Randy Dotinga

SEATTLE – Multiple sclerosis (MS) presents quite differently in children than adults, a neurologist told colleagues, but many treatments are the same. The key is to remember the unique needs of pediatric MS patients, their specific challenges, and the difference that can be made through therapy.

Brian Hoyle/MDedge News

“We need to treat them when they’re young, perhaps, to prevent disability later on,” said Jennifer Graves, MD, PhD, director of neuroimmunology research at the University of California, San Diego, and director of the Rady Children’s Pediatric MS Clinic.

Fortunately, “they tend to respond to any DMT [disease-modifying therapy] you give them,” said Dr. Graves, who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike the adult version, pediatric MS is almost never progressive, she said, and the relapsing form affects 85%-99% of those with the condition.

And children with MS suffer from high relapse rates. “In some of the more recent studies, the annual relapse rates have been two to even five to six times higher than in adults,” she related.

For acute relapses, Dr. Graves recommends IV methylprednisolone as a first-line treatment. High-dose oral steroids can be appropriate in teenagers, and plasma exchange is a second-line option.

DMT does work in children. “They’re just so inflammatory, having so much activity, that they tend to respond to anything,” she noted.

With few exceptions, DMTs have been tested in children, she said. But the trials in children have tended to be small, and only fingolimod (Gilenya) is Food and Drug Administration–approved for pediatric patients (aged 10-18 years).

What’s the best DMT for kids? “There is evidence that the higher-potency drugs may work better in some patients,” Dr. Graves said. “I diagnosed a 4 year old with MS. With an annual relapse rate of 6, I had no hesitancy about jumping to the highest-potency agent I had available.”

She cautioned, however, that there may never be deep insight into the best choices because of it is not feasible to study all the available DMTs in children.

Dr. Graves offered these tips about treating children with MS:

• Be prepared to spend long periods educating children and their parents. “You think you spend a long time with your adult patients? Double it,” she said. “Most new patient appointments will be 90 minutes at least. Negotiate that time for the patients in your clinic who are very young.”
• Don’t separate kids from parents. “I discourage parents from asking their children to leave the room. Everyone should know what the choices are as much as possible and having the children on the same page can help with compliance,” Dr. Graves said.
• Consider unique safety considerations. “Children are less likely to be JC [John Cunningham] virus antibody-positive than adults, and we can feel more confident with agents that cause PML [progressive multifocal leukoencephalopathy],” she said. “But they’re more likely to convert on our watch.”
• Consider mentioning sexual function to teens. As adolescents, “they’re unsure of sexual function to begin with, and they often don’t know if they’re normal in terms of sexual function.” Don’t forget that contraceptives may be appropriate because some MS drugs are teratogenic. “Have a lengthy and realistic conversation about birth control,” Dr. Graves said, “and maybe ask the parents to leave the room.”

Dr. Graves disclosed receiving speaking honoraria from Novartis and Sanofi Genzyme, and grants from Biogen and Genentech.

SEATTLE – Multiple sclerosis (MS) presents quite differently in children than adults, a neurologist told colleagues, but many treatments are the same. The key is to remember the unique needs of pediatric MS patients, their specific challenges, and the difference that can be made through therapy.

Brian Hoyle/MDedge News

“We need to treat them when they’re young, perhaps, to prevent disability later on,” said Jennifer Graves, MD, PhD, director of neuroimmunology research at the University of California, San Diego, and director of the Rady Children’s Pediatric MS Clinic.

Fortunately, “they tend to respond to any DMT [disease-modifying therapy] you give them,” said Dr. Graves, who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike the adult version, pediatric MS is almost never progressive, she said, and the relapsing form affects 85%-99% of those with the condition.

And children with MS suffer from high relapse rates. “In some of the more recent studies, the annual relapse rates have been two to even five to six times higher than in adults,” she related.

For acute relapses, Dr. Graves recommends IV methylprednisolone as a first-line treatment. High-dose oral steroids can be appropriate in teenagers, and plasma exchange is a second-line option.

DMT does work in children. “They’re just so inflammatory, having so much activity, that they tend to respond to anything,” she noted.

With few exceptions, DMTs have been tested in children, she said. But the trials in children have tended to be small, and only fingolimod (Gilenya) is Food and Drug Administration–approved for pediatric patients (aged 10-18 years).

What’s the best DMT for kids? “There is evidence that the higher-potency drugs may work better in some patients,” Dr. Graves said. “I diagnosed a 4 year old with MS. With an annual relapse rate of 6, I had no hesitancy about jumping to the highest-potency agent I had available.”

She cautioned, however, that there may never be deep insight into the best choices because of it is not feasible to study all the available DMTs in children.

Dr. Graves offered these tips about treating children with MS:

• Be prepared to spend long periods educating children and their parents. “You think you spend a long time with your adult patients? Double it,” she said. “Most new patient appointments will be 90 minutes at least. Negotiate that time for the patients in your clinic who are very young.”
• Don’t separate kids from parents. “I discourage parents from asking their children to leave the room. Everyone should know what the choices are as much as possible and having the children on the same page can help with compliance,” Dr. Graves said.
• Consider unique safety considerations. “Children are less likely to be JC [John Cunningham] virus antibody-positive than adults, and we can feel more confident with agents that cause PML [progressive multifocal leukoencephalopathy],” she said. “But they’re more likely to convert on our watch.”
• Consider mentioning sexual function to teens. As adolescents, “they’re unsure of sexual function to begin with, and they often don’t know if they’re normal in terms of sexual function.” Don’t forget that contraceptives may be appropriate because some MS drugs are teratogenic. “Have a lengthy and realistic conversation about birth control,” Dr. Graves said, “and maybe ask the parents to leave the room.”

Dr. Graves disclosed receiving speaking honoraria from Novartis and Sanofi Genzyme, and grants from Biogen and Genentech.

SEATTLE – Multiple sclerosis (MS) presents quite differently in children than adults, a neurologist told colleagues, but many treatments are the same. The key is to remember the unique needs of pediatric MS patients, their specific challenges, and the difference that can be made through therapy.

Brian Hoyle/MDedge News

“We need to treat them when they’re young, perhaps, to prevent disability later on,” said Jennifer Graves, MD, PhD, director of neuroimmunology research at the University of California, San Diego, and director of the Rady Children’s Pediatric MS Clinic.

Fortunately, “they tend to respond to any DMT [disease-modifying therapy] you give them,” said Dr. Graves, who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike the adult version, pediatric MS is almost never progressive, she said, and the relapsing form affects 85%-99% of those with the condition.

And children with MS suffer from high relapse rates. “In some of the more recent studies, the annual relapse rates have been two to even five to six times higher than in adults,” she related.

For acute relapses, Dr. Graves recommends IV methylprednisolone as a first-line treatment. High-dose oral steroids can be appropriate in teenagers, and plasma exchange is a second-line option.

DMT does work in children. “They’re just so inflammatory, having so much activity, that they tend to respond to anything,” she noted.

With few exceptions, DMTs have been tested in children, she said. But the trials in children have tended to be small, and only fingolimod (Gilenya) is Food and Drug Administration–approved for pediatric patients (aged 10-18 years).

What’s the best DMT for kids? “There is evidence that the higher-potency drugs may work better in some patients,” Dr. Graves said. “I diagnosed a 4 year old with MS. With an annual relapse rate of 6, I had no hesitancy about jumping to the highest-potency agent I had available.”

She cautioned, however, that there may never be deep insight into the best choices because of it is not feasible to study all the available DMTs in children.

Dr. Graves offered these tips about treating children with MS:

• Be prepared to spend long periods educating children and their parents. “You think you spend a long time with your adult patients? Double it,” she said. “Most new patient appointments will be 90 minutes at least. Negotiate that time for the patients in your clinic who are very young.”
• Don’t separate kids from parents. “I discourage parents from asking their children to leave the room. Everyone should know what the choices are as much as possible and having the children on the same page can help with compliance,” Dr. Graves said.
• Consider unique safety considerations. “Children are less likely to be JC [John Cunningham] virus antibody-positive than adults, and we can feel more confident with agents that cause PML [progressive multifocal leukoencephalopathy],” she said. “But they’re more likely to convert on our watch.”
• Consider mentioning sexual function to teens. As adolescents, “they’re unsure of sexual function to begin with, and they often don’t know if they’re normal in terms of sexual function.” Don’t forget that contraceptives may be appropriate because some MS drugs are teratogenic. “Have a lengthy and realistic conversation about birth control,” Dr. Graves said, “and maybe ask the parents to leave the room.”

Dr. Graves disclosed receiving speaking honoraria from Novartis and Sanofi Genzyme, and grants from Biogen and Genentech.

SAN FRANCISCO – Significant and rapid weight loss, fueled by a low-calorie diet, seemed to boost long-term diabetes prevention in patients who were prediabetic, a new study finds. And to the surprise of researchers, the results were the same regardless of dietary and exercise interventions more than 3 years after the initial weight loss.

