SAN DIEGO – Weight loss from intermittently cutting calories has a positive effect on cognitive, immunologic, and other outcomes for patients with multiple sclerosis (MS), new research suggests.

Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.

Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

High adherence rate

Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.

The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.

Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.

In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.

Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.

Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.

Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.

“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
 

Maintain healthy weight

The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.

There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.

Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.

However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.

She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
 

Superb study

Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.

“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.

Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.

The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – Weight loss from intermittently cutting calories has a positive effect on cognitive, immunologic, and other outcomes for patients with multiple sclerosis (MS), new research suggests.

Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.

Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

High adherence rate

Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.

The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.

Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.

In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.

Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.

Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.

Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.

“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
 

Maintain healthy weight

The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.

There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.

Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.

However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.

She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
 

Superb study

Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.

“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.

Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.

The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – Weight loss from intermittently cutting calories has a positive effect on cognitive, immunologic, and other outcomes for patients with multiple sclerosis (MS), new research suggests.

Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.

Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

High adherence rate

Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.

The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.

Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.

In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.

Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.

Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.

Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.

“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
 

Maintain healthy weight

The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.

There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.

Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.

However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.

She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
 

Superb study

Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.

“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.

Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.

The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – The prevalence of psychiatric morbidity is significantly higher among patients with multiple sclerosis (MS) versus controls in each of the 5 years prior to the onset of the disease, new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.

These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.

With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Psychiatric morbidity during the prodromal phase of MS

Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.

Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.

The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.

The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.

The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.

The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.

Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.

It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.

In addition to psychiatric complaints, MS patients experience other symptoms, including  pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.

Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.

He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
 

When does MS start?

Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.

He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”

Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.

The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – The prevalence of psychiatric morbidity is significantly higher among patients with multiple sclerosis (MS) versus controls in each of the 5 years prior to the onset of the disease, new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.

These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.

With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Psychiatric morbidity during the prodromal phase of MS

Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.

Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.

The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.

The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.

The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.

The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.

Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.

It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.

In addition to psychiatric complaints, MS patients experience other symptoms, including  pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.

Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.

He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
 

When does MS start?

Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.

He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”

Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.

The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – The prevalence of psychiatric morbidity is significantly higher among patients with multiple sclerosis (MS) versus controls in each of the 5 years prior to the onset of the disease, new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.

These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.

With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Psychiatric morbidity during the prodromal phase of MS

Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.

Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.

The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.

The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.

The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.

The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.

Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.

It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.

In addition to psychiatric complaints, MS patients experience other symptoms, including  pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.

Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.

He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
 

When does MS start?

Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.

He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”

Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.

The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Migraine is the single most common neurologic condition worldwide and is particularly predominant among women during their reproductive years. There are many important questions that arise when women with migraine start pregnancy planning, most of which involve acute and preventive medication use and red flags for headache in pregnancy. As of yet, there have been no large-scale epidemiologic studies looking at pregnancy risks for people with migraine. Specifically, if migraine is a statistically significant vascular risk factor, does it incur additional risks in pregnancy, which is a prothrombotic state?

Purdue-Smithe and colleagues reviewed a large longitudinal study, the Nurses' Health Study II, a biennial questionnaire that took place from 1989 to 2009 and in which the questions changed yearly. Migraine was assessed on the basis of whether the participants had been given a diagnosis of migraine (or migraine with aura) by a medical professional; outcomes of pregnancy were also determined on the basis of participants providing a comprehensive reproductive history, including pregnancy outcome, gestation length, birth weight, and pregnancy complications.

A total of 2234 participants were included in this study; 1989 of them reported a history of physician-diagnosed migraine, with 1078 classified as having migraine with aura and 1156 classified as having migraine without aura. Adverse pregnancy outcomes more frequently affect multiple gestations; a sensitivity analysis was conducted to restrict the data here to singleton pregnancies. Individuals with migraine were more likely to report a history of infertility, obesity, and oral contraceptive use than were those without migraine. A history of migraine was associated with greater risks for preterm delivery, gestational hypertension, and preeclampsia; however, it was not associated with gestational diabetes or low birth weight. Theses outcomes were independent of age during pregnancy.

This wide-ranging study does allow us to better discuss potential risks for our patients with migraine. In addition to discussions about estrogen contraception use and stroke risk, it is worth taking a minute to discuss potential pregnancy risks that are more associated with migraine. This will allow our patients to be better aligned with their obstetricians, who can determine if other factors may further elevate these risks. Highlighting areas of risk can allow for better recognition of these potential negative outcomes much earlier.

There is a well-known association between calcitonin gene related peptide (CGRP) and migraine, but what is less understood is how CGRP affects specific features of migraine. CGRP is found in the gut and is therefore thought to have an association with migraine-related nausea, but other migraine associated symptoms, such as photophobia, are less well understood. Schiano di Cola and colleagues sought to determine the effectiveness of galcanezumab specifically in regard to ictal photophobia pain.

They enrolled 80 patients with either high-frequency episodic migraine or chronic migraine who were taking galcanezumab; 47 were included as expressing photophobia as a significant migraine-associated symptom at baseline. The patients were evaluated after 3 months and again after 6 months of treatment. They were asked to record headache days, migraine days, consumption of acute medication, and pain intensity. Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) scores were also followed up. Improvement with photophobia was determined as either no improvement, slight improvement, moderate improvement, or high improvement. After 3 months of treatment, 68% of patients reported a significant improvement in ictal photophobia, 11 patients reported moderate improvement, and six patients a slight improvement. Two patients reported improvement only after 6 months of treatment.

