Randy Dotinga

The medical marijuana landscape is changing so fast that Colorado Neurological Institute neurologist Allen C. Bowling, MD, PhD, already needs to update a presentation he gave about cannabis in multiple sclerosis in late May.

The laws vary widely. Some states don’t allow patients to smoke medical marijuana, and some don’t allow visitors to use out-of-state registry ID cards. And certain states limit the use of medical marijuana to specific conditions. Medical marijuana use by patients with MS is specifically allowed in many states, including Alaska, Arizona, Florida, Minnesota, and several others.

There’s another complexity: According to procon.org, 17 states have laws about the use of cannabidiol. In Georgia, for instance, the use of some cannabis oil is allowed for the treatment of MS and other conditions.

In the wake of the FDA ruling, Dr. Bowling spoke in an interview about cannabis, MS, and the questions that neurologists should be asking themselves.

Q: What are studies telling us about cannabis and MS?

A: There are lots of clinical studies – 19 randomized controlled trials. A consistent finding is that there’s benefit in terms of pain and people’s subjective sense of spasticity (Neurology. 2014 Apr 29;82(17):1556-63).

Q: During your CMSC presentation, you talked about how “fidelity” has been a problem in cannabis research. Could you elaborate on what you mean?

A: The products used in these studies are generally standardized, research-grade products that you can’t buy in any U.S. dispensary.

Cannabis is complex and contains more than 100 different potentially pharmacologically active molecules. You can’t conclude that if you see a product in clinical trials, you’ll then be able to walk into a dispensary for recreational or medical cannabis and get a product that produces the same effect.

Q: What have you seen in your own patient population in terms of cannabis use?

A: I find what’s been found with the studies: It helps with pain and people’s sense of muscle stiffness.

It’s especially helpful in people with pain and spasticity that breaks through in the late afternoon or at night when they’re trying to go to sleep. Just a little bit of cannabis can get them through those difficult times and improve their quality of life.

Q: What choices do patients make regarding whether to get high from the cannabis they use?

A: Some have absolutely zero interest in getting high, and they try to avoid the THC-containing products. Other like getting high in addition to getting help with pain and spasticity.

Q: Who should not use medical marijuana in the MS community?

A: Patients who don’t have symptoms that could respond.

I’m also very concerned about patients who are 25 years and younger because of the effects that cannabis can have on brain development out to age 25 and the higher risk of addiction in people who are younger.

Q: What do you think the future will hold on the cannabis front?

A: Now that it’s less of a taboo topic, there’s an ever-growing number of trials each year, including very high-quality studies.

Pharmaceutically produced, cannabis-based medicines will be a growing area. Epidiolex is a perfect example of that.

It’s important for physicians to know that the way cannabis-based medicine is produced by a pharmaceutical company is different in so many levels than the cannabis in states with recreational and medical marijuana.

Q: What are some ways that the pharmaceutical products are different?

A: The rigor of the production process, the standardization, the purity, the correct labeling and expiration dates. Plus, the lack of the use of pesticides and other contaminants. And they’re distributed by pharmacists.

Q: What should neurologists be thinking if they’re considering whether to recommend cannabis to their patients?

A: This is a very complex topic, and it’s not something that most of us have training in. You can’t sit down for 1 or 2 hours, get up to speed, and have your own well-informed opinion on it. You really need to put more time and effort.

Q: What are some issues that neurologists should consider?

A: You really need to find out what your state is doing about it and see how you feel about that.

How is your state administering medical and/or recreational marijuana? The administration of these programs is extremely different from state to state. Do these details satisfy you, and are you content having your patients interface with these programs?

Dr. Bowling reports no relevant disclosures.

The medical marijuana landscape is changing so fast that Colorado Neurological Institute neurologist Allen C. Bowling, MD, PhD, already needs to update a presentation he gave about cannabis in multiple sclerosis in late May.

The laws vary widely. Some states don’t allow patients to smoke medical marijuana, and some don’t allow visitors to use out-of-state registry ID cards. And certain states limit the use of medical marijuana to specific conditions. Medical marijuana use by patients with MS is specifically allowed in many states, including Alaska, Arizona, Florida, Minnesota, and several others.

There’s another complexity: According to procon.org, 17 states have laws about the use of cannabidiol. In Georgia, for instance, the use of some cannabis oil is allowed for the treatment of MS and other conditions.

In the wake of the FDA ruling, Dr. Bowling spoke in an interview about cannabis, MS, and the questions that neurologists should be asking themselves.

Q: What are studies telling us about cannabis and MS?

A: There are lots of clinical studies – 19 randomized controlled trials. A consistent finding is that there’s benefit in terms of pain and people’s subjective sense of spasticity (Neurology. 2014 Apr 29;82(17):1556-63).

Q: During your CMSC presentation, you talked about how “fidelity” has been a problem in cannabis research. Could you elaborate on what you mean?

A: The products used in these studies are generally standardized, research-grade products that you can’t buy in any U.S. dispensary.

Cannabis is complex and contains more than 100 different potentially pharmacologically active molecules. You can’t conclude that if you see a product in clinical trials, you’ll then be able to walk into a dispensary for recreational or medical cannabis and get a product that produces the same effect.

Q: What have you seen in your own patient population in terms of cannabis use?

A: I find what’s been found with the studies: It helps with pain and people’s sense of muscle stiffness.

It’s especially helpful in people with pain and spasticity that breaks through in the late afternoon or at night when they’re trying to go to sleep. Just a little bit of cannabis can get them through those difficult times and improve their quality of life.

Q: What choices do patients make regarding whether to get high from the cannabis they use?

A: Some have absolutely zero interest in getting high, and they try to avoid the THC-containing products. Other like getting high in addition to getting help with pain and spasticity.

Q: Who should not use medical marijuana in the MS community?

A: Patients who don’t have symptoms that could respond.

I’m also very concerned about patients who are 25 years and younger because of the effects that cannabis can have on brain development out to age 25 and the higher risk of addiction in people who are younger.

Q: What do you think the future will hold on the cannabis front?

A: Now that it’s less of a taboo topic, there’s an ever-growing number of trials each year, including very high-quality studies.

Pharmaceutically produced, cannabis-based medicines will be a growing area. Epidiolex is a perfect example of that.

It’s important for physicians to know that the way cannabis-based medicine is produced by a pharmaceutical company is different in so many levels than the cannabis in states with recreational and medical marijuana.

Q: What are some ways that the pharmaceutical products are different?

A: The rigor of the production process, the standardization, the purity, the correct labeling and expiration dates. Plus, the lack of the use of pesticides and other contaminants. And they’re distributed by pharmacists.

Q: What should neurologists be thinking if they’re considering whether to recommend cannabis to their patients?

A: This is a very complex topic, and it’s not something that most of us have training in. You can’t sit down for 1 or 2 hours, get up to speed, and have your own well-informed opinion on it. You really need to put more time and effort.

Q: What are some issues that neurologists should consider?

A: You really need to find out what your state is doing about it and see how you feel about that.

How is your state administering medical and/or recreational marijuana? The administration of these programs is extremely different from state to state. Do these details satisfy you, and are you content having your patients interface with these programs?

Dr. Bowling reports no relevant disclosures.

The medical marijuana landscape is changing so fast that Colorado Neurological Institute neurologist Allen C. Bowling, MD, PhD, already needs to update a presentation he gave about cannabis in multiple sclerosis in late May.

The laws vary widely. Some states don’t allow patients to smoke medical marijuana, and some don’t allow visitors to use out-of-state registry ID cards. And certain states limit the use of medical marijuana to specific conditions. Medical marijuana use by patients with MS is specifically allowed in many states, including Alaska, Arizona, Florida, Minnesota, and several others.

