A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

Click to view the Digital Edition.

In this issue: 

Hepatocellular Carcinoma
Special care for veterans, changes in staging, and biomarkers for early diagnosis

Lung Cancer
Guideline updates and racial disparities in veterans

Multiple Myeloma
Improving survival in the VA

Colorectal Cancer
Barriers to follow-up colonoscopies after FIT testing 

B-Cell Lymphomas
Findings from the VA's National TeleOncology Program and recent therapy updates

Breast Cancer
A look at the VA's Risk Assessment Pipeline and incidence among veterans vs the general population

Genitourinary Cancers
Molecular testing in prostate cancer, improving survival for metastatic RCC, and links between bladder cancer and Agent Orange exposure

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

Click to view the Digital Edition.

In this issue: 

Hepatocellular Carcinoma
Special care for veterans, changes in staging, and biomarkers for early diagnosis

Lung Cancer
Guideline updates and racial disparities in veterans

Multiple Myeloma
Improving survival in the VA

Colorectal Cancer
Barriers to follow-up colonoscopies after FIT testing 

B-Cell Lymphomas
Findings from the VA's National TeleOncology Program and recent therapy updates

Breast Cancer
A look at the VA's Risk Assessment Pipeline and incidence among veterans vs the general population

Genitourinary Cancers
Molecular testing in prostate cancer, improving survival for metastatic RCC, and links between bladder cancer and Agent Orange exposure

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

Click to view the Digital Edition.

In this issue: 

Hepatocellular Carcinoma
Special care for veterans, changes in staging, and biomarkers for early diagnosis

Lung Cancer
Guideline updates and racial disparities in veterans

Multiple Myeloma
Improving survival in the VA

Colorectal Cancer
Barriers to follow-up colonoscopies after FIT testing 

B-Cell Lymphomas
Findings from the VA's National TeleOncology Program and recent therapy updates

Breast Cancer
A look at the VA's Risk Assessment Pipeline and incidence among veterans vs the general population

Genitourinary Cancers
Molecular testing in prostate cancer, improving survival for metastatic RCC, and links between bladder cancer and Agent Orange exposure

I had a premed college student with me, a young lady trying to figure out if medicine was for her, and what exactly a neurologist does.

The patient, a gentlemen in his mid-70s, had just left. He had some unusual symptoms. Not implausible, but the kind of case where the answers don’t come together easily. I’d ordered tests for the usual suspects and walked him up front.

When I got back she asked me “what do you think is wrong with him?”

Without thinking I said “I have no idea.” By this time I’d turned to some scheduling messages from my secretary, and didn’t register the student’s surprise for a moment.

I mean, I’m an attending physician. To her I’m the epitome of the career. I got accepted to (and survived) medical school. I made it through residency and fellowship and have almost 26 years of trench-earned experience behind me (hard to believe for me, too, sometimes). And yet I’d just said I didn’t know what was going on.

Reversing the roles and thinking back to the late 1980s, I probably would have felt the same way she did.

Of course “I have no idea” is a bit of unintentional hyperbole. I have some idea, just not a clear answer yet. I’d turned over the possible locations and causes, and so ordered tests to help narrow it down. As one of my attendings in residency used to say, “some days you need a rifle, some days a shotgun” to figure it out.

Being a doctor, even a good one (I hope I am, but not making any guarantees) doesn’t mean you know everything, or have the ability to figure it out immediately. Otherwise we wouldn’t need imaging, labs, and a host of other tests. Sherlock Holmes was a lot of things, but Watson was the doctor.

To those at the beginning of their careers, just like it was to us then, this is a revelation. Aren’t we supposed to know everything? We probably once believed we would, too, someday.

What we learn through training and years of experience isn’t so much the answers to everything as much as the road map on how to get there. What combination of tests and decisions will hopefully lead us to the correct point.

Most of us realize that intuitively at this point, but it can be hard to explain to others. We have patients ask “what do you think is going on?” and we often have no answer other than “not sure yet, but I’ll try to find out.”

We don’t realize how far we’ve come until we see ourselves in someone who’s starting the same journey. And that’s something you can’t teach.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I had a premed college student with me, a young lady trying to figure out if medicine was for her, and what exactly a neurologist does.

The patient, a gentlemen in his mid-70s, had just left. He had some unusual symptoms. Not implausible, but the kind of case where the answers don’t come together easily. I’d ordered tests for the usual suspects and walked him up front.

When I got back she asked me “what do you think is wrong with him?”

Without thinking I said “I have no idea.” By this time I’d turned to some scheduling messages from my secretary, and didn’t register the student’s surprise for a moment.

I mean, I’m an attending physician. To her I’m the epitome of the career. I got accepted to (and survived) medical school. I made it through residency and fellowship and have almost 26 years of trench-earned experience behind me (hard to believe for me, too, sometimes). And yet I’d just said I didn’t know what was going on.

Reversing the roles and thinking back to the late 1980s, I probably would have felt the same way she did.

Of course “I have no idea” is a bit of unintentional hyperbole. I have some idea, just not a clear answer yet. I’d turned over the possible locations and causes, and so ordered tests to help narrow it down. As one of my attendings in residency used to say, “some days you need a rifle, some days a shotgun” to figure it out.

Being a doctor, even a good one (I hope I am, but not making any guarantees) doesn’t mean you know everything, or have the ability to figure it out immediately. Otherwise we wouldn’t need imaging, labs, and a host of other tests. Sherlock Holmes was a lot of things, but Watson was the doctor.

To those at the beginning of their careers, just like it was to us then, this is a revelation. Aren’t we supposed to know everything? We probably once believed we would, too, someday.

What we learn through training and years of experience isn’t so much the answers to everything as much as the road map on how to get there. What combination of tests and decisions will hopefully lead us to the correct point.

Most of us realize that intuitively at this point, but it can be hard to explain to others. We have patients ask “what do you think is going on?” and we often have no answer other than “not sure yet, but I’ll try to find out.”

We don’t realize how far we’ve come until we see ourselves in someone who’s starting the same journey. And that’s something you can’t teach.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I had a premed college student with me, a young lady trying to figure out if medicine was for her, and what exactly a neurologist does.

The patient, a gentlemen in his mid-70s, had just left. He had some unusual symptoms. Not implausible, but the kind of case where the answers don’t come together easily. I’d ordered tests for the usual suspects and walked him up front.

When I got back she asked me “what do you think is wrong with him?”

Without thinking I said “I have no idea.” By this time I’d turned to some scheduling messages from my secretary, and didn’t register the student’s surprise for a moment.

I mean, I’m an attending physician. To her I’m the epitome of the career. I got accepted to (and survived) medical school. I made it through residency and fellowship and have almost 26 years of trench-earned experience behind me (hard to believe for me, too, sometimes). And yet I’d just said I didn’t know what was going on.

Reversing the roles and thinking back to the late 1980s, I probably would have felt the same way she did.

Of course “I have no idea” is a bit of unintentional hyperbole. I have some idea, just not a clear answer yet. I’d turned over the possible locations and causes, and so ordered tests to help narrow it down. As one of my attendings in residency used to say, “some days you need a rifle, some days a shotgun” to figure it out.

Being a doctor, even a good one (I hope I am, but not making any guarantees) doesn’t mean you know everything, or have the ability to figure it out immediately. Otherwise we wouldn’t need imaging, labs, and a host of other tests. Sherlock Holmes was a lot of things, but Watson was the doctor.

To those at the beginning of their careers, just like it was to us then, this is a revelation. Aren’t we supposed to know everything? We probably once believed we would, too, someday.

What we learn through training and years of experience isn’t so much the answers to everything as much as the road map on how to get there. What combination of tests and decisions will hopefully lead us to the correct point.

Most of us realize that intuitively at this point, but it can be hard to explain to others. We have patients ask “what do you think is going on?” and we often have no answer other than “not sure yet, but I’ll try to find out.”

We don’t realize how far we’ve come until we see ourselves in someone who’s starting the same journey. And that’s something you can’t teach.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A recently filed lawsuit against Johnson & Johnson can serve as an example to use when advocating for patients who have insurance through their employers that can potentially hurt them physically and financially. When your patient has an employer-funded health insurance plan where the employer directly pays for all medical costs — called an ERISA plan for the federal law that governs employee benefit plans, the Employee Retirement Income Security Act — there are certain accountability, fairness, and fiduciary responsibilities that the employers must meet. These so-called ERISA plans do not have to follow state utilization management legislation that addresses harmful changes in insurers’ formularies and other policies, so when the plans are not properly overseen and do not mandate the delivery of proper care at the lowest cost, both the patient and employer may be losing out.

