M. Alexander Otto

 

SEATTLE – Bismuth subgallate (Devrom) is a big help with an embarrassing and underappreciated problem after loop duodenal switch: smelly flatulence and stool.

Bismuth subgallate, an over the counter product that’s been on the market for decades, has been primarily studied to eliminate the odor of flatulence and bowel movements in ostomates, according to Walter Medlin, MD, a surgeon at the Bariatric Medicine Institute in Salt Lake City.

Loop duodenal switch (LDS) generally causes fat and starch malabsorption, which is good for weight loss but can result in odor problems that can “give rise to social and family conflicts” and be disabling.

“A lot of patients have this complaint, but they tend not to talk to their physicians about it,” Dr. Medlin said at the World Congress of Endoscopic Surgery hosted by SAGES & CAGS.

Enter bismuth subgallate. Dr. Medlin and his team randomized 36 LDS patients to 200-mg capsules, two per meal, or to placebo for a week. Patients then underwent a one-week washout period, then crossed over to bismuth subgallate or placebo for another week. Patients and surgeons were blinded to treatment groups.

Subjects were at least 6 months out from LDS to give their gut a chance to adapt to the surgery. Patients with GI infections and those on confounding medications were among those excluded from the study. The mean age of the patients was 48 years, and there were slightly more women than men.

Subjects filled out the Gastrointestinal Quality of Life Index questionnaire at baseline and after both treatment periods. The index assesses digestive symptoms, physical status, emotional status, social performance, and treatment effects. Additional measures were added: Patients rated stool smell, flatulence smell, and concerns about each on a 4-point scale.

 

Twenty-nine patients completed the study; five were lost to follow-up, and two withdrew. With bismuth subgallate, scores improved by about 1.5 points on all four questions about stool and flatulence odor.

“Most of these patients had complaints of ‘all the time’ or ‘very frequent’ odor issues, and this really takes [those complaints] down to ‘occasional’ or ‘rare.’ It’s a pretty big change,” Dr. Medlin said.

Total Gastrointestinal Quality of Life Index scores improved as well, from a mean at baseline of 93 points up to 109 points out of a possible score of 160 points. Scores on the digestive portion improved from 49 to 60 points. Bismuth subgallate outperformed placebo significantly on both measures. There were trends toward improvement in other domains as well.

Stools darkened in one patient, and the tongue darkened in another; both are well-known side effects. There were no drug toxicities.

 

The study “is an important contribution. Duodenal switch is the most effective [bariatric] operation we do, but a lot of patients aren’t utilizing it because of this concern [about flatulence smell],” said the moderator of Dr. Medlin’s presentation, John Morton, MD, chief of bariatric and minimally invasive surgery at Stanford (Calif.) University.

Perhaps the biggest problem with bismuth subgallate is getting a hold of it, as Dr. Medlin and others noted. It’s not sold in stores but can be purchased online, including from its maker Parthenon at about $14 for a hundred capsules. The product is also available as a chewable.

The product probably helps by blocking bacterial breakdown of food residues in the colon, among other actions. “It really is an intestinal deodorant. I find patients are interested in having access to this tool” and might not need as much as in the trial, said Dr. Medlin, who stocks it in his office.

The study was funded by an unrestricted education grant from Parthenon. The investigators had no relevant disclosures.

[email protected]

SOURCE: Zaveri H et al. SAGES 2018, Abstract S028.

 

SEATTLE – Bismuth subgallate (Devrom) is a big help with an embarrassing and underappreciated problem after loop duodenal switch: smelly flatulence and stool.

Bismuth subgallate, an over the counter product that’s been on the market for decades, has been primarily studied to eliminate the odor of flatulence and bowel movements in ostomates, according to Walter Medlin, MD, a surgeon at the Bariatric Medicine Institute in Salt Lake City.

Loop duodenal switch (LDS) generally causes fat and starch malabsorption, which is good for weight loss but can result in odor problems that can “give rise to social and family conflicts” and be disabling.

“A lot of patients have this complaint, but they tend not to talk to their physicians about it,” Dr. Medlin said at the World Congress of Endoscopic Surgery hosted by SAGES & CAGS.

Enter bismuth subgallate. Dr. Medlin and his team randomized 36 LDS patients to 200-mg capsules, two per meal, or to placebo for a week. Patients then underwent a one-week washout period, then crossed over to bismuth subgallate or placebo for another week. Patients and surgeons were blinded to treatment groups.

Subjects were at least 6 months out from LDS to give their gut a chance to adapt to the surgery. Patients with GI infections and those on confounding medications were among those excluded from the study. The mean age of the patients was 48 years, and there were slightly more women than men.

Subjects filled out the Gastrointestinal Quality of Life Index questionnaire at baseline and after both treatment periods. The index assesses digestive symptoms, physical status, emotional status, social performance, and treatment effects. Additional measures were added: Patients rated stool smell, flatulence smell, and concerns about each on a 4-point scale.

 

Twenty-nine patients completed the study; five were lost to follow-up, and two withdrew. With bismuth subgallate, scores improved by about 1.5 points on all four questions about stool and flatulence odor.

“Most of these patients had complaints of ‘all the time’ or ‘very frequent’ odor issues, and this really takes [those complaints] down to ‘occasional’ or ‘rare.’ It’s a pretty big change,” Dr. Medlin said.

Total Gastrointestinal Quality of Life Index scores improved as well, from a mean at baseline of 93 points up to 109 points out of a possible score of 160 points. Scores on the digestive portion improved from 49 to 60 points. Bismuth subgallate outperformed placebo significantly on both measures. There were trends toward improvement in other domains as well.

Stools darkened in one patient, and the tongue darkened in another; both are well-known side effects. There were no drug toxicities.

 

The study “is an important contribution. Duodenal switch is the most effective [bariatric] operation we do, but a lot of patients aren’t utilizing it because of this concern [about flatulence smell],” said the moderator of Dr. Medlin’s presentation, John Morton, MD, chief of bariatric and minimally invasive surgery at Stanford (Calif.) University.

Perhaps the biggest problem with bismuth subgallate is getting a hold of it, as Dr. Medlin and others noted. It’s not sold in stores but can be purchased online, including from its maker Parthenon at about $14 for a hundred capsules. The product is also available as a chewable.

The product probably helps by blocking bacterial breakdown of food residues in the colon, among other actions. “It really is an intestinal deodorant. I find patients are interested in having access to this tool” and might not need as much as in the trial, said Dr. Medlin, who stocks it in his office.

The study was funded by an unrestricted education grant from Parthenon. The investigators had no relevant disclosures.

[email protected]

SOURCE: Zaveri H et al. SAGES 2018, Abstract S028.

 

SEATTLE – Bismuth subgallate (Devrom) is a big help with an embarrassing and underappreciated problem after loop duodenal switch: smelly flatulence and stool.

Bismuth subgallate, an over the counter product that’s been on the market for decades, has been primarily studied to eliminate the odor of flatulence and bowel movements in ostomates, according to Walter Medlin, MD, a surgeon at the Bariatric Medicine Institute in Salt Lake City.

Loop duodenal switch (LDS) generally causes fat and starch malabsorption, which is good for weight loss but can result in odor problems that can “give rise to social and family conflicts” and be disabling.

“A lot of patients have this complaint, but they tend not to talk to their physicians about it,” Dr. Medlin said at the World Congress of Endoscopic Surgery hosted by SAGES & CAGS.

Enter bismuth subgallate. Dr. Medlin and his team randomized 36 LDS patients to 200-mg capsules, two per meal, or to placebo for a week. Patients then underwent a one-week washout period, then crossed over to bismuth subgallate or placebo for another week. Patients and surgeons were blinded to treatment groups.

Subjects were at least 6 months out from LDS to give their gut a chance to adapt to the surgery. Patients with GI infections and those on confounding medications were among those excluded from the study. The mean age of the patients was 48 years, and there were slightly more women than men.

Subjects filled out the Gastrointestinal Quality of Life Index questionnaire at baseline and after both treatment periods. The index assesses digestive symptoms, physical status, emotional status, social performance, and treatment effects. Additional measures were added: Patients rated stool smell, flatulence smell, and concerns about each on a 4-point scale.

 

Twenty-nine patients completed the study; five were lost to follow-up, and two withdrew. With bismuth subgallate, scores improved by about 1.5 points on all four questions about stool and flatulence odor.

“Most of these patients had complaints of ‘all the time’ or ‘very frequent’ odor issues, and this really takes [those complaints] down to ‘occasional’ or ‘rare.’ It’s a pretty big change,” Dr. Medlin said.

Total Gastrointestinal Quality of Life Index scores improved as well, from a mean at baseline of 93 points up to 109 points out of a possible score of 160 points. Scores on the digestive portion improved from 49 to 60 points. Bismuth subgallate outperformed placebo significantly on both measures. There were trends toward improvement in other domains as well.

Stools darkened in one patient, and the tongue darkened in another; both are well-known side effects. There were no drug toxicities.

 

The study “is an important contribution. Duodenal switch is the most effective [bariatric] operation we do, but a lot of patients aren’t utilizing it because of this concern [about flatulence smell],” said the moderator of Dr. Medlin’s presentation, John Morton, MD, chief of bariatric and minimally invasive surgery at Stanford (Calif.) University.

Perhaps the biggest problem with bismuth subgallate is getting a hold of it, as Dr. Medlin and others noted. It’s not sold in stores but can be purchased online, including from its maker Parthenon at about $14 for a hundred capsules. The product is also available as a chewable.

The product probably helps by blocking bacterial breakdown of food residues in the colon, among other actions. “It really is an intestinal deodorant. I find patients are interested in having access to this tool” and might not need as much as in the trial, said Dr. Medlin, who stocks it in his office.

The study was funded by an unrestricted education grant from Parthenon. The investigators had no relevant disclosures.

[email protected]

SOURCE: Zaveri H et al. SAGES 2018, Abstract S028.