Post hoc analysis revealed photophobia improvement was not statistically significant in patients who are considered responders to galcanezumab compared with nonresponders. Photophobia improvement was most apparent in patients who were considered triptan responders. It was also more common in people with high-frequency episodic migraine rather than in those with chronic migraine. Migraine disability scores were noted to be higher in participants who did not notice photophobia improvement.

This study highlights the necessity to focus on factors beyond simply migraine frequency and severity. Many of the most disabling characteristics of migraine may not be related to pain directly. More research is currently being undertaken regarding the mechanisms that underlie photophobia in migraine. Ultimately, this will lead to more focused treatment for patients who may have other disabling symptoms associated with their headache disorder.

So much has already been written regarding the association between migraine and vascular risk factors. Migraine is considered a statistically significant risk factor for stroke specifically; migraine with aura has been noted to have a stronger association. Acarsoy and colleagues longitudinally examined the risk for stroke for any cause as it relates to migraine in both middle-aged and older populations.

This prospective population-based trial was embedded in a large Netherlands-based study among middle-aged and older community residents of Rotterdam. A total of 7266 participants were interviewed; 6925 participants had both migraine and stroke information available. Migraine was assessed with a questionnaire based on The International Classification of Headache Disorders (ICHD) criteria. Stroke status was assessed based on World Health Organization criteria and verified from medical records. Participants in this study were continuously monitored for incident stroke through an automatic linking of the study database to national health database files.

Other risk factors selected were body mass index (BMI), smoking history, education level, and physical activity, as well as any history of coronary artery disease, hypertension, or hypercholesterolemia. The average age of the study population was 65.7 years. Among participants with migraine, 20% had a history of migraine with aura. Among all stroke events, 84% were ischemic, and 11% were hemorrhagic. There was no significant difference in stroke-free survival probability between people with and without migraine. Although there was an association between migraine and stroke risk in middle and older ages, this was not statistically significant.

This study highlights, the appropriateness of educating migraine patients in regard to stroke risk. Specifically, patients should not be overly concerned regarding their migraine history. However, this study suggests that there does remain an association, but that this still remains somewhat unclear and less statistically significant in relation to age. When weighing vascular risk factors, more appropriate risks, such as elevated BMI, smoking history, hypertension, and the like should be highlighted, much more so than a history of migraine.

Migraine is the single most common neurologic condition worldwide and is particularly predominant among women during their reproductive years. There are many important questions that arise when women with migraine start pregnancy planning, most of which involve acute and preventive medication use and red flags for headache in pregnancy. As of yet, there have been no large-scale epidemiologic studies looking at pregnancy risks for people with migraine. Specifically, if migraine is a statistically significant vascular risk factor, does it incur additional risks in pregnancy, which is a prothrombotic state?

Purdue-Smithe and colleagues reviewed a large longitudinal study, the Nurses' Health Study II, a biennial questionnaire that took place from 1989 to 2009 and in which the questions changed yearly. Migraine was assessed on the basis of whether the participants had been given a diagnosis of migraine (or migraine with aura) by a medical professional; outcomes of pregnancy were also determined on the basis of participants providing a comprehensive reproductive history, including pregnancy outcome, gestation length, birth weight, and pregnancy complications.

A total of 2234 participants were included in this study; 1989 of them reported a history of physician-diagnosed migraine, with 1078 classified as having migraine with aura and 1156 classified as having migraine without aura. Adverse pregnancy outcomes more frequently affect multiple gestations; a sensitivity analysis was conducted to restrict the data here to singleton pregnancies. Individuals with migraine were more likely to report a history of infertility, obesity, and oral contraceptive use than were those without migraine. A history of migraine was associated with greater risks for preterm delivery, gestational hypertension, and preeclampsia; however, it was not associated with gestational diabetes or low birth weight. Theses outcomes were independent of age during pregnancy.

This wide-ranging study does allow us to better discuss potential risks for our patients with migraine. In addition to discussions about estrogen contraception use and stroke risk, it is worth taking a minute to discuss potential pregnancy risks that are more associated with migraine. This will allow our patients to be better aligned with their obstetricians, who can determine if other factors may further elevate these risks. Highlighting areas of risk can allow for better recognition of these potential negative outcomes much earlier.

There is a well-known association between calcitonin gene related peptide (CGRP) and migraine, but what is less understood is how CGRP affects specific features of migraine. CGRP is found in the gut and is therefore thought to have an association with migraine-related nausea, but other migraine associated symptoms, such as photophobia, are less well understood. Schiano di Cola and colleagues sought to determine the effectiveness of galcanezumab specifically in regard to ictal photophobia pain.

They enrolled 80 patients with either high-frequency episodic migraine or chronic migraine who were taking galcanezumab; 47 were included as expressing photophobia as a significant migraine-associated symptom at baseline. The patients were evaluated after 3 months and again after 6 months of treatment. They were asked to record headache days, migraine days, consumption of acute medication, and pain intensity. Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) scores were also followed up. Improvement with photophobia was determined as either no improvement, slight improvement, moderate improvement, or high improvement. After 3 months of treatment, 68% of patients reported a significant improvement in ictal photophobia, 11 patients reported moderate improvement, and six patients a slight improvement. Two patients reported improvement only after 6 months of treatment.