The J&J lawsuit serves as a bellwether warning to self-insured employers to demand transparency from their third-party administrators so as not to (knowingly or unknowingly) breach their fiduciary duty to their health plans and employees. These duties include ensuring reasonable plan costs as well as acting in the best interest of their employees. There were multiple complaints in the lawsuit by a J&J employee, stating that she paid a much higher price for her multiple sclerosis drug through the plan than the price she eventually found at a lower cost pharmacy. The allegations state that J&J failed to show prudence in its selection of a pharmacy benefit manager (PBM). In addition, the company failed to negotiate better drug pricing terms, and the design of the drug plan steered patients to the PBM specialty pharmacy, resulting in higher prices for the employees. All of these led to higher drug costs and premiums for employees, which, according to the lawsuit, is a breach of J&J’s fiduciary duties.

Why Should Rheumatologists Care About This?

With all insurance plans, it feels as though we are dealing with obstacles every day that keep us from giving the excellent rheumatologic care that our patients deserve. Self-insured employers now account for over 50% of commercial health plans, and as rheumatologists caring for the employees of these companies, we can use those transparency, accountability, and fiduciary responsibilities of the employer to ensure that our patients are getting the proper care at the lowest cost.

Not only is the J&J lawsuit a warning to self-insured employers, but a reminder to rheumatologists to be on the lookout for drug pricing issues and formulary construction that leads to higher pricing for employees and the plan. For example, make note if your patient is forced to fail a much higher priced self-injectable biologic before using a much lower cost infusible medication. Or if the plan mandates the use of the much higher priced adalimumab biosimilars over the lower priced biosimilars or even the highest priced JAK inhibitor over the lowest priced one. Let’s not forget mandated white bagging, which is often much more expensive to the plan than the buy-and-bill model through a rheumatologist’s office.

Recently, we have been able to help rheumatology practices get exemptions from white-bagging mandates that large self-insured employers often have in their plan documents. We have been able to show that the cost of obtaining the medication through specialty pharmacy (SP) is much higher than through the buy-and-bill model. Mandating that the plan spend more money on SP drugs, as opposed to allowing the rheumatologist to buy and bill, could easily be interpreted as a breach of fiduciary duty on the part of the employer by mandating a higher cost model.
 

CSRO Payer Issue Response Team

I have written about the Coalition of State Rheumatology Organizations (CSRO)’s Payer Issue Response Team (PIRT) in the past. Rheumatologists around the country can send to PIRT any problems that they are having with payers. A recent PIRT submission involved a white-bagging mandate for an employee of a very large international Fortune 500 company. This particular example is important because of the response by the VP of Global Benefits for this company. Express Scripts is the administrator of pharmacy benefits for this company. The rheumatologist was told that he could not buy and bill for an infusible medicine but would have to obtain the drug through Express Scripts’ SP. He then asked Express Scripts for the SP medication’s cost to the health plan in order to compare the SP price versus what the buy-and-bill model would cost this company. Express Scripts would not respond to this simple transparency question; often, PBMs claim that this is proprietary information.

I was able to speak with the company’s VP of Global Benefits regarding this issue. First of all, he stated that his company was not mandating white bagging. I explained to him that the plan documents had white bagging as the only option for acquisition of provider-administered drugs. A rheumatologist would have to apply for an exemption to buy and bill, and in this case, it was denied. This is essentially a mandate.

I gave the VP of Global Benefits an example of another large Fortune 500 company (UPS) that spent over $30,000 per year more on an infusible medication when obtained through SP than what it cost them under a buy-and-bill model. I had hoped that this example would impress upon the VP the importance of transparency in pricing and claims to prevent his company from unknowingly costing the health plan more and its being construed as a breach of fiduciary duty. It was explained to me by the VP of Global Benefits that his company is part of the National Drug Purchasers Coalition and they trust Express Scripts to do the right thing for them. As they say, “You can lead a horse to water, but can’t make it drink.”
 

Liability of a Plan That Physically Harms an Employee?

A slightly different example of a self-insured employer, presumably unknowingly, allowing its third-party administrator to mishandle the care of an employee was recently brought to me by a rheumatologist in North Carolina. She takes care of an employee who has rheumatoid arthritis with severe interstitial lung disease (ILD). The employee’s pulmonary status was stabilized on several courses of Rituxan (reference product of rituximab). Recently, BlueCross BlueShield of North Carolina, the third-party administrator of this employer’s plan, mandated a switch to a biosimilar of rituximab for the treatment of the ILD. The rheumatologist appealed the nonmedical switch but gave the patient the biosimilar so as not to delay care. Her patient’s condition is now deteriorating with progression of the ILD, and she once again has asked for an exemption to use Rituxan, which had initially stabilized the patient. Her staff told her that the BCBSNC rep said that the patient would have to have a life-threatening infusion reaction (and present the bill for the ambulance) before they would approve a return to the reference product. An employer that knowingly or unknowingly allows a third-party administrator to act in such a way as to endanger the life of an employee could be considered to be breaching its fiduciary duty. (Disclaimer: I am not an attorney — merely a rheumatologist with common sense. Nor am I making any qualitative statement about biosimilars.)

We now have a lawsuit to which you can refer when advocating for our patients who are employed by large, self-insured employers. It is unfortunate that it is not the third-party administrators or PBMs that can be sued, as they are generally not the fiduciaries for the plan. It is the unsuspecting employers who “trust” their brokers/consultants and the third-party administrators to do the right thing. Please continue to send us your payer issues. And if your patient works for a self-insured employer, I will continue to remind the CEO, CFO, and chief compliance officer that an employer with an ERISA health plan can potentially face legal action if the health plan’s actions or decisions cause harm to an employee’s health — physically or in the wallet.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

A recently filed lawsuit against Johnson & Johnson can serve as an example to use when advocating for patients who have insurance through their employers that can potentially hurt them physically and financially. When your patient has an employer-funded health insurance plan where the employer directly pays for all medical costs — called an ERISA plan for the federal law that governs employee benefit plans, the Employee Retirement Income Security Act — there are certain accountability, fairness, and fiduciary responsibilities that the employers must meet. These so-called ERISA plans do not have to follow state utilization management legislation that addresses harmful changes in insurers’ formularies and other policies, so when the plans are not properly overseen and do not mandate the delivery of proper care at the lowest cost, both the patient and employer may be losing out.

The J&J lawsuit serves as a bellwether warning to self-insured employers to demand transparency from their third-party administrators so as not to (knowingly or unknowingly) breach their fiduciary duty to their health plans and employees. These duties include ensuring reasonable plan costs as well as acting in the best interest of their employees. There were multiple complaints in the lawsuit by a J&J employee, stating that she paid a much higher price for her multiple sclerosis drug through the plan than the price she eventually found at a lower cost pharmacy. The allegations state that J&J failed to show prudence in its selection of a pharmacy benefit manager (PBM). In addition, the company failed to negotiate better drug pricing terms, and the design of the drug plan steered patients to the PBM specialty pharmacy, resulting in higher prices for the employees. All of these led to higher drug costs and premiums for employees, which, according to the lawsuit, is a breach of J&J’s fiduciary duties.

Why Should Rheumatologists Care About This?

With all insurance plans, it feels as though we are dealing with obstacles every day that keep us from giving the excellent rheumatologic care that our patients deserve. Self-insured employers now account for over 50% of commercial health plans, and as rheumatologists caring for the employees of these companies, we can use those transparency, accountability, and fiduciary responsibilities of the employer to ensure that our patients are getting the proper care at the lowest cost.

Not only is the J&J lawsuit a warning to self-insured employers, but a reminder to rheumatologists to be on the lookout for drug pricing issues and formulary construction that leads to higher pricing for employees and the plan. For example, make note if your patient is forced to fail a much higher priced self-injectable biologic before using a much lower cost infusible medication. Or if the plan mandates the use of the much higher priced adalimumab biosimilars over the lower priced biosimilars or even the highest priced JAK inhibitor over the lowest priced one. Let’s not forget mandated white bagging, which is often much more expensive to the plan than the buy-and-bill model through a rheumatologist’s office.

Recently, we have been able to help rheumatology practices get exemptions from white-bagging mandates that large self-insured employers often have in their plan documents. We have been able to show that the cost of obtaining the medication through specialty pharmacy (SP) is much higher than through the buy-and-bill model. Mandating that the plan spend more money on SP drugs, as opposed to allowing the rheumatologist to buy and bill, could easily be interpreted as a breach of fiduciary duty on the part of the employer by mandating a higher cost model.
 