There’s another complexity: According to procon.org, 17 states have laws about the use of cannabidiol. In Georgia, for instance, the use of some cannabis oil is allowed for the treatment of MS and other conditions.

In the wake of the FDA ruling, Dr. Bowling spoke in an interview about cannabis, MS, and the questions that neurologists should be asking themselves.

Q: What are studies telling us about cannabis and MS?

A: There are lots of clinical studies – 19 randomized controlled trials. A consistent finding is that there’s benefit in terms of pain and people’s subjective sense of spasticity (Neurology. 2014 Apr 29;82(17):1556-63).

Q: During your CMSC presentation, you talked about how “fidelity” has been a problem in cannabis research. Could you elaborate on what you mean?

A: The products used in these studies are generally standardized, research-grade products that you can’t buy in any U.S. dispensary.

Cannabis is complex and contains more than 100 different potentially pharmacologically active molecules. You can’t conclude that if you see a product in clinical trials, you’ll then be able to walk into a dispensary for recreational or medical cannabis and get a product that produces the same effect.

Q: What have you seen in your own patient population in terms of cannabis use?

A: I find what’s been found with the studies: It helps with pain and people’s sense of muscle stiffness.

It’s especially helpful in people with pain and spasticity that breaks through in the late afternoon or at night when they’re trying to go to sleep. Just a little bit of cannabis can get them through those difficult times and improve their quality of life.

Q: What choices do patients make regarding whether to get high from the cannabis they use?

A: Some have absolutely zero interest in getting high, and they try to avoid the THC-containing products. Other like getting high in addition to getting help with pain and spasticity.

Q: Who should not use medical marijuana in the MS community?

A: Patients who don’t have symptoms that could respond.

I’m also very concerned about patients who are 25 years and younger because of the effects that cannabis can have on brain development out to age 25 and the higher risk of addiction in people who are younger.

Q: What do you think the future will hold on the cannabis front?

A: Now that it’s less of a taboo topic, there’s an ever-growing number of trials each year, including very high-quality studies.

Pharmaceutically produced, cannabis-based medicines will be a growing area. Epidiolex is a perfect example of that.

It’s important for physicians to know that the way cannabis-based medicine is produced by a pharmaceutical company is different in so many levels than the cannabis in states with recreational and medical marijuana.

Q: What are some ways that the pharmaceutical products are different?

A: The rigor of the production process, the standardization, the purity, the correct labeling and expiration dates. Plus, the lack of the use of pesticides and other contaminants. And they’re distributed by pharmacists.

Q: What should neurologists be thinking if they’re considering whether to recommend cannabis to their patients?

A: This is a very complex topic, and it’s not something that most of us have training in. You can’t sit down for 1 or 2 hours, get up to speed, and have your own well-informed opinion on it. You really need to put more time and effort.

Q: What are some issues that neurologists should consider?

A: You really need to find out what your state is doing about it and see how you feel about that.

How is your state administering medical and/or recreational marijuana? The administration of these programs is extremely different from state to state. Do these details satisfy you, and are you content having your patients interface with these programs?

Dr. Bowling reports no relevant disclosures.

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

sworcester@mdedge.com

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

sworcester@mdedge.com

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

sworcester@mdedge.com

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

SAN DIEGO – Disturbed sleep is one of the symptoms of withdrawal from marijuana, and it can wreak havoc on the lives of people with cannabis use disorder who are trying to quit. Now, a new study provides more evidence about the problem and suggests that the sleep aid zolpidem is not a solution on its own.

Zolpidem seemed to help subjects sleep better, but the effect lasted only as long as they took the drug. And the subjects who took zolpidem were not significantly more likely to abstain from cannabis in the long term.

“Zolpidem or other hypnotics may have some efficacy as a pharmacotherapy to relieve short-term sleep disruption in the treatment of cannabis use disorder. But they should only be used in cases where abstinence-induced insomnia is a significant barrier to cessation and only in combination with other evidence-based interventions to address key aspects of cannabis use disorder,” study coauthor Dustin C. Lee, PhD, of Johns Hopkins University, Baltimore, said in an interview. He presented the study findings at the annual meeting of the College on Problems of Drug Dependence.

Previous research, including studies by some of the authors of the new report, suggests that people trying to withdraw from cannabis often suffer from sleep disturbances.

In a 2010 study, for instance, researchers interviewed 469 adult cannabis users in the Baltimore area who had tried to quit outside of treatment programs. Nearly half reported trouble falling asleep, while 20%-36% reported sleep-related symptoms, such as sleeping more or less than usual, having unusual dreams, and waking during the night (Drug Alcohol Depend. 2010 Sep 1;111[1-2]:120-7).

Another factor could be at play: Cannabis users may sleep better while they use the drug, then lose the benefit when they try to withdraw.

“Studies have demonstrated that acute use of cannabis reduces sleep latency and increases stage 3 sleep, informally referred to as ‘deep’ or ‘slow-wave’ sleep, which means individuals fall asleep faster and remain in deep sleep longer after using cannabis,” Dr. Lee said.

SAN DIEGO – Disturbed sleep is one of the symptoms of withdrawal from marijuana, and it can wreak havoc on the lives of people with cannabis use disorder who are trying to quit. Now, a new study provides more evidence about the problem and suggests that the sleep aid zolpidem is not a solution on its own.

Zolpidem seemed to help subjects sleep better, but the effect lasted only as long as they took the drug. And the subjects who took zolpidem were not significantly more likely to abstain from cannabis in the long term.

“Zolpidem or other hypnotics may have some efficacy as a pharmacotherapy to relieve short-term sleep disruption in the treatment of cannabis use disorder. But they should only be used in cases where abstinence-induced insomnia is a significant barrier to cessation and only in combination with other evidence-based interventions to address key aspects of cannabis use disorder,” study coauthor Dustin C. Lee, PhD, of Johns Hopkins University, Baltimore, said in an interview. He presented the study findings at the annual meeting of the College on Problems of Drug Dependence.

Previous research, including studies by some of the authors of the new report, suggests that people trying to withdraw from cannabis often suffer from sleep disturbances.

In a 2010 study, for instance, researchers interviewed 469 adult cannabis users in the Baltimore area who had tried to quit outside of treatment programs. Nearly half reported trouble falling asleep, while 20%-36% reported sleep-related symptoms, such as sleeping more or less than usual, having unusual dreams, and waking during the night (Drug Alcohol Depend. 2010 Sep 1;111[1-2]:120-7).

Another factor could be at play: Cannabis users may sleep better while they use the drug, then lose the benefit when they try to withdraw.

“Studies have demonstrated that acute use of cannabis reduces sleep latency and increases stage 3 sleep, informally referred to as ‘deep’ or ‘slow-wave’ sleep, which means individuals fall asleep faster and remain in deep sleep longer after using cannabis,” Dr. Lee said.

SAN DIEGO – Disturbed sleep is one of the symptoms of withdrawal from marijuana, and it can wreak havoc on the lives of people with cannabis use disorder who are trying to quit. Now, a new study provides more evidence about the problem and suggests that the sleep aid zolpidem is not a solution on its own.

Zolpidem seemed to help subjects sleep better, but the effect lasted only as long as they took the drug. And the subjects who took zolpidem were not significantly more likely to abstain from cannabis in the long term.

“Zolpidem or other hypnotics may have some efficacy as a pharmacotherapy to relieve short-term sleep disruption in the treatment of cannabis use disorder. But they should only be used in cases where abstinence-induced insomnia is a significant barrier to cessation and only in combination with other evidence-based interventions to address key aspects of cannabis use disorder,” study coauthor Dustin C. Lee, PhD, of Johns Hopkins University, Baltimore, said in an interview. He presented the study findings at the annual meeting of the College on Problems of Drug Dependence.