Post hoc analysis revealed photophobia improvement was not statistically significant in patients who are considered responders to galcanezumab compared with nonresponders. Photophobia improvement was most apparent in patients who were considered triptan responders. It was also more common in people with high-frequency episodic migraine rather than in those with chronic migraine. Migraine disability scores were noted to be higher in participants who did not notice photophobia improvement.

This study highlights the necessity to focus on factors beyond simply migraine frequency and severity. Many of the most disabling characteristics of migraine may not be related to pain directly. More research is currently being undertaken regarding the mechanisms that underlie photophobia in migraine. Ultimately, this will lead to more focused treatment for patients who may have other disabling symptoms associated with their headache disorder.

So much has already been written regarding the association between migraine and vascular risk factors. Migraine is considered a statistically significant risk factor for stroke specifically; migraine with aura has been noted to have a stronger association. Acarsoy and colleagues longitudinally examined the risk for stroke for any cause as it relates to migraine in both middle-aged and older populations.

This prospective population-based trial was embedded in a large Netherlands-based study among middle-aged and older community residents of Rotterdam. A total of 7266 participants were interviewed; 6925 participants had both migraine and stroke information available. Migraine was assessed with a questionnaire based on The International Classification of Headache Disorders (ICHD) criteria. Stroke status was assessed based on World Health Organization criteria and verified from medical records. Participants in this study were continuously monitored for incident stroke through an automatic linking of the study database to national health database files.

Other risk factors selected were body mass index (BMI), smoking history, education level, and physical activity, as well as any history of coronary artery disease, hypertension, or hypercholesterolemia. The average age of the study population was 65.7 years. Among participants with migraine, 20% had a history of migraine with aura. Among all stroke events, 84% were ischemic, and 11% were hemorrhagic. There was no significant difference in stroke-free survival probability between people with and without migraine. Although there was an association between migraine and stroke risk in middle and older ages, this was not statistically significant.

This study highlights, the appropriateness of educating migraine patients in regard to stroke risk. Specifically, patients should not be overly concerned regarding their migraine history. However, this study suggests that there does remain an association, but that this still remains somewhat unclear and less statistically significant in relation to age. When weighing vascular risk factors, more appropriate risks, such as elevated BMI, smoking history, hypertension, and the like should be highlighted, much more so than a history of migraine.

Migraine is the single most common neurologic condition worldwide and is particularly predominant among women during their reproductive years. There are many important questions that arise when women with migraine start pregnancy planning, most of which involve acute and preventive medication use and red flags for headache in pregnancy. As of yet, there have been no large-scale epidemiologic studies looking at pregnancy risks for people with migraine. Specifically, if migraine is a statistically significant vascular risk factor, does it incur additional risks in pregnancy, which is a prothrombotic state?

Purdue-Smithe and colleagues reviewed a large longitudinal study, the Nurses' Health Study II, a biennial questionnaire that took place from 1989 to 2009 and in which the questions changed yearly. Migraine was assessed on the basis of whether the participants had been given a diagnosis of migraine (or migraine with aura) by a medical professional; outcomes of pregnancy were also determined on the basis of participants providing a comprehensive reproductive history, including pregnancy outcome, gestation length, birth weight, and pregnancy complications.

A total of 2234 participants were included in this study; 1989 of them reported a history of physician-diagnosed migraine, with 1078 classified as having migraine with aura and 1156 classified as having migraine without aura. Adverse pregnancy outcomes more frequently affect multiple gestations; a sensitivity analysis was conducted to restrict the data here to singleton pregnancies. Individuals with migraine were more likely to report a history of infertility, obesity, and oral contraceptive use than were those without migraine. A history of migraine was associated with greater risks for preterm delivery, gestational hypertension, and preeclampsia; however, it was not associated with gestational diabetes or low birth weight. Theses outcomes were independent of age during pregnancy.

This wide-ranging study does allow us to better discuss potential risks for our patients with migraine. In addition to discussions about estrogen contraception use and stroke risk, it is worth taking a minute to discuss potential pregnancy risks that are more associated with migraine. This will allow our patients to be better aligned with their obstetricians, who can determine if other factors may further elevate these risks. Highlighting areas of risk can allow for better recognition of these potential negative outcomes much earlier.

There is a well-known association between calcitonin gene related peptide (CGRP) and migraine, but what is less understood is how CGRP affects specific features of migraine. CGRP is found in the gut and is therefore thought to have an association with migraine-related nausea, but other migraine associated symptoms, such as photophobia, are less well understood. Schiano di Cola and colleagues sought to determine the effectiveness of galcanezumab specifically in regard to ictal photophobia pain.

They enrolled 80 patients with either high-frequency episodic migraine or chronic migraine who were taking galcanezumab; 47 were included as expressing photophobia as a significant migraine-associated symptom at baseline. The patients were evaluated after 3 months and again after 6 months of treatment. They were asked to record headache days, migraine days, consumption of acute medication, and pain intensity. Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) scores were also followed up. Improvement with photophobia was determined as either no improvement, slight improvement, moderate improvement, or high improvement. After 3 months of treatment, 68% of patients reported a significant improvement in ictal photophobia, 11 patients reported moderate improvement, and six patients a slight improvement. Two patients reported improvement only after 6 months of treatment.