CSRO Payer Issue Response Team

I have written about the Coalition of State Rheumatology Organizations (CSRO)’s Payer Issue Response Team (PIRT) in the past. Rheumatologists around the country can send to PIRT any problems that they are having with payers. A recent PIRT submission involved a white-bagging mandate for an employee of a very large international Fortune 500 company. This particular example is important because of the response by the VP of Global Benefits for this company. Express Scripts is the administrator of pharmacy benefits for this company. The rheumatologist was told that he could not buy and bill for an infusible medicine but would have to obtain the drug through Express Scripts’ SP. He then asked Express Scripts for the SP medication’s cost to the health plan in order to compare the SP price versus what the buy-and-bill model would cost this company. Express Scripts would not respond to this simple transparency question; often, PBMs claim that this is proprietary information.

I was able to speak with the company’s VP of Global Benefits regarding this issue. First of all, he stated that his company was not mandating white bagging. I explained to him that the plan documents had white bagging as the only option for acquisition of provider-administered drugs. A rheumatologist would have to apply for an exemption to buy and bill, and in this case, it was denied. This is essentially a mandate.

I gave the VP of Global Benefits an example of another large Fortune 500 company (UPS) that spent over $30,000 per year more on an infusible medication when obtained through SP than what it cost them under a buy-and-bill model. I had hoped that this example would impress upon the VP the importance of transparency in pricing and claims to prevent his company from unknowingly costing the health plan more and its being construed as a breach of fiduciary duty. It was explained to me by the VP of Global Benefits that his company is part of the National Drug Purchasers Coalition and they trust Express Scripts to do the right thing for them. As they say, “You can lead a horse to water, but can’t make it drink.”
 

Liability of a Plan That Physically Harms an Employee?

A slightly different example of a self-insured employer, presumably unknowingly, allowing its third-party administrator to mishandle the care of an employee was recently brought to me by a rheumatologist in North Carolina. She takes care of an employee who has rheumatoid arthritis with severe interstitial lung disease (ILD). The employee’s pulmonary status was stabilized on several courses of Rituxan (reference product of rituximab). Recently, BlueCross BlueShield of North Carolina, the third-party administrator of this employer’s plan, mandated a switch to a biosimilar of rituximab for the treatment of the ILD. The rheumatologist appealed the nonmedical switch but gave the patient the biosimilar so as not to delay care. Her patient’s condition is now deteriorating with progression of the ILD, and she once again has asked for an exemption to use Rituxan, which had initially stabilized the patient. Her staff told her that the BCBSNC rep said that the patient would have to have a life-threatening infusion reaction (and present the bill for the ambulance) before they would approve a return to the reference product. An employer that knowingly or unknowingly allows a third-party administrator to act in such a way as to endanger the life of an employee could be considered to be breaching its fiduciary duty. (Disclaimer: I am not an attorney — merely a rheumatologist with common sense. Nor am I making any qualitative statement about biosimilars.)

We now have a lawsuit to which you can refer when advocating for our patients who are employed by large, self-insured employers. It is unfortunate that it is not the third-party administrators or PBMs that can be sued, as they are generally not the fiduciaries for the plan. It is the unsuspecting employers who “trust” their brokers/consultants and the third-party administrators to do the right thing. Please continue to send us your payer issues. And if your patient works for a self-insured employer, I will continue to remind the CEO, CFO, and chief compliance officer that an employer with an ERISA health plan can potentially face legal action if the health plan’s actions or decisions cause harm to an employee’s health — physically or in the wallet.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

A recently filed lawsuit against Johnson & Johnson can serve as an example to use when advocating for patients who have insurance through their employers that can potentially hurt them physically and financially. When your patient has an employer-funded health insurance plan where the employer directly pays for all medical costs — called an ERISA plan for the federal law that governs employee benefit plans, the Employee Retirement Income Security Act — there are certain accountability, fairness, and fiduciary responsibilities that the employers must meet. These so-called ERISA plans do not have to follow state utilization management legislation that addresses harmful changes in insurers’ formularies and other policies, so when the plans are not properly overseen and do not mandate the delivery of proper care at the lowest cost, both the patient and employer may be losing out.

The J&J lawsuit serves as a bellwether warning to self-insured employers to demand transparency from their third-party administrators so as not to (knowingly or unknowingly) breach their fiduciary duty to their health plans and employees. These duties include ensuring reasonable plan costs as well as acting in the best interest of their employees. There were multiple complaints in the lawsuit by a J&J employee, stating that she paid a much higher price for her multiple sclerosis drug through the plan than the price she eventually found at a lower cost pharmacy. The allegations state that J&J failed to show prudence in its selection of a pharmacy benefit manager (PBM). In addition, the company failed to negotiate better drug pricing terms, and the design of the drug plan steered patients to the PBM specialty pharmacy, resulting in higher prices for the employees. All of these led to higher drug costs and premiums for employees, which, according to the lawsuit, is a breach of J&J’s fiduciary duties.

Why Should Rheumatologists Care About This?

With all insurance plans, it feels as though we are dealing with obstacles every day that keep us from giving the excellent rheumatologic care that our patients deserve. Self-insured employers now account for over 50% of commercial health plans, and as rheumatologists caring for the employees of these companies, we can use those transparency, accountability, and fiduciary responsibilities of the employer to ensure that our patients are getting the proper care at the lowest cost.

Not only is the J&J lawsuit a warning to self-insured employers, but a reminder to rheumatologists to be on the lookout for drug pricing issues and formulary construction that leads to higher pricing for employees and the plan. For example, make note if your patient is forced to fail a much higher priced self-injectable biologic before using a much lower cost infusible medication. Or if the plan mandates the use of the much higher priced adalimumab biosimilars over the lower priced biosimilars or even the highest priced JAK inhibitor over the lowest priced one. Let’s not forget mandated white bagging, which is often much more expensive to the plan than the buy-and-bill model through a rheumatologist’s office.

Recently, we have been able to help rheumatology practices get exemptions from white-bagging mandates that large self-insured employers often have in their plan documents. We have been able to show that the cost of obtaining the medication through specialty pharmacy (SP) is much higher than through the buy-and-bill model. Mandating that the plan spend more money on SP drugs, as opposed to allowing the rheumatologist to buy and bill, could easily be interpreted as a breach of fiduciary duty on the part of the employer by mandating a higher cost model.
 

CSRO Payer Issue Response Team

I have written about the Coalition of State Rheumatology Organizations (CSRO)’s Payer Issue Response Team (PIRT) in the past. Rheumatologists around the country can send to PIRT any problems that they are having with payers. A recent PIRT submission involved a white-bagging mandate for an employee of a very large international Fortune 500 company. This particular example is important because of the response by the VP of Global Benefits for this company. Express Scripts is the administrator of pharmacy benefits for this company. The rheumatologist was told that he could not buy and bill for an infusible medicine but would have to obtain the drug through Express Scripts’ SP. He then asked Express Scripts for the SP medication’s cost to the health plan in order to compare the SP price versus what the buy-and-bill model would cost this company. Express Scripts would not respond to this simple transparency question; often, PBMs claim that this is proprietary information.

I was able to speak with the company’s VP of Global Benefits regarding this issue. First of all, he stated that his company was not mandating white bagging. I explained to him that the plan documents had white bagging as the only option for acquisition of provider-administered drugs. A rheumatologist would have to apply for an exemption to buy and bill, and in this case, it was denied. This is essentially a mandate.

I gave the VP of Global Benefits an example of another large Fortune 500 company (UPS) that spent over $30,000 per year more on an infusible medication when obtained through SP than what it cost them under a buy-and-bill model. I had hoped that this example would impress upon the VP the importance of transparency in pricing and claims to prevent his company from unknowingly costing the health plan more and its being construed as a breach of fiduciary duty. It was explained to me by the VP of Global Benefits that his company is part of the National Drug Purchasers Coalition and they trust Express Scripts to do the right thing for them. As they say, “You can lead a horse to water, but can’t make it drink.”
 

Liability of a Plan That Physically Harms an Employee?

A slightly different example of a self-insured employer, presumably unknowingly, allowing its third-party administrator to mishandle the care of an employee was recently brought to me by a rheumatologist in North Carolina. She takes care of an employee who has rheumatoid arthritis with severe interstitial lung disease (ILD). The employee’s pulmonary status was stabilized on several courses of Rituxan (reference product of rituximab). Recently, BlueCross BlueShield of North Carolina, the third-party administrator of this employer’s plan, mandated a switch to a biosimilar of rituximab for the treatment of the ILD. The rheumatologist appealed the nonmedical switch but gave the patient the biosimilar so as not to delay care. Her patient’s condition is now deteriorating with progression of the ILD, and she once again has asked for an exemption to use Rituxan, which had initially stabilized the patient. Her staff told her that the BCBSNC rep said that the patient would have to have a life-threatening infusion reaction (and present the bill for the ambulance) before they would approve a return to the reference product. An employer that knowingly or unknowingly allows a third-party administrator to act in such a way as to endanger the life of an employee could be considered to be breaching its fiduciary duty. (Disclaimer: I am not an attorney — merely a rheumatologist with common sense. Nor am I making any qualitative statement about biosimilars.)