There’s a big limitation, though: About half of the participants who initially lost weight dropped out during the 3-year study, and data about them are not yet available. Still, only 4% of those who completed the study converted to diabetes, compared with expected rates of as much as 16%.

This is a “fantastic success,” co-lead investigator and physiologist, Ian Macdonald, PhD, of the University of Nottingham (England), said in a presentation of the PREVIEW study at the annual scientific sessions of the American Diabetes Association.

The randomized, controlled, multicenter trial recruited 2,223 participants with prediabetes in several European countries and Australia and New Zealand. The participants, of whom about two-thirds were women, were aged 25-70 years (average, 52 years) and had an average body mass index of 35 kg/m².

They were assigned to a 2-month, rapid weight-loss program in which they were limited to no more than 800 calories per day. “The participants were fully briefed on the risks to health associated with prediabetes and on the problems of diabetes itself, and they were highly motivated to take part in the study,” Dr. Macdonald said in an interview after the presentation.

A total of 1,857 participants achieved the required weight loss of at least 8% and were then assigned to one of four interventions: a high-protein, low-glycemic diet (either with moderate- or high-intensity physical activity) or a moderate-protein, moderate-glycemic diet (either with moderate- or high-intensity physical activity).

A total of 962 participants remained in the study for another 34 months until completion, with roughly the same number (235-244) in each of the four intervention groups.

The researchers expected that 16% of those in the moderate-diet group would convert to type 2 diabetes, as would 11% of those in the high-protein, low-glycemic group, Dr. Macdonald said in the presentation.

The researchers, who offered limited statistical detail about the study, did not disclose how many participants in each group actually developed diabetes by 36 months (January 2019). Dr. Macdonald said in the interview that those numbers would not be available until the study has been accepted for publication. He noted, however, that the numbers in the two groups were nearly identical, and the researchers disclosed that the overall number was just 4% (n = 62).

That number is “substantially less than would be predicted,” Dr. Macdonald noted in the presentation, adding that “there is no difference” between the interventions.

He said protein consumption in the high-protein diet was not sustained, probably because of lack of adherence. In contrast, the physical activity in the groups increased significantly at the beginning of the study, he said, and “it did not fall off too badly.”

According to Dr. Macdonald, the prevention of progression to diabetes “was almost certainly because of this large, initial weight loss, which was at least partially and impressively sustained. A high-protein, low-glycemic diet was not superior to a moderate-protein, moderate-glycemic diet in relation to prevention of type 2 diabetes.”

The study was funded by the European Union and various other sources, including national funds, in the participating countries. Dr. Macdonald reported advisory board service with Nestlé Research, European Juice Manufacturers, and Mars.

SAN FRANCISCO – Significant and rapid weight loss, fueled by a low-calorie diet, seemed to boost long-term diabetes prevention in patients who were prediabetic, a new study finds. And to the surprise of researchers, the results were the same regardless of dietary and exercise interventions more than 3 years after the initial weight loss.

There’s a big limitation, though: About half of the participants who initially lost weight dropped out during the 3-year study, and data about them are not yet available. Still, only 4% of those who completed the study converted to diabetes, compared with expected rates of as much as 16%.

This is a “fantastic success,” co-lead investigator and physiologist, Ian Macdonald, PhD, of the University of Nottingham (England), said in a presentation of the PREVIEW study at the annual scientific sessions of the American Diabetes Association.

The randomized, controlled, multicenter trial recruited 2,223 participants with prediabetes in several European countries and Australia and New Zealand. The participants, of whom about two-thirds were women, were aged 25-70 years (average, 52 years) and had an average body mass index of 35 kg/m².

They were assigned to a 2-month, rapid weight-loss program in which they were limited to no more than 800 calories per day. “The participants were fully briefed on the risks to health associated with prediabetes and on the problems of diabetes itself, and they were highly motivated to take part in the study,” Dr. Macdonald said in an interview after the presentation.

A total of 1,857 participants achieved the required weight loss of at least 8% and were then assigned to one of four interventions: a high-protein, low-glycemic diet (either with moderate- or high-intensity physical activity) or a moderate-protein, moderate-glycemic diet (either with moderate- or high-intensity physical activity).

A total of 962 participants remained in the study for another 34 months until completion, with roughly the same number (235-244) in each of the four intervention groups.

The researchers expected that 16% of those in the moderate-diet group would convert to type 2 diabetes, as would 11% of those in the high-protein, low-glycemic group, Dr. Macdonald said in the presentation.

The researchers, who offered limited statistical detail about the study, did not disclose how many participants in each group actually developed diabetes by 36 months (January 2019). Dr. Macdonald said in the interview that those numbers would not be available until the study has been accepted for publication. He noted, however, that the numbers in the two groups were nearly identical, and the researchers disclosed that the overall number was just 4% (n = 62).

That number is “substantially less than would be predicted,” Dr. Macdonald noted in the presentation, adding that “there is no difference” between the interventions.

He said protein consumption in the high-protein diet was not sustained, probably because of lack of adherence. In contrast, the physical activity in the groups increased significantly at the beginning of the study, he said, and “it did not fall off too badly.”

According to Dr. Macdonald, the prevention of progression to diabetes “was almost certainly because of this large, initial weight loss, which was at least partially and impressively sustained. A high-protein, low-glycemic diet was not superior to a moderate-protein, moderate-glycemic diet in relation to prevention of type 2 diabetes.”

The study was funded by the European Union and various other sources, including national funds, in the participating countries. Dr. Macdonald reported advisory board service with Nestlé Research, European Juice Manufacturers, and Mars.

SAN FRANCISCO – Significant and rapid weight loss, fueled by a low-calorie diet, seemed to boost long-term diabetes prevention in patients who were prediabetic, a new study finds. And to the surprise of researchers, the results were the same regardless of dietary and exercise interventions more than 3 years after the initial weight loss.

There’s a big limitation, though: About half of the participants who initially lost weight dropped out during the 3-year study, and data about them are not yet available. Still, only 4% of those who completed the study converted to diabetes, compared with expected rates of as much as 16%.

This is a “fantastic success,” co-lead investigator and physiologist, Ian Macdonald, PhD, of the University of Nottingham (England), said in a presentation of the PREVIEW study at the annual scientific sessions of the American Diabetes Association.

The randomized, controlled, multicenter trial recruited 2,223 participants with prediabetes in several European countries and Australia and New Zealand. The participants, of whom about two-thirds were women, were aged 25-70 years (average, 52 years) and had an average body mass index of 35 kg/m².

They were assigned to a 2-month, rapid weight-loss program in which they were limited to no more than 800 calories per day. “The participants were fully briefed on the risks to health associated with prediabetes and on the problems of diabetes itself, and they were highly motivated to take part in the study,” Dr. Macdonald said in an interview after the presentation.

A total of 1,857 participants achieved the required weight loss of at least 8% and were then assigned to one of four interventions: a high-protein, low-glycemic diet (either with moderate- or high-intensity physical activity) or a moderate-protein, moderate-glycemic diet (either with moderate- or high-intensity physical activity).

A total of 962 participants remained in the study for another 34 months until completion, with roughly the same number (235-244) in each of the four intervention groups.

The researchers expected that 16% of those in the moderate-diet group would convert to type 2 diabetes, as would 11% of those in the high-protein, low-glycemic group, Dr. Macdonald said in the presentation.

The researchers, who offered limited statistical detail about the study, did not disclose how many participants in each group actually developed diabetes by 36 months (January 2019). Dr. Macdonald said in the interview that those numbers would not be available until the study has been accepted for publication. He noted, however, that the numbers in the two groups were nearly identical, and the researchers disclosed that the overall number was just 4% (n = 62).

That number is “substantially less than would be predicted,” Dr. Macdonald noted in the presentation, adding that “there is no difference” between the interventions.

He said protein consumption in the high-protein diet was not sustained, probably because of lack of adherence. In contrast, the physical activity in the groups increased significantly at the beginning of the study, he said, and “it did not fall off too badly.”

According to Dr. Macdonald, the prevention of progression to diabetes “was almost certainly because of this large, initial weight loss, which was at least partially and impressively sustained. A high-protein, low-glycemic diet was not superior to a moderate-protein, moderate-glycemic diet in relation to prevention of type 2 diabetes.”

The study was funded by the European Union and various other sources, including national funds, in the participating countries. Dr. Macdonald reported advisory board service with Nestlé Research, European Juice Manufacturers, and Mars.

SAN FRANCISCO – A large, long-term study is linking yet another glucagon-like peptide–1 receptor agonist diabetes drug to positive cardiovascular outcomes: Patients with type 2 diabetes and heart disease risk factors who took dulaglutide for about 5 years during the REWIND study had a 12% lower risk of major adverse cardiovascular events, compared with those who took placebo.