Post hoc analysis revealed photophobia improvement was not statistically significant in patients who are considered responders to galcanezumab compared with nonresponders. Photophobia improvement was most apparent in patients who were considered triptan responders. It was also more common in people with high-frequency episodic migraine rather than in those with chronic migraine. Migraine disability scores were noted to be higher in participants who did not notice photophobia improvement.

This study highlights the necessity to focus on factors beyond simply migraine frequency and severity. Many of the most disabling characteristics of migraine may not be related to pain directly. More research is currently being undertaken regarding the mechanisms that underlie photophobia in migraine. Ultimately, this will lead to more focused treatment for patients who may have other disabling symptoms associated with their headache disorder.

So much has already been written regarding the association between migraine and vascular risk factors. Migraine is considered a statistically significant risk factor for stroke specifically; migraine with aura has been noted to have a stronger association. Acarsoy and colleagues longitudinally examined the risk for stroke for any cause as it relates to migraine in both middle-aged and older populations.

This prospective population-based trial was embedded in a large Netherlands-based study among middle-aged and older community residents of Rotterdam. A total of 7266 participants were interviewed; 6925 participants had both migraine and stroke information available. Migraine was assessed with a questionnaire based on The International Classification of Headache Disorders (ICHD) criteria. Stroke status was assessed based on World Health Organization criteria and verified from medical records. Participants in this study were continuously monitored for incident stroke through an automatic linking of the study database to national health database files.

Other risk factors selected were body mass index (BMI), smoking history, education level, and physical activity, as well as any history of coronary artery disease, hypertension, or hypercholesterolemia. The average age of the study population was 65.7 years. Among participants with migraine, 20% had a history of migraine with aura. Among all stroke events, 84% were ischemic, and 11% were hemorrhagic. There was no significant difference in stroke-free survival probability between people with and without migraine. Although there was an association between migraine and stroke risk in middle and older ages, this was not statistically significant.

This study highlights, the appropriateness of educating migraine patients in regard to stroke risk. Specifically, patients should not be overly concerned regarding their migraine history. However, this study suggests that there does remain an association, but that this still remains somewhat unclear and less statistically significant in relation to age. When weighing vascular risk factors, more appropriate risks, such as elevated BMI, smoking history, hypertension, and the like should be highlighted, much more so than a history of migraine.

Two recent studies examined interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Albrecht and colleagues examined the prevalence of ILD in German patients with RA using a nationwide claims database from 2007 to 2020. Using diagnosis codes for seropositive and seronegative RA (along with disease-modifying antirheumatic drug prescriptions) as well as ILD, they found the prevalence of ILD to be relatively stable from 1.6% to 2.2%, and that incidence was stable (reported as 0.13%-0.21% per year, rather than per patient-year) over the course of the study. There is likely some misclassification with the primary reliance on diagnosis codes (of the included patients with RA only 44% were seropositive). They also excluded drug-induced ILD by diagnosis code, which may not be sufficient. Overall, the prevalence of ILD seems on the low end of what might be expected and may reflect a need for earlier evaluation to detect subclinical ILD.

Kronzer and colleagues performed a case-control study of 84 patients with incident RA-ILD compared with 233 patients with RA without ILD to evaluate the risk associated with specific anticitrullinated protein antibodies (ACPA) for the development of ILD. Compared with the clinical risk factors of smoking, disease activity, obesity, and glucocorticoid use, six "fine-specificity" ACPA were better able to predict ILD risk, with immunoglobulin (Ig) A2 to citrullinated histone 4 associated with an odds ratio (OR) of 0.08, and the others (IgA2 to citrullinated histone 2A, IgA2 to native cyclic histone 2A, IgA2 to native histone 2A, IgG to cyclic citrullinated filaggrin, and IgG to native cyclic filaggrin) were associated with OR of 2.5-5.5 for ILD. In combination with clinical characteristics, the authors developed a risk score with 93% specificity for RA-ILD that should be validated in other populations.

Suh and colleagues examined the association of RA with another less well-studied organ complication, end-stage renal disease (ESRD), using a large national insurance database. Once again, the accuracy of diagnosis is not fully clear using International Classification of Diseases, Tenth Edition (ICD-10), codes for classification. Overall, people with RA had a higher risk for ESRD than did people without RA, regardless of sex or smoking status. Because no immediate mechanistic connection between RA and ESRD is evident, it is possible that part of the increased risk is due to medications used in RA treatment, such as nonsteroidal anti-inflammatory drugs, but this hypothesis remains to be tested.

Finally, a footnote to the success of the treat-to-target strategy (T2T) in RA comes in a study by Ramiro and colleagues of the RA-BIODAM cohort, which, along with other studies, has shown the success of T2T in achieving and maintaining long-term clinical remission in RA. The effect of T2T on radiographic progression, however, is less clear. In this study, over 500 patients were followed for 2 years and a comparison between the T2T strategy and radiographic damage was made. The T2T strategy consisted of intensification of treatment if the Disease Activity Score (DAS-44) did not achieve a goal of < 1.6. This was compared with the radiographic damage (based on the change in Sharp-van der Heijde score[SvdH]) over a 6-month period. Overall, the change in progression was not different among patients who were treated with a stricter adherence to T2T (ie, a higher proportion of T2T) compared with those who were not, suggesting that a looser application of T2T will not necessarily cause a worsening of radiographic progression. It is possible, given the intervals of assessment in this study, that a longer follow-up after T2T is necessary to detect progression, or, given that patients were not randomly assigned, patients who were more strictly treated with T2T were already at higher risk for radiographic progression. However, this study is also helpful in understanding how insights from controlled trials may play out in usual clinical practice.