 

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

At a median of 2.7 years after CKD diagnosis, 595 (24.1%) developed a serious clinical event, defined in the study as end-stage renal disease, end-stage liver disease, cardiovascular disease, malignancy, other AIDS events, or death. Almost 8% of patients developed a serious clinical event within a year of CKD diagnosis. Smoking, diabetes, dyslipidemia, body mass index below 18 kg/m², and poor HIV control were identified as modifiable risk factors.

The incidence of serious clinical events following CKD diagnosis was 68.9 events per 1,000 patient-years. Among the HIV patients without CKD, the incidence was 23 events per 1,000 patient-years.

“In an era when many HIV patients require much less management due to effective antiretroviral treatment, those living with CKD have a much higher burden of serious clinical events and require much closer monitoring. Modifiable risk factors ... play a central role in CKD morbidity and mortality, highlighting the need for increased awareness, effective treatment, and preventative measures. In particular, smoking seems to be quite important for all” serious adverse outcomes, “so that’s a good place to start,” Dr. Ryom said at the Conference on Retroviruses & Opportunistic Infections.

Most of the 2,467 HIV patients with CKD were white men who have sex with men. At baseline, the median age was 60 years, and median CD4 cell count was above 500. One in three were smokers, 22.4% were HCV positive, and most had viral loads below 400 copies/mL. More than half of the patients were estimated to have died within 5 years of CKD diagnosis.

CKD was defined as two estimated glomerular filtration rates at or below 60 mL/min per 1.73 m² taken at least 3 months apart, or a 25% decrease in eGFR when patients entered the study at that level.

 

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

 

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

At a median of 2.7 years after CKD diagnosis, 595 (24.1%) developed a serious clinical event, defined in the study as end-stage renal disease, end-stage liver disease, cardiovascular disease, malignancy, other AIDS events, or death. Almost 8% of patients developed a serious clinical event within a year of CKD diagnosis. Smoking, diabetes, dyslipidemia, body mass index below 18 kg/m², and poor HIV control were identified as modifiable risk factors.

The incidence of serious clinical events following CKD diagnosis was 68.9 events per 1,000 patient-years. Among the HIV patients without CKD, the incidence was 23 events per 1,000 patient-years.

“In an era when many HIV patients require much less management due to effective antiretroviral treatment, those living with CKD have a much higher burden of serious clinical events and require much closer monitoring. Modifiable risk factors ... play a central role in CKD morbidity and mortality, highlighting the need for increased awareness, effective treatment, and preventative measures. In particular, smoking seems to be quite important for all” serious adverse outcomes, “so that’s a good place to start,” Dr. Ryom said at the Conference on Retroviruses & Opportunistic Infections.

Most of the 2,467 HIV patients with CKD were white men who have sex with men. At baseline, the median age was 60 years, and median CD4 cell count was above 500. One in three were smokers, 22.4% were HCV positive, and most had viral loads below 400 copies/mL. More than half of the patients were estimated to have died within 5 years of CKD diagnosis.

CKD was defined as two estimated glomerular filtration rates at or below 60 mL/min per 1.73 m² taken at least 3 months apart, or a 25% decrease in eGFR when patients entered the study at that level.

 

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

 

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

At a median of 2.7 years after CKD diagnosis, 595 (24.1%) developed a serious clinical event, defined in the study as end-stage renal disease, end-stage liver disease, cardiovascular disease, malignancy, other AIDS events, or death. Almost 8% of patients developed a serious clinical event within a year of CKD diagnosis. Smoking, diabetes, dyslipidemia, body mass index below 18 kg/m², and poor HIV control were identified as modifiable risk factors.

The incidence of serious clinical events following CKD diagnosis was 68.9 events per 1,000 patient-years. Among the HIV patients without CKD, the incidence was 23 events per 1,000 patient-years.

“In an era when many HIV patients require much less management due to effective antiretroviral treatment, those living with CKD have a much higher burden of serious clinical events and require much closer monitoring. Modifiable risk factors ... play a central role in CKD morbidity and mortality, highlighting the need for increased awareness, effective treatment, and preventative measures. In particular, smoking seems to be quite important for all” serious adverse outcomes, “so that’s a good place to start,” Dr. Ryom said at the Conference on Retroviruses & Opportunistic Infections.

Most of the 2,467 HIV patients with CKD were white men who have sex with men. At baseline, the median age was 60 years, and median CD4 cell count was above 500. One in three were smokers, 22.4% were HCV positive, and most had viral loads below 400 copies/mL. More than half of the patients were estimated to have died within 5 years of CKD diagnosis.

CKD was defined as two estimated glomerular filtration rates at or below 60 mL/min per 1.73 m² taken at least 3 months apart, or a 25% decrease in eGFR when patients entered the study at that level.

 

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

 

ORLANDO – Elevated red blood cell distribution width and mean platelet volume were correlated with cardiovascular disease in a review of 39,510 psoriasis patients conducted by researchers at Case Western Reserve University, Cleveland.*

It’s generally accepted that psoriasis increases the risk of cardiovascular disease (CVD), but it’s not clear who’s most at risk. “We really wanted to find something that is cheap and easy to risk stratify these patients” said lead investigator Rosalynn Conic, MD, of Case Western’s department of dermatology.

Red blood cell distribution width (RDW) – a measure of the range of red blood cell volumes in a given sample – and mean platelet volume (MPV) fit the bill. In many places, they are already routinely reported on CBCs, so there’s no need for any special equipment or tests. Meanwhile, RDW and MPV elevations have been previously linked to CVD risk in the HIV and cardiology literature. The investigators wondered if they’d find a similar association in psoriasis, so they queried nearly 40,000 patients in the Explorys electronic health record database.

What they found was “very impressive, for sure,” Dr. Conic said at the International Investigative Dermatology meeting.

The incidence of MI was highest among the 1,920 patients (5%) with elevated RDW and MPV (odds ratio, 3.4; 95% confidence interval, 2.7-4.2; P less than .001), followed by the 7,060 (18%) patients with high RDW and normal MPV (OR, 2.4; 95% CI, 2.1-2.8; P less than .001), as compared with normal/low MPV and RDW patients.

Elevated RDW or elevated RDW plus MPV increased the odds of atrial fibrillation, coronary artery disease, heart failure, and peripheral vascular disease anywhere from 2 to 8.3 times (P less than .001). Among psoriatic arthritis patients, elevated RDW almost doubled the risk of MI (OR, 1.8; P less than .001). Results were adjusted for age, gender, and hypertension.

In a subanalysis of treatment effects, 4 of 23 psoriasis patients at Case Western had elevated RDWs at baseline. Values normalized in the three patients who achieved a 75% reduction in the Psoriasis Area and Severity Index score after about a year of systemic treatment.

 

“We aim to validate [the study results] with a Veterans Administration data set,” Dr. Conic said. If it pans out, “one use would be to send [patients with elevated values] to a cardiologist earlier” so other CVD risk factors can be monitored and treated. The findings also add to the case for good control, she noted.

Systemic inflammation is the common denominator between the blood value elevations and CVD. The same inflammatory cytokines that cause skin problems in psoriasis also stimulate bone marrow to release immature red blood cells, which are larger than mature cells, leading to an increased RDW. Similarly, elevated MPV indicates a higher number of larger, younger platelets in the blood.

“It’s probably something along those lines, but I think we need to go back to basic science and really figure it out,” Dr. Conic said.

Patients were 18-65 years old. The study excluded patients with diabetes, Crohn’s disease, RA, and generalized atherosclerosis.

The National Institutes of Health funded the work. Dr. Conic reported no relevant financial disclosures.

*This article was updated on May 30, 2018.

[email protected]

SOURCE: Conic R et al. IID 2018, Abstract 550.

 

ORLANDO – Elevated red blood cell distribution width and mean platelet volume were correlated with cardiovascular disease in a review of 39,510 psoriasis patients conducted by researchers at Case Western Reserve University, Cleveland.*

It’s generally accepted that psoriasis increases the risk of cardiovascular disease (CVD), but it’s not clear who’s most at risk. “We really wanted to find something that is cheap and easy to risk stratify these patients” said lead investigator Rosalynn Conic, MD, of Case Western’s department of dermatology.

Red blood cell distribution width (RDW) – a measure of the range of red blood cell volumes in a given sample – and mean platelet volume (MPV) fit the bill. In many places, they are already routinely reported on CBCs, so there’s no need for any special equipment or tests. Meanwhile, RDW and MPV elevations have been previously linked to CVD risk in the HIV and cardiology literature. The investigators wondered if they’d find a similar association in psoriasis, so they queried nearly 40,000 patients in the Explorys electronic health record database.

What they found was “very impressive, for sure,” Dr. Conic said at the International Investigative Dermatology meeting.

The incidence of MI was highest among the 1,920 patients (5%) with elevated RDW and MPV (odds ratio, 3.4; 95% confidence interval, 2.7-4.2; P less than .001), followed by the 7,060 (18%) patients with high RDW and normal MPV (OR, 2.4; 95% CI, 2.1-2.8; P less than .001), as compared with normal/low MPV and RDW patients.

Elevated RDW or elevated RDW plus MPV increased the odds of atrial fibrillation, coronary artery disease, heart failure, and peripheral vascular disease anywhere from 2 to 8.3 times (P less than .001). Among psoriatic arthritis patients, elevated RDW almost doubled the risk of MI (OR, 1.8; P less than .001). Results were adjusted for age, gender, and hypertension.

In a subanalysis of treatment effects, 4 of 23 psoriasis patients at Case Western had elevated RDWs at baseline. Values normalized in the three patients who achieved a 75% reduction in the Psoriasis Area and Severity Index score after about a year of systemic treatment.

 

“We aim to validate [the study results] with a Veterans Administration data set,” Dr. Conic said. If it pans out, “one use would be to send [patients with elevated values] to a cardiologist earlier” so other CVD risk factors can be monitored and treated. The findings also add to the case for good control, she noted.