These new findings on cardiac risk are unusual compared with other newer-generation diabetes drugs, because a high percentage of the participants did not have existing cardiovascular disease. In addition, the study population had a higher percentage of women, compared with previous studies.

“We feel very strongly that the participants were similar to the ... ambulatory patients with type 2 diabetes with cardiovascular risk who are routinely seen in clinical practice,” study coauthor Jeffrey L. Probstfield, MD, of the University of Washington, Seattle, saidin a presentation at the annual scientific sessions of the American Diabetes Association. The findings were published simultaneously in The Lancet (2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

Dulaglutide’s serious adverse-effect profile was similar to that of placebo, the study authors noted, and the drug also showed benefits in renal outcomes, as reported in a separate study (Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31150-3.

The Food and Drug Administration has mandated that six glucagon-like peptide–1 receptor agonists (GLP-1 RAs) – albiglutide (Tanzeum), exenatide (Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), semaglutide (Ozempic) and dulaglutide (Trulicity) – undergo testing of cardiovascular outcomes. Dulaglutide is the fourth, following albiglutide, liraglutide, and semaglutide, to show consistent, statistically significant reduction in major adverse cardiovascular events (MACE).

For the double-blind, randomized, placebo-controlled REWIND study, researchers recruited 9,901 participants who were at least 50 years old with type 2 diabetes, a hemoglobin A_1c (HbA_1c) level of 9.5% or less, and a body mass index of more than 23 kg/m². The participants came from 371 sites in 24 countries, including the United States and Canada. More than 80% were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and other blood pressure drugs were also common.

The average mean age was 66 years; 46% of the participants were women, three-quarters were white, and 31% had previous cardiovascular disease. Previous GLP-1 RA studies of this type had markedly lower percentages of women – the other studies comprised 30%-39% women – and included higher percentages of participants with previous cardiovascular disease (73%-100%).

Of the participants in the current study, 4,949 were assigned to receive dulaglutide and 4,952 to receive placebo. They were followed for a median 5.4 years. About 57% never stopped using the drug, and 11% of those in the drug group and 7.5% in the placebo group stopped use because of adverse effects.

In regard to diabetes outcomes, HbA_1c levels fell in the drug group by a mean –0.61% (95% confidence interval, –0.65 to –0.58; P less than .0001), compared with placebo. Their weight decreased by a mean –1.5 kg (95% CI, -1.7 to -1.3; P less than .0001) Systolic blood pressure and LDL cholesterol levels were slightly lower in the drug group, but heart rate was higher.

On the heart front, MACE fell by 12% in the drug group, compared with placebo (hazard ratio, 0.88; 95% CI, 0.79-0.99; P = .026). “The effect of the intervention begins [within] the first year and continued in a progressive, proportional fashion throughout the follow-up period,” said study lead author Hertzel C. Gerstein, MD, of McMaster University and Hamilton Health Sciences, Hamilton, Ont.

However, she called attention to the results that pinpointed higher levels of microvascular-related eye outcomes (HR, 1.24; 95% CI, 0.92-1.68) and fatal myocardial infarction (HR, 1.29; 95% CI, 0.72-2.30) in the dulaglutide group. Both of those outcomes were rare – 171 eye outcomes and 46 fatal myocardial infarctions overall. She also questioned whether the adherence rates would be as high in a real-world setting.

Eli Lilly funded the study. Three of the authors were employees of Eli Lilly, eight reported financial relationships with the company, five reported financial relationships with other firms, and the remaining authors reported no competing interests.

SOURCE: Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

SAN FRANCISCO – A large, long-term study is linking yet another glucagon-like peptide–1 receptor agonist diabetes drug to positive cardiovascular outcomes: Patients with type 2 diabetes and heart disease risk factors who took dulaglutide for about 5 years during the REWIND study had a 12% lower risk of major adverse cardiovascular events, compared with those who took placebo.

These new findings on cardiac risk are unusual compared with other newer-generation diabetes drugs, because a high percentage of the participants did not have existing cardiovascular disease. In addition, the study population had a higher percentage of women, compared with previous studies.

“We feel very strongly that the participants were similar to the ... ambulatory patients with type 2 diabetes with cardiovascular risk who are routinely seen in clinical practice,” study coauthor Jeffrey L. Probstfield, MD, of the University of Washington, Seattle, saidin a presentation at the annual scientific sessions of the American Diabetes Association. The findings were published simultaneously in The Lancet (2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

Dulaglutide’s serious adverse-effect profile was similar to that of placebo, the study authors noted, and the drug also showed benefits in renal outcomes, as reported in a separate study (Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31150-3.

The Food and Drug Administration has mandated that six glucagon-like peptide–1 receptor agonists (GLP-1 RAs) – albiglutide (Tanzeum), exenatide (Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), semaglutide (Ozempic) and dulaglutide (Trulicity) – undergo testing of cardiovascular outcomes. Dulaglutide is the fourth, following albiglutide, liraglutide, and semaglutide, to show consistent, statistically significant reduction in major adverse cardiovascular events (MACE).

For the double-blind, randomized, placebo-controlled REWIND study, researchers recruited 9,901 participants who were at least 50 years old with type 2 diabetes, a hemoglobin A_1c (HbA_1c) level of 9.5% or less, and a body mass index of more than 23 kg/m². The participants came from 371 sites in 24 countries, including the United States and Canada. More than 80% were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and other blood pressure drugs were also common.

The average mean age was 66 years; 46% of the participants were women, three-quarters were white, and 31% had previous cardiovascular disease. Previous GLP-1 RA studies of this type had markedly lower percentages of women – the other studies comprised 30%-39% women – and included higher percentages of participants with previous cardiovascular disease (73%-100%).

Of the participants in the current study, 4,949 were assigned to receive dulaglutide and 4,952 to receive placebo. They were followed for a median 5.4 years. About 57% never stopped using the drug, and 11% of those in the drug group and 7.5% in the placebo group stopped use because of adverse effects.

In regard to diabetes outcomes, HbA_1c levels fell in the drug group by a mean –0.61% (95% confidence interval, –0.65 to –0.58; P less than .0001), compared with placebo. Their weight decreased by a mean –1.5 kg (95% CI, -1.7 to -1.3; P less than .0001) Systolic blood pressure and LDL cholesterol levels were slightly lower in the drug group, but heart rate was higher.

On the heart front, MACE fell by 12% in the drug group, compared with placebo (hazard ratio, 0.88; 95% CI, 0.79-0.99; P = .026). “The effect of the intervention begins [within] the first year and continued in a progressive, proportional fashion throughout the follow-up period,” said study lead author Hertzel C. Gerstein, MD, of McMaster University and Hamilton Health Sciences, Hamilton, Ont.

However, she called attention to the results that pinpointed higher levels of microvascular-related eye outcomes (HR, 1.24; 95% CI, 0.92-1.68) and fatal myocardial infarction (HR, 1.29; 95% CI, 0.72-2.30) in the dulaglutide group. Both of those outcomes were rare – 171 eye outcomes and 46 fatal myocardial infarctions overall. She also questioned whether the adherence rates would be as high in a real-world setting.

Eli Lilly funded the study. Three of the authors were employees of Eli Lilly, eight reported financial relationships with the company, five reported financial relationships with other firms, and the remaining authors reported no competing interests.

SOURCE: Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

SAN FRANCISCO – A large, long-term study is linking yet another glucagon-like peptide–1 receptor agonist diabetes drug to positive cardiovascular outcomes: Patients with type 2 diabetes and heart disease risk factors who took dulaglutide for about 5 years during the REWIND study had a 12% lower risk of major adverse cardiovascular events, compared with those who took placebo.

These new findings on cardiac risk are unusual compared with other newer-generation diabetes drugs, because a high percentage of the participants did not have existing cardiovascular disease. In addition, the study population had a higher percentage of women, compared with previous studies.

“We feel very strongly that the participants were similar to the ... ambulatory patients with type 2 diabetes with cardiovascular risk who are routinely seen in clinical practice,” study coauthor Jeffrey L. Probstfield, MD, of the University of Washington, Seattle, saidin a presentation at the annual scientific sessions of the American Diabetes Association. The findings were published simultaneously in The Lancet (2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

Dulaglutide’s serious adverse-effect profile was similar to that of placebo, the study authors noted, and the drug also showed benefits in renal outcomes, as reported in a separate study (Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31150-3.

The Food and Drug Administration has mandated that six glucagon-like peptide–1 receptor agonists (GLP-1 RAs) – albiglutide (Tanzeum), exenatide (Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), semaglutide (Ozempic) and dulaglutide (Trulicity) – undergo testing of cardiovascular outcomes. Dulaglutide is the fourth, following albiglutide, liraglutide, and semaglutide, to show consistent, statistically significant reduction in major adverse cardiovascular events (MACE).