Two recent studies examined interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Albrecht and colleagues examined the prevalence of ILD in German patients with RA using a nationwide claims database from 2007 to 2020. Using diagnosis codes for seropositive and seronegative RA (along with disease-modifying antirheumatic drug prescriptions) as well as ILD, they found the prevalence of ILD to be relatively stable from 1.6% to 2.2%, and that incidence was stable (reported as 0.13%-0.21% per year, rather than per patient-year) over the course of the study. There is likely some misclassification with the primary reliance on diagnosis codes (of the included patients with RA only 44% were seropositive). They also excluded drug-induced ILD by diagnosis code, which may not be sufficient. Overall, the prevalence of ILD seems on the low end of what might be expected and may reflect a need for earlier evaluation to detect subclinical ILD.

Kronzer and colleagues performed a case-control study of 84 patients with incident RA-ILD compared with 233 patients with RA without ILD to evaluate the risk associated with specific anticitrullinated protein antibodies (ACPA) for the development of ILD. Compared with the clinical risk factors of smoking, disease activity, obesity, and glucocorticoid use, six "fine-specificity" ACPA were better able to predict ILD risk, with immunoglobulin (Ig) A2 to citrullinated histone 4 associated with an odds ratio (OR) of 0.08, and the others (IgA2 to citrullinated histone 2A, IgA2 to native cyclic histone 2A, IgA2 to native histone 2A, IgG to cyclic citrullinated filaggrin, and IgG to native cyclic filaggrin) were associated with OR of 2.5-5.5 for ILD. In combination with clinical characteristics, the authors developed a risk score with 93% specificity for RA-ILD that should be validated in other populations.

Suh and colleagues examined the association of RA with another less well-studied organ complication, end-stage renal disease (ESRD), using a large national insurance database. Once again, the accuracy of diagnosis is not fully clear using International Classification of Diseases, Tenth Edition (ICD-10), codes for classification. Overall, people with RA had a higher risk for ESRD than did people without RA, regardless of sex or smoking status. Because no immediate mechanistic connection between RA and ESRD is evident, it is possible that part of the increased risk is due to medications used in RA treatment, such as nonsteroidal anti-inflammatory drugs, but this hypothesis remains to be tested.

Finally, a footnote to the success of the treat-to-target strategy (T2T) in RA comes in a study by Ramiro and colleagues of the RA-BIODAM cohort, which, along with other studies, has shown the success of T2T in achieving and maintaining long-term clinical remission in RA. The effect of T2T on radiographic progression, however, is less clear. In this study, over 500 patients were followed for 2 years and a comparison between the T2T strategy and radiographic damage was made. The T2T strategy consisted of intensification of treatment if the Disease Activity Score (DAS-44) did not achieve a goal of < 1.6. This was compared with the radiographic damage (based on the change in Sharp-van der Heijde score[SvdH]) over a 6-month period. Overall, the change in progression was not different among patients who were treated with a stricter adherence to T2T (ie, a higher proportion of T2T) compared with those who were not, suggesting that a looser application of T2T will not necessarily cause a worsening of radiographic progression. It is possible, given the intervals of assessment in this study, that a longer follow-up after T2T is necessary to detect progression, or, given that patients were not randomly assigned, patients who were more strictly treated with T2T were already at higher risk for radiographic progression. However, this study is also helpful in understanding how insights from controlled trials may play out in usual clinical practice.

Two recent studies examined interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Albrecht and colleagues examined the prevalence of ILD in German patients with RA using a nationwide claims database from 2007 to 2020. Using diagnosis codes for seropositive and seronegative RA (along with disease-modifying antirheumatic drug prescriptions) as well as ILD, they found the prevalence of ILD to be relatively stable from 1.6% to 2.2%, and that incidence was stable (reported as 0.13%-0.21% per year, rather than per patient-year) over the course of the study. There is likely some misclassification with the primary reliance on diagnosis codes (of the included patients with RA only 44% were seropositive). They also excluded drug-induced ILD by diagnosis code, which may not be sufficient. Overall, the prevalence of ILD seems on the low end of what might be expected and may reflect a need for earlier evaluation to detect subclinical ILD.

Kronzer and colleagues performed a case-control study of 84 patients with incident RA-ILD compared with 233 patients with RA without ILD to evaluate the risk associated with specific anticitrullinated protein antibodies (ACPA) for the development of ILD. Compared with the clinical risk factors of smoking, disease activity, obesity, and glucocorticoid use, six "fine-specificity" ACPA were better able to predict ILD risk, with immunoglobulin (Ig) A2 to citrullinated histone 4 associated with an odds ratio (OR) of 0.08, and the others (IgA2 to citrullinated histone 2A, IgA2 to native cyclic histone 2A, IgA2 to native histone 2A, IgG to cyclic citrullinated filaggrin, and IgG to native cyclic filaggrin) were associated with OR of 2.5-5.5 for ILD. In combination with clinical characteristics, the authors developed a risk score with 93% specificity for RA-ILD that should be validated in other populations.