Previous research, including studies by some of the authors of the new report, suggests that people trying to withdraw from cannabis often suffer from sleep disturbances.

In a 2010 study, for instance, researchers interviewed 469 adult cannabis users in the Baltimore area who had tried to quit outside of treatment programs. Nearly half reported trouble falling asleep, while 20%-36% reported sleep-related symptoms, such as sleeping more or less than usual, having unusual dreams, and waking during the night (Drug Alcohol Depend. 2010 Sep 1;111[1-2]:120-7).

Another factor could be at play: Cannabis users may sleep better while they use the drug, then lose the benefit when they try to withdraw.

“Studies have demonstrated that acute use of cannabis reduces sleep latency and increases stage 3 sleep, informally referred to as ‘deep’ or ‘slow-wave’ sleep, which means individuals fall asleep faster and remain in deep sleep longer after using cannabis,” Dr. Lee said.

ORLANDO – Researchers have been able to sustain a dramatic reduction in hypoglycemia incidents at nine St. Louis–area hospitals, thanks to a computer algorithm that warns medical staff when patients appear to be on the road to dangerously low blood sugar levels.

Robert Lodge/MDedge Medical News

SOURCE: Tobin G et al. ADA 2018. Abstract 397-P.

ORLANDO – Researchers have been able to sustain a dramatic reduction in hypoglycemia incidents at nine St. Louis–area hospitals, thanks to a computer algorithm that warns medical staff when patients appear to be on the road to dangerously low blood sugar levels.

Robert Lodge/MDedge Medical News

SOURCE: Tobin G et al. ADA 2018. Abstract 397-P.

ORLANDO – Researchers have been able to sustain a dramatic reduction in hypoglycemia incidents at nine St. Louis–area hospitals, thanks to a computer algorithm that warns medical staff when patients appear to be on the road to dangerously low blood sugar levels.

Robert Lodge/MDedge Medical News

SOURCE: Tobin G et al. ADA 2018. Abstract 397-P.

SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”

So say opioid users who are opening up to researchers about the deadly new American drug landscape.

There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.

• Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
• In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
• Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”

Some say pursue fentanyl

In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”

She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”

As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
 

Comments from users about fentanyl

• “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
• “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”

Risk-reduction techniques embraced

• In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
• Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”

Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.

“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”

Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.

SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”

So say opioid users who are opening up to researchers about the deadly new American drug landscape.

There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.

• Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
• In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
• Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”

Some say pursue fentanyl

In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”

She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”

As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
 

Comments from users about fentanyl

• “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
• “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”

Risk-reduction techniques embraced

• In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
• Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”

Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.

“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”

Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.

SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”

So say opioid users who are opening up to researchers about the deadly new American drug landscape.

There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.

• Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
• In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
• Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”

Some say pursue fentanyl

In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”

She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”

As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
 

Comments from users about fentanyl

• “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
• “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”

Risk-reduction techniques embraced

• In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
• Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”

Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.

“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”

Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.

SAN DIEGO – As the deadly opioid epidemic continues, a new study suggests that a fast-rising number of users are turning to another drug of abuse – methamphetamine. In some cases, a researcher says, their co-use is reminiscent of the fad for “speedball” mixtures of cocaine and heroin.

During 2011-2017, the percentage of surveyed opioid users seeking treatment who reported also using methamphetamine over the past month skyrocketed from 19% to 34%, researchers reported at the 2018 annual meeting of the College on Problems of Drug Dependence.

Use of crystal meth specifically went up by 82% and the use of prescription stimulants rose by 15%. By contrast, use of marijuana went up by just 6%, while the use of muscle relaxants and prescription sleep drugs fell by more than half.

The findings matter, because the use of multiple illicit drugs is even more dangerous than one alone, said study coauthor and doctoral candidate Matthew S. Ellis, of Washington University in St. Louis, in an interview. “Illicit opioids carry their own serious risks such as unknown purity, not knowing if heroin is laced with fentanyl, or inexperience of users who are used to clearly marked prescription pills. Add in a secondary drug, also often used in non-oral ways, and your risk for overdose is going to significantly increase.”

The rising use of methamphetamine, which comes in such forms as crystal meth, has been overshadowed by news about the opioid epidemic. Still, as a 2018 Lancet report put it, “while the opioid crisis has exploded, the lull in the methamphetamine epidemic has quietly and swiftly reversed course, now accounting for 11% of the total number of overdose deaths.”

In regard to co-use of opioids and methamphetamines, the report said, “in states including Wisconsin and Oregon, new patterns suggest they are beginning to overlap as increasing numbers of people use both drugs” (Lancet. 2018 Feb. 24;391[10122]:713).

Meanwhile, the New York Times published a story in February 2018 headlined “Meth, the forgotten killer, is back. And it’s everywhere.” It noted that meth overdose deaths in Oregon outpace those from opioids and added: “At the United States border, agents are seizing 10-20 times the amounts they did a decade ago. Methamphetamine, experts say, has never been purer, cheaper, or more lethal.”

Overall, there’s little known about co-use of opioids and methamphetamines, said study lead author Mr. Ellis. “The reason for this is that opioid use patterns and populations of users have drastically changed in the past 20 years, and continue to do so,” he said. “Methamphetamine is becoming increasingly available at the same time that heroin and illicit fentanyl are as well. Reports suggest that the United States has shifted from a market of home-grown methamphetamine to that manufactured and sent from other countries, creating a broader market than previously seen.”

For the new study, Mr. Ellis and his colleagues examined statistics from a U.S. surveillance program of opioid users entering substance abuse programs. They focused on 13,521 participants in 47 states during 2011-2017.

Of 12 drug classes examined, only co-use of methamphetamine rose significantly over the 6-year period, Mr. Ellis said.

Among demographic and geographic groups, the researchers saw the largest increases in co-use of the two drugs in the West, Northeast, and Midwest regions, in rural and suburban areas, among groups aged 18-44 years, and among whites.

Why is co-use among opioid users increasing? “We have begun to do some qualitative work with a number of participants suggesting they use opioids and methamphetamine to balance each other out,” Mr. Ellis said. “So an addict can use opioids, but if they need to go to work, they can reinvigorate themselves with methamphetamine.”

Mr. Ellis said “this is not necessarily a new trend,” noting that the co-use of the drugs is akin to the “speedball” – a mixture of cocaine and heroin designed to blend their opposite modes of action.

However, Mr. Ellis said, “the rates we are seeing appear to be much higher than what was seen for speedballs. The increases in production and spread of illicit opioids and methamphetamine into an existing market of those previously using prescription opioids was a perfect storm for these two drugs to be a problem, both separately and together.”

He said researchers also are finding that “if methamphetamine is the only thing an opioid addict can find, they will use it to stave off withdrawals as well.”

Indeed, National Public Radio reported in June 2018 that “as opioids are becoming harder to obtain, more and more users are turning to cheap methamphetamine” in Ohio’s tiny Vinton County, near Columbus.

Moving forward, Mr. Ellis said, “we cannot treat substance use in a silo of a single drug. If we attempt to treat opioid abusers by simply treating their opioid abuse – and not other drugs – then we have less of a chance of success. More of a focus needs to be put on the fact that the vast majority of opioid abusers are polysubstance users.”

The study is funded by the RADARS (Researched Abuse, Diversion and Addiction-Related Surveillance) System, an independent, nonprofit postmarketing surveillance system supported by subscription fees from pharmaceutical manufacturers that use RADARS data to track medication use and meet regulatory obligations. The study authors report no relevant disclosures.

SAN DIEGO – As the deadly opioid epidemic continues, a new study suggests that a fast-rising number of users are turning to another drug of abuse – methamphetamine. In some cases, a researcher says, their co-use is reminiscent of the fad for “speedball” mixtures of cocaine and heroin.