Systemic inflammation is the common denominator between the blood value elevations and CVD. The same inflammatory cytokines that cause skin problems in psoriasis also stimulate bone marrow to release immature red blood cells, which are larger than mature cells, leading to an increased RDW. Similarly, elevated MPV indicates a higher number of larger, younger platelets in the blood.

“It’s probably something along those lines, but I think we need to go back to basic science and really figure it out,” Dr. Conic said.

Patients were 18-65 years old. The study excluded patients with diabetes, Crohn’s disease, RA, and generalized atherosclerosis.

The National Institutes of Health funded the work. Dr. Conic reported no relevant financial disclosures.

*This article was updated on May 30, 2018.

[email protected]

SOURCE: Conic R et al. IID 2018, Abstract 550.

 

ORLANDO – Elevated red blood cell distribution width and mean platelet volume were correlated with cardiovascular disease in a review of 39,510 psoriasis patients conducted by researchers at Case Western Reserve University, Cleveland.*

It’s generally accepted that psoriasis increases the risk of cardiovascular disease (CVD), but it’s not clear who’s most at risk. “We really wanted to find something that is cheap and easy to risk stratify these patients” said lead investigator Rosalynn Conic, MD, of Case Western’s department of dermatology.

Red blood cell distribution width (RDW) – a measure of the range of red blood cell volumes in a given sample – and mean platelet volume (MPV) fit the bill. In many places, they are already routinely reported on CBCs, so there’s no need for any special equipment or tests. Meanwhile, RDW and MPV elevations have been previously linked to CVD risk in the HIV and cardiology literature. The investigators wondered if they’d find a similar association in psoriasis, so they queried nearly 40,000 patients in the Explorys electronic health record database.

What they found was “very impressive, for sure,” Dr. Conic said at the International Investigative Dermatology meeting.

The incidence of MI was highest among the 1,920 patients (5%) with elevated RDW and MPV (odds ratio, 3.4; 95% confidence interval, 2.7-4.2; P less than .001), followed by the 7,060 (18%) patients with high RDW and normal MPV (OR, 2.4; 95% CI, 2.1-2.8; P less than .001), as compared with normal/low MPV and RDW patients.

Elevated RDW or elevated RDW plus MPV increased the odds of atrial fibrillation, coronary artery disease, heart failure, and peripheral vascular disease anywhere from 2 to 8.3 times (P less than .001). Among psoriatic arthritis patients, elevated RDW almost doubled the risk of MI (OR, 1.8; P less than .001). Results were adjusted for age, gender, and hypertension.

In a subanalysis of treatment effects, 4 of 23 psoriasis patients at Case Western had elevated RDWs at baseline. Values normalized in the three patients who achieved a 75% reduction in the Psoriasis Area and Severity Index score after about a year of systemic treatment.

 

“We aim to validate [the study results] with a Veterans Administration data set,” Dr. Conic said. If it pans out, “one use would be to send [patients with elevated values] to a cardiologist earlier” so other CVD risk factors can be monitored and treated. The findings also add to the case for good control, she noted.

Systemic inflammation is the common denominator between the blood value elevations and CVD. The same inflammatory cytokines that cause skin problems in psoriasis also stimulate bone marrow to release immature red blood cells, which are larger than mature cells, leading to an increased RDW. Similarly, elevated MPV indicates a higher number of larger, younger platelets in the blood.

“It’s probably something along those lines, but I think we need to go back to basic science and really figure it out,” Dr. Conic said.

Patients were 18-65 years old. The study excluded patients with diabetes, Crohn’s disease, RA, and generalized atherosclerosis.

The National Institutes of Health funded the work. Dr. Conic reported no relevant financial disclosures.

*This article was updated on May 30, 2018.

[email protected]

SOURCE: Conic R et al. IID 2018, Abstract 550.

LOS ANGELES – Researchers reported favorable results for the dietary supplement sulforaphane in a small, ongoing trial of children with autism.

Sulforaphane is a compound in cruciferous vegetables, especially 3-day-old broccoli sprouts. It’s sold widely online and in stores, often as broccoli sprout extract, for anticancer and other effects.

The idea of using it for autism came about after investigators noticed that, in the lab, it induced some of the cellular changes associated with fever, including upregulation of heat shock proteins, according to Kanwaljit Singh, MD, a pediatrics instructor at the University of Massachusetts, Worcester.

Fever has been reported to improve autism symptoms. So, several years ago, “we decided to do a pilot study with sulforaphane” to see if it had a similar effect, Dr. Singh said at the annual meeting of the American Academy of Neurology.

At 18 weeks, 29 young autistic men randomized to the supplement outperformed 15 randomized to placebo on the Aberrant Behavior Checklist and other measures. It was the first study of sulforaphane for autism, and it got a good deal of press attention when it was published in 2014; Dr. Singh was the lead author (Proc Natl Acad Sci U S A. 2014 Oct 28;111[43]:15550-5).

“Because we had a very good signal in our pilot study, we decided to do a slightly larger, slightly more complex clinical trial, which is ongoing right now,” he said. The results aren’t due until the second half of 2018, but he gave an interim report at the meeting.

There are 50 children with autism in the new study, aged 3-12 years. Half are randomized to sulforaphane, half to placebo, for the first 15 weeks, then all are switched to open-label sulforaphane for 15 weeks more, followed by a 6-week washout period.

 

The randomized portion is still blinded. But so far, 31% have responded positively at 15 weeks, meaning a much or very much improved score in at least two domains on the Ohio Autism Clinical Global Impressions Scale; domains cover social interaction, violent behavior, communication, and other areas.

Among the patients who have completed the study, the response rate at week 30 almost doubled, to 56%. “We don’t know which patients were on sulforaphane and which were on placebo” in the randomized phase, Dr. Singh said. “But we think because the response doubled” when the second half of the children were switched to sulforaphane, “there should probably not be a very large placebo effect here.”

Meanwhile, after the washout period, “some patients still do well, but many more [go] back to baseline,” added Dr. Singh, the senior investigator in the new trial.

The most common side effects are insomnia (28%), vomiting (19%), flatulence (17%), diarrhea (15%), and constipation (13%). A few patients have dropped out because of insomnia and diarrhea; more have dropped out because they simply didn’t want to take the pills – 125 mg of broccoli seed powder three to eight times a day, depending on weight.

 

Other groups are looking into sulforaphane, too – not just for autism, but also for schizophrenia, prostate cancer, and other indications.

The U.S. Department of Defense is funding the research. The investigators said they have no relevant disclosures.

[email protected]

SOURCE: Zimmerman A et al. Neurology. 2018 Apr 22; 90(15 Suppl.):N1.002.

LOS ANGELES – Researchers reported favorable results for the dietary supplement sulforaphane in a small, ongoing trial of children with autism.

Sulforaphane is a compound in cruciferous vegetables, especially 3-day-old broccoli sprouts. It’s sold widely online and in stores, often as broccoli sprout extract, for anticancer and other effects.

The idea of using it for autism came about after investigators noticed that, in the lab, it induced some of the cellular changes associated with fever, including upregulation of heat shock proteins, according to Kanwaljit Singh, MD, a pediatrics instructor at the University of Massachusetts, Worcester.

Fever has been reported to improve autism symptoms. So, several years ago, “we decided to do a pilot study with sulforaphane” to see if it had a similar effect, Dr. Singh said at the annual meeting of the American Academy of Neurology.

At 18 weeks, 29 young autistic men randomized to the supplement outperformed 15 randomized to placebo on the Aberrant Behavior Checklist and other measures. It was the first study of sulforaphane for autism, and it got a good deal of press attention when it was published in 2014; Dr. Singh was the lead author (Proc Natl Acad Sci U S A. 2014 Oct 28;111[43]:15550-5).

“Because we had a very good signal in our pilot study, we decided to do a slightly larger, slightly more complex clinical trial, which is ongoing right now,” he said. The results aren’t due until the second half of 2018, but he gave an interim report at the meeting.

There are 50 children with autism in the new study, aged 3-12 years. Half are randomized to sulforaphane, half to placebo, for the first 15 weeks, then all are switched to open-label sulforaphane for 15 weeks more, followed by a 6-week washout period.

 

The randomized portion is still blinded. But so far, 31% have responded positively at 15 weeks, meaning a much or very much improved score in at least two domains on the Ohio Autism Clinical Global Impressions Scale; domains cover social interaction, violent behavior, communication, and other areas.

Among the patients who have completed the study, the response rate at week 30 almost doubled, to 56%. “We don’t know which patients were on sulforaphane and which were on placebo” in the randomized phase, Dr. Singh said. “But we think because the response doubled” when the second half of the children were switched to sulforaphane, “there should probably not be a very large placebo effect here.”

Meanwhile, after the washout period, “some patients still do well, but many more [go] back to baseline,” added Dr. Singh, the senior investigator in the new trial.

The most common side effects are insomnia (28%), vomiting (19%), flatulence (17%), diarrhea (15%), and constipation (13%). A few patients have dropped out because of insomnia and diarrhea; more have dropped out because they simply didn’t want to take the pills – 125 mg of broccoli seed powder three to eight times a day, depending on weight.

 

Other groups are looking into sulforaphane, too – not just for autism, but also for schizophrenia, prostate cancer, and other indications.

The U.S. Department of Defense is funding the research. The investigators said they have no relevant disclosures.

[email protected]

SOURCE: Zimmerman A et al. Neurology. 2018 Apr 22; 90(15 Suppl.):N1.002.

LOS ANGELES – Researchers reported favorable results for the dietary supplement sulforaphane in a small, ongoing trial of children with autism.

Sulforaphane is a compound in cruciferous vegetables, especially 3-day-old broccoli sprouts. It’s sold widely online and in stores, often as broccoli sprout extract, for anticancer and other effects.

The idea of using it for autism came about after investigators noticed that, in the lab, it induced some of the cellular changes associated with fever, including upregulation of heat shock proteins, according to Kanwaljit Singh, MD, a pediatrics instructor at the University of Massachusetts, Worcester.