For the double-blind, randomized, placebo-controlled REWIND study, researchers recruited 9,901 participants who were at least 50 years old with type 2 diabetes, a hemoglobin A_1c (HbA_1c) level of 9.5% or less, and a body mass index of more than 23 kg/m². The participants came from 371 sites in 24 countries, including the United States and Canada. More than 80% were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and other blood pressure drugs were also common.

The average mean age was 66 years; 46% of the participants were women, three-quarters were white, and 31% had previous cardiovascular disease. Previous GLP-1 RA studies of this type had markedly lower percentages of women – the other studies comprised 30%-39% women – and included higher percentages of participants with previous cardiovascular disease (73%-100%).

Of the participants in the current study, 4,949 were assigned to receive dulaglutide and 4,952 to receive placebo. They were followed for a median 5.4 years. About 57% never stopped using the drug, and 11% of those in the drug group and 7.5% in the placebo group stopped use because of adverse effects.

In regard to diabetes outcomes, HbA_1c levels fell in the drug group by a mean –0.61% (95% confidence interval, –0.65 to –0.58; P less than .0001), compared with placebo. Their weight decreased by a mean –1.5 kg (95% CI, -1.7 to -1.3; P less than .0001) Systolic blood pressure and LDL cholesterol levels were slightly lower in the drug group, but heart rate was higher.

On the heart front, MACE fell by 12% in the drug group, compared with placebo (hazard ratio, 0.88; 95% CI, 0.79-0.99; P = .026). “The effect of the intervention begins [within] the first year and continued in a progressive, proportional fashion throughout the follow-up period,” said study lead author Hertzel C. Gerstein, MD, of McMaster University and Hamilton Health Sciences, Hamilton, Ont.

However, she called attention to the results that pinpointed higher levels of microvascular-related eye outcomes (HR, 1.24; 95% CI, 0.92-1.68) and fatal myocardial infarction (HR, 1.29; 95% CI, 0.72-2.30) in the dulaglutide group. Both of those outcomes were rare – 171 eye outcomes and 46 fatal myocardial infarctions overall. She also questioned whether the adherence rates would be as high in a real-world setting.

Eli Lilly funded the study. Three of the authors were employees of Eli Lilly, eight reported financial relationships with the company, five reported financial relationships with other firms, and the remaining authors reported no competing interests.

SOURCE: Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SAN FRANCISCO – Vitamin D supplementation did not significantly reduce the risk of progression from prediabetes to type 2 diabetes, according to the landmark D2d study.

A possible reason why the observed reduction was not statistically significant was that most participants already had acceptable levels of vitamin D. Still, the intervention “did not significantly reduce the risk [of diabetes],” Anastassios G. Pittas, MD, professor of medicine at Tufts Medical Center, Boston, said at the annual scientific sessions of the American Diabetes Association.

Vitamin D supplementation has been a hot topic on a range of medical fronts. As a 2016 report noted, “low vitamin D levels are also associated with hypertension, cancer, and cardiovascular disease. In addition, [diabetes] and chronic kidney disease (CKD) are also related to vitamin D levels. Vitamin D deficiency has been linked to onset and progression of [diabetes],” (World J Diabetes. 2016;7[5]:89-100).

However, as the report noted, “evidence regarding vitamin D levels and [diabetes] is contradictory, and well-controlled studies are needed.”

For the D2d study, which was coordinated out of the division of endocrinology at Tufts Medical Center, Dr. Pittas and associates recruited 2,423 patients who were considered to have prediabetes, with at least 2 of 3 ADA criteria: fasting plasma glucose level of 100-125 mg/dL; plasma glucose level 2 hours after a 75-g oral glucose load of 140-199 mg/dL; and hemoglobin A_1c (HbA_1c) level of 5.7%-6.4%.

All of the patients were at least 30 years old with the exception of American Indians, Alaska Natives, Native Hawaiians and other Pacific Islanders who were allowed to be aged 25-30 years. About 22% had low vitamin D levels.

The mean age of the patients was 60 years, mean body mass index was 32, 45% were women, and 33% were non-white. The trial was powered to show a reduction of 25% or more in diabetes risk with vitamin D.

The researchers randomly assigned 1,211 patients to take a once-daily capsule of vitamin D3 (cholecalciferol; 4,000 IU per day); 1,212 received a placebo.

Patients in the vitamin D group greatly boosted their mean serum 25-hydroxyvitamin D levels, from 27.7 ng/mL at baseline to 54.3 ng/mL at 24 months. In contrast, those in the placebo group saw little change, going from 28.2 ng/mL at baseline to 28.8 ng/mL at 24 months.

At a median follow-up of 2.5 years, with 99% of the study participants remaining in the trial, 616 patients developed diabetes (293 in the vitamin D group, 323 in the placebo group).

The risk was lower in the vitamin D group although the difference was not statistically significant. An analysis revealed no clear differences in any of the subgroups (race, age, body mass index, latitude-based geographic location, calcium supplement intake, and others).

However, a post hoc analysis of patients with vitamin D deficiency, which is defined by the National Academy of Medicine as having a 25-hydroxyvitamin D level of less than 12 ng/mL, showed that the vitamin D group had a 62% reduction in risk of diabetes, compared with placebo.

“Response to a nutritional intervention depends on nutritional status at baseline. Thus, if vitamin D has an effect on diabetes prevention, then people with lower levels of serum 25-hydroxyvitamin D would be expected to have a larger effect from supplementation than would those with higher baseline levels,” Dr. Pittas said.

SOURCE: Pittas AG et al. ADA 2019

This article was updated on 6/18/2019.

SAN FRANCISCO – Vitamin D supplementation did not significantly reduce the risk of progression from prediabetes to type 2 diabetes, according to the landmark D2d study.

A possible reason why the observed reduction was not statistically significant was that most participants already had acceptable levels of vitamin D. Still, the intervention “did not significantly reduce the risk [of diabetes],” Anastassios G. Pittas, MD, professor of medicine at Tufts Medical Center, Boston, said at the annual scientific sessions of the American Diabetes Association.

Vitamin D supplementation has been a hot topic on a range of medical fronts. As a 2016 report noted, “low vitamin D levels are also associated with hypertension, cancer, and cardiovascular disease. In addition, [diabetes] and chronic kidney disease (CKD) are also related to vitamin D levels. Vitamin D deficiency has been linked to onset and progression of [diabetes],” (World J Diabetes. 2016;7[5]:89-100).

However, as the report noted, “evidence regarding vitamin D levels and [diabetes] is contradictory, and well-controlled studies are needed.”

For the D2d study, which was coordinated out of the division of endocrinology at Tufts Medical Center, Dr. Pittas and associates recruited 2,423 patients who were considered to have prediabetes, with at least 2 of 3 ADA criteria: fasting plasma glucose level of 100-125 mg/dL; plasma glucose level 2 hours after a 75-g oral glucose load of 140-199 mg/dL; and hemoglobin A_1c (HbA_1c) level of 5.7%-6.4%.

All of the patients were at least 30 years old with the exception of American Indians, Alaska Natives, Native Hawaiians and other Pacific Islanders who were allowed to be aged 25-30 years. About 22% had low vitamin D levels.

The mean age of the patients was 60 years, mean body mass index was 32, 45% were women, and 33% were non-white. The trial was powered to show a reduction of 25% or more in diabetes risk with vitamin D.

The researchers randomly assigned 1,211 patients to take a once-daily capsule of vitamin D3 (cholecalciferol; 4,000 IU per day); 1,212 received a placebo.

Patients in the vitamin D group greatly boosted their mean serum 25-hydroxyvitamin D levels, from 27.7 ng/mL at baseline to 54.3 ng/mL at 24 months. In contrast, those in the placebo group saw little change, going from 28.2 ng/mL at baseline to 28.8 ng/mL at 24 months.

At a median follow-up of 2.5 years, with 99% of the study participants remaining in the trial, 616 patients developed diabetes (293 in the vitamin D group, 323 in the placebo group).

The risk was lower in the vitamin D group although the difference was not statistically significant. An analysis revealed no clear differences in any of the subgroups (race, age, body mass index, latitude-based geographic location, calcium supplement intake, and others).

However, a post hoc analysis of patients with vitamin D deficiency, which is defined by the National Academy of Medicine as having a 25-hydroxyvitamin D level of less than 12 ng/mL, showed that the vitamin D group had a 62% reduction in risk of diabetes, compared with placebo.

“Response to a nutritional intervention depends on nutritional status at baseline. Thus, if vitamin D has an effect on diabetes prevention, then people with lower levels of serum 25-hydroxyvitamin D would be expected to have a larger effect from supplementation than would those with higher baseline levels,” Dr. Pittas said.

SOURCE: Pittas AG et al. ADA 2019

This article was updated on 6/18/2019.

SAN FRANCISCO – Vitamin D supplementation did not significantly reduce the risk of progression from prediabetes to type 2 diabetes, according to the landmark D2d study.