During 2011-2017, the percentage of surveyed opioid users seeking treatment who reported also using methamphetamine over the past month skyrocketed from 19% to 34%, researchers reported at the 2018 annual meeting of the College on Problems of Drug Dependence.

Use of crystal meth specifically went up by 82% and the use of prescription stimulants rose by 15%. By contrast, use of marijuana went up by just 6%, while the use of muscle relaxants and prescription sleep drugs fell by more than half.

The findings matter, because the use of multiple illicit drugs is even more dangerous than one alone, said study coauthor and doctoral candidate Matthew S. Ellis, of Washington University in St. Louis, in an interview. “Illicit opioids carry their own serious risks such as unknown purity, not knowing if heroin is laced with fentanyl, or inexperience of users who are used to clearly marked prescription pills. Add in a secondary drug, also often used in non-oral ways, and your risk for overdose is going to significantly increase.”

The rising use of methamphetamine, which comes in such forms as crystal meth, has been overshadowed by news about the opioid epidemic. Still, as a 2018 Lancet report put it, “while the opioid crisis has exploded, the lull in the methamphetamine epidemic has quietly and swiftly reversed course, now accounting for 11% of the total number of overdose deaths.”

In regard to co-use of opioids and methamphetamines, the report said, “in states including Wisconsin and Oregon, new patterns suggest they are beginning to overlap as increasing numbers of people use both drugs” (Lancet. 2018 Feb. 24;391[10122]:713).

Meanwhile, the New York Times published a story in February 2018 headlined “Meth, the forgotten killer, is back. And it’s everywhere.” It noted that meth overdose deaths in Oregon outpace those from opioids and added: “At the United States border, agents are seizing 10-20 times the amounts they did a decade ago. Methamphetamine, experts say, has never been purer, cheaper, or more lethal.”

Overall, there’s little known about co-use of opioids and methamphetamines, said study lead author Mr. Ellis. “The reason for this is that opioid use patterns and populations of users have drastically changed in the past 20 years, and continue to do so,” he said. “Methamphetamine is becoming increasingly available at the same time that heroin and illicit fentanyl are as well. Reports suggest that the United States has shifted from a market of home-grown methamphetamine to that manufactured and sent from other countries, creating a broader market than previously seen.”

For the new study, Mr. Ellis and his colleagues examined statistics from a U.S. surveillance program of opioid users entering substance abuse programs. They focused on 13,521 participants in 47 states during 2011-2017.

Of 12 drug classes examined, only co-use of methamphetamine rose significantly over the 6-year period, Mr. Ellis said.

Among demographic and geographic groups, the researchers saw the largest increases in co-use of the two drugs in the West, Northeast, and Midwest regions, in rural and suburban areas, among groups aged 18-44 years, and among whites.

Why is co-use among opioid users increasing? “We have begun to do some qualitative work with a number of participants suggesting they use opioids and methamphetamine to balance each other out,” Mr. Ellis said. “So an addict can use opioids, but if they need to go to work, they can reinvigorate themselves with methamphetamine.”

Mr. Ellis said “this is not necessarily a new trend,” noting that the co-use of the drugs is akin to the “speedball” – a mixture of cocaine and heroin designed to blend their opposite modes of action.

However, Mr. Ellis said, “the rates we are seeing appear to be much higher than what was seen for speedballs. The increases in production and spread of illicit opioids and methamphetamine into an existing market of those previously using prescription opioids was a perfect storm for these two drugs to be a problem, both separately and together.”

He said researchers also are finding that “if methamphetamine is the only thing an opioid addict can find, they will use it to stave off withdrawals as well.”

Indeed, National Public Radio reported in June 2018 that “as opioids are becoming harder to obtain, more and more users are turning to cheap methamphetamine” in Ohio’s tiny Vinton County, near Columbus.

Moving forward, Mr. Ellis said, “we cannot treat substance use in a silo of a single drug. If we attempt to treat opioid abusers by simply treating their opioid abuse – and not other drugs – then we have less of a chance of success. More of a focus needs to be put on the fact that the vast majority of opioid abusers are polysubstance users.”

The study is funded by the RADARS (Researched Abuse, Diversion and Addiction-Related Surveillance) System, an independent, nonprofit postmarketing surveillance system supported by subscription fees from pharmaceutical manufacturers that use RADARS data to track medication use and meet regulatory obligations. The study authors report no relevant disclosures.

SAN DIEGO – As the deadly opioid epidemic continues, a new study suggests that a fast-rising number of users are turning to another drug of abuse – methamphetamine. In some cases, a researcher says, their co-use is reminiscent of the fad for “speedball” mixtures of cocaine and heroin.

During 2011-2017, the percentage of surveyed opioid users seeking treatment who reported also using methamphetamine over the past month skyrocketed from 19% to 34%, researchers reported at the 2018 annual meeting of the College on Problems of Drug Dependence.

Use of crystal meth specifically went up by 82% and the use of prescription stimulants rose by 15%. By contrast, use of marijuana went up by just 6%, while the use of muscle relaxants and prescription sleep drugs fell by more than half.

The findings matter, because the use of multiple illicit drugs is even more dangerous than one alone, said study coauthor and doctoral candidate Matthew S. Ellis, of Washington University in St. Louis, in an interview. “Illicit opioids carry their own serious risks such as unknown purity, not knowing if heroin is laced with fentanyl, or inexperience of users who are used to clearly marked prescription pills. Add in a secondary drug, also often used in non-oral ways, and your risk for overdose is going to significantly increase.”

The rising use of methamphetamine, which comes in such forms as crystal meth, has been overshadowed by news about the opioid epidemic. Still, as a 2018 Lancet report put it, “while the opioid crisis has exploded, the lull in the methamphetamine epidemic has quietly and swiftly reversed course, now accounting for 11% of the total number of overdose deaths.”

In regard to co-use of opioids and methamphetamines, the report said, “in states including Wisconsin and Oregon, new patterns suggest they are beginning to overlap as increasing numbers of people use both drugs” (Lancet. 2018 Feb. 24;391[10122]:713).

Meanwhile, the New York Times published a story in February 2018 headlined “Meth, the forgotten killer, is back. And it’s everywhere.” It noted that meth overdose deaths in Oregon outpace those from opioids and added: “At the United States border, agents are seizing 10-20 times the amounts they did a decade ago. Methamphetamine, experts say, has never been purer, cheaper, or more lethal.”

Overall, there’s little known about co-use of opioids and methamphetamines, said study lead author Mr. Ellis. “The reason for this is that opioid use patterns and populations of users have drastically changed in the past 20 years, and continue to do so,” he said. “Methamphetamine is becoming increasingly available at the same time that heroin and illicit fentanyl are as well. Reports suggest that the United States has shifted from a market of home-grown methamphetamine to that manufactured and sent from other countries, creating a broader market than previously seen.”

For the new study, Mr. Ellis and his colleagues examined statistics from a U.S. surveillance program of opioid users entering substance abuse programs. They focused on 13,521 participants in 47 states during 2011-2017.

Of 12 drug classes examined, only co-use of methamphetamine rose significantly over the 6-year period, Mr. Ellis said.

Among demographic and geographic groups, the researchers saw the largest increases in co-use of the two drugs in the West, Northeast, and Midwest regions, in rural and suburban areas, among groups aged 18-44 years, and among whites.

Why is co-use among opioid users increasing? “We have begun to do some qualitative work with a number of participants suggesting they use opioids and methamphetamine to balance each other out,” Mr. Ellis said. “So an addict can use opioids, but if they need to go to work, they can reinvigorate themselves with methamphetamine.”

Mr. Ellis said “this is not necessarily a new trend,” noting that the co-use of the drugs is akin to the “speedball” – a mixture of cocaine and heroin designed to blend their opposite modes of action.