Fever has been reported to improve autism symptoms. So, several years ago, “we decided to do a pilot study with sulforaphane” to see if it had a similar effect, Dr. Singh said at the annual meeting of the American Academy of Neurology.

At 18 weeks, 29 young autistic men randomized to the supplement outperformed 15 randomized to placebo on the Aberrant Behavior Checklist and other measures. It was the first study of sulforaphane for autism, and it got a good deal of press attention when it was published in 2014; Dr. Singh was the lead author (Proc Natl Acad Sci U S A. 2014 Oct 28;111[43]:15550-5).

“Because we had a very good signal in our pilot study, we decided to do a slightly larger, slightly more complex clinical trial, which is ongoing right now,” he said. The results aren’t due until the second half of 2018, but he gave an interim report at the meeting.

There are 50 children with autism in the new study, aged 3-12 years. Half are randomized to sulforaphane, half to placebo, for the first 15 weeks, then all are switched to open-label sulforaphane for 15 weeks more, followed by a 6-week washout period.

 

The randomized portion is still blinded. But so far, 31% have responded positively at 15 weeks, meaning a much or very much improved score in at least two domains on the Ohio Autism Clinical Global Impressions Scale; domains cover social interaction, violent behavior, communication, and other areas.

Among the patients who have completed the study, the response rate at week 30 almost doubled, to 56%. “We don’t know which patients were on sulforaphane and which were on placebo” in the randomized phase, Dr. Singh said. “But we think because the response doubled” when the second half of the children were switched to sulforaphane, “there should probably not be a very large placebo effect here.”

Meanwhile, after the washout period, “some patients still do well, but many more [go] back to baseline,” added Dr. Singh, the senior investigator in the new trial.

The most common side effects are insomnia (28%), vomiting (19%), flatulence (17%), diarrhea (15%), and constipation (13%). A few patients have dropped out because of insomnia and diarrhea; more have dropped out because they simply didn’t want to take the pills – 125 mg of broccoli seed powder three to eight times a day, depending on weight.

 

Other groups are looking into sulforaphane, too – not just for autism, but also for schizophrenia, prostate cancer, and other indications.

The U.S. Department of Defense is funding the research. The investigators said they have no relevant disclosures.

[email protected]

SOURCE: Zimmerman A et al. Neurology. 2018 Apr 22; 90(15 Suppl.):N1.002.

 

LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.

“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.

There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.

ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.

There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.

M. Alexander Otto/MDedge News

The team reviewed 74 children with ADEM who presented at three pediatric neurology centers during 2005-2017, at a median age of 4.5 years. There were about equal numbers of boys and girls, and all had MRI abnormalities consistent with ADEM. Fifty children (68%) were MOG-ab positive.

 

Twenty-seven antibody-positive children (54%) relapsed, versus 3 of the 24 negative children (13%). Relapse was almost six times more likely with MOB-Ab (95% confidence interval [CI], 1.8-19.7; P = .002). The overall relapse rate of 42% (31/74) was higher than in previous studies, probably because of longer follow-up, lasting years in some cases.

Sixteen children (22%) presented with seizures, which nearly tripled the risk of relapse, although the finding wasn’t statistically significant (95% CI, 0.9-9.2; P = .06). There was a trend toward more seizures at onset in the MOG-Ab group.

Twelve children (16.2%) developed post-ADEM epilepsy, all but one MOG-Ab positive. The median time to seizure onset was 3 months. All of the children remained on antiepileptic medications at 2-year follow-up.

Oligoclonal bands were found in 8 of 37 children tested (22%), and also markedly increased the risk of post-ADEM seizures (odds ratio, 8.7; 95% CI, 1.5-54; P = .01).

 

“The majority of the children that we’ve looked at remain MOG-Ab positive. There may be a trend in antibody titers going down, but overall we didn’t find titers clinically useful. I know two children where titers went down. They relapsed,” and the titers went “up again, so we don’t’ really use them clinically for treatment,” Dr. Hacohen said.

“I think there is more to do” when it comes to optimizing ADEM management. “It’s a very heterogeneous [condition, and] I don’t want to put [everyone] on immunosuppression for years. I’ve got one patient who had an event, and 7 years later had a second event, and then was back to normal in a week.” On the other hand, “10%-20% of our patients do quite poorly and relapse on all treatments,” she said.

The investigators didn’t have any disclosures and there was no industry funding for the work.

[email protected]

SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.

 

LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.

“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.

There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.

ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.

There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.

M. Alexander Otto/MDedge News

The team reviewed 74 children with ADEM who presented at three pediatric neurology centers during 2005-2017, at a median age of 4.5 years. There were about equal numbers of boys and girls, and all had MRI abnormalities consistent with ADEM. Fifty children (68%) were MOG-ab positive.

 

Twenty-seven antibody-positive children (54%) relapsed, versus 3 of the 24 negative children (13%). Relapse was almost six times more likely with MOB-Ab (95% confidence interval [CI], 1.8-19.7; P = .002). The overall relapse rate of 42% (31/74) was higher than in previous studies, probably because of longer follow-up, lasting years in some cases.

Sixteen children (22%) presented with seizures, which nearly tripled the risk of relapse, although the finding wasn’t statistically significant (95% CI, 0.9-9.2; P = .06). There was a trend toward more seizures at onset in the MOG-Ab group.

Twelve children (16.2%) developed post-ADEM epilepsy, all but one MOG-Ab positive. The median time to seizure onset was 3 months. All of the children remained on antiepileptic medications at 2-year follow-up.

Oligoclonal bands were found in 8 of 37 children tested (22%), and also markedly increased the risk of post-ADEM seizures (odds ratio, 8.7; 95% CI, 1.5-54; P = .01).

 

“The majority of the children that we’ve looked at remain MOG-Ab positive. There may be a trend in antibody titers going down, but overall we didn’t find titers clinically useful. I know two children where titers went down. They relapsed,” and the titers went “up again, so we don’t’ really use them clinically for treatment,” Dr. Hacohen said.

“I think there is more to do” when it comes to optimizing ADEM management. “It’s a very heterogeneous [condition, and] I don’t want to put [everyone] on immunosuppression for years. I’ve got one patient who had an event, and 7 years later had a second event, and then was back to normal in a week.” On the other hand, “10%-20% of our patients do quite poorly and relapse on all treatments,” she said.

The investigators didn’t have any disclosures and there was no industry funding for the work.

[email protected]

SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.

 

LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.

“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.

There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.

ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.

There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.

M. Alexander Otto/MDedge News

The team reviewed 74 children with ADEM who presented at three pediatric neurology centers during 2005-2017, at a median age of 4.5 years. There were about equal numbers of boys and girls, and all had MRI abnormalities consistent with ADEM. Fifty children (68%) were MOG-ab positive.

 

Twenty-seven antibody-positive children (54%) relapsed, versus 3 of the 24 negative children (13%). Relapse was almost six times more likely with MOB-Ab (95% confidence interval [CI], 1.8-19.7; P = .002). The overall relapse rate of 42% (31/74) was higher than in previous studies, probably because of longer follow-up, lasting years in some cases.

Sixteen children (22%) presented with seizures, which nearly tripled the risk of relapse, although the finding wasn’t statistically significant (95% CI, 0.9-9.2; P = .06). There was a trend toward more seizures at onset in the MOG-Ab group.

Twelve children (16.2%) developed post-ADEM epilepsy, all but one MOG-Ab positive. The median time to seizure onset was 3 months. All of the children remained on antiepileptic medications at 2-year follow-up.

Oligoclonal bands were found in 8 of 37 children tested (22%), and also markedly increased the risk of post-ADEM seizures (odds ratio, 8.7; 95% CI, 1.5-54; P = .01).

 

“The majority of the children that we’ve looked at remain MOG-Ab positive. There may be a trend in antibody titers going down, but overall we didn’t find titers clinically useful. I know two children where titers went down. They relapsed,” and the titers went “up again, so we don’t’ really use them clinically for treatment,” Dr. Hacohen said.

“I think there is more to do” when it comes to optimizing ADEM management. “It’s a very heterogeneous [condition, and] I don’t want to put [everyone] on immunosuppression for years. I’ve got one patient who had an event, and 7 years later had a second event, and then was back to normal in a week.” On the other hand, “10%-20% of our patients do quite poorly and relapse on all treatments,” she said.

The investigators didn’t have any disclosures and there was no industry funding for the work.

[email protected]

SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.

 

LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.

They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.

M. Alexander Otto/MDedge News

But all the trials for everolimus and sirolimus (Rapamune), the other mTOR [mammalian target of rapamycin] inhibitor used in tuberous sclerosis complex (TSC), were done in older children and adults, so there’s uncertainty about using them in infants, and wide variation in how they’re used. Also, the few available case reports and series raise the possibility that side effects might be more common and perhaps serious in the very young, according to Darcy Krueger, MD, PhD, director of the Tuberous Sclerosis Clinic at Cincinnati Children’s Hospital.

“I get emails all the time saying ‘how would you start treatment at this age?’ and we say there are no data,” he said at the American Academy of Neurology annual meeting.

Dr. Krueger presented a survey of 19 TSC centers to get the ball rolling. They reported on treating 45 children under 2 years old, at least one child at each center. The goal of the survey was to establish a baseline “to allow us to move forward with what proper studies would look like, and what needs to be done. Two-thirds of patients have seizures before their first birthday; we need to establish a safety [and efficacy] profile well before 2 years of age,” and evidence-based guidelines, he said.

On average, everolimus treatment started at 11.7 months, and continued for 27 months. Sirolimus treatment started at a mean of 16 months and continued for 16 months. Dosing ranged from once a week to daily. In contrast to case reports that skew heavily toward rhabdomyomas, most of the children were treated for epilepsy and subependymal giant cell astrocytoma (SEGA). Almost all the centers had participated in a clinical evaluation of everolimus for TSC epilepsy and SEGAs in older children, “so there was familiarity and a comfort level” for those indications, Dr. Krueger said.