A possible reason why the observed reduction was not statistically significant was that most participants already had acceptable levels of vitamin D. Still, the intervention “did not significantly reduce the risk [of diabetes],” Anastassios G. Pittas, MD, professor of medicine at Tufts Medical Center, Boston, said at the annual scientific sessions of the American Diabetes Association.

Vitamin D supplementation has been a hot topic on a range of medical fronts. As a 2016 report noted, “low vitamin D levels are also associated with hypertension, cancer, and cardiovascular disease. In addition, [diabetes] and chronic kidney disease (CKD) are also related to vitamin D levels. Vitamin D deficiency has been linked to onset and progression of [diabetes],” (World J Diabetes. 2016;7[5]:89-100).

However, as the report noted, “evidence regarding vitamin D levels and [diabetes] is contradictory, and well-controlled studies are needed.”

For the D2d study, which was coordinated out of the division of endocrinology at Tufts Medical Center, Dr. Pittas and associates recruited 2,423 patients who were considered to have prediabetes, with at least 2 of 3 ADA criteria: fasting plasma glucose level of 100-125 mg/dL; plasma glucose level 2 hours after a 75-g oral glucose load of 140-199 mg/dL; and hemoglobin A_1c (HbA_1c) level of 5.7%-6.4%.

All of the patients were at least 30 years old with the exception of American Indians, Alaska Natives, Native Hawaiians and other Pacific Islanders who were allowed to be aged 25-30 years. About 22% had low vitamin D levels.

The mean age of the patients was 60 years, mean body mass index was 32, 45% were women, and 33% were non-white. The trial was powered to show a reduction of 25% or more in diabetes risk with vitamin D.

The researchers randomly assigned 1,211 patients to take a once-daily capsule of vitamin D3 (cholecalciferol; 4,000 IU per day); 1,212 received a placebo.

Patients in the vitamin D group greatly boosted their mean serum 25-hydroxyvitamin D levels, from 27.7 ng/mL at baseline to 54.3 ng/mL at 24 months. In contrast, those in the placebo group saw little change, going from 28.2 ng/mL at baseline to 28.8 ng/mL at 24 months.

At a median follow-up of 2.5 years, with 99% of the study participants remaining in the trial, 616 patients developed diabetes (293 in the vitamin D group, 323 in the placebo group).

The risk was lower in the vitamin D group although the difference was not statistically significant. An analysis revealed no clear differences in any of the subgroups (race, age, body mass index, latitude-based geographic location, calcium supplement intake, and others).

However, a post hoc analysis of patients with vitamin D deficiency, which is defined by the National Academy of Medicine as having a 25-hydroxyvitamin D level of less than 12 ng/mL, showed that the vitamin D group had a 62% reduction in risk of diabetes, compared with placebo.

“Response to a nutritional intervention depends on nutritional status at baseline. Thus, if vitamin D has an effect on diabetes prevention, then people with lower levels of serum 25-hydroxyvitamin D would be expected to have a larger effect from supplementation than would those with higher baseline levels,” Dr. Pittas said.

SOURCE: Pittas AG et al. ADA 2019

This article was updated on 6/18/2019.

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – Patients with multiple sclerosis (MS) may be able to improve cognitive function through a brief course in mindfulness meditation, a new report suggests.

“The present study demonstrated significant improvement in processing speed, a core area of impairment in individuals with MS, following 4 weeks of mindfulness meditation,” said lead author Heena R. Manglani, a graduate student at the Ohio State University, Columbus. She spoke in an interview and in a presentation about the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 43%-70% of people with MS experience cognitive decline. This decline “has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions, and visual perceptual function,” reported the authors of a 2017 review (Rev Neurosci. 2017 Nov 27;28[8]:845-860).

For the new study, researchers tested two strategies for cognitive enhancement in patients with MS. All study participants were aged 31-59 years and relapse free within the previous 30 days; most had relapsing remitting MS, and most did not show signs of cognitive decline.

The researchers assigned 20 patients to a 4-week adaptive computerized cognitive training program and 20 patients to a 4-week mindfulness meditation training program. Another 21 patients were assigned to a control group.

The adaptive training program relied on computerized games designed to boost processing speed, attention, and working memory. The mindfulness training focused on components such as awareness of breathing and of bodily sensations.

Researchers found that “the magnitude of cognitive gain from pre- to post training was greatest in participants in the mindfulness group, who did better than participants in either of the other two groups,” Ms. Manglani said.

Compared with the adaptive cognitive training and the control group, she said, the mindfulness meditation group showed statistically significant improvement in processing speed per scores on the Symbol Digit Modalities Test, which rose from 52.2 before training to 58.4 post training.

The interventions did not appear to have any effect on Paced Auditory Serial Addition scores, which measure working memory.

The findings suggest that “less than 20 hours of mindfulness may be effective in significantly improving processing speed in MS,” Ms. Manglani said. “It is much shorter than a typically delivered program. We hypothesize that you are training attention with mindfulness training. Attention has a lot of overlap with processing speed.”

Ms. Manglani noted that this was a pilot study, and she acknowledged that fairly few participants – only five or six in each group – showed signs of cognitive decline. The study also did not explore whether cognitive improvements translated to real-life changes in cognition.

“This effect needs to be replicated in a larger sample,” Ms. Manglani said, “and future studies are needed to establish the lasting effects of such training and how improvements in cognitive function may generalize to greater engagement in vocational and leisure activities and higher quality of life.”

The study was funded by the National Multiple Sclerosis Society and the National Institutes of Health. The authors reported no relevant disclosures except for one coauthor who received honoraria from Sanofi Genzyme and funding from the National Multiple Sclerosis Society and the NIH.
 

SEATTLE – Patients with multiple sclerosis (MS) may be able to improve cognitive function through a brief course in mindfulness meditation, a new report suggests.

“The present study demonstrated significant improvement in processing speed, a core area of impairment in individuals with MS, following 4 weeks of mindfulness meditation,” said lead author Heena R. Manglani, a graduate student at the Ohio State University, Columbus. She spoke in an interview and in a presentation about the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 43%-70% of people with MS experience cognitive decline. This decline “has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions, and visual perceptual function,” reported the authors of a 2017 review (Rev Neurosci. 2017 Nov 27;28[8]:845-860).

For the new study, researchers tested two strategies for cognitive enhancement in patients with MS. All study participants were aged 31-59 years and relapse free within the previous 30 days; most had relapsing remitting MS, and most did not show signs of cognitive decline.

The researchers assigned 20 patients to a 4-week adaptive computerized cognitive training program and 20 patients to a 4-week mindfulness meditation training program. Another 21 patients were assigned to a control group.

The adaptive training program relied on computerized games designed to boost processing speed, attention, and working memory. The mindfulness training focused on components such as awareness of breathing and of bodily sensations.

Researchers found that “the magnitude of cognitive gain from pre- to post training was greatest in participants in the mindfulness group, who did better than participants in either of the other two groups,” Ms. Manglani said.

Compared with the adaptive cognitive training and the control group, she said, the mindfulness meditation group showed statistically significant improvement in processing speed per scores on the Symbol Digit Modalities Test, which rose from 52.2 before training to 58.4 post training.

The interventions did not appear to have any effect on Paced Auditory Serial Addition scores, which measure working memory.

The findings suggest that “less than 20 hours of mindfulness may be effective in significantly improving processing speed in MS,” Ms. Manglani said. “It is much shorter than a typically delivered program. We hypothesize that you are training attention with mindfulness training. Attention has a lot of overlap with processing speed.”

Ms. Manglani noted that this was a pilot study, and she acknowledged that fairly few participants – only five or six in each group – showed signs of cognitive decline. The study also did not explore whether cognitive improvements translated to real-life changes in cognition.

“This effect needs to be replicated in a larger sample,” Ms. Manglani said, “and future studies are needed to establish the lasting effects of such training and how improvements in cognitive function may generalize to greater engagement in vocational and leisure activities and higher quality of life.”

The study was funded by the National Multiple Sclerosis Society and the National Institutes of Health. The authors reported no relevant disclosures except for one coauthor who received honoraria from Sanofi Genzyme and funding from the National Multiple Sclerosis Society and the NIH.
 

SEATTLE – Patients with multiple sclerosis (MS) may be able to improve cognitive function through a brief course in mindfulness meditation, a new report suggests.

“The present study demonstrated significant improvement in processing speed, a core area of impairment in individuals with MS, following 4 weeks of mindfulness meditation,” said lead author Heena R. Manglani, a graduate student at the Ohio State University, Columbus. She spoke in an interview and in a presentation about the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 43%-70% of people with MS experience cognitive decline. This decline “has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions, and visual perceptual function,” reported the authors of a 2017 review (Rev Neurosci. 2017 Nov 27;28[8]:845-860).