We now have a lawsuit to which you can refer when advocating for our patients who are employed by large, self-insured employers. It is unfortunate that it is not the third-party administrators or PBMs that can be sued, as they are generally not the fiduciaries for the plan. It is the unsuspecting employers who “trust” their brokers/consultants and the third-party administrators to do the right thing. Please continue to send us your payer issues. And if your patient works for a self-insured employer, I will continue to remind the CEO, CFO, and chief compliance officer that an employer with an ERISA health plan can potentially face legal action if the health plan’s actions or decisions cause harm to an employee’s health — physically or in the wallet.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

WEST PALM BEACH, FLORIDA — Top-line results of two phase 3 trials evaluating the BTK inhibitor evobrutinib for treatment of multiple sclerosis (MS) were negative when released several months ago, but the hope for a signal of benefit on secondary endpoints was dashed when the full results of the trials were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum.

Based on prior drug development, including the promise seen in a phase 2 trial, “these negative results were quite disappointing,” reported Xavier Montalban, MD, director, department of neurology, Catalunya Center for Multiple Sclerosis, Hospital Universitario Vall d’Hebron, Barcelona, Spain.

In the evolutionRMS1 and 2 phase 3 trials, 2285 relapsing-remitting MS patients with active disease were randomized to 45 mg of twice-daily oral evobrutinib or 14 mg once-daily teriflunomide, a pyrimidine synthesis inhibitor already widely used for the treatment of MS. The trial, conducted in 52 countries, was double-blind and double-dummy.

Ted Bosworth/MDedge News

No Outcome Supported an Evobrutinib Advantage

Numerically, the mean number of T1 gadolinium-enhancing lesions was greater among those randomized to evobrutinib while the mean number of new or enlarging T2 lesions was lower. However, none of these differences in either study reached statistical significance.

The lower serum neurofilament light chain (sNfL) levels were significant (P = .032) in one of the two trials, but the difference was modest, and Dr. Montalban stated that the difference “was probably not clinically significant.”

Almost all of the patients had multiple relapses before being enrolled in the study, but only 36.5% had received a prior disease-modifying therapy. According to Dr. Montalban, the baseline characteristics of the patients enrolled were “nothing special,” in that they were very much “like the types of patients enrolled in trials like these.”

In general, both drugs were well tolerated with a comparable safety profile. The exception was a greater proportion of patients randomized to evobrutinib who developed elevated liver function tests, including a greater proportion with a level at least 5 times the upper limit of normal. All normalized after treatment was discontinued.

This is the first phase 3 trial of a BTK inhibitor in MS, according to Dr. Montalban, who pointed out that evobrutinib did perform as well as a highly active agent, even if it could not show superiority.

There is limited likelihood that further ongoing analyses will uncover meaningful activity not detected in the primary and secondary outcomes, but Dr. Montalban said that there is a possibility that a higher dose or a BTK inhibitor with different characteristics might still produce the types of clinical benefits hypothesized in this initial trial.

Asked to speculate about the results if the RM1 and RM2 trials had a noninferiority rather than a superiority design been employed, Dr. Montalban said that evobrutinib relative to teriflunomide appears to be “similar but more toxic.”

The recent excitement building for the potential of BTK inhibitors in MS was not helped by a second, but much smaller, late-breaker study that evaluated tolebrutinib. The primary endpoint of that study, conducted with just seven patients, was complete resolution of paramagnetic rim lesions (PRL), a prognostically important composition of macrophages, microglia, and iron seen in the central nervous system (CNS) on imaging.
 

No Resolution of CNS Lesions

Even after 48 weeks, none of the lesions had resolved, according to Maria I. Gaitán, MD, acting director of the Translational Neuroradiology Unit of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland.

Again, although these findings were disappointing, Dr. Gaitán said there are a number of explanations for the result that do not preclude a benefit from BTK inhibitors in future studies.

“Complete resolution of PRL might be a bar that was too high,” she said, noting that favorable changes in these lesions could have occurred even if the characteristic iron deposits persisted. She also suggested that dosing might not have been optimized to halt or reverse disease activity in the CNS. Like Dr. Montalban, she suggested that BTK inhibitors with different characteristics might succeed where tolebrutinib failed.

Dr. Freedman, current president of ACTRIMS, agreed that these data should not be interpreted as ruling out a clinical role for BTK inhibitors. Pointing to the substantial body of data supporting this mechanism for reversing inflammation in the CNS, he declared that “the story is not over.”

Dr. Montalban reported financial relationships with Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman La Roche, Immunic, Janssen, Mylan, NervGen, Novartis, Sanofi-Genzyme, Teva, TG Therapeutics, and Merck, which provided funding for the RMS 1 and 2 trials. Dr. Freedman reported financial relationships with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Hoffman La Roche, Merck, Novartis, and Teva Canada Innovation. Dr. Gaitán reported no potential conflicts of interest.

WEST PALM BEACH, FLORIDA — Top-line results of two phase 3 trials evaluating the BTK inhibitor evobrutinib for treatment of multiple sclerosis (MS) were negative when released several months ago, but the hope for a signal of benefit on secondary endpoints was dashed when the full results of the trials were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum.

Based on prior drug development, including the promise seen in a phase 2 trial, “these negative results were quite disappointing,” reported Xavier Montalban, MD, director, department of neurology, Catalunya Center for Multiple Sclerosis, Hospital Universitario Vall d’Hebron, Barcelona, Spain.

In the evolutionRMS1 and 2 phase 3 trials, 2285 relapsing-remitting MS patients with active disease were randomized to 45 mg of twice-daily oral evobrutinib or 14 mg once-daily teriflunomide, a pyrimidine synthesis inhibitor already widely used for the treatment of MS. The trial, conducted in 52 countries, was double-blind and double-dummy.

Ted Bosworth/MDedge News

No Outcome Supported an Evobrutinib Advantage

Numerically, the mean number of T1 gadolinium-enhancing lesions was greater among those randomized to evobrutinib while the mean number of new or enlarging T2 lesions was lower. However, none of these differences in either study reached statistical significance.

The lower serum neurofilament light chain (sNfL) levels were significant (P = .032) in one of the two trials, but the difference was modest, and Dr. Montalban stated that the difference “was probably not clinically significant.”

Almost all of the patients had multiple relapses before being enrolled in the study, but only 36.5% had received a prior disease-modifying therapy. According to Dr. Montalban, the baseline characteristics of the patients enrolled were “nothing special,” in that they were very much “like the types of patients enrolled in trials like these.”

In general, both drugs were well tolerated with a comparable safety profile. The exception was a greater proportion of patients randomized to evobrutinib who developed elevated liver function tests, including a greater proportion with a level at least 5 times the upper limit of normal. All normalized after treatment was discontinued.

This is the first phase 3 trial of a BTK inhibitor in MS, according to Dr. Montalban, who pointed out that evobrutinib did perform as well as a highly active agent, even if it could not show superiority.

There is limited likelihood that further ongoing analyses will uncover meaningful activity not detected in the primary and secondary outcomes, but Dr. Montalban said that there is a possibility that a higher dose or a BTK inhibitor with different characteristics might still produce the types of clinical benefits hypothesized in this initial trial.

Asked to speculate about the results if the RM1 and RM2 trials had a noninferiority rather than a superiority design been employed, Dr. Montalban said that evobrutinib relative to teriflunomide appears to be “similar but more toxic.”

The recent excitement building for the potential of BTK inhibitors in MS was not helped by a second, but much smaller, late-breaker study that evaluated tolebrutinib. The primary endpoint of that study, conducted with just seven patients, was complete resolution of paramagnetic rim lesions (PRL), a prognostically important composition of macrophages, microglia, and iron seen in the central nervous system (CNS) on imaging.
 

No Resolution of CNS Lesions

Even after 48 weeks, none of the lesions had resolved, according to Maria I. Gaitán, MD, acting director of the Translational Neuroradiology Unit of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland.

Again, although these findings were disappointing, Dr. Gaitán said there are a number of explanations for the result that do not preclude a benefit from BTK inhibitors in future studies.

“Complete resolution of PRL might be a bar that was too high,” she said, noting that favorable changes in these lesions could have occurred even if the characteristic iron deposits persisted. She also suggested that dosing might not have been optimized to halt or reverse disease activity in the CNS. Like Dr. Montalban, she suggested that BTK inhibitors with different characteristics might succeed where tolebrutinib failed.