Everolimus was used much more often than was sirolimus, which probably reflects ongoing clinical development of the drug. A handful of children switched between the two, probably because of side effects. Most centers reported a favorable response. The average initial daily dose of everolimus was 1.05 mg/m²; the average initial daily dose of sirolimus was 0.42 mg/m².

 

Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.

“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.

There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.

Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.

[email protected]

SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.

 

LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.

They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.

M. Alexander Otto/MDedge News

But all the trials for everolimus and sirolimus (Rapamune), the other mTOR [mammalian target of rapamycin] inhibitor used in tuberous sclerosis complex (TSC), were done in older children and adults, so there’s uncertainty about using them in infants, and wide variation in how they’re used. Also, the few available case reports and series raise the possibility that side effects might be more common and perhaps serious in the very young, according to Darcy Krueger, MD, PhD, director of the Tuberous Sclerosis Clinic at Cincinnati Children’s Hospital.

“I get emails all the time saying ‘how would you start treatment at this age?’ and we say there are no data,” he said at the American Academy of Neurology annual meeting.

Dr. Krueger presented a survey of 19 TSC centers to get the ball rolling. They reported on treating 45 children under 2 years old, at least one child at each center. The goal of the survey was to establish a baseline “to allow us to move forward with what proper studies would look like, and what needs to be done. Two-thirds of patients have seizures before their first birthday; we need to establish a safety [and efficacy] profile well before 2 years of age,” and evidence-based guidelines, he said.

On average, everolimus treatment started at 11.7 months, and continued for 27 months. Sirolimus treatment started at a mean of 16 months and continued for 16 months. Dosing ranged from once a week to daily. In contrast to case reports that skew heavily toward rhabdomyomas, most of the children were treated for epilepsy and subependymal giant cell astrocytoma (SEGA). Almost all the centers had participated in a clinical evaluation of everolimus for TSC epilepsy and SEGAs in older children, “so there was familiarity and a comfort level” for those indications, Dr. Krueger said.

Everolimus was used much more often than was sirolimus, which probably reflects ongoing clinical development of the drug. A handful of children switched between the two, probably because of side effects. Most centers reported a favorable response. The average initial daily dose of everolimus was 1.05 mg/m²; the average initial daily dose of sirolimus was 0.42 mg/m².

 

Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.

“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.

There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.

Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.

[email protected]

SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.

 

LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.

They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.

M. Alexander Otto/MDedge News

But all the trials for everolimus and sirolimus (Rapamune), the other mTOR [mammalian target of rapamycin] inhibitor used in tuberous sclerosis complex (TSC), were done in older children and adults, so there’s uncertainty about using them in infants, and wide variation in how they’re used. Also, the few available case reports and series raise the possibility that side effects might be more common and perhaps serious in the very young, according to Darcy Krueger, MD, PhD, director of the Tuberous Sclerosis Clinic at Cincinnati Children’s Hospital.

“I get emails all the time saying ‘how would you start treatment at this age?’ and we say there are no data,” he said at the American Academy of Neurology annual meeting.

Dr. Krueger presented a survey of 19 TSC centers to get the ball rolling. They reported on treating 45 children under 2 years old, at least one child at each center. The goal of the survey was to establish a baseline “to allow us to move forward with what proper studies would look like, and what needs to be done. Two-thirds of patients have seizures before their first birthday; we need to establish a safety [and efficacy] profile well before 2 years of age,” and evidence-based guidelines, he said.

On average, everolimus treatment started at 11.7 months, and continued for 27 months. Sirolimus treatment started at a mean of 16 months and continued for 16 months. Dosing ranged from once a week to daily. In contrast to case reports that skew heavily toward rhabdomyomas, most of the children were treated for epilepsy and subependymal giant cell astrocytoma (SEGA). Almost all the centers had participated in a clinical evaluation of everolimus for TSC epilepsy and SEGAs in older children, “so there was familiarity and a comfort level” for those indications, Dr. Krueger said.

Everolimus was used much more often than was sirolimus, which probably reflects ongoing clinical development of the drug. A handful of children switched between the two, probably because of side effects. Most centers reported a favorable response. The average initial daily dose of everolimus was 1.05 mg/m²; the average initial daily dose of sirolimus was 0.42 mg/m².

 

Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.

“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.

There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.

Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.

[email protected]

SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

Meanwhile, PD patients had lower insulin levels from 30 minutes onwards and a lower insulin AUC, although not significantly so.

In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.

“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.

Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.

The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”

 

Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m². Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.

PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.

“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.

There was no external funding, and the investigators had nothing to disclose.

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

Meanwhile, PD patients had lower insulin levels from 30 minutes onwards and a lower insulin AUC, although not significantly so.

In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.

“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.

Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.

The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”

 

Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m². Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.

PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.

“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.

There was no external funding, and the investigators had nothing to disclose.

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

Meanwhile, PD patients had lower insulin levels from 30 minutes onwards and a lower insulin AUC, although not significantly so.

In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.

“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.

Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.

The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”

 

Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m². Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.

PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.

“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.

There was no external funding, and the investigators had nothing to disclose.

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

 

SEATTLE – Endoscopic stent migration fell from 41% of stent cases to 15% after surgeons at Lenox Hill Hospital, New York, started to secure stents with a single, proximal figure-of-eight overstitch.

Anastomotic leaks are a major and potentially fatal complication of bariatric surgery. Stents are one of the fix options: An expanding tube is rolled down over the wound to take the pressure off and give it time to heal. The stent is removed after the leak closes, which can take a few weeks or longer.

The approach has been around for over a decade, but migration remains a significant concern; many surgeons don’t fix endothelial stents in place.

Stents designed specifically for the procedure will likely address the problem in the near future, but for now, the overstitch helps at Lenox Hill. Meanwhile, “it’s important to [realize] that stent migration did not adversely impact [bariatric surgery] failure rates, nor was migration associated with the incidence of revision surgery,” said surgery resident Varun Krishnan, MD.

Dr. Krishnan was the lead investigator on a review of 37 leak cases at Lenox Hill from 2005 to 2017, 17 before overstitch was begun in 2012, and 20 afterwards, with follow-up out to 71 months. The results were presented at the World Congress of Endoscopic Surgery hosted by SAGES & CAGS. The senior investigator was Lenox Hill surgeon Julio Teixeira, MD, FACS, associate professor of medicine at Hofstra University, Hempstead, N.Y. He reported the first use of stents for bariatric leaks in 2007 (Surg Obes Relat Dis. 2007 Jan-Feb;3[1]:68-71).

The goal of the review was to address lingering concerns about long-term effects of stents on weight loss and other issues. In the end, “our experience with stenting has been very positive. It’s a very good [option] for treating leaks after bariatric surgery,” Dr. Krishnan said,

The overall success rate was 95%. The 2 failures were both in the sleeve gastrectomy patient group, which made up 43% of the 37 leak cases. The leaks were fixed in one sleeve patient with conversion to a Roux-en-Y gastric bypass, and the other with a stent redo. Both were in the overstitch group.

 

“We had better success with gastric bypass [patients], probably due to anatomy,” Dr. Krishnan noted. Sleeves leave patients with higher intraluminal pressures, which complicate leak healing.

Stents didn’t have any impact on weight loss. Patients lost a mean of 57% of their excess body weight over an average of 21 months.

Out of 20 patients with available data, 5 were readmitted for oral intolerance, another major concern with endoscopic stents; 3 had their stents removed because of it. None required total parenteral nutrition.

Among 17 patients with available data, 7 (41.7%) had poststent reflux; all of them reported proton-pump inhibitor histories.

 

Of the 37 total cases, 15 patients (41%) had Roux-en-Y bypasses. The remaining six bypass patients received either duodenal switches or foregut procedures.

Two sleeve and four bypass patients (16%) had revisions. One was the conversion to bypass after stent failure, but the others were for intussusception, strictures, reflux, and other problems that didn’t seem related to stents. About six patients were restented, the one case for stent failure plus five or so for migration.

Patients were an average of about 40 years old, and 70% were women. Average preop body mass index was over 40 kg/m². The one death in the series was from fungal sepsis a year after stent removal.

In response to an audience question, Dr. Krishnan noted that the distal tip of the stent was placed just after the gastrojejunal anastomosis in bypass cases. Also, bariatric surgeons do the endoscopy at Lenox Hill and place the stents.

The investigators did not report any relevant disclosures, and there was no outside funding.
 

[email protected]

 

SEATTLE – Endoscopic stent migration fell from 41% of stent cases to 15% after surgeons at Lenox Hill Hospital, New York, started to secure stents with a single, proximal figure-of-eight overstitch.

Anastomotic leaks are a major and potentially fatal complication of bariatric surgery. Stents are one of the fix options: An expanding tube is rolled down over the wound to take the pressure off and give it time to heal. The stent is removed after the leak closes, which can take a few weeks or longer.

The approach has been around for over a decade, but migration remains a significant concern; many surgeons don’t fix endothelial stents in place.

Stents designed specifically for the procedure will likely address the problem in the near future, but for now, the overstitch helps at Lenox Hill. Meanwhile, “it’s important to [realize] that stent migration did not adversely impact [bariatric surgery] failure rates, nor was migration associated with the incidence of revision surgery,” said surgery resident Varun Krishnan, MD.

Dr. Krishnan was the lead investigator on a review of 37 leak cases at Lenox Hill from 2005 to 2017, 17 before overstitch was begun in 2012, and 20 afterwards, with follow-up out to 71 months. The results were presented at the World Congress of Endoscopic Surgery hosted by SAGES & CAGS. The senior investigator was Lenox Hill surgeon Julio Teixeira, MD, FACS, associate professor of medicine at Hofstra University, Hempstead, N.Y. He reported the first use of stents for bariatric leaks in 2007 (Surg Obes Relat Dis. 2007 Jan-Feb;3[1]:68-71).