However, Mr. Ellis said, “the rates we are seeing appear to be much higher than what was seen for speedballs. The increases in production and spread of illicit opioids and methamphetamine into an existing market of those previously using prescription opioids was a perfect storm for these two drugs to be a problem, both separately and together.”

He said researchers also are finding that “if methamphetamine is the only thing an opioid addict can find, they will use it to stave off withdrawals as well.”

Indeed, National Public Radio reported in June 2018 that “as opioids are becoming harder to obtain, more and more users are turning to cheap methamphetamine” in Ohio’s tiny Vinton County, near Columbus.

Moving forward, Mr. Ellis said, “we cannot treat substance use in a silo of a single drug. If we attempt to treat opioid abusers by simply treating their opioid abuse – and not other drugs – then we have less of a chance of success. More of a focus needs to be put on the fact that the vast majority of opioid abusers are polysubstance users.”

The study is funded by the RADARS (Researched Abuse, Diversion and Addiction-Related Surveillance) System, an independent, nonprofit postmarketing surveillance system supported by subscription fees from pharmaceutical manufacturers that use RADARS data to track medication use and meet regulatory obligations. The study authors report no relevant disclosures.

SAN DIEGO – Heroin, methamphetamine, and cocaine might not seem to have much in common with germs, but chemist Kim D. Janda, PhD, and his colleagues are trying to trick the human body into looking at them the same way: As invaders who must be conquered.

And what’s the best way to prepare the immune system for a fight? Train it through vaccination – the key to so many victories over viruses and bacteria.

For decades now, Dr. Janda, of the Scripps Research Institute in La Jolla, Calif., and other scientists have tried to develop a vaccine that would blunt the effects of substances of abuse, such as illicit drugs and even tobacco. The idea is to arm the immune system with antibodies that will prevent some or all drug components from breaking through the blood-brain barrier and producing psychoactive reactions.

In a follow-up interview after his presentation at the annual meeting of the College on Problems of Drug Dependence, Dr. Janda spoke about the history of research in this area, the potential workings of a vaccine, and the challenges of moving his own research forward.

Question: What’s the history of scientists’ efforts to develop a vaccine against drugs of abuse?

Answer: People looked at it back in the 1970s, but it didn’t really pan out. It was pretty dormant until we published research about a cocaine vaccine in 1995.

We worked on that for a while, then we looked at methamphetamine, Rohypnol, and opioids. There have been clinical trials for nicotine and cocaine, but they’ve failed.

Q: How are these vaccines expected to work?

A: The idea of the vaccines is that you don’t get high, so you won’t feel the effect of the drugs. They’ll never reach the pleasure centers that they’re supposed to.



Q: Is the idea that everyone would get a vaccine against, say, cocaine or heroin, like we routinely get vaccines against various diseases?

A: For an infectious disease like measles or mumps, you give vaccinations, and herd immunity develops. That’s not the case here. These work in a different manner, and they’re not going to be useful for people who don’t want to get off the drug. Instead, they’re going to be useful for people who want to obtain sobriety. If someone has a weak moment and tries to take the drug to get high, this would hopefully stop that from happening. It could also help overdoses in some cases, since you’re not getting that much drug into the central nervous system where it can cause cardiac arrest.



Q: How often would people be vaccinated?

A: These are vaccines that will be on board for a certain amount of time. We envision 3-4 shots over a 3-month period. You’d come back once a month for 3 months, and you’d be good for maybe 4-6 months.



Q: Where does your research stand now?

A: We’ve made a lot of advances with the opioids, and they’re good enough to put a vaccine in the clinic. I’m still trying to get some more money so we could hopefully move toward a clinical trial. Money is the issue. It’s always the issue. But we have to get up to the plate and take our swings – and find if we’ll strike out or get a hit.

SAN DIEGO – Heroin, methamphetamine, and cocaine might not seem to have much in common with germs, but chemist Kim D. Janda, PhD, and his colleagues are trying to trick the human body into looking at them the same way: As invaders who must be conquered.

And what’s the best way to prepare the immune system for a fight? Train it through vaccination – the key to so many victories over viruses and bacteria.

For decades now, Dr. Janda, of the Scripps Research Institute in La Jolla, Calif., and other scientists have tried to develop a vaccine that would blunt the effects of substances of abuse, such as illicit drugs and even tobacco. The idea is to arm the immune system with antibodies that will prevent some or all drug components from breaking through the blood-brain barrier and producing psychoactive reactions.

In a follow-up interview after his presentation at the annual meeting of the College on Problems of Drug Dependence, Dr. Janda spoke about the history of research in this area, the potential workings of a vaccine, and the challenges of moving his own research forward.

Question: What’s the history of scientists’ efforts to develop a vaccine against drugs of abuse?

Answer: People looked at it back in the 1970s, but it didn’t really pan out. It was pretty dormant until we published research about a cocaine vaccine in 1995.

We worked on that for a while, then we looked at methamphetamine, Rohypnol, and opioids. There have been clinical trials for nicotine and cocaine, but they’ve failed.

Q: How are these vaccines expected to work?

A: The idea of the vaccines is that you don’t get high, so you won’t feel the effect of the drugs. They’ll never reach the pleasure centers that they’re supposed to.



Q: Is the idea that everyone would get a vaccine against, say, cocaine or heroin, like we routinely get vaccines against various diseases?

A: For an infectious disease like measles or mumps, you give vaccinations, and herd immunity develops. That’s not the case here. These work in a different manner, and they’re not going to be useful for people who don’t want to get off the drug. Instead, they’re going to be useful for people who want to obtain sobriety. If someone has a weak moment and tries to take the drug to get high, this would hopefully stop that from happening. It could also help overdoses in some cases, since you’re not getting that much drug into the central nervous system where it can cause cardiac arrest.



Q: How often would people be vaccinated?

A: These are vaccines that will be on board for a certain amount of time. We envision 3-4 shots over a 3-month period. You’d come back once a month for 3 months, and you’d be good for maybe 4-6 months.



Q: Where does your research stand now?

A: We’ve made a lot of advances with the opioids, and they’re good enough to put a vaccine in the clinic. I’m still trying to get some more money so we could hopefully move toward a clinical trial. Money is the issue. It’s always the issue. But we have to get up to the plate and take our swings – and find if we’ll strike out or get a hit.

SAN DIEGO – Heroin, methamphetamine, and cocaine might not seem to have much in common with germs, but chemist Kim D. Janda, PhD, and his colleagues are trying to trick the human body into looking at them the same way: As invaders who must be conquered.

And what’s the best way to prepare the immune system for a fight? Train it through vaccination – the key to so many victories over viruses and bacteria.

For decades now, Dr. Janda, of the Scripps Research Institute in La Jolla, Calif., and other scientists have tried to develop a vaccine that would blunt the effects of substances of abuse, such as illicit drugs and even tobacco. The idea is to arm the immune system with antibodies that will prevent some or all drug components from breaking through the blood-brain barrier and producing psychoactive reactions.

In a follow-up interview after his presentation at the annual meeting of the College on Problems of Drug Dependence, Dr. Janda spoke about the history of research in this area, the potential workings of a vaccine, and the challenges of moving his own research forward.

Question: What’s the history of scientists’ efforts to develop a vaccine against drugs of abuse?

Answer: People looked at it back in the 1970s, but it didn’t really pan out. It was pretty dormant until we published research about a cocaine vaccine in 1995.

We worked on that for a while, then we looked at methamphetamine, Rohypnol, and opioids. There have been clinical trials for nicotine and cocaine, but they’ve failed.

Q: How are these vaccines expected to work?

A: The idea of the vaccines is that you don’t get high, so you won’t feel the effect of the drugs. They’ll never reach the pleasure centers that they’re supposed to.