Dr. Freedman, current president of ACTRIMS, agreed that these data should not be interpreted as ruling out a clinical role for BTK inhibitors. Pointing to the substantial body of data supporting this mechanism for reversing inflammation in the CNS, he declared that “the story is not over.”

Dr. Montalban reported financial relationships with Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman La Roche, Immunic, Janssen, Mylan, NervGen, Novartis, Sanofi-Genzyme, Teva, TG Therapeutics, and Merck, which provided funding for the RMS 1 and 2 trials. Dr. Freedman reported financial relationships with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Hoffman La Roche, Merck, Novartis, and Teva Canada Innovation. Dr. Gaitán reported no potential conflicts of interest.

WEST PALM BEACH, FLORIDA — Top-line results of two phase 3 trials evaluating the BTK inhibitor evobrutinib for treatment of multiple sclerosis (MS) were negative when released several months ago, but the hope for a signal of benefit on secondary endpoints was dashed when the full results of the trials were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum.

Based on prior drug development, including the promise seen in a phase 2 trial, “these negative results were quite disappointing,” reported Xavier Montalban, MD, director, department of neurology, Catalunya Center for Multiple Sclerosis, Hospital Universitario Vall d’Hebron, Barcelona, Spain.

In the evolutionRMS1 and 2 phase 3 trials, 2285 relapsing-remitting MS patients with active disease were randomized to 45 mg of twice-daily oral evobrutinib or 14 mg once-daily teriflunomide, a pyrimidine synthesis inhibitor already widely used for the treatment of MS. The trial, conducted in 52 countries, was double-blind and double-dummy.

Ted Bosworth/MDedge News

No Outcome Supported an Evobrutinib Advantage

Numerically, the mean number of T1 gadolinium-enhancing lesions was greater among those randomized to evobrutinib while the mean number of new or enlarging T2 lesions was lower. However, none of these differences in either study reached statistical significance.

The lower serum neurofilament light chain (sNfL) levels were significant (P = .032) in one of the two trials, but the difference was modest, and Dr. Montalban stated that the difference “was probably not clinically significant.”

Almost all of the patients had multiple relapses before being enrolled in the study, but only 36.5% had received a prior disease-modifying therapy. According to Dr. Montalban, the baseline characteristics of the patients enrolled were “nothing special,” in that they were very much “like the types of patients enrolled in trials like these.”

In general, both drugs were well tolerated with a comparable safety profile. The exception was a greater proportion of patients randomized to evobrutinib who developed elevated liver function tests, including a greater proportion with a level at least 5 times the upper limit of normal. All normalized after treatment was discontinued.

This is the first phase 3 trial of a BTK inhibitor in MS, according to Dr. Montalban, who pointed out that evobrutinib did perform as well as a highly active agent, even if it could not show superiority.

There is limited likelihood that further ongoing analyses will uncover meaningful activity not detected in the primary and secondary outcomes, but Dr. Montalban said that there is a possibility that a higher dose or a BTK inhibitor with different characteristics might still produce the types of clinical benefits hypothesized in this initial trial.

Asked to speculate about the results if the RM1 and RM2 trials had a noninferiority rather than a superiority design been employed, Dr. Montalban said that evobrutinib relative to teriflunomide appears to be “similar but more toxic.”

The recent excitement building for the potential of BTK inhibitors in MS was not helped by a second, but much smaller, late-breaker study that evaluated tolebrutinib. The primary endpoint of that study, conducted with just seven patients, was complete resolution of paramagnetic rim lesions (PRL), a prognostically important composition of macrophages, microglia, and iron seen in the central nervous system (CNS) on imaging.
 

No Resolution of CNS Lesions

Even after 48 weeks, none of the lesions had resolved, according to Maria I. Gaitán, MD, acting director of the Translational Neuroradiology Unit of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland.

Again, although these findings were disappointing, Dr. Gaitán said there are a number of explanations for the result that do not preclude a benefit from BTK inhibitors in future studies.

“Complete resolution of PRL might be a bar that was too high,” she said, noting that favorable changes in these lesions could have occurred even if the characteristic iron deposits persisted. She also suggested that dosing might not have been optimized to halt or reverse disease activity in the CNS. Like Dr. Montalban, she suggested that BTK inhibitors with different characteristics might succeed where tolebrutinib failed.

Dr. Freedman, current president of ACTRIMS, agreed that these data should not be interpreted as ruling out a clinical role for BTK inhibitors. Pointing to the substantial body of data supporting this mechanism for reversing inflammation in the CNS, he declared that “the story is not over.”

Dr. Montalban reported financial relationships with Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman La Roche, Immunic, Janssen, Mylan, NervGen, Novartis, Sanofi-Genzyme, Teva, TG Therapeutics, and Merck, which provided funding for the RMS 1 and 2 trials. Dr. Freedman reported financial relationships with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Hoffman La Roche, Merck, Novartis, and Teva Canada Innovation. Dr. Gaitán reported no potential conflicts of interest.

Epilepsy was linked to a significantly increased the risk for hospitalization and death from COVID-19 early in the pandemic, while healthcare utilization rates in this patient population declined, data from two linked studies showed. 

Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%. 

“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.

The findings were published online March 5 in Epilepsia. 
 

Skill Shifting 

Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.

During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.

To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.

Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy. 

The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.

Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37). 

After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001). 

The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.

Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants. 
 

Consultations Canceled 

In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic. 

In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls. 

However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)

The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted. 

“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.

Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.

A version of this article appeared on Medscape.com .

Epilepsy was linked to a significantly increased the risk for hospitalization and death from COVID-19 early in the pandemic, while healthcare utilization rates in this patient population declined, data from two linked studies showed. 

Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%. 

“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.

The findings were published online March 5 in Epilepsia. 
 

Skill Shifting 

Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.

During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.

To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.

Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy. 

The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.

Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37). 

After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001). 

The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.

Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants. 
 

Consultations Canceled 

In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic. 

In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls. 

However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)

The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted. 

“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.

Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.

A version of this article appeared on Medscape.com .

Epilepsy was linked to a significantly increased the risk for hospitalization and death from COVID-19 early in the pandemic, while healthcare utilization rates in this patient population declined, data from two linked studies showed. 

Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%. 

“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.

The findings were published online March 5 in Epilepsia. 
 

Skill Shifting 

Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.

During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.

To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.

Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy. 

The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.

Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37). 

After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001). 

The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.

Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants. 
 

Consultations Canceled 

In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic. 

In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls. 

However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)

The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted. 

“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.

Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.

A version of this article appeared on Medscape.com .

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

On a November morning in 2022, James Messenger opened wide and swallowed a capsule like no other.

Messenger was no stranger to taking pills.

He’d first experimented with prescription opioids as a teenager in Morgantown, West Virginia, battled addiction on-and-off since, and known more than 70 people who had fatally overdosed. So, when asked to test a new “smart pill” that could detect an overdose in progress and call for help, he didn’t hesitate to join the study.

“I’ve lost pretty much every good friend I’ve ever had to this,” said Mr. Messenger. “This pill could save a lot of lives.”

The new Vitals Monitoring capsule he tested is just one example in a growing effort to radically rethink what the humble pill is capable of.

As far back as 1965, scientists introduced the Heidelberg capsule, an electronic pill that measured acidity from within the gut. In 1994, the University of Buffalo coined the term “smart pill” with a device promising to ferry medicine to a precise spot in the intestine, “like the tiny ship in the film Fantastic Voyage.” And in 2001, the US Food and Drug Administration (FDA) approved the first video capsule endoscope, a miniature-camera-toting pill that enabled noninvasive imaging of the small intestine.

Despite these milestones, the smart pill revolution has been slow to catch on due to cost, technological limitations, and some resistance among clinicians and patients.

But now, nearly 300 iterations are in various stages of development, according to a 2022 analysis. Advances in materials, imaging, and artificial intelligence (AI) are helping address everything from sleep apnea to HIV/AIDS to gut disorders via real-time tracking and real-time help.

“These technologies could enable us to shift the paradigm from ‘Let’s wait until the patient comes to us and find out what happened’ to ‘Let’s see how things are changing in real time, intervene now, and personalize that intervention,’ ” said Peter Chai, MD, associate professor of emergency medicine and health technology researcher at Brigham and Women’s Hospital in Boston.
 

Tracking Vitals From the Inside Out

Already, overdose-reversal agents like naloxone are saving lives. But more than 60% of overdoses occur when no one is around to administer them.

“While we need to focus on treatment, we also need to come up with more acute ways to save individuals when treatment doesn’t work or relapse occurs,” said James J. Mahoney III, PhD, director of addictions research at the Rockefeller Neuroscience Institute at West Virginia University (WVU), Morgantown.