The goal of the review was to address lingering concerns about long-term effects of stents on weight loss and other issues. In the end, “our experience with stenting has been very positive. It’s a very good [option] for treating leaks after bariatric surgery,” Dr. Krishnan said,

The overall success rate was 95%. The 2 failures were both in the sleeve gastrectomy patient group, which made up 43% of the 37 leak cases. The leaks were fixed in one sleeve patient with conversion to a Roux-en-Y gastric bypass, and the other with a stent redo. Both were in the overstitch group.

 

“We had better success with gastric bypass [patients], probably due to anatomy,” Dr. Krishnan noted. Sleeves leave patients with higher intraluminal pressures, which complicate leak healing.

Stents didn’t have any impact on weight loss. Patients lost a mean of 57% of their excess body weight over an average of 21 months.

Out of 20 patients with available data, 5 were readmitted for oral intolerance, another major concern with endoscopic stents; 3 had their stents removed because of it. None required total parenteral nutrition.

Among 17 patients with available data, 7 (41.7%) had poststent reflux; all of them reported proton-pump inhibitor histories.

 

Of the 37 total cases, 15 patients (41%) had Roux-en-Y bypasses. The remaining six bypass patients received either duodenal switches or foregut procedures.

Two sleeve and four bypass patients (16%) had revisions. One was the conversion to bypass after stent failure, but the others were for intussusception, strictures, reflux, and other problems that didn’t seem related to stents. About six patients were restented, the one case for stent failure plus five or so for migration.

Patients were an average of about 40 years old, and 70% were women. Average preop body mass index was over 40 kg/m². The one death in the series was from fungal sepsis a year after stent removal.

In response to an audience question, Dr. Krishnan noted that the distal tip of the stent was placed just after the gastrojejunal anastomosis in bypass cases. Also, bariatric surgeons do the endoscopy at Lenox Hill and place the stents.

The investigators did not report any relevant disclosures, and there was no outside funding.
 

[email protected]

 

SEATTLE – Endoscopic stent migration fell from 41% of stent cases to 15% after surgeons at Lenox Hill Hospital, New York, started to secure stents with a single, proximal figure-of-eight overstitch.

Anastomotic leaks are a major and potentially fatal complication of bariatric surgery. Stents are one of the fix options: An expanding tube is rolled down over the wound to take the pressure off and give it time to heal. The stent is removed after the leak closes, which can take a few weeks or longer.

The approach has been around for over a decade, but migration remains a significant concern; many surgeons don’t fix endothelial stents in place.

Stents designed specifically for the procedure will likely address the problem in the near future, but for now, the overstitch helps at Lenox Hill. Meanwhile, “it’s important to [realize] that stent migration did not adversely impact [bariatric surgery] failure rates, nor was migration associated with the incidence of revision surgery,” said surgery resident Varun Krishnan, MD.

Dr. Krishnan was the lead investigator on a review of 37 leak cases at Lenox Hill from 2005 to 2017, 17 before overstitch was begun in 2012, and 20 afterwards, with follow-up out to 71 months. The results were presented at the World Congress of Endoscopic Surgery hosted by SAGES & CAGS. The senior investigator was Lenox Hill surgeon Julio Teixeira, MD, FACS, associate professor of medicine at Hofstra University, Hempstead, N.Y. He reported the first use of stents for bariatric leaks in 2007 (Surg Obes Relat Dis. 2007 Jan-Feb;3[1]:68-71).

The goal of the review was to address lingering concerns about long-term effects of stents on weight loss and other issues. In the end, “our experience with stenting has been very positive. It’s a very good [option] for treating leaks after bariatric surgery,” Dr. Krishnan said,

The overall success rate was 95%. The 2 failures were both in the sleeve gastrectomy patient group, which made up 43% of the 37 leak cases. The leaks were fixed in one sleeve patient with conversion to a Roux-en-Y gastric bypass, and the other with a stent redo. Both were in the overstitch group.

 

“We had better success with gastric bypass [patients], probably due to anatomy,” Dr. Krishnan noted. Sleeves leave patients with higher intraluminal pressures, which complicate leak healing.

Stents didn’t have any impact on weight loss. Patients lost a mean of 57% of their excess body weight over an average of 21 months.

Out of 20 patients with available data, 5 were readmitted for oral intolerance, another major concern with endoscopic stents; 3 had their stents removed because of it. None required total parenteral nutrition.

Among 17 patients with available data, 7 (41.7%) had poststent reflux; all of them reported proton-pump inhibitor histories.

 

Of the 37 total cases, 15 patients (41%) had Roux-en-Y bypasses. The remaining six bypass patients received either duodenal switches or foregut procedures.

Two sleeve and four bypass patients (16%) had revisions. One was the conversion to bypass after stent failure, but the others were for intussusception, strictures, reflux, and other problems that didn’t seem related to stents. About six patients were restented, the one case for stent failure plus five or so for migration.

Patients were an average of about 40 years old, and 70% were women. Average preop body mass index was over 40 kg/m². The one death in the series was from fungal sepsis a year after stent removal.

In response to an audience question, Dr. Krishnan noted that the distal tip of the stent was placed just after the gastrojejunal anastomosis in bypass cases. Also, bariatric surgeons do the endoscopy at Lenox Hill and place the stents.

The investigators did not report any relevant disclosures, and there was no outside funding.
 

[email protected]

BOSTON – Fewer than 12% of HIV infected men will clear new hepatitis C infections on their own.

If they haven’t had a 2-log drop in their hepatitis C virus (HCV) RNA loads after a month, they aren’t going to clear the infection, and need direct-acting antiretrovirals (DAAs), according to an observational European study of 465 HIV patients with newly acquired HCV infections, almost all of them men who have sex with men (MSM).

The findings spoke to a hot topic at the Conference on Retroviruses & Opportunistic Infections (CROI): DAAs for acute HCV infection in patients with HIV. It’s a pressing problem; the incidence of sexually transmitted HCV among MSM with HIV is rising worldwide.

However, on both sides of the Atlantic, DAAs are indicated only for chronic HCV, which usually means infection for 6 months or more, because a third or so of patients will clear the infection on their own. The drugs are expensive, and reimbursements don’t generally kick in until after the waiting period.

That’s a problem with HIV coinfection, and not just because far fewer patients will rid themselves of the virus. HCV is most likely to be spread by sexual contact in the acute phase; allowing patients destined to become chronic carriers to linger without treatment means that the infection will probably spread to new partners, according to researchers at CROI,

Proactive measures could help. Swiss investigators reported a 50% drop in new HCV infections when HIV-positive MSM were screened for the infection then treated immediately with DAAs. Some at the meeting argued that HCV screening – and treatment – should be automatic for patients taking pre-exposure HIV prophylaxis, as well as for newly diagnosed HIV.

Several said that, on a population level, treatment in the acute phase would save money by preventing new infections. It’s also cheaper to treat in the acute phase because coinfected patients only need 8 weeks of DAA treatment rather than the usual 12-16 for chronic infection, according to another European study at the meeting.

“The idea of targeting acute HCV makes a lot of sense on all levels. If treatment” among patients with HIV “is two-thirds as long and more than two-thirds have persistent infection, there is no reason to hold” off just because of cost, said David Thomas, MD, director of the division of infectious diseases at Johns Hopkins University, Baltimore, who moderated the study presentations.

 

Eight weeks is enough

The efficacy of an 8-week treatment course was established in a study of 63 MSM in the Netherlands and Belgium. They were 47 years old, on average, and all but three were HIV positive; two-thirds had HCV genotype 1, and the rest had genotype 4, some with extremely high viral loads.

Subjects received grazoprevir/elbasvir (Zepatier) once daily for 8 weeks, beginning at a mean of 4.5 months after their estimated infection date, and all within 6 months. Twelve weeks after the end of therapy, 59 (94%) were negative for HCV RNA on blood tests. Three of the patients who were still positive for HCV had new infections; the remaining patient had relapsed, and was the only true treatment failure.

“We can say that 8 weeks of grazoprevir/elbasvir for acute HCV was safe, highly effective, and noninferior compared to studies with longer treatment. On an individual level, you can wait for spontaneous clearance, but on the population level, by treating all patients in the acute phase, you prevent spread of hepatitis C,” said lead investigator Anne Boerekamps, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands.

 

The 2-log cutoff

“We are withholding effective treatment from people just because we’re concerned about the money,” said Christoph Boesecke, MD, of Bonn (Germany) University Hospital, who was the lead investigator in the study that found low spontaneous clearance rates with HIV coinfection.

Almost all the 465 subjects were on combination antiretroviral HIV therapy. Most had HCV genotype 1, but there were also type 3 and 4 cases. The investigators followed their subjects for at least a year after HCV infection. Just 55 (11.8%) cleared the infection on their own.

“Almost 90% of acutely infected patients face a chronic course. ... DAA drug labels, as well as clinical guidelines, need to be amended to allow usage of DAA during the acute phase of HCV infection in a high-risk population,” Dr. Boesecke and his team concluded.

Clearance was harbingered by a 2-log decline in HCV RNA by week 4. The 2-log drop cutoff is “the best predictor [we have] ... to identify patients” for early treatment. “There may be some patients you overtreat, but we have to keep in mind that we are not causing any harms with DAAs; maybe harms in terms of money, but not in terms of toxicity,” he said.

The message is beginning to get out. New European AIDS Clinical Society guidelines recommend DAA treatment for patients with HIV who don’t have a 2-log drop after a month.

 

‘Treatment as prevention’ works

The Swiss study added evidence to the frequent assertion at CROI that early treatment stops the spread of HCV.

The investigators screened 3,722 MSM from the Swiss HIV Cohort Study and found 178 (4.8%) men with replicating genotype 1 or 4 HCV infections. Of these cases, 31 were deemed incident and 147 chronic. Almost all the men agreed to treatment with standard-of-care DAAs, usually grazoprevir/elbasvir plus or minus ribavirin. Just about everyone had a sustained virologic response 12 weeks later.