For the new study, researchers tested two strategies for cognitive enhancement in patients with MS. All study participants were aged 31-59 years and relapse free within the previous 30 days; most had relapsing remitting MS, and most did not show signs of cognitive decline.

The researchers assigned 20 patients to a 4-week adaptive computerized cognitive training program and 20 patients to a 4-week mindfulness meditation training program. Another 21 patients were assigned to a control group.

The adaptive training program relied on computerized games designed to boost processing speed, attention, and working memory. The mindfulness training focused on components such as awareness of breathing and of bodily sensations.

Researchers found that “the magnitude of cognitive gain from pre- to post training was greatest in participants in the mindfulness group, who did better than participants in either of the other two groups,” Ms. Manglani said.

Compared with the adaptive cognitive training and the control group, she said, the mindfulness meditation group showed statistically significant improvement in processing speed per scores on the Symbol Digit Modalities Test, which rose from 52.2 before training to 58.4 post training.

The interventions did not appear to have any effect on Paced Auditory Serial Addition scores, which measure working memory.

The findings suggest that “less than 20 hours of mindfulness may be effective in significantly improving processing speed in MS,” Ms. Manglani said. “It is much shorter than a typically delivered program. We hypothesize that you are training attention with mindfulness training. Attention has a lot of overlap with processing speed.”

Ms. Manglani noted that this was a pilot study, and she acknowledged that fairly few participants – only five or six in each group – showed signs of cognitive decline. The study also did not explore whether cognitive improvements translated to real-life changes in cognition.

“This effect needs to be replicated in a larger sample,” Ms. Manglani said, “and future studies are needed to establish the lasting effects of such training and how improvements in cognitive function may generalize to greater engagement in vocational and leisure activities and higher quality of life.”

The study was funded by the National Multiple Sclerosis Society and the National Institutes of Health. The authors reported no relevant disclosures except for one coauthor who received honoraria from Sanofi Genzyme and funding from the National Multiple Sclerosis Society and the NIH.
 

SEATTLE – Failed in-vitro fertilization (IVF) treatment appears to boost the risk of relapse in women with multiple sclerosis (MS). Does successful IVF have the same effect? The preliminary results of a new study suggests it does, a finding that may influence how physicians track patients during pregnancy.

“We found that IVF can still cause a relapse even if it is successful,” study lead author Maria Claudia Manieri, a graduate student at Harvard Medical School’s Partners MS Center, said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

Multiple studies have linked infertility treatment in women with MS to relapses. In a 2013 review, researchers analyzed several papers, and “all of them reported an increase in annualized relapse rate after ART [assisted reproductive treatment]. Furthermore, in a recent study, clinical worsening was associated with an increase in MRI activity” (Clin Immunol. 2013 Nov;149(2):219-24).

For the new report, based on statistics from the New England Multiple Sclerosis Pregnancy Prospective Cohort Study, Ms. Manieri and colleagues collected data on 91 women (mean age = 33). Eleven were unsuccessful in conceiving, and 80 successfully conceived.

Three of the 91 women (3%) used intrauterine insemination as a fertility treatment. Another 9 (10%) relied on ART; all used IVF except for 1 who underwent intracytoplasmic sperm injection.

The new report is a preliminary analysis of early data, Ms. Manieri said. The study has recruited about one-sixth of its participants, she said, and will track women beyond pregnancy to explore long-term outcomes in their children.

Eleven women relapsed during pregnancy, including 9 who were using fertility treatment (P = .003). Of those 9, 7 women (78%) used ART.

No other factor other than fertility treatment predicted intrapartum relapses. The relapses during pregnancy started at 21 weeks (± 12 weeks) of gestational age and lasted for 4 weeks (± 2 weeks).

Of those who successfully conceived, 4 of 5 (80%) who used fertility treatment relapsed, compared with 7 of 64 (11%) who didn’t use fertility treatment. Of women who did not successfully conceive, 2 of 3 (67%) relapsed among those who used fertility treatment vs. 1 of 7 (14%) of those who didn’t.

It’s not clear how infertility treatment may be boosting MS relapse in women, but the 2013 review offered these possibilities: “temporary interruption of disease modified therapies, stressful events associated with infertility, and immunological changes induced by hormones such as increase in pro-inflammatory cytokines and anti-MOG antibodies, as well as an increase in immune cell migration across the blood-brain-barrier.”

MS tends to improve during pregnancy, and it’s common for neurologists to not see patients for extended periods, Ms. Manieri said. In light of the findings, she said, it may be wise for neurologists to continue follow-up appointments during pregnancy. “Avoid delaying care and keep monitoring the patient,” she advised.

The study was funded by Sanofi Genzyme and a gift from Michelle and Christopher Rondeau. The study authors report no relevant disclosures.

SEATTLE – Failed in-vitro fertilization (IVF) treatment appears to boost the risk of relapse in women with multiple sclerosis (MS). Does successful IVF have the same effect? The preliminary results of a new study suggests it does, a finding that may influence how physicians track patients during pregnancy.

“We found that IVF can still cause a relapse even if it is successful,” study lead author Maria Claudia Manieri, a graduate student at Harvard Medical School’s Partners MS Center, said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

Multiple studies have linked infertility treatment in women with MS to relapses. In a 2013 review, researchers analyzed several papers, and “all of them reported an increase in annualized relapse rate after ART [assisted reproductive treatment]. Furthermore, in a recent study, clinical worsening was associated with an increase in MRI activity” (Clin Immunol. 2013 Nov;149(2):219-24).

For the new report, based on statistics from the New England Multiple Sclerosis Pregnancy Prospective Cohort Study, Ms. Manieri and colleagues collected data on 91 women (mean age = 33). Eleven were unsuccessful in conceiving, and 80 successfully conceived.

Three of the 91 women (3%) used intrauterine insemination as a fertility treatment. Another 9 (10%) relied on ART; all used IVF except for 1 who underwent intracytoplasmic sperm injection.

The new report is a preliminary analysis of early data, Ms. Manieri said. The study has recruited about one-sixth of its participants, she said, and will track women beyond pregnancy to explore long-term outcomes in their children.

Eleven women relapsed during pregnancy, including 9 who were using fertility treatment (P = .003). Of those 9, 7 women (78%) used ART.

No other factor other than fertility treatment predicted intrapartum relapses. The relapses during pregnancy started at 21 weeks (± 12 weeks) of gestational age and lasted for 4 weeks (± 2 weeks).

Of those who successfully conceived, 4 of 5 (80%) who used fertility treatment relapsed, compared with 7 of 64 (11%) who didn’t use fertility treatment. Of women who did not successfully conceive, 2 of 3 (67%) relapsed among those who used fertility treatment vs. 1 of 7 (14%) of those who didn’t.

It’s not clear how infertility treatment may be boosting MS relapse in women, but the 2013 review offered these possibilities: “temporary interruption of disease modified therapies, stressful events associated with infertility, and immunological changes induced by hormones such as increase in pro-inflammatory cytokines and anti-MOG antibodies, as well as an increase in immune cell migration across the blood-brain-barrier.”

MS tends to improve during pregnancy, and it’s common for neurologists to not see patients for extended periods, Ms. Manieri said. In light of the findings, she said, it may be wise for neurologists to continue follow-up appointments during pregnancy. “Avoid delaying care and keep monitoring the patient,” she advised.

The study was funded by Sanofi Genzyme and a gift from Michelle and Christopher Rondeau. The study authors report no relevant disclosures.

SEATTLE – Failed in-vitro fertilization (IVF) treatment appears to boost the risk of relapse in women with multiple sclerosis (MS). Does successful IVF have the same effect? The preliminary results of a new study suggests it does, a finding that may influence how physicians track patients during pregnancy.

“We found that IVF can still cause a relapse even if it is successful,” study lead author Maria Claudia Manieri, a graduate student at Harvard Medical School’s Partners MS Center, said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

Multiple studies have linked infertility treatment in women with MS to relapses. In a 2013 review, researchers analyzed several papers, and “all of them reported an increase in annualized relapse rate after ART [assisted reproductive treatment]. Furthermore, in a recent study, clinical worsening was associated with an increase in MRI activity” (Clin Immunol. 2013 Nov;149(2):219-24).

For the new report, based on statistics from the New England Multiple Sclerosis Pregnancy Prospective Cohort Study, Ms. Manieri and colleagues collected data on 91 women (mean age = 33). Eleven were unsuccessful in conceiving, and 80 successfully conceived.

Three of the 91 women (3%) used intrauterine insemination as a fertility treatment. Another 9 (10%) relied on ART; all used IVF except for 1 who underwent intracytoplasmic sperm injection.

The new report is a preliminary analysis of early data, Ms. Manieri said. The study has recruited about one-sixth of its participants, she said, and will track women beyond pregnancy to explore long-term outcomes in their children.

Eleven women relapsed during pregnancy, including 9 who were using fertility treatment (P = .003). Of those 9, 7 women (78%) used ART.