Enter Celero Systems, a Massachusetts-based digital health company that has developed a vitamin-sized capsule packed with tiny sensors, microprocessors, and a radio antenna. It can measure breathing, heart rate, and core temperature — all from deep within the gut.

Respiratory distress is a hallmark early sign of an overdose. But it can be hard to monitor from a distance, especially in populations without access to a charged smartwatch.

Dr. Mahoney imagines a day when patients at risk could be given a weekly pill like Celero’s. If their respiratory rate drops below a dangerous level, it could alert loved ones or, better yet, release an overdose-reversal drug.

“It’s early days,” stressed Dr. Mahoney, whose team has been conducting pilot tests of the pill. “But initial data look promising.”

For one study, published in the journal Device in November 2023, the research team administered an overdose of fentanyl to anesthetized pigs with the pill in their stomachs. The capsule was able to detect respiratory depression within a minute and alert researchers via their laptop in time to step in.

When they gave the pill to 10 volunteers undergoing sleep studies at WVU, they found it could detect respiration rate with an accuracy of 93% compared with external monitoring devices — a feature that could also help diagnose sleep apnea or chronic obstructive pulmonary disease without expensive, intrusive tests.

Accuracy for heart rate was nearly 97%.

In another yet-to-be published trial, Dr. Mahoney tested the device with 10 volunteers in a residential treatment center to determine how well it could be tolerated.

Among the participants was Mr. Messenger, who said the thought of being tracked didn’t bother him.

“It was simple — just like taking a multivitamin,” said Mr. Messenger, now 34, sober, and working as a peer recovery support specialist at a hospital in his hometown. “It could be a great way to keep people alive long enough for them to get their head wrapped around the idea of treatment.”
 

Boosting Medication Adherence

At Brigham and Women’s Hospital, Dr. Chai is experimenting with a different smart pill — one he believes could help curb the ongoing HIV/AIDS epidemic.

Developed by Florida-based etectRx, the ID-Cap consists of a gelatin capsule embedded with a tiny radiofrequency transmitter, similar to the kind in retail antitheft devices. The capsule can be filled with a variety of medications. When swallowed, stomach acid dissolves the gel and activates the transmitter, which sends a signal to a receiver on a smartwatch, smartphone, or wall-mounted reader to confirm the medication was taken. If it isn’t, the patient’s smartphone or smart speaker might nudge them with a reminder or a family member might be notified.

In recent trials of men at a high risk for HIV, the system improved adherence to the once-daily prevention regimen pre-exposure prophylaxis (PrEP) by double digits.

“PrEP is almost 99% effective in preventing HIV, but you have to take it,” said Dr. Chai, who led the trials. “That seems like such a simple thing, but anyone who is chronically on medication can tell you just how difficult it can be.”

The pill is not the first designed to improve adherence. In 2017, the FDA approved the first digital ingestion tracking system, Abilify MyCite, for the treatment of schizophrenia and bipolar disorder. But its maker, Proteus Digital Health, filed for bankruptcy in 2020 after struggling to recruit patients willing to be tracked. (Some expressed privacy concerns. Others disliked the uncomfortable patch that received and forwarded the signal.)

More recent designs have been streamlined to ditch the patch, said etectRx senior vice president of operations Chris Carnes, PhD. And the cost of making a pill this kind of “smart” has come down to about a dollar.

So far, said Dr. Chai, in the patients he’s worked with, perceived benefits generally outweigh privacy concerns.

Studies are now underway in patients with heart disease and tuberculosis, and the company hopes to move into the aging and memory care space where medication-adherence is a serious problem.

“For us, or any company in this space, to succeed, you have to have a strong business case,” said Dr. Carnes. “If family members can keep their loved ones at home a little longer at an additional cost of $30 a month, that’s a no-brainer.”
 

Pillcams 2.0

Twenty-three years ago, the first video capsule endoscopy made it possible to image the small intestine via a tiny camera you swallow.

Such “pillcams” offered a more patient-friendly way to diagnose small bowel disorders, such as gastrointestinal bleeding and Crohn’s disease. Rather than undergoing sedation or anesthesia, as required during tube-based endoscopy, patients can go about their day as the pill painlessly passes through their gastrointestinal (GI) tract, capturing and recording data and images.

But the pills have their downsides.

Because they move passively, driven by movement in the intestine, they can miss trouble spots. Their ability to image the esophagus, stomach, and colon has proven limited. And unlike other procedures, like colonoscopy, they can’t intervene with therapy, like removing polyps.

The pillcam “had so much promise, to sort of revolutionize endoscopy, but it never really got the adoption that it seemed like it might,” said Andrew Meltzer, MD, professor of emergency medicine at the GW School of Medicine and Health Sciences in Washington.

That could soon change, he said, thanks to advances in locomotion and AI.

In a recent study of 40 patients, Dr. Meltzer tested a new magnetically controlled capsule endoscopy. Standing at a patient’s side, he could use a joystick to steer the pill around the stomach, capturing images in real time.

The pilot study, published in June 2023, found that the pill clearly identified six key stomach landmarks accurately 95% of the time and didn’t miss any lesions caught with traditional endoscopy. Notably, 80% of the patients preferred the pillcam over the tube.

“They are awake. They can go to work as soon as they leave. And it’s easy for them to tolerate,” Dr. Meltzer said.

More research is necessary, but Dr. Meltzer believes the technology could be particularly useful in the emergency department, allowing doctors to rule out high-risk bleeds in the stomach on the spot without admitting patients unnecessarily or making them return for a traditional scope.

“It has the potential to increase screening and provide more cost-effective care in emergencies,” he said.

It could also be useful in the telemedicine space, allowing a doctor to “drive” the pill from afar to diagnose a distant patient.

Someday, AI could enable the capsule to drive itself, so a doctor could merely press a button and wait. Or it could be adapted to treat what it finds, like administering a drug or cauterizing a bleed.

“If we can come up with a Mars rover which can explore other planets, we should be able to have something that can explore the stomach remotely,” Dr. Meltzer said.
 

Swallowing the Future

At the California Institute of Technology, researchers have developed a “location-aware” smart pill that uses magnetic fields to help pinpoint its location in the twists and turns of intestines. This could be useful for monitoring food in the GI tract to determine why things aren’t moving.

Other researchers are using AI models to enhance the transmission of video from inside the body and reduce the time it takes to interpret images.

One group at the Massachusetts Institute of Technology has developed a vibrating weight loss capsule designed to stimulate receptors in the gut to signal the brain that the person is full.

Not everyone is a fan of the smart-pill revolution. Some critics have raised concerns about privacy. Others fear that doctors risk yielding too much power to technology. Even those who are excited about the pills’ possibilities temper their optimism with caution.

None of these smart pills have gone mainstream yet in clinical practice, said Vivek Kaul, MD, professor of medicine at the University of Rochester Medical Center, Rochester, New York, and secretary general of the World Gastroenterology Organization.

Clinical validation, accessibility, and insurance coverage “will be critical in shaping their role,” he said. “But overall, it would be fair to state that this technology has come of age and the future is bright.”
 

A version of this article appeared on Medscape.com.

On a November morning in 2022, James Messenger opened wide and swallowed a capsule like no other.

Messenger was no stranger to taking pills.

He’d first experimented with prescription opioids as a teenager in Morgantown, West Virginia, battled addiction on-and-off since, and known more than 70 people who had fatally overdosed. So, when asked to test a new “smart pill” that could detect an overdose in progress and call for help, he didn’t hesitate to join the study.

“I’ve lost pretty much every good friend I’ve ever had to this,” said Mr. Messenger. “This pill could save a lot of lives.”

The new Vitals Monitoring capsule he tested is just one example in a growing effort to radically rethink what the humble pill is capable of.

As far back as 1965, scientists introduced the Heidelberg capsule, an electronic pill that measured acidity from within the gut. In 1994, the University of Buffalo coined the term “smart pill” with a device promising to ferry medicine to a precise spot in the intestine, “like the tiny ship in the film Fantastic Voyage.” And in 2001, the US Food and Drug Administration (FDA) approved the first video capsule endoscope, a miniature-camera-toting pill that enabled noninvasive imaging of the small intestine.

Despite these milestones, the smart pill revolution has been slow to catch on due to cost, technological limitations, and some resistance among clinicians and patients.

But now, nearly 300 iterations are in various stages of development, according to a 2022 analysis. Advances in materials, imaging, and artificial intelligence (AI) are helping address everything from sleep apnea to HIV/AIDS to gut disorders via real-time tracking and real-time help.