Suh and colleagues examined the association of RA with another less well-studied organ complication, end-stage renal disease (ESRD), using a large national insurance database. Once again, the accuracy of diagnosis is not fully clear using International Classification of Diseases, Tenth Edition (ICD-10), codes for classification. Overall, people with RA had a higher risk for ESRD than did people without RA, regardless of sex or smoking status. Because no immediate mechanistic connection between RA and ESRD is evident, it is possible that part of the increased risk is due to medications used in RA treatment, such as nonsteroidal anti-inflammatory drugs, but this hypothesis remains to be tested.

Finally, a footnote to the success of the treat-to-target strategy (T2T) in RA comes in a study by Ramiro and colleagues of the RA-BIODAM cohort, which, along with other studies, has shown the success of T2T in achieving and maintaining long-term clinical remission in RA. The effect of T2T on radiographic progression, however, is less clear. In this study, over 500 patients were followed for 2 years and a comparison between the T2T strategy and radiographic damage was made. The T2T strategy consisted of intensification of treatment if the Disease Activity Score (DAS-44) did not achieve a goal of < 1.6. This was compared with the radiographic damage (based on the change in Sharp-van der Heijde score[SvdH]) over a 6-month period. Overall, the change in progression was not different among patients who were treated with a stricter adherence to T2T (ie, a higher proportion of T2T) compared with those who were not, suggesting that a looser application of T2T will not necessarily cause a worsening of radiographic progression. It is possible, given the intervals of assessment in this study, that a longer follow-up after T2T is necessary to detect progression, or, given that patients were not randomly assigned, patients who were more strictly treated with T2T were already at higher risk for radiographic progression. However, this study is also helpful in understanding how insights from controlled trials may play out in usual clinical practice.

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

Specific sputum markers, including higher sputum eosinophils, macrophages, and lymphocyte counts, were associated with remission after interleukin-5 (IL-5)–targeted therapy for patients with severe eosinophilic asthma. The finding was based on data from 52 individuals.

Although IL-5 therapies have been shown to be effective for improving asthma, patients’ responses vary, write Catherine Moermans, PhD, of Liège University, Belgium, and colleagues.

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments, and reliable biomarkers for predicting treatment response are lacking, they say.

In an observational study published in the journal Chest, the researchers recruited 52 adults with severe asthma who began anti–IL-5 treatment at a single center. The primary outcome was remission of asthma.

Remission was defined as meeting all of the following criteria 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire scores lower than 1.5 and/or asthma test greater than 19; forced expiratory volume in 1 second (FEV₁) of at least 80% predicted; and/or improvement of FEV₁ equal to or larger than 10%, and a blood eosinophil count lower than 300 cells/mL.

Prior to treatment, the researchers measured eosinophil peroxidase (EPX), immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels in the sputum of each patient.

At follow-up, 11 patients met the criteria for remission. These patients had significantly higher sputum eosinophil counts, sputum macrophage counts, and lymphocyte counts at baseline, compared with those not in remission (P = .006, P = .02, and P = .04, respectively). Sputum neutrophil percentage levels were significantly lower in patients whose asthma was in remission, compared with those whose asthma was not in remission (P = .007).

At the protein level, remission patients also showed higher baseline levels of sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein, compared with patients who did not achieve remission (P = .046, P = .04, P = .002, P = .001, and P = .006, respectively).

Overall, EPX and IL-5 measures showed the best combination of sensitivity and specificity, as well as the best area under the curve, the researchers write.

Patients in remission were significantly more likely to be men (8 of 11 patients), a finding that reflected previous studies, the researchers write. The finding of eosinophilic inflammation associated with stronger response to anti–IL-5 therapy also reflected previous studies, but the current study showed that “with a comparable blood eosinophil level at baseline before biotherapy, the response can be highly variable.”

The study findings were limited by several factors, including the small sample size and the lack of a formal definition of remission. Other research needs include an analysis based on nonresponse or suboptimal response predictors, the researchers note.

The results suggest that sputum type 2 markers are potential predictors of remission after anti–IL-5 treatment in adults with severe eosinophilic asthma, although the results must be validated in a larger, multicenter cohort, they conclude.

The study was supported by GlaxoSmithKline and AstraZeneca. Several coauthors have relationships with these companies. Dr. Moermans has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Specific sputum markers, including higher sputum eosinophils, macrophages, and lymphocyte counts, were associated with remission after interleukin-5 (IL-5)–targeted therapy for patients with severe eosinophilic asthma. The finding was based on data from 52 individuals.

Although IL-5 therapies have been shown to be effective for improving asthma, patients’ responses vary, write Catherine Moermans, PhD, of Liège University, Belgium, and colleagues.

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments, and reliable biomarkers for predicting treatment response are lacking, they say.

In an observational study published in the journal Chest, the researchers recruited 52 adults with severe asthma who began anti–IL-5 treatment at a single center. The primary outcome was remission of asthma.

Remission was defined as meeting all of the following criteria 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire scores lower than 1.5 and/or asthma test greater than 19; forced expiratory volume in 1 second (FEV₁) of at least 80% predicted; and/or improvement of FEV₁ equal to or larger than 10%, and a blood eosinophil count lower than 300 cells/mL.

Prior to treatment, the researchers measured eosinophil peroxidase (EPX), immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels in the sputum of each patient.

At follow-up, 11 patients met the criteria for remission. These patients had significantly higher sputum eosinophil counts, sputum macrophage counts, and lymphocyte counts at baseline, compared with those not in remission (P = .006, P = .02, and P = .04, respectively). Sputum neutrophil percentage levels were significantly lower in patients whose asthma was in remission, compared with those whose asthma was not in remission (P = .007).