Q: Is the idea that everyone would get a vaccine against, say, cocaine or heroin, like we routinely get vaccines against various diseases?

A: For an infectious disease like measles or mumps, you give vaccinations, and herd immunity develops. That’s not the case here. These work in a different manner, and they’re not going to be useful for people who don’t want to get off the drug. Instead, they’re going to be useful for people who want to obtain sobriety. If someone has a weak moment and tries to take the drug to get high, this would hopefully stop that from happening. It could also help overdoses in some cases, since you’re not getting that much drug into the central nervous system where it can cause cardiac arrest.



Q: How often would people be vaccinated?

A: These are vaccines that will be on board for a certain amount of time. We envision 3-4 shots over a 3-month period. You’d come back once a month for 3 months, and you’d be good for maybe 4-6 months.



Q: Where does your research stand now?

A: We’ve made a lot of advances with the opioids, and they’re good enough to put a vaccine in the clinic. I’m still trying to get some more money so we could hopefully move toward a clinical trial. Money is the issue. It’s always the issue. But we have to get up to the plate and take our swings – and find if we’ll strike out or get a hit.

ORLANDO – The pancreas is drawing wider interest among scientists: In one study, researchers report that already-shrunken organs keep atrophying in young people with recently diagnosed type 1 diabetes mellitus (T1DM) even as they go through adolescent growth. And another study finds that the pancreas is smaller in first-degree relatives of people with T1DM, especially relatives with pre-T1DM.

“Pancreas volume is a really exciting area of research because it may tell us something about diabetes that we just didn’t understand before,” said pediatric endocrinologist Michael J. Haller, MD, of the University of Florida, Gainesville, in an interview. Dr. Haller is coauthor of the study into pancreas volume in first-degree relatives. That study’s findings, along with the results of a Vanderbilt University/University of Texas study into pancreas volume in early T1DM, were presented at the annual meeting of the American Diabetes Association.

Scientists already know that the pancreas is 40% smaller in people who have lived with T1DM, Dr. Haller said, and “we now know that occurs long before the clinical diagnosis has been made.”

The pancreas volume mystery, he said, revolves around the fact that only 2%-3% of the organ is made up of beta cells, which make insulin. So why is there a 40% reduction in the pancreas overall? “It tells you the other parts of the pancreas are experiencing considerable damage because of the process,” he said.

In the Vanderbilt/UT study, led by Jack Virostko, PhD, at Vanderbilt University, Nashville, Tenn., researchers examined pancreas volume via MRI in patients with recent-onset T1DM (n = 51; mean age = 14 years, range 8-24 years).

The patients had a smaller median pancreas volume (29.6 mL) than similarly aged controls (49.6 mL; n = 51; P less than .001), and the gap held up after adjustment for factors like age, weight, and body mass index.

Pancreas volumes increased in controls over time as the subjects grew, but shrank even more in those with T1DM over the next year (P less than .001).

“Their research suggests there is a bit of ongoing reduction in volume,” Dr. Haller said. “That’s an area of debate in the literature, and additional larger datasets are being collected to prove or disprove that.”

For his study, Dr. Haller and University of Florida colleagues examined pancreas volume in 223 subjects (average age = 20 years; 45% males).

They found that relative pancreas volume was significantly lower vs. age-matched controls in subjects with recent-onset T1DM and in their first-degree relatives, regardless of their T1DM-related autoantibody status. First-degree relatives whose T1DM-related autoantibody status was positive – a sign of pre-T1DM – had smaller pancreas volumes than controls.

“This suggests there’s a stepwise reduction in volume that may help us understand risk better for certain patients,” Dr. Haller said.

In the future, he said, physicians may be able to use pancreas volume to distinguish between patients who otherwise appear to face the same T1DM risk. As a result, he said, they could adjust treatment accordingly.

“The datasets still need to become more robust, but it’s a really translatable kind of research,” he said, especially since it relies on MRIs “that you could use at any hospital.”

SOURCE: Campbell-Thompson ML et al. ADA 2018. Abstract 1816-P; Virostko J et al. ADA 2018. Abstract 233-OR.

ORLANDO – The pancreas is drawing wider interest among scientists: In one study, researchers report that already-shrunken organs keep atrophying in young people with recently diagnosed type 1 diabetes mellitus (T1DM) even as they go through adolescent growth. And another study finds that the pancreas is smaller in first-degree relatives of people with T1DM, especially relatives with pre-T1DM.

“Pancreas volume is a really exciting area of research because it may tell us something about diabetes that we just didn’t understand before,” said pediatric endocrinologist Michael J. Haller, MD, of the University of Florida, Gainesville, in an interview. Dr. Haller is coauthor of the study into pancreas volume in first-degree relatives. That study’s findings, along with the results of a Vanderbilt University/University of Texas study into pancreas volume in early T1DM, were presented at the annual meeting of the American Diabetes Association.

Scientists already know that the pancreas is 40% smaller in people who have lived with T1DM, Dr. Haller said, and “we now know that occurs long before the clinical diagnosis has been made.”

The pancreas volume mystery, he said, revolves around the fact that only 2%-3% of the organ is made up of beta cells, which make insulin. So why is there a 40% reduction in the pancreas overall? “It tells you the other parts of the pancreas are experiencing considerable damage because of the process,” he said.

In the Vanderbilt/UT study, led by Jack Virostko, PhD, at Vanderbilt University, Nashville, Tenn., researchers examined pancreas volume via MRI in patients with recent-onset T1DM (n = 51; mean age = 14 years, range 8-24 years).

The patients had a smaller median pancreas volume (29.6 mL) than similarly aged controls (49.6 mL; n = 51; P less than .001), and the gap held up after adjustment for factors like age, weight, and body mass index.

Pancreas volumes increased in controls over time as the subjects grew, but shrank even more in those with T1DM over the next year (P less than .001).

“Their research suggests there is a bit of ongoing reduction in volume,” Dr. Haller said. “That’s an area of debate in the literature, and additional larger datasets are being collected to prove or disprove that.”

For his study, Dr. Haller and University of Florida colleagues examined pancreas volume in 223 subjects (average age = 20 years; 45% males).

They found that relative pancreas volume was significantly lower vs. age-matched controls in subjects with recent-onset T1DM and in their first-degree relatives, regardless of their T1DM-related autoantibody status. First-degree relatives whose T1DM-related autoantibody status was positive – a sign of pre-T1DM – had smaller pancreas volumes than controls.

“This suggests there’s a stepwise reduction in volume that may help us understand risk better for certain patients,” Dr. Haller said.

In the future, he said, physicians may be able to use pancreas volume to distinguish between patients who otherwise appear to face the same T1DM risk. As a result, he said, they could adjust treatment accordingly.

“The datasets still need to become more robust, but it’s a really translatable kind of research,” he said, especially since it relies on MRIs “that you could use at any hospital.”

SOURCE: Campbell-Thompson ML et al. ADA 2018. Abstract 1816-P; Virostko J et al. ADA 2018. Abstract 233-OR.

ORLANDO – The pancreas is drawing wider interest among scientists: In one study, researchers report that already-shrunken organs keep atrophying in young people with recently diagnosed type 1 diabetes mellitus (T1DM) even as they go through adolescent growth. And another study finds that the pancreas is smaller in first-degree relatives of people with T1DM, especially relatives with pre-T1DM.

“Pancreas volume is a really exciting area of research because it may tell us something about diabetes that we just didn’t understand before,” said pediatric endocrinologist Michael J. Haller, MD, of the University of Florida, Gainesville, in an interview. Dr. Haller is coauthor of the study into pancreas volume in first-degree relatives. That study’s findings, along with the results of a Vanderbilt University/University of Texas study into pancreas volume in early T1DM, were presented at the annual meeting of the American Diabetes Association.