“These technologies could enable us to shift the paradigm from ‘Let’s wait until the patient comes to us and find out what happened’ to ‘Let’s see how things are changing in real time, intervene now, and personalize that intervention,’ ” said Peter Chai, MD, associate professor of emergency medicine and health technology researcher at Brigham and Women’s Hospital in Boston.
 

Tracking Vitals From the Inside Out

Already, overdose-reversal agents like naloxone are saving lives. But more than 60% of overdoses occur when no one is around to administer them.

“While we need to focus on treatment, we also need to come up with more acute ways to save individuals when treatment doesn’t work or relapse occurs,” said James J. Mahoney III, PhD, director of addictions research at the Rockefeller Neuroscience Institute at West Virginia University (WVU), Morgantown.

Enter Celero Systems, a Massachusetts-based digital health company that has developed a vitamin-sized capsule packed with tiny sensors, microprocessors, and a radio antenna. It can measure breathing, heart rate, and core temperature — all from deep within the gut.

Respiratory distress is a hallmark early sign of an overdose. But it can be hard to monitor from a distance, especially in populations without access to a charged smartwatch.

Dr. Mahoney imagines a day when patients at risk could be given a weekly pill like Celero’s. If their respiratory rate drops below a dangerous level, it could alert loved ones or, better yet, release an overdose-reversal drug.

“It’s early days,” stressed Dr. Mahoney, whose team has been conducting pilot tests of the pill. “But initial data look promising.”

For one study, published in the journal Device in November 2023, the research team administered an overdose of fentanyl to anesthetized pigs with the pill in their stomachs. The capsule was able to detect respiratory depression within a minute and alert researchers via their laptop in time to step in.

When they gave the pill to 10 volunteers undergoing sleep studies at WVU, they found it could detect respiration rate with an accuracy of 93% compared with external monitoring devices — a feature that could also help diagnose sleep apnea or chronic obstructive pulmonary disease without expensive, intrusive tests.

Accuracy for heart rate was nearly 97%.

In another yet-to-be published trial, Dr. Mahoney tested the device with 10 volunteers in a residential treatment center to determine how well it could be tolerated.

Among the participants was Mr. Messenger, who said the thought of being tracked didn’t bother him.

“It was simple — just like taking a multivitamin,” said Mr. Messenger, now 34, sober, and working as a peer recovery support specialist at a hospital in his hometown. “It could be a great way to keep people alive long enough for them to get their head wrapped around the idea of treatment.”
 

Boosting Medication Adherence

At Brigham and Women’s Hospital, Dr. Chai is experimenting with a different smart pill — one he believes could help curb the ongoing HIV/AIDS epidemic.

Developed by Florida-based etectRx, the ID-Cap consists of a gelatin capsule embedded with a tiny radiofrequency transmitter, similar to the kind in retail antitheft devices. The capsule can be filled with a variety of medications. When swallowed, stomach acid dissolves the gel and activates the transmitter, which sends a signal to a receiver on a smartwatch, smartphone, or wall-mounted reader to confirm the medication was taken. If it isn’t, the patient’s smartphone or smart speaker might nudge them with a reminder or a family member might be notified.

In recent trials of men at a high risk for HIV, the system improved adherence to the once-daily prevention regimen pre-exposure prophylaxis (PrEP) by double digits.

“PrEP is almost 99% effective in preventing HIV, but you have to take it,” said Dr. Chai, who led the trials. “That seems like such a simple thing, but anyone who is chronically on medication can tell you just how difficult it can be.”

The pill is not the first designed to improve adherence. In 2017, the FDA approved the first digital ingestion tracking system, Abilify MyCite, for the treatment of schizophrenia and bipolar disorder. But its maker, Proteus Digital Health, filed for bankruptcy in 2020 after struggling to recruit patients willing to be tracked. (Some expressed privacy concerns. Others disliked the uncomfortable patch that received and forwarded the signal.)

More recent designs have been streamlined to ditch the patch, said etectRx senior vice president of operations Chris Carnes, PhD. And the cost of making a pill this kind of “smart” has come down to about a dollar.

So far, said Dr. Chai, in the patients he’s worked with, perceived benefits generally outweigh privacy concerns.

Studies are now underway in patients with heart disease and tuberculosis, and the company hopes to move into the aging and memory care space where medication-adherence is a serious problem.

“For us, or any company in this space, to succeed, you have to have a strong business case,” said Dr. Carnes. “If family members can keep their loved ones at home a little longer at an additional cost of $30 a month, that’s a no-brainer.”
 

Pillcams 2.0

Twenty-three years ago, the first video capsule endoscopy made it possible to image the small intestine via a tiny camera you swallow.

Such “pillcams” offered a more patient-friendly way to diagnose small bowel disorders, such as gastrointestinal bleeding and Crohn’s disease. Rather than undergoing sedation or anesthesia, as required during tube-based endoscopy, patients can go about their day as the pill painlessly passes through their gastrointestinal (GI) tract, capturing and recording data and images.

But the pills have their downsides.

Because they move passively, driven by movement in the intestine, they can miss trouble spots. Their ability to image the esophagus, stomach, and colon has proven limited. And unlike other procedures, like colonoscopy, they can’t intervene with therapy, like removing polyps.

The pillcam “had so much promise, to sort of revolutionize endoscopy, but it never really got the adoption that it seemed like it might,” said Andrew Meltzer, MD, professor of emergency medicine at the GW School of Medicine and Health Sciences in Washington.

That could soon change, he said, thanks to advances in locomotion and AI.

In a recent study of 40 patients, Dr. Meltzer tested a new magnetically controlled capsule endoscopy. Standing at a patient’s side, he could use a joystick to steer the pill around the stomach, capturing images in real time.

The pilot study, published in June 2023, found that the pill clearly identified six key stomach landmarks accurately 95% of the time and didn’t miss any lesions caught with traditional endoscopy. Notably, 80% of the patients preferred the pillcam over the tube.

“They are awake. They can go to work as soon as they leave. And it’s easy for them to tolerate,” Dr. Meltzer said.

More research is necessary, but Dr. Meltzer believes the technology could be particularly useful in the emergency department, allowing doctors to rule out high-risk bleeds in the stomach on the spot without admitting patients unnecessarily or making them return for a traditional scope.

“It has the potential to increase screening and provide more cost-effective care in emergencies,” he said.

It could also be useful in the telemedicine space, allowing a doctor to “drive” the pill from afar to diagnose a distant patient.

Someday, AI could enable the capsule to drive itself, so a doctor could merely press a button and wait. Or it could be adapted to treat what it finds, like administering a drug or cauterizing a bleed.

“If we can come up with a Mars rover which can explore other planets, we should be able to have something that can explore the stomach remotely,” Dr. Meltzer said.
 

Swallowing the Future

At the California Institute of Technology, researchers have developed a “location-aware” smart pill that uses magnetic fields to help pinpoint its location in the twists and turns of intestines. This could be useful for monitoring food in the GI tract to determine why things aren’t moving.

Other researchers are using AI models to enhance the transmission of video from inside the body and reduce the time it takes to interpret images.

One group at the Massachusetts Institute of Technology has developed a vibrating weight loss capsule designed to stimulate receptors in the gut to signal the brain that the person is full.

Not everyone is a fan of the smart-pill revolution. Some critics have raised concerns about privacy. Others fear that doctors risk yielding too much power to technology. Even those who are excited about the pills’ possibilities temper their optimism with caution.

None of these smart pills have gone mainstream yet in clinical practice, said Vivek Kaul, MD, professor of medicine at the University of Rochester Medical Center, Rochester, New York, and secretary general of the World Gastroenterology Organization.

Clinical validation, accessibility, and insurance coverage “will be critical in shaping their role,” he said. “But overall, it would be fair to state that this technology has come of age and the future is bright.”
 

A version of this article appeared on Medscape.com.

On a November morning in 2022, James Messenger opened wide and swallowed a capsule like no other.

Messenger was no stranger to taking pills.

He’d first experimented with prescription opioids as a teenager in Morgantown, West Virginia, battled addiction on-and-off since, and known more than 70 people who had fatally overdosed. So, when asked to test a new “smart pill” that could detect an overdose in progress and call for help, he didn’t hesitate to join the study.

“I’ve lost pretty much every good friend I’ve ever had to this,” said Mr. Messenger. “This pill could save a lot of lives.”

The new Vitals Monitoring capsule he tested is just one example in a growing effort to radically rethink what the humble pill is capable of.

As far back as 1965, scientists introduced the Heidelberg capsule, an electronic pill that measured acidity from within the gut. In 1994, the University of Buffalo coined the term “smart pill” with a device promising to ferry medicine to a precise spot in the intestine, “like the tiny ship in the film Fantastic Voyage.” And in 2001, the US Food and Drug Administration (FDA) approved the first video capsule endoscope, a miniature-camera-toting pill that enabled noninvasive imaging of the small intestine.