At the protein level, remission patients also showed higher baseline levels of sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein, compared with patients who did not achieve remission (P = .046, P = .04, P = .002, P = .001, and P = .006, respectively).

Overall, EPX and IL-5 measures showed the best combination of sensitivity and specificity, as well as the best area under the curve, the researchers write.

Patients in remission were significantly more likely to be men (8 of 11 patients), a finding that reflected previous studies, the researchers write. The finding of eosinophilic inflammation associated with stronger response to anti–IL-5 therapy also reflected previous studies, but the current study showed that “with a comparable blood eosinophil level at baseline before biotherapy, the response can be highly variable.”

The study findings were limited by several factors, including the small sample size and the lack of a formal definition of remission. Other research needs include an analysis based on nonresponse or suboptimal response predictors, the researchers note.

The results suggest that sputum type 2 markers are potential predictors of remission after anti–IL-5 treatment in adults with severe eosinophilic asthma, although the results must be validated in a larger, multicenter cohort, they conclude.

The study was supported by GlaxoSmithKline and AstraZeneca. Several coauthors have relationships with these companies. Dr. Moermans has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Specific sputum markers, including higher sputum eosinophils, macrophages, and lymphocyte counts, were associated with remission after interleukin-5 (IL-5)–targeted therapy for patients with severe eosinophilic asthma. The finding was based on data from 52 individuals.

Although IL-5 therapies have been shown to be effective for improving asthma, patients’ responses vary, write Catherine Moermans, PhD, of Liège University, Belgium, and colleagues.

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments, and reliable biomarkers for predicting treatment response are lacking, they say.

In an observational study published in the journal Chest, the researchers recruited 52 adults with severe asthma who began anti–IL-5 treatment at a single center. The primary outcome was remission of asthma.

Remission was defined as meeting all of the following criteria 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire scores lower than 1.5 and/or asthma test greater than 19; forced expiratory volume in 1 second (FEV₁) of at least 80% predicted; and/or improvement of FEV₁ equal to or larger than 10%, and a blood eosinophil count lower than 300 cells/mL.

Prior to treatment, the researchers measured eosinophil peroxidase (EPX), immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels in the sputum of each patient.

At follow-up, 11 patients met the criteria for remission. These patients had significantly higher sputum eosinophil counts, sputum macrophage counts, and lymphocyte counts at baseline, compared with those not in remission (P = .006, P = .02, and P = .04, respectively). Sputum neutrophil percentage levels were significantly lower in patients whose asthma was in remission, compared with those whose asthma was not in remission (P = .007).

At the protein level, remission patients also showed higher baseline levels of sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein, compared with patients who did not achieve remission (P = .046, P = .04, P = .002, P = .001, and P = .006, respectively).

Overall, EPX and IL-5 measures showed the best combination of sensitivity and specificity, as well as the best area under the curve, the researchers write.

Patients in remission were significantly more likely to be men (8 of 11 patients), a finding that reflected previous studies, the researchers write. The finding of eosinophilic inflammation associated with stronger response to anti–IL-5 therapy also reflected previous studies, but the current study showed that “with a comparable blood eosinophil level at baseline before biotherapy, the response can be highly variable.”

The study findings were limited by several factors, including the small sample size and the lack of a formal definition of remission. Other research needs include an analysis based on nonresponse or suboptimal response predictors, the researchers note.

The results suggest that sputum type 2 markers are potential predictors of remission after anti–IL-5 treatment in adults with severe eosinophilic asthma, although the results must be validated in a larger, multicenter cohort, they conclude.

The study was supported by GlaxoSmithKline and AstraZeneca. Several coauthors have relationships with these companies. Dr. Moermans has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

Both asthma and chronic obstructive pulmonary disease can be challenging to diagnose, and medication-driven episodes of sedation or hypoventilation are often overlooked as causes of acute exacerbations in these conditions, according to a letter published in The Lancet Respiratory Medicine.

“We are concerned about the number of patients we have seen with asthma or chronic obstructive pulmonary disease (COPD) exacerbations who have been prescribed sedative medications,” write Christos V. Chalitsios, PhD, of the University of Nottingham, England, and colleagues.

The authors note that exacerbations are the main complications of both asthma and COPD, and stress the importance of identifying causes and preventive strategies.

Sedatives such as opioids have been shown to depress respiratory drive, reduce muscle tone, and increase the risk of pneumonia, they write. The authors also propose that the risk of sedative-induced aspiration or hypoventilation would be associated with medications including pregabalin, gabapentin, and amitriptyline.

Other mechanisms may be involved in the association between sedatives and exacerbations in asthma and COPD. For example, sedative medications can suppress coughing, which may promote airway mucous compaction and possible infection, the authors write.

Most research involving prevention of asthma and COPD exacerbations has not addressed the potential impact of sedatives taken for reasons outside of obstructive lung disease, the authors say.

“Although the risk of sedation and hypoventilation events are known to be increased by opioids and antipsychotic drugs, there has not been a systematic assessment of commonly prescribed medications with potential respiratory side-effects, including gabapentin, amitriptyline, and pregabalin,” they write.