Scientists already know that the pancreas is 40% smaller in people who have lived with T1DM, Dr. Haller said, and “we now know that occurs long before the clinical diagnosis has been made.”

The pancreas volume mystery, he said, revolves around the fact that only 2%-3% of the organ is made up of beta cells, which make insulin. So why is there a 40% reduction in the pancreas overall? “It tells you the other parts of the pancreas are experiencing considerable damage because of the process,” he said.

In the Vanderbilt/UT study, led by Jack Virostko, PhD, at Vanderbilt University, Nashville, Tenn., researchers examined pancreas volume via MRI in patients with recent-onset T1DM (n = 51; mean age = 14 years, range 8-24 years).

The patients had a smaller median pancreas volume (29.6 mL) than similarly aged controls (49.6 mL; n = 51; P less than .001), and the gap held up after adjustment for factors like age, weight, and body mass index.

Pancreas volumes increased in controls over time as the subjects grew, but shrank even more in those with T1DM over the next year (P less than .001).

“Their research suggests there is a bit of ongoing reduction in volume,” Dr. Haller said. “That’s an area of debate in the literature, and additional larger datasets are being collected to prove or disprove that.”

For his study, Dr. Haller and University of Florida colleagues examined pancreas volume in 223 subjects (average age = 20 years; 45% males).

They found that relative pancreas volume was significantly lower vs. age-matched controls in subjects with recent-onset T1DM and in their first-degree relatives, regardless of their T1DM-related autoantibody status. First-degree relatives whose T1DM-related autoantibody status was positive – a sign of pre-T1DM – had smaller pancreas volumes than controls.

“This suggests there’s a stepwise reduction in volume that may help us understand risk better for certain patients,” Dr. Haller said.

In the future, he said, physicians may be able to use pancreas volume to distinguish between patients who otherwise appear to face the same T1DM risk. As a result, he said, they could adjust treatment accordingly.

“The datasets still need to become more robust, but it’s a really translatable kind of research,” he said, especially since it relies on MRIs “that you could use at any hospital.”

SOURCE: Campbell-Thompson ML et al. ADA 2018. Abstract 1816-P; Virostko J et al. ADA 2018. Abstract 233-OR.

ORLANDO – Higher risk translates to higher benefits. That’s the message of a new analysis of the ODYSSEY Outcomes trial in the PCSK9-inhibitor alirocumab that finds people with diabetes gained about twice the reduction in risk of major adverse cardiac events as their non-diabetic counterparts.

“Patients with diabetes and a recent heart attack are at double the risk of a cardiovascular event in the next 3 years as are nondiabetics, despite guideline-based care,” said study presenting author Kausik Ray, MD, ChB, of the School of Public Health of Imperial College London, in an interview. “These patients in our study had LDL of around 89 mg/dL despite high-intensity statins. Current guidelines recommend a goal of LDL of 55 mg/dL in this group. We brought LDL down to around 38 mg/ dL, and showed that by doing this, diabetics derived a greater reduction in the risk of major cardiovascular events. A greater absolute benefit was observed, and a smaller number needed to treat.”

Dr. Ray presented the study findings, a prespecified analysis of results of ODYSSEY Outcomes, at the annual scientific sessions of the American Diabetes Association.

The trial randomly assigned 18,924 patients with recent acute coronary syndrome and LDL cholesterol of at least 70 mg/dL, despite maximum statin therapy, to 75 mg of alirocumab every 2 weeks or placebo. Doses of alirocumab were increased blindly, to 150 mg, to reach LDL cholesterol levels of 25-50 mg/dL.

During a median 2.8 years of follow-up, the overall cumulative rate of major cardiac adverse events (coronary heart disease death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina) occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for an absolute risk reduction of 1.6% and a statistically significant and clinically meaningful 15% reduction in relative risk. The results were presented at the annual scientific sessions of the American College of Cardiology in March.

In the current analysis, in patients with diabetes, the cumulative rate of incidents was 14.1% (380 of 2,693) with alirocumab and 16.4% (452 of 2,751) with placebo, for an ARR of 2.3%.

The ARRs for the prediabetes and normoglycemia groups were both 1.2%.

Dr. Ray noted that there’s no sign that the drug works differently in patients with diabetes. “The drug works in the same way and as effectively in everyone: LDL came down by 64% at 16 weeks in everyone. But absolute risk depends upon absolute risk to start with. So, in higher-risk patients, the absolute benefit is greater.”

According to Dr. Ray, the number needed to treat is 43 over 30 months for people with diabetes and 73 over 30 months for people without diabetes.

Prediman K. Shah, MD, director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai Medical Center and professor of medicine at the University of California, Los Angeles, questioned the cost effectiveness of the medication in an interview.

“Even among the diabetics, the absolute risk reduction is about 2%, which is underwhelming considering the high cost,” he said. “If the cost were to drop to levels closer to cost of statins, such a small risk reduction may be worth the expense.”

Insurers have been skeptical of covering alirocumab because of its $14,000/year cost. However, Sanofi and Regeneron, which jointly market alirocumab, announced in March 2018 that they “will offer U.S. payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price for Praluent Injection (alirocumab) in alignment with a new value assessment for high-risk patients from the [United States].”

In response, Dr. Ray said “the benefits quoted are time-to-first-event, and these are modest. But if you look at recurrent events, which represent the natural course of disease, then the benefits and absolute benefits are greater. These are add-on therapies and will never be used in every single patient at current cost.”

Glen J. Pearson, PharmD, of the University of Alberta, Edmonton, said in an interview that, “while these absolute numbers do seem relatively small, it must be remembered that these patients are already receiving very effective therapies to reduce their risk of future cardiovascular outcomes.”

ODYSSEY Outcomes was funded by Sanofi and Regeneron. The presenter reports various disclosures including consulting and research support relationships with Sanofi and Regeneron. The other study authors report various disclosures. Dr. Pearson reports no relevant disclosures. Dr. Shah reports receiving grant support from Sanofi Regeneron.

SOURCE: Ray K et al. ADA 2018, Abstract 6-LB.

ORLANDO – Higher risk translates to higher benefits. That’s the message of a new analysis of the ODYSSEY Outcomes trial in the PCSK9-inhibitor alirocumab that finds people with diabetes gained about twice the reduction in risk of major adverse cardiac events as their non-diabetic counterparts.

“Patients with diabetes and a recent heart attack are at double the risk of a cardiovascular event in the next 3 years as are nondiabetics, despite guideline-based care,” said study presenting author Kausik Ray, MD, ChB, of the School of Public Health of Imperial College London, in an interview. “These patients in our study had LDL of around 89 mg/dL despite high-intensity statins. Current guidelines recommend a goal of LDL of 55 mg/dL in this group. We brought LDL down to around 38 mg/ dL, and showed that by doing this, diabetics derived a greater reduction in the risk of major cardiovascular events. A greater absolute benefit was observed, and a smaller number needed to treat.”

Dr. Ray presented the study findings, a prespecified analysis of results of ODYSSEY Outcomes, at the annual scientific sessions of the American Diabetes Association.

The trial randomly assigned 18,924 patients with recent acute coronary syndrome and LDL cholesterol of at least 70 mg/dL, despite maximum statin therapy, to 75 mg of alirocumab every 2 weeks or placebo. Doses of alirocumab were increased blindly, to 150 mg, to reach LDL cholesterol levels of 25-50 mg/dL.

During a median 2.8 years of follow-up, the overall cumulative rate of major cardiac adverse events (coronary heart disease death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina) occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for an absolute risk reduction of 1.6% and a statistically significant and clinically meaningful 15% reduction in relative risk. The results were presented at the annual scientific sessions of the American College of Cardiology in March.