The team rescreened the men after about a year, and found 28 infections; 16 were newly acquired, almost a 50% drop from baseline. The remaining 12 infections were chronic cases not treated earlier.

“Systemic screening followed by prompt DAA treatment can serve as a model to eliminate HCV in coinfected MSM,” said lead investigator Dominique Braun, MD, of the University of Zurich.

Dr. Boesecke is a consultant and/or speaker for AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Thomas is a Merck consultant. Dr. Boerekamps and Dr. Braun’s studies were both funded by Merck, maker of elbasvir/grazoprevir.

[email protected]

SOURCE: Anne Boerekamps. 2018 CROI, Abstract 128. Christoph Boesecke. 2018 CROI, Abstract 129. Dominique Braun. 2018 CROI, Abstract 81LB.






 

BOSTON – Fewer than 12% of HIV infected men will clear new hepatitis C infections on their own.

If they haven’t had a 2-log drop in their hepatitis C virus (HCV) RNA loads after a month, they aren’t going to clear the infection, and need direct-acting antiretrovirals (DAAs), according to an observational European study of 465 HIV patients with newly acquired HCV infections, almost all of them men who have sex with men (MSM).

The findings spoke to a hot topic at the Conference on Retroviruses & Opportunistic Infections (CROI): DAAs for acute HCV infection in patients with HIV. It’s a pressing problem; the incidence of sexually transmitted HCV among MSM with HIV is rising worldwide.

However, on both sides of the Atlantic, DAAs are indicated only for chronic HCV, which usually means infection for 6 months or more, because a third or so of patients will clear the infection on their own. The drugs are expensive, and reimbursements don’t generally kick in until after the waiting period.

That’s a problem with HIV coinfection, and not just because far fewer patients will rid themselves of the virus. HCV is most likely to be spread by sexual contact in the acute phase; allowing patients destined to become chronic carriers to linger without treatment means that the infection will probably spread to new partners, according to researchers at CROI,

Proactive measures could help. Swiss investigators reported a 50% drop in new HCV infections when HIV-positive MSM were screened for the infection then treated immediately with DAAs. Some at the meeting argued that HCV screening – and treatment – should be automatic for patients taking pre-exposure HIV prophylaxis, as well as for newly diagnosed HIV.

Several said that, on a population level, treatment in the acute phase would save money by preventing new infections. It’s also cheaper to treat in the acute phase because coinfected patients only need 8 weeks of DAA treatment rather than the usual 12-16 for chronic infection, according to another European study at the meeting.

“The idea of targeting acute HCV makes a lot of sense on all levels. If treatment” among patients with HIV “is two-thirds as long and more than two-thirds have persistent infection, there is no reason to hold” off just because of cost, said David Thomas, MD, director of the division of infectious diseases at Johns Hopkins University, Baltimore, who moderated the study presentations.

 

Eight weeks is enough

The efficacy of an 8-week treatment course was established in a study of 63 MSM in the Netherlands and Belgium. They were 47 years old, on average, and all but three were HIV positive; two-thirds had HCV genotype 1, and the rest had genotype 4, some with extremely high viral loads.

Subjects received grazoprevir/elbasvir (Zepatier) once daily for 8 weeks, beginning at a mean of 4.5 months after their estimated infection date, and all within 6 months. Twelve weeks after the end of therapy, 59 (94%) were negative for HCV RNA on blood tests. Three of the patients who were still positive for HCV had new infections; the remaining patient had relapsed, and was the only true treatment failure.

“We can say that 8 weeks of grazoprevir/elbasvir for acute HCV was safe, highly effective, and noninferior compared to studies with longer treatment. On an individual level, you can wait for spontaneous clearance, but on the population level, by treating all patients in the acute phase, you prevent spread of hepatitis C,” said lead investigator Anne Boerekamps, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands.

 

The 2-log cutoff

“We are withholding effective treatment from people just because we’re concerned about the money,” said Christoph Boesecke, MD, of Bonn (Germany) University Hospital, who was the lead investigator in the study that found low spontaneous clearance rates with HIV coinfection.

Almost all the 465 subjects were on combination antiretroviral HIV therapy. Most had HCV genotype 1, but there were also type 3 and 4 cases. The investigators followed their subjects for at least a year after HCV infection. Just 55 (11.8%) cleared the infection on their own.

“Almost 90% of acutely infected patients face a chronic course. ... DAA drug labels, as well as clinical guidelines, need to be amended to allow usage of DAA during the acute phase of HCV infection in a high-risk population,” Dr. Boesecke and his team concluded.

Clearance was harbingered by a 2-log decline in HCV RNA by week 4. The 2-log drop cutoff is “the best predictor [we have] ... to identify patients” for early treatment. “There may be some patients you overtreat, but we have to keep in mind that we are not causing any harms with DAAs; maybe harms in terms of money, but not in terms of toxicity,” he said.

The message is beginning to get out. New European AIDS Clinical Society guidelines recommend DAA treatment for patients with HIV who don’t have a 2-log drop after a month.

 

‘Treatment as prevention’ works

The Swiss study added evidence to the frequent assertion at CROI that early treatment stops the spread of HCV.

The investigators screened 3,722 MSM from the Swiss HIV Cohort Study and found 178 (4.8%) men with replicating genotype 1 or 4 HCV infections. Of these cases, 31 were deemed incident and 147 chronic. Almost all the men agreed to treatment with standard-of-care DAAs, usually grazoprevir/elbasvir plus or minus ribavirin. Just about everyone had a sustained virologic response 12 weeks later.

The team rescreened the men after about a year, and found 28 infections; 16 were newly acquired, almost a 50% drop from baseline. The remaining 12 infections were chronic cases not treated earlier.

“Systemic screening followed by prompt DAA treatment can serve as a model to eliminate HCV in coinfected MSM,” said lead investigator Dominique Braun, MD, of the University of Zurich.

Dr. Boesecke is a consultant and/or speaker for AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Thomas is a Merck consultant. Dr. Boerekamps and Dr. Braun’s studies were both funded by Merck, maker of elbasvir/grazoprevir.

[email protected]

SOURCE: Anne Boerekamps. 2018 CROI, Abstract 128. Christoph Boesecke. 2018 CROI, Abstract 129. Dominique Braun. 2018 CROI, Abstract 81LB.






 

BOSTON – Fewer than 12% of HIV infected men will clear new hepatitis C infections on their own.

If they haven’t had a 2-log drop in their hepatitis C virus (HCV) RNA loads after a month, they aren’t going to clear the infection, and need direct-acting antiretrovirals (DAAs), according to an observational European study of 465 HIV patients with newly acquired HCV infections, almost all of them men who have sex with men (MSM).

The findings spoke to a hot topic at the Conference on Retroviruses & Opportunistic Infections (CROI): DAAs for acute HCV infection in patients with HIV. It’s a pressing problem; the incidence of sexually transmitted HCV among MSM with HIV is rising worldwide.

However, on both sides of the Atlantic, DAAs are indicated only for chronic HCV, which usually means infection for 6 months or more, because a third or so of patients will clear the infection on their own. The drugs are expensive, and reimbursements don’t generally kick in until after the waiting period.

That’s a problem with HIV coinfection, and not just because far fewer patients will rid themselves of the virus. HCV is most likely to be spread by sexual contact in the acute phase; allowing patients destined to become chronic carriers to linger without treatment means that the infection will probably spread to new partners, according to researchers at CROI,

Proactive measures could help. Swiss investigators reported a 50% drop in new HCV infections when HIV-positive MSM were screened for the infection then treated immediately with DAAs. Some at the meeting argued that HCV screening – and treatment – should be automatic for patients taking pre-exposure HIV prophylaxis, as well as for newly diagnosed HIV.

Several said that, on a population level, treatment in the acute phase would save money by preventing new infections. It’s also cheaper to treat in the acute phase because coinfected patients only need 8 weeks of DAA treatment rather than the usual 12-16 for chronic infection, according to another European study at the meeting.

“The idea of targeting acute HCV makes a lot of sense on all levels. If treatment” among patients with HIV “is two-thirds as long and more than two-thirds have persistent infection, there is no reason to hold” off just because of cost, said David Thomas, MD, director of the division of infectious diseases at Johns Hopkins University, Baltimore, who moderated the study presentations.

 

Eight weeks is enough

The efficacy of an 8-week treatment course was established in a study of 63 MSM in the Netherlands and Belgium. They were 47 years old, on average, and all but three were HIV positive; two-thirds had HCV genotype 1, and the rest had genotype 4, some with extremely high viral loads.

Subjects received grazoprevir/elbasvir (Zepatier) once daily for 8 weeks, beginning at a mean of 4.5 months after their estimated infection date, and all within 6 months. Twelve weeks after the end of therapy, 59 (94%) were negative for HCV RNA on blood tests. Three of the patients who were still positive for HCV had new infections; the remaining patient had relapsed, and was the only true treatment failure.

“We can say that 8 weeks of grazoprevir/elbasvir for acute HCV was safe, highly effective, and noninferior compared to studies with longer treatment. On an individual level, you can wait for spontaneous clearance, but on the population level, by treating all patients in the acute phase, you prevent spread of hepatitis C,” said lead investigator Anne Boerekamps, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands.

 

The 2-log cutoff

“We are withholding effective treatment from people just because we’re concerned about the money,” said Christoph Boesecke, MD, of Bonn (Germany) University Hospital, who was the lead investigator in the study that found low spontaneous clearance rates with HIV coinfection.

Almost all the 465 subjects were on combination antiretroviral HIV therapy. Most had HCV genotype 1, but there were also type 3 and 4 cases. The investigators followed their subjects for at least a year after HCV infection. Just 55 (11.8%) cleared the infection on their own.

“Almost 90% of acutely infected patients face a chronic course. ... DAA drug labels, as well as clinical guidelines, need to be amended to allow usage of DAA during the acute phase of HCV infection in a high-risk population,” Dr. Boesecke and his team concluded.