Polypharmacy is increasingly common and results in many patients with asthma or COPD presenting for treatment of acute exacerbations while on a combination of gabapentin, pregabalin, amitriptyline, and opioids, the authors note; “however, there is little data or disease-specific guidance on how best to manage this problem, which often starts with a prescription in primary care,” they write. Simply stopping sedatives is not an option for many patients given the addictive nature of these drugs and the unlikely resolution of the condition for which the drugs were prescribed, the authors say. However, “cautious dose reduction” of sedatives is possible once patients understand the reason, they add.

Clinicians may be able to suggest reduced doses and alternative treatments to patients with asthma and COPD while highlighting the risk of respiratory depression and polypharmacy – “potentially reducing the number of exacerbations of obstructive lung disease,” the authors conclude.

The study received no outside funding. The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Both asthma and chronic obstructive pulmonary disease can be challenging to diagnose, and medication-driven episodes of sedation or hypoventilation are often overlooked as causes of acute exacerbations in these conditions, according to a letter published in The Lancet Respiratory Medicine.

“We are concerned about the number of patients we have seen with asthma or chronic obstructive pulmonary disease (COPD) exacerbations who have been prescribed sedative medications,” write Christos V. Chalitsios, PhD, of the University of Nottingham, England, and colleagues.

The authors note that exacerbations are the main complications of both asthma and COPD, and stress the importance of identifying causes and preventive strategies.

Sedatives such as opioids have been shown to depress respiratory drive, reduce muscle tone, and increase the risk of pneumonia, they write. The authors also propose that the risk of sedative-induced aspiration or hypoventilation would be associated with medications including pregabalin, gabapentin, and amitriptyline.

Other mechanisms may be involved in the association between sedatives and exacerbations in asthma and COPD. For example, sedative medications can suppress coughing, which may promote airway mucous compaction and possible infection, the authors write.

Most research involving prevention of asthma and COPD exacerbations has not addressed the potential impact of sedatives taken for reasons outside of obstructive lung disease, the authors say.

“Although the risk of sedation and hypoventilation events are known to be increased by opioids and antipsychotic drugs, there has not been a systematic assessment of commonly prescribed medications with potential respiratory side-effects, including gabapentin, amitriptyline, and pregabalin,” they write.

Polypharmacy is increasingly common and results in many patients with asthma or COPD presenting for treatment of acute exacerbations while on a combination of gabapentin, pregabalin, amitriptyline, and opioids, the authors note; “however, there is little data or disease-specific guidance on how best to manage this problem, which often starts with a prescription in primary care,” they write. Simply stopping sedatives is not an option for many patients given the addictive nature of these drugs and the unlikely resolution of the condition for which the drugs were prescribed, the authors say. However, “cautious dose reduction” of sedatives is possible once patients understand the reason, they add.

Clinicians may be able to suggest reduced doses and alternative treatments to patients with asthma and COPD while highlighting the risk of respiratory depression and polypharmacy – “potentially reducing the number of exacerbations of obstructive lung disease,” the authors conclude.

The study received no outside funding. The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Both asthma and chronic obstructive pulmonary disease can be challenging to diagnose, and medication-driven episodes of sedation or hypoventilation are often overlooked as causes of acute exacerbations in these conditions, according to a letter published in The Lancet Respiratory Medicine.

“We are concerned about the number of patients we have seen with asthma or chronic obstructive pulmonary disease (COPD) exacerbations who have been prescribed sedative medications,” write Christos V. Chalitsios, PhD, of the University of Nottingham, England, and colleagues.

The authors note that exacerbations are the main complications of both asthma and COPD, and stress the importance of identifying causes and preventive strategies.

Sedatives such as opioids have been shown to depress respiratory drive, reduce muscle tone, and increase the risk of pneumonia, they write. The authors also propose that the risk of sedative-induced aspiration or hypoventilation would be associated with medications including pregabalin, gabapentin, and amitriptyline.

Other mechanisms may be involved in the association between sedatives and exacerbations in asthma and COPD. For example, sedative medications can suppress coughing, which may promote airway mucous compaction and possible infection, the authors write.

Most research involving prevention of asthma and COPD exacerbations has not addressed the potential impact of sedatives taken for reasons outside of obstructive lung disease, the authors say.

“Although the risk of sedation and hypoventilation events are known to be increased by opioids and antipsychotic drugs, there has not been a systematic assessment of commonly prescribed medications with potential respiratory side-effects, including gabapentin, amitriptyline, and pregabalin,” they write.

Polypharmacy is increasingly common and results in many patients with asthma or COPD presenting for treatment of acute exacerbations while on a combination of gabapentin, pregabalin, amitriptyline, and opioids, the authors note; “however, there is little data or disease-specific guidance on how best to manage this problem, which often starts with a prescription in primary care,” they write. Simply stopping sedatives is not an option for many patients given the addictive nature of these drugs and the unlikely resolution of the condition for which the drugs were prescribed, the authors say. However, “cautious dose reduction” of sedatives is possible once patients understand the reason, they add.

Clinicians may be able to suggest reduced doses and alternative treatments to patients with asthma and COPD while highlighting the risk of respiratory depression and polypharmacy – “potentially reducing the number of exacerbations of obstructive lung disease,” the authors conclude.

The study received no outside funding. The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

A version of this article first appeared on Medscape.com.

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

A version of this article first appeared on Medscape.com.

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

A version of this article first appeared on Medscape.com.