In the current analysis, in patients with diabetes, the cumulative rate of incidents was 14.1% (380 of 2,693) with alirocumab and 16.4% (452 of 2,751) with placebo, for an ARR of 2.3%.

The ARRs for the prediabetes and normoglycemia groups were both 1.2%.

Dr. Ray noted that there’s no sign that the drug works differently in patients with diabetes. “The drug works in the same way and as effectively in everyone: LDL came down by 64% at 16 weeks in everyone. But absolute risk depends upon absolute risk to start with. So, in higher-risk patients, the absolute benefit is greater.”

According to Dr. Ray, the number needed to treat is 43 over 30 months for people with diabetes and 73 over 30 months for people without diabetes.

Prediman K. Shah, MD, director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai Medical Center and professor of medicine at the University of California, Los Angeles, questioned the cost effectiveness of the medication in an interview.

“Even among the diabetics, the absolute risk reduction is about 2%, which is underwhelming considering the high cost,” he said. “If the cost were to drop to levels closer to cost of statins, such a small risk reduction may be worth the expense.”

Insurers have been skeptical of covering alirocumab because of its $14,000/year cost. However, Sanofi and Regeneron, which jointly market alirocumab, announced in March 2018 that they “will offer U.S. payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price for Praluent Injection (alirocumab) in alignment with a new value assessment for high-risk patients from the [United States].”

In response, Dr. Ray said “the benefits quoted are time-to-first-event, and these are modest. But if you look at recurrent events, which represent the natural course of disease, then the benefits and absolute benefits are greater. These are add-on therapies and will never be used in every single patient at current cost.”

Glen J. Pearson, PharmD, of the University of Alberta, Edmonton, said in an interview that, “while these absolute numbers do seem relatively small, it must be remembered that these patients are already receiving very effective therapies to reduce their risk of future cardiovascular outcomes.”

ODYSSEY Outcomes was funded by Sanofi and Regeneron. The presenter reports various disclosures including consulting and research support relationships with Sanofi and Regeneron. The other study authors report various disclosures. Dr. Pearson reports no relevant disclosures. Dr. Shah reports receiving grant support from Sanofi Regeneron.

SOURCE: Ray K et al. ADA 2018, Abstract 6-LB.

ORLANDO – Higher risk translates to higher benefits. That’s the message of a new analysis of the ODYSSEY Outcomes trial in the PCSK9-inhibitor alirocumab that finds people with diabetes gained about twice the reduction in risk of major adverse cardiac events as their non-diabetic counterparts.

“Patients with diabetes and a recent heart attack are at double the risk of a cardiovascular event in the next 3 years as are nondiabetics, despite guideline-based care,” said study presenting author Kausik Ray, MD, ChB, of the School of Public Health of Imperial College London, in an interview. “These patients in our study had LDL of around 89 mg/dL despite high-intensity statins. Current guidelines recommend a goal of LDL of 55 mg/dL in this group. We brought LDL down to around 38 mg/ dL, and showed that by doing this, diabetics derived a greater reduction in the risk of major cardiovascular events. A greater absolute benefit was observed, and a smaller number needed to treat.”

Dr. Ray presented the study findings, a prespecified analysis of results of ODYSSEY Outcomes, at the annual scientific sessions of the American Diabetes Association.

The trial randomly assigned 18,924 patients with recent acute coronary syndrome and LDL cholesterol of at least 70 mg/dL, despite maximum statin therapy, to 75 mg of alirocumab every 2 weeks or placebo. Doses of alirocumab were increased blindly, to 150 mg, to reach LDL cholesterol levels of 25-50 mg/dL.

During a median 2.8 years of follow-up, the overall cumulative rate of major cardiac adverse events (coronary heart disease death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina) occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for an absolute risk reduction of 1.6% and a statistically significant and clinically meaningful 15% reduction in relative risk. The results were presented at the annual scientific sessions of the American College of Cardiology in March.

In the current analysis, in patients with diabetes, the cumulative rate of incidents was 14.1% (380 of 2,693) with alirocumab and 16.4% (452 of 2,751) with placebo, for an ARR of 2.3%.

The ARRs for the prediabetes and normoglycemia groups were both 1.2%.

Dr. Ray noted that there’s no sign that the drug works differently in patients with diabetes. “The drug works in the same way and as effectively in everyone: LDL came down by 64% at 16 weeks in everyone. But absolute risk depends upon absolute risk to start with. So, in higher-risk patients, the absolute benefit is greater.”

According to Dr. Ray, the number needed to treat is 43 over 30 months for people with diabetes and 73 over 30 months for people without diabetes.

Prediman K. Shah, MD, director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai Medical Center and professor of medicine at the University of California, Los Angeles, questioned the cost effectiveness of the medication in an interview.

“Even among the diabetics, the absolute risk reduction is about 2%, which is underwhelming considering the high cost,” he said. “If the cost were to drop to levels closer to cost of statins, such a small risk reduction may be worth the expense.”

Insurers have been skeptical of covering alirocumab because of its $14,000/year cost. However, Sanofi and Regeneron, which jointly market alirocumab, announced in March 2018 that they “will offer U.S. payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price for Praluent Injection (alirocumab) in alignment with a new value assessment for high-risk patients from the [United States].”

In response, Dr. Ray said “the benefits quoted are time-to-first-event, and these are modest. But if you look at recurrent events, which represent the natural course of disease, then the benefits and absolute benefits are greater. These are add-on therapies and will never be used in every single patient at current cost.”

Glen J. Pearson, PharmD, of the University of Alberta, Edmonton, said in an interview that, “while these absolute numbers do seem relatively small, it must be remembered that these patients are already receiving very effective therapies to reduce their risk of future cardiovascular outcomes.”

ODYSSEY Outcomes was funded by Sanofi and Regeneron. The presenter reports various disclosures including consulting and research support relationships with Sanofi and Regeneron. The other study authors report various disclosures. Dr. Pearson reports no relevant disclosures. Dr. Shah reports receiving grant support from Sanofi Regeneron.

SOURCE: Ray K et al. ADA 2018, Abstract 6-LB.

ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.

Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).

The current study includes data on to 419,425 children (51% boys) born at Kaiser Permanente Southern California hospitals from 1995-2012. The children were followed for a median of 6.9 years, through 2017.

A total of 621 children were exposed in utero to T1D , 9,453 to T2D, 11,922 to gestational diabetes diagnosed by 26 weeks, and 24,505 to gestational diabetes diagnosed after 26 weeks.

Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.

Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).

The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).

Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.

The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)

The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).

In addition, the study doesn’t track maternal glucose levels over time.

Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.

One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.

SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.

ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.

Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).

The current study includes data on to 419,425 children (51% boys) born at Kaiser Permanente Southern California hospitals from 1995-2012. The children were followed for a median of 6.9 years, through 2017.

A total of 621 children were exposed in utero to T1D , 9,453 to T2D, 11,922 to gestational diabetes diagnosed by 26 weeks, and 24,505 to gestational diabetes diagnosed after 26 weeks.

Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.

Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).

The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).

Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.

The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)

The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).

In addition, the study doesn’t track maternal glucose levels over time.

Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.

One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.

SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.

ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.

Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).

The current study includes data on to 419,425 children (51% boys) born at Kaiser Permanente Southern California hospitals from 1995-2012. The children were followed for a median of 6.9 years, through 2017.

A total of 621 children were exposed in utero to T1D , 9,453 to T2D, 11,922 to gestational diabetes diagnosed by 26 weeks, and 24,505 to gestational diabetes diagnosed after 26 weeks.

Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.

Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).

The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).

Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.

The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)

The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).

In addition, the study doesn’t track maternal glucose levels over time.

Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.

One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.

SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.