Clearance was harbingered by a 2-log decline in HCV RNA by week 4. The 2-log drop cutoff is “the best predictor [we have] ... to identify patients” for early treatment. “There may be some patients you overtreat, but we have to keep in mind that we are not causing any harms with DAAs; maybe harms in terms of money, but not in terms of toxicity,” he said.

The message is beginning to get out. New European AIDS Clinical Society guidelines recommend DAA treatment for patients with HIV who don’t have a 2-log drop after a month.

 

‘Treatment as prevention’ works

The Swiss study added evidence to the frequent assertion at CROI that early treatment stops the spread of HCV.

The investigators screened 3,722 MSM from the Swiss HIV Cohort Study and found 178 (4.8%) men with replicating genotype 1 or 4 HCV infections. Of these cases, 31 were deemed incident and 147 chronic. Almost all the men agreed to treatment with standard-of-care DAAs, usually grazoprevir/elbasvir plus or minus ribavirin. Just about everyone had a sustained virologic response 12 weeks later.

The team rescreened the men after about a year, and found 28 infections; 16 were newly acquired, almost a 50% drop from baseline. The remaining 12 infections were chronic cases not treated earlier.

“Systemic screening followed by prompt DAA treatment can serve as a model to eliminate HCV in coinfected MSM,” said lead investigator Dominique Braun, MD, of the University of Zurich.

Dr. Boesecke is a consultant and/or speaker for AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Thomas is a Merck consultant. Dr. Boerekamps and Dr. Braun’s studies were both funded by Merck, maker of elbasvir/grazoprevir.

[email protected]

SOURCE: Anne Boerekamps. 2018 CROI, Abstract 128. Christoph Boesecke. 2018 CROI, Abstract 129. Dominique Braun. 2018 CROI, Abstract 81LB.






 

 

Novartis’s tisagenlecleucel (Kymriah) is now approved for adults with relapsed or refractory large B-cell lymphoma after failure of two or more lines of systemic therapy.

The Food and Drug Administration approved the expanded indication on May 1. The chimeric antigen receptor (CAR) T-cell therapy was initially approved in Aug. 2017 for refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old. The new approval brings tisagenlecleucel into direct competition with Gilead Science’s CAR T-cell therapy axicabtagene ciloleucel (Yescarta), which was approved in Oct. 2017 for B-cell lymphoma.

Courtesy Novartis

Tisagenlecleucel’s list price is $475,000 for ALL, but it will be priced at $373,000 for lymphoma, the same as the Gilead product, according to a Novartis spokeswoman.

Besides matching the competition, she said the lower price is because tisagenlecleucel takes longer to work for lymphoma, and the response isn’t as potent as for childhood ALL. Novartis is looking into chronic lymphocytic leukemia, multiple myeloma, and solid tumor indications for tisagenlecleucel and other CAR T-cell agents, she added.

The Centers for Medicare & Medicaid Services recently committed to covering outpatient administration of both agents for their initial indications; Novartis is working with CMS for coverage of the new lymphoma indication.

With both products, T cells are collected then shipped off to a company facility where a CAR gene is spliced into their DNA, essentially programming the T cells to attack the targeted cancer. The cells are then infused back into the patient.

In the phase 2 JULIET trial, tisagenlecleucel showed an overall response rate of 50% among 68 B-cell lymphoma patients, with 32% achieving complete response (CR) and 18% achieving partial response (PR). The median duration of response was not reached.

 

Axicabtagene ciloleucel’s label reports an objective response rate of 72% among 101 patients, with CR in 51% and PR in 21%. Median duration of response was 9.2 months but was also not reached among complete responders.

“Different trials. Different CARTs. Different levels of disease. Our drug is cryopreserved and theirs is not. No way to compare them,” the Novartis spokeswoman said when asked about the response differences.

T-cell reprogramming isn’t clean at this point in medical history; both agents carry black box warnings of potentially fatal cytokine release syndrome and neurologic toxicity, and both are subject to Risk Evaluation and Mitigation Strategy programs.

The B-cell lymphoma indication for both therapies includes diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The Gilead product carries an additional indication for primary mediastinal large B-cell lymphoma. Neither agent is indicated for primary central nervous system lymphoma. Both labels say that patients should not donate blood, organs, or tissues after treatment. Tisagenlecleucel labeling also notes that some commercial HIV nucleic acid tests may yield false positives after treatment.

Novartis said in a press release that T cells are treated at the company’s Morris Plains, N.J., facility with a turnaround time of about 22 days. Cryopreservation of the harvested cells gives providers some flexibility in treatment timing.

[email protected]

 

Novartis’s tisagenlecleucel (Kymriah) is now approved for adults with relapsed or refractory large B-cell lymphoma after failure of two or more lines of systemic therapy.

The Food and Drug Administration approved the expanded indication on May 1. The chimeric antigen receptor (CAR) T-cell therapy was initially approved in Aug. 2017 for refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old. The new approval brings tisagenlecleucel into direct competition with Gilead Science’s CAR T-cell therapy axicabtagene ciloleucel (Yescarta), which was approved in Oct. 2017 for B-cell lymphoma.

Courtesy Novartis

Tisagenlecleucel’s list price is $475,000 for ALL, but it will be priced at $373,000 for lymphoma, the same as the Gilead product, according to a Novartis spokeswoman.

Besides matching the competition, she said the lower price is because tisagenlecleucel takes longer to work for lymphoma, and the response isn’t as potent as for childhood ALL. Novartis is looking into chronic lymphocytic leukemia, multiple myeloma, and solid tumor indications for tisagenlecleucel and other CAR T-cell agents, she added.

The Centers for Medicare & Medicaid Services recently committed to covering outpatient administration of both agents for their initial indications; Novartis is working with CMS for coverage of the new lymphoma indication.

With both products, T cells are collected then shipped off to a company facility where a CAR gene is spliced into their DNA, essentially programming the T cells to attack the targeted cancer. The cells are then infused back into the patient.

In the phase 2 JULIET trial, tisagenlecleucel showed an overall response rate of 50% among 68 B-cell lymphoma patients, with 32% achieving complete response (CR) and 18% achieving partial response (PR). The median duration of response was not reached.

 

Axicabtagene ciloleucel’s label reports an objective response rate of 72% among 101 patients, with CR in 51% and PR in 21%. Median duration of response was 9.2 months but was also not reached among complete responders.

“Different trials. Different CARTs. Different levels of disease. Our drug is cryopreserved and theirs is not. No way to compare them,” the Novartis spokeswoman said when asked about the response differences.

T-cell reprogramming isn’t clean at this point in medical history; both agents carry black box warnings of potentially fatal cytokine release syndrome and neurologic toxicity, and both are subject to Risk Evaluation and Mitigation Strategy programs.

The B-cell lymphoma indication for both therapies includes diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The Gilead product carries an additional indication for primary mediastinal large B-cell lymphoma. Neither agent is indicated for primary central nervous system lymphoma. Both labels say that patients should not donate blood, organs, or tissues after treatment. Tisagenlecleucel labeling also notes that some commercial HIV nucleic acid tests may yield false positives after treatment.

Novartis said in a press release that T cells are treated at the company’s Morris Plains, N.J., facility with a turnaround time of about 22 days. Cryopreservation of the harvested cells gives providers some flexibility in treatment timing.

[email protected]

 

Novartis’s tisagenlecleucel (Kymriah) is now approved for adults with relapsed or refractory large B-cell lymphoma after failure of two or more lines of systemic therapy.

The Food and Drug Administration approved the expanded indication on May 1. The chimeric antigen receptor (CAR) T-cell therapy was initially approved in Aug. 2017 for refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old. The new approval brings tisagenlecleucel into direct competition with Gilead Science’s CAR T-cell therapy axicabtagene ciloleucel (Yescarta), which was approved in Oct. 2017 for B-cell lymphoma.

Courtesy Novartis

Tisagenlecleucel’s list price is $475,000 for ALL, but it will be priced at $373,000 for lymphoma, the same as the Gilead product, according to a Novartis spokeswoman.

Besides matching the competition, she said the lower price is because tisagenlecleucel takes longer to work for lymphoma, and the response isn’t as potent as for childhood ALL. Novartis is looking into chronic lymphocytic leukemia, multiple myeloma, and solid tumor indications for tisagenlecleucel and other CAR T-cell agents, she added.

The Centers for Medicare & Medicaid Services recently committed to covering outpatient administration of both agents for their initial indications; Novartis is working with CMS for coverage of the new lymphoma indication.

With both products, T cells are collected then shipped off to a company facility where a CAR gene is spliced into their DNA, essentially programming the T cells to attack the targeted cancer. The cells are then infused back into the patient.

In the phase 2 JULIET trial, tisagenlecleucel showed an overall response rate of 50% among 68 B-cell lymphoma patients, with 32% achieving complete response (CR) and 18% achieving partial response (PR). The median duration of response was not reached.

 

Axicabtagene ciloleucel’s label reports an objective response rate of 72% among 101 patients, with CR in 51% and PR in 21%. Median duration of response was 9.2 months but was also not reached among complete responders.

“Different trials. Different CARTs. Different levels of disease. Our drug is cryopreserved and theirs is not. No way to compare them,” the Novartis spokeswoman said when asked about the response differences.

T-cell reprogramming isn’t clean at this point in medical history; both agents carry black box warnings of potentially fatal cytokine release syndrome and neurologic toxicity, and both are subject to Risk Evaluation and Mitigation Strategy programs.

The B-cell lymphoma indication for both therapies includes diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The Gilead product carries an additional indication for primary mediastinal large B-cell lymphoma. Neither agent is indicated for primary central nervous system lymphoma. Both labels say that patients should not donate blood, organs, or tissues after treatment. Tisagenlecleucel labeling also notes that some commercial HIV nucleic acid tests may yield false positives after treatment.

Novartis said in a press release that T cells are treated at the company’s Morris Plains, N.J., facility with a turnaround time of about 22 days. Cryopreservation of the harvested cells gives providers some flexibility in treatment timing.

[email protected]