No other factor other than fertility treatment predicted intrapartum relapses. The relapses during pregnancy started at 21 weeks (± 12 weeks) of gestational age and lasted for 4 weeks (± 2 weeks).

Of those who successfully conceived, 4 of 5 (80%) who used fertility treatment relapsed, compared with 7 of 64 (11%) who didn’t use fertility treatment. Of women who did not successfully conceive, 2 of 3 (67%) relapsed among those who used fertility treatment vs. 1 of 7 (14%) of those who didn’t.

It’s not clear how infertility treatment may be boosting MS relapse in women, but the 2013 review offered these possibilities: “temporary interruption of disease modified therapies, stressful events associated with infertility, and immunological changes induced by hormones such as increase in pro-inflammatory cytokines and anti-MOG antibodies, as well as an increase in immune cell migration across the blood-brain-barrier.”

MS tends to improve during pregnancy, and it’s common for neurologists to not see patients for extended periods, Ms. Manieri said. In light of the findings, she said, it may be wise for neurologists to continue follow-up appointments during pregnancy. “Avoid delaying care and keep monitoring the patient,” she advised.

The study was funded by Sanofi Genzyme and a gift from Michelle and Christopher Rondeau. The study authors report no relevant disclosures.

SEATTLE – Patients with multiple sclerosis (MS) who stopped taking their disease-modifying therapy (DMT) for more than 60 days had significantly higher rates of relapse, hospitalization, emergency department visits and outpatient visits, a new study finds. Their nonmedication health care costs were higher, too.

“This information will help to inform patients about downstream economic risks of being off therapy. This may also help to inform payers of the importance of making DMTs easily and quickly available to patients with MS to prevent greater costs of health care resource utilization down the road,” study lead author Jacqueline A. Nicholas, MD, MPH, a clinical neuroimmunologist at OhioHealth Multiple Sclerosis Center, said in an interview. She spoke prior to the presentation of the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Dr. Nicholas and her colleagues launched their study to better understand the economic and medical impacts of lapses in oral DMT.

The researchers used a claims database to track 8,779 patients with MS during 2011-2015 who had at least one claim for an oral DMT drug. The subjects were aged 18-63; 15% had a drug lapse of more than 60 days. After propensity matching, the subjects in both groups – 60-day lapse or not – had a mean age of 44 years.

An analysis found that “lapses in oral DMT use led to increased relapses, increased health care utilization, and higher costs incurred by individuals with MS,” Dr. Nicholas said.

Over an 18-month follow-up period, those with drug lapses of more than 60 days had 28% more relapses than did the other subjects (mean 1.2 vs. 0.8; P less than .0001).

Those with lapses greater than 60 days also had 40% more hospitalizations (0.2 vs. 0.1; P = .0003), 25% more emergency department visits (0.6 vs. 0.5; P = .0098), and 22% more outpatient visits (6.2 vs. 4.8; P less than .0001).

Nonmedication costs were 25% higher among patients with a greater than 60-day lapse ($16,012 vs. $12,092; P = .0006).

Moving forward, the researchers wrote, “more research is needed to better understand the reasons for lapses in therapy and the impact of lapse timing and lapse duration on outcomes in patients with MS receiving once- or twice-daily oral [disease-modifying drugs].”

The researchers noted that they don’t have information about the reasons why patients lapsed. They added that the information comes mainly from commercial insurers.

EMD Serono, a division of Merck KGaA, provided funding for the study. Dr. Nicholas disclosed grant support from EMD Serono, and two other study authors are employees of the company. Another two authors worked for a consulting firm that received funding from EMD Serono to conduct the study.

SEATTLE – Patients with multiple sclerosis (MS) who stopped taking their disease-modifying therapy (DMT) for more than 60 days had significantly higher rates of relapse, hospitalization, emergency department visits and outpatient visits, a new study finds. Their nonmedication health care costs were higher, too.

“This information will help to inform patients about downstream economic risks of being off therapy. This may also help to inform payers of the importance of making DMTs easily and quickly available to patients with MS to prevent greater costs of health care resource utilization down the road,” study lead author Jacqueline A. Nicholas, MD, MPH, a clinical neuroimmunologist at OhioHealth Multiple Sclerosis Center, said in an interview. She spoke prior to the presentation of the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Dr. Nicholas and her colleagues launched their study to better understand the economic and medical impacts of lapses in oral DMT.

The researchers used a claims database to track 8,779 patients with MS during 2011-2015 who had at least one claim for an oral DMT drug. The subjects were aged 18-63; 15% had a drug lapse of more than 60 days. After propensity matching, the subjects in both groups – 60-day lapse or not – had a mean age of 44 years.

An analysis found that “lapses in oral DMT use led to increased relapses, increased health care utilization, and higher costs incurred by individuals with MS,” Dr. Nicholas said.

Over an 18-month follow-up period, those with drug lapses of more than 60 days had 28% more relapses than did the other subjects (mean 1.2 vs. 0.8; P less than .0001).

Those with lapses greater than 60 days also had 40% more hospitalizations (0.2 vs. 0.1; P = .0003), 25% more emergency department visits (0.6 vs. 0.5; P = .0098), and 22% more outpatient visits (6.2 vs. 4.8; P less than .0001).

Nonmedication costs were 25% higher among patients with a greater than 60-day lapse ($16,012 vs. $12,092; P = .0006).

Moving forward, the researchers wrote, “more research is needed to better understand the reasons for lapses in therapy and the impact of lapse timing and lapse duration on outcomes in patients with MS receiving once- or twice-daily oral [disease-modifying drugs].”

The researchers noted that they don’t have information about the reasons why patients lapsed. They added that the information comes mainly from commercial insurers.

EMD Serono, a division of Merck KGaA, provided funding for the study. Dr. Nicholas disclosed grant support from EMD Serono, and two other study authors are employees of the company. Another two authors worked for a consulting firm that received funding from EMD Serono to conduct the study.

SEATTLE – Patients with multiple sclerosis (MS) who stopped taking their disease-modifying therapy (DMT) for more than 60 days had significantly higher rates of relapse, hospitalization, emergency department visits and outpatient visits, a new study finds. Their nonmedication health care costs were higher, too.

“This information will help to inform patients about downstream economic risks of being off therapy. This may also help to inform payers of the importance of making DMTs easily and quickly available to patients with MS to prevent greater costs of health care resource utilization down the road,” study lead author Jacqueline A. Nicholas, MD, MPH, a clinical neuroimmunologist at OhioHealth Multiple Sclerosis Center, said in an interview. She spoke prior to the presentation of the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Dr. Nicholas and her colleagues launched their study to better understand the economic and medical impacts of lapses in oral DMT.

The researchers used a claims database to track 8,779 patients with MS during 2011-2015 who had at least one claim for an oral DMT drug. The subjects were aged 18-63; 15% had a drug lapse of more than 60 days. After propensity matching, the subjects in both groups – 60-day lapse or not – had a mean age of 44 years.

An analysis found that “lapses in oral DMT use led to increased relapses, increased health care utilization, and higher costs incurred by individuals with MS,” Dr. Nicholas said.

Over an 18-month follow-up period, those with drug lapses of more than 60 days had 28% more relapses than did the other subjects (mean 1.2 vs. 0.8; P less than .0001).

Those with lapses greater than 60 days also had 40% more hospitalizations (0.2 vs. 0.1; P = .0003), 25% more emergency department visits (0.6 vs. 0.5; P = .0098), and 22% more outpatient visits (6.2 vs. 4.8; P less than .0001).

Nonmedication costs were 25% higher among patients with a greater than 60-day lapse ($16,012 vs. $12,092; P = .0006).

Moving forward, the researchers wrote, “more research is needed to better understand the reasons for lapses in therapy and the impact of lapse timing and lapse duration on outcomes in patients with MS receiving once- or twice-daily oral [disease-modifying drugs].”

The researchers noted that they don’t have information about the reasons why patients lapsed. They added that the information comes mainly from commercial insurers.

EMD Serono, a division of Merck KGaA, provided funding for the study. Dr. Nicholas disclosed grant support from EMD Serono, and two other study authors are employees of the company. Another two authors worked for a consulting firm that received funding from EMD Serono to conduct the study.

SEATTLE – When it comes to pain in patients with multiple sclerosis, two pain specialists offered this advice: Mind the gap. While pain is a major burden in MS, there’s a huge hole in research about the best treatments. That means medical professionals and patients can only rely on a few signposts for navigation.

But the medical literature does offer glimmers of insight into drug treatments, said Brett R. Stacey, MD, and Pamela Stitzlein Davies, MS, ARNP, FAANP, both of the University of Washington, Seattle, in presentations at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 44%-66% of patients with MS report pain. Their experiences are similar to those of other patients with pain, Dr. Stacey said, although there are some exceptions. Trigeminal neuralgia is not uncommon in patients with MS, and level of pain fluctuates markedly in MS patients.

