to meeting requests and offer clearer guidance about appropriate study designs and outcome measures, both experts emphasized. The median time for FDA to approve a drug application is about 180 days, while approving new gastroenterology agents takes nearly twice as long, according to Dr. Lichtenstein. “There is clearly a discrepancy, and it would be nice if we moved the bar closer. As an investigator, I need to know which trials are acceptable in design, and what endpoints are clearly defined, with examples,” he said. “If I have a question, I need a point of contact to call to get an answer in rapid time, instead of having to wait for months, and I need to know which biomarkers are appropriate to use.”

Dr. Harris agreed. “There should be tension between FDA and industry – that is part of the process,” he said. “But open communication and rapid response to meeting requests are crucial.”

Timeliness and transparency are especially important as FDA transitions “from being a classic regulator to a proactive partner in drug development,” Dr. Harris said. “What industry needs and expects from FDA is greater certainty on the path. Companies may or may not like a particular FDA guidance document, but they greatly appreciate the clarity that guidance documents provide.”

Dr. Lichtenstein disclosed ties to AbbVie, Hospira, Pfizer, and numerous other pharmaceutical companies. Dr. Harris is employed by Lyric Pharmaceuticals and disclosed relationships with several other biopharmaceutical companies.