“There are no [Food and Drug Administration]–approved drugs specifically for painful MS. There are few clinical trials and no first-line evidence about first-choice medicine,” Dr. Stacey said. As a result, he said, all drug options are off-label.

Based on his experience, the best first-line options for pain in MS appear to be the antidepressants duloxetine (Cymbalta), venlafaxine (Effexor), nortriptyline (Pamelor), desipramine (Norpramin), and amitriptyline, as well as the nerve pain drugs pregabalin (Lyrica) and gabapentin.

In regard to antidepressants, “most patients you give these medications to are not going to have a meaningful response. None of them are typically a home run” for pain in MS, Dr. Stacey said.

Duloxetine, he added, is expensive even as a generic, and nausea is possible within the first few days. It’s time to try something else if nausea sticks around for 5 days, he said.

However, there is a special benefit for duloxetine, he said: “For lower back pain, nothing is better. But that doesn’t mean the evidence is fantastic.”

Gabapentin, he said, “is relatively benign in terms of serious adverse effects,” although significant weight gain is possible. “It does not work for pain that doesn’t have a sensitization element. A lot of people throw gabapentin at things for which it will never work.”

Pregabalin, on the other hand, “can be potentially effective when other things like gabapentin and tricyclics have failed,” he said.

Second-line treatments include the lidocaine patch, tramadol, and the capsaicin 8% patch (Qutenza). And third-line treatments include botulinum toxin A and opioids.

Ms. Davies, who focused her presentation on opioids and pain in MS, agreed about the appropriate role of opioids. “They should be considered third-line, fourth-line, fifth-line, further down,” she said. “There’s a limited role for them in pain related to MS,” she said, specifically in regard to neuropathic pain.

There’s very little research into opioids in MS, she added, and their role is limited by side effects and the possibility of overdose.

Another option is low-dose naltrexone (Revia, Vivitrol), a drug used to treat alcohol and drug dependence. “Here in our clinic, patient after patient asks about naltrexone for everything,” Dr. Stacey said.

The treatment requires the use of a compounding pharmacy, he said, and evidence in MS consists of small studies with mixed results.

Dr. Stacey also addressed trigeminal neuralgia, which affects an estimated 5%-10% of patients with MS. For this condition, he said, “everything works less well in MS patients than non-MS patients.” Drug treatments include the seizure/nerve pain medication carbamazepine (Equetro, Carbatrol, Tegretol) and the seizure medication oxcarbazepine (Oxtellar, Trileptal), he said. Surgery is also an option.

SEATTLE – When it comes to pain in patients with multiple sclerosis, two pain specialists offered this advice: Mind the gap. While pain is a major burden in MS, there’s a huge hole in research about the best treatments. That means medical professionals and patients can only rely on a few signposts for navigation.

But the medical literature does offer glimmers of insight into drug treatments, said Brett R. Stacey, MD, and Pamela Stitzlein Davies, MS, ARNP, FAANP, both of the University of Washington, Seattle, in presentations at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 44%-66% of patients with MS report pain. Their experiences are similar to those of other patients with pain, Dr. Stacey said, although there are some exceptions. Trigeminal neuralgia is not uncommon in patients with MS, and level of pain fluctuates markedly in MS patients.

“There are no [Food and Drug Administration]–approved drugs specifically for painful MS. There are few clinical trials and no first-line evidence about first-choice medicine,” Dr. Stacey said. As a result, he said, all drug options are off-label.

Based on his experience, the best first-line options for pain in MS appear to be the antidepressants duloxetine (Cymbalta), venlafaxine (Effexor), nortriptyline (Pamelor), desipramine (Norpramin), and amitriptyline, as well as the nerve pain drugs pregabalin (Lyrica) and gabapentin.

In regard to antidepressants, “most patients you give these medications to are not going to have a meaningful response. None of them are typically a home run” for pain in MS, Dr. Stacey said.

Duloxetine, he added, is expensive even as a generic, and nausea is possible within the first few days. It’s time to try something else if nausea sticks around for 5 days, he said.

However, there is a special benefit for duloxetine, he said: “For lower back pain, nothing is better. But that doesn’t mean the evidence is fantastic.”

Gabapentin, he said, “is relatively benign in terms of serious adverse effects,” although significant weight gain is possible. “It does not work for pain that doesn’t have a sensitization element. A lot of people throw gabapentin at things for which it will never work.”

Pregabalin, on the other hand, “can be potentially effective when other things like gabapentin and tricyclics have failed,” he said.

Second-line treatments include the lidocaine patch, tramadol, and the capsaicin 8% patch (Qutenza). And third-line treatments include botulinum toxin A and opioids.

Ms. Davies, who focused her presentation on opioids and pain in MS, agreed about the appropriate role of opioids. “They should be considered third-line, fourth-line, fifth-line, further down,” she said. “There’s a limited role for them in pain related to MS,” she said, specifically in regard to neuropathic pain.

There’s very little research into opioids in MS, she added, and their role is limited by side effects and the possibility of overdose.

Another option is low-dose naltrexone (Revia, Vivitrol), a drug used to treat alcohol and drug dependence. “Here in our clinic, patient after patient asks about naltrexone for everything,” Dr. Stacey said.

The treatment requires the use of a compounding pharmacy, he said, and evidence in MS consists of small studies with mixed results.

Dr. Stacey also addressed trigeminal neuralgia, which affects an estimated 5%-10% of patients with MS. For this condition, he said, “everything works less well in MS patients than non-MS patients.” Drug treatments include the seizure/nerve pain medication carbamazepine (Equetro, Carbatrol, Tegretol) and the seizure medication oxcarbazepine (Oxtellar, Trileptal), he said. Surgery is also an option.

SEATTLE – When it comes to pain in patients with multiple sclerosis, two pain specialists offered this advice: Mind the gap. While pain is a major burden in MS, there’s a huge hole in research about the best treatments. That means medical professionals and patients can only rely on a few signposts for navigation.

But the medical literature does offer glimmers of insight into drug treatments, said Brett R. Stacey, MD, and Pamela Stitzlein Davies, MS, ARNP, FAANP, both of the University of Washington, Seattle, in presentations at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 44%-66% of patients with MS report pain. Their experiences are similar to those of other patients with pain, Dr. Stacey said, although there are some exceptions. Trigeminal neuralgia is not uncommon in patients with MS, and level of pain fluctuates markedly in MS patients.

“There are no [Food and Drug Administration]–approved drugs specifically for painful MS. There are few clinical trials and no first-line evidence about first-choice medicine,” Dr. Stacey said. As a result, he said, all drug options are off-label.

Based on his experience, the best first-line options for pain in MS appear to be the antidepressants duloxetine (Cymbalta), venlafaxine (Effexor), nortriptyline (Pamelor), desipramine (Norpramin), and amitriptyline, as well as the nerve pain drugs pregabalin (Lyrica) and gabapentin.

In regard to antidepressants, “most patients you give these medications to are not going to have a meaningful response. None of them are typically a home run” for pain in MS, Dr. Stacey said.

Duloxetine, he added, is expensive even as a generic, and nausea is possible within the first few days. It’s time to try something else if nausea sticks around for 5 days, he said.

However, there is a special benefit for duloxetine, he said: “For lower back pain, nothing is better. But that doesn’t mean the evidence is fantastic.”

Gabapentin, he said, “is relatively benign in terms of serious adverse effects,” although significant weight gain is possible. “It does not work for pain that doesn’t have a sensitization element. A lot of people throw gabapentin at things for which it will never work.”

Pregabalin, on the other hand, “can be potentially effective when other things like gabapentin and tricyclics have failed,” he said.

Second-line treatments include the lidocaine patch, tramadol, and the capsaicin 8% patch (Qutenza). And third-line treatments include botulinum toxin A and opioids.

Ms. Davies, who focused her presentation on opioids and pain in MS, agreed about the appropriate role of opioids. “They should be considered third-line, fourth-line, fifth-line, further down,” she said. “There’s a limited role for them in pain related to MS,” she said, specifically in regard to neuropathic pain.

There’s very little research into opioids in MS, she added, and their role is limited by side effects and the possibility of overdose.

Another option is low-dose naltrexone (Revia, Vivitrol), a drug used to treat alcohol and drug dependence. “Here in our clinic, patient after patient asks about naltrexone for everything,” Dr. Stacey said.

The treatment requires the use of a compounding pharmacy, he said, and evidence in MS consists of small studies with mixed results.

Dr. Stacey also addressed trigeminal neuralgia, which affects an estimated 5%-10% of patients with MS. For this condition, he said, “everything works less well in MS patients than non-MS patients.” Drug treatments include the seizure/nerve pain medication carbamazepine (Equetro, Carbatrol, Tegretol) and the seizure medication oxcarbazepine (Oxtellar, Trileptal), he said. Surgery is also an option.