Despite these milestones, the smart pill revolution has been slow to catch on due to cost, technological limitations, and some resistance among clinicians and patients.

But now, nearly 300 iterations are in various stages of development, according to a 2022 analysis. Advances in materials, imaging, and artificial intelligence (AI) are helping address everything from sleep apnea to HIV/AIDS to gut disorders via real-time tracking and real-time help.

“These technologies could enable us to shift the paradigm from ‘Let’s wait until the patient comes to us and find out what happened’ to ‘Let’s see how things are changing in real time, intervene now, and personalize that intervention,’ ” said Peter Chai, MD, associate professor of emergency medicine and health technology researcher at Brigham and Women’s Hospital in Boston.
 

Tracking Vitals From the Inside Out

Already, overdose-reversal agents like naloxone are saving lives. But more than 60% of overdoses occur when no one is around to administer them.

“While we need to focus on treatment, we also need to come up with more acute ways to save individuals when treatment doesn’t work or relapse occurs,” said James J. Mahoney III, PhD, director of addictions research at the Rockefeller Neuroscience Institute at West Virginia University (WVU), Morgantown.

Enter Celero Systems, a Massachusetts-based digital health company that has developed a vitamin-sized capsule packed with tiny sensors, microprocessors, and a radio antenna. It can measure breathing, heart rate, and core temperature — all from deep within the gut.

Respiratory distress is a hallmark early sign of an overdose. But it can be hard to monitor from a distance, especially in populations without access to a charged smartwatch.

Dr. Mahoney imagines a day when patients at risk could be given a weekly pill like Celero’s. If their respiratory rate drops below a dangerous level, it could alert loved ones or, better yet, release an overdose-reversal drug.

“It’s early days,” stressed Dr. Mahoney, whose team has been conducting pilot tests of the pill. “But initial data look promising.”

For one study, published in the journal Device in November 2023, the research team administered an overdose of fentanyl to anesthetized pigs with the pill in their stomachs. The capsule was able to detect respiratory depression within a minute and alert researchers via their laptop in time to step in.

When they gave the pill to 10 volunteers undergoing sleep studies at WVU, they found it could detect respiration rate with an accuracy of 93% compared with external monitoring devices — a feature that could also help diagnose sleep apnea or chronic obstructive pulmonary disease without expensive, intrusive tests.

Accuracy for heart rate was nearly 97%.

In another yet-to-be published trial, Dr. Mahoney tested the device with 10 volunteers in a residential treatment center to determine how well it could be tolerated.

Among the participants was Mr. Messenger, who said the thought of being tracked didn’t bother him.

“It was simple — just like taking a multivitamin,” said Mr. Messenger, now 34, sober, and working as a peer recovery support specialist at a hospital in his hometown. “It could be a great way to keep people alive long enough for them to get their head wrapped around the idea of treatment.”
 

Boosting Medication Adherence

At Brigham and Women’s Hospital, Dr. Chai is experimenting with a different smart pill — one he believes could help curb the ongoing HIV/AIDS epidemic.

Developed by Florida-based etectRx, the ID-Cap consists of a gelatin capsule embedded with a tiny radiofrequency transmitter, similar to the kind in retail antitheft devices. The capsule can be filled with a variety of medications. When swallowed, stomach acid dissolves the gel and activates the transmitter, which sends a signal to a receiver on a smartwatch, smartphone, or wall-mounted reader to confirm the medication was taken. If it isn’t, the patient’s smartphone or smart speaker might nudge them with a reminder or a family member might be notified.

In recent trials of men at a high risk for HIV, the system improved adherence to the once-daily prevention regimen pre-exposure prophylaxis (PrEP) by double digits.

“PrEP is almost 99% effective in preventing HIV, but you have to take it,” said Dr. Chai, who led the trials. “That seems like such a simple thing, but anyone who is chronically on medication can tell you just how difficult it can be.”

The pill is not the first designed to improve adherence. In 2017, the FDA approved the first digital ingestion tracking system, Abilify MyCite, for the treatment of schizophrenia and bipolar disorder. But its maker, Proteus Digital Health, filed for bankruptcy in 2020 after struggling to recruit patients willing to be tracked. (Some expressed privacy concerns. Others disliked the uncomfortable patch that received and forwarded the signal.)

More recent designs have been streamlined to ditch the patch, said etectRx senior vice president of operations Chris Carnes, PhD. And the cost of making a pill this kind of “smart” has come down to about a dollar.

So far, said Dr. Chai, in the patients he’s worked with, perceived benefits generally outweigh privacy concerns.

Studies are now underway in patients with heart disease and tuberculosis, and the company hopes to move into the aging and memory care space where medication-adherence is a serious problem.

“For us, or any company in this space, to succeed, you have to have a strong business case,” said Dr. Carnes. “If family members can keep their loved ones at home a little longer at an additional cost of $30 a month, that’s a no-brainer.”
 

Pillcams 2.0

Twenty-three years ago, the first video capsule endoscopy made it possible to image the small intestine via a tiny camera you swallow.

Such “pillcams” offered a more patient-friendly way to diagnose small bowel disorders, such as gastrointestinal bleeding and Crohn’s disease. Rather than undergoing sedation or anesthesia, as required during tube-based endoscopy, patients can go about their day as the pill painlessly passes through their gastrointestinal (GI) tract, capturing and recording data and images.

But the pills have their downsides.

Because they move passively, driven by movement in the intestine, they can miss trouble spots. Their ability to image the esophagus, stomach, and colon has proven limited. And unlike other procedures, like colonoscopy, they can’t intervene with therapy, like removing polyps.

The pillcam “had so much promise, to sort of revolutionize endoscopy, but it never really got the adoption that it seemed like it might,” said Andrew Meltzer, MD, professor of emergency medicine at the GW School of Medicine and Health Sciences in Washington.

That could soon change, he said, thanks to advances in locomotion and AI.

In a recent study of 40 patients, Dr. Meltzer tested a new magnetically controlled capsule endoscopy. Standing at a patient’s side, he could use a joystick to steer the pill around the stomach, capturing images in real time.

The pilot study, published in June 2023, found that the pill clearly identified six key stomach landmarks accurately 95% of the time and didn’t miss any lesions caught with traditional endoscopy. Notably, 80% of the patients preferred the pillcam over the tube.

“They are awake. They can go to work as soon as they leave. And it’s easy for them to tolerate,” Dr. Meltzer said.

More research is necessary, but Dr. Meltzer believes the technology could be particularly useful in the emergency department, allowing doctors to rule out high-risk bleeds in the stomach on the spot without admitting patients unnecessarily or making them return for a traditional scope.

“It has the potential to increase screening and provide more cost-effective care in emergencies,” he said.

It could also be useful in the telemedicine space, allowing a doctor to “drive” the pill from afar to diagnose a distant patient.

Someday, AI could enable the capsule to drive itself, so a doctor could merely press a button and wait. Or it could be adapted to treat what it finds, like administering a drug or cauterizing a bleed.

“If we can come up with a Mars rover which can explore other planets, we should be able to have something that can explore the stomach remotely,” Dr. Meltzer said.
 

Swallowing the Future

At the California Institute of Technology, researchers have developed a “location-aware” smart pill that uses magnetic fields to help pinpoint its location in the twists and turns of intestines. This could be useful for monitoring food in the GI tract to determine why things aren’t moving.

Other researchers are using AI models to enhance the transmission of video from inside the body and reduce the time it takes to interpret images.

One group at the Massachusetts Institute of Technology has developed a vibrating weight loss capsule designed to stimulate receptors in the gut to signal the brain that the person is full.

Not everyone is a fan of the smart-pill revolution. Some critics have raised concerns about privacy. Others fear that doctors risk yielding too much power to technology. Even those who are excited about the pills’ possibilities temper their optimism with caution.

None of these smart pills have gone mainstream yet in clinical practice, said Vivek Kaul, MD, professor of medicine at the University of Rochester Medical Center, Rochester, New York, and secretary general of the World Gastroenterology Organization.

Clinical validation, accessibility, and insurance coverage “will be critical in shaping their role,” he said. “But overall, it would be fair to state that this technology has come of age and the future is bright.”
 

A version of this article appeared on Medscape.com.

The American College of Cardiology has published a new update to its consensus decision pathway for the treatment of heart failure with reduced ejection fraction (HFrEF).

Chair of the consensus document Writing Committee Thomas M. Maddox, MD, explained to this news organization that this new Decision Pathway provides a practical, streamlined update to frontline clinicians treating patients with heart failure and incorporates evidence from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

The authors said that the treatment of heart failure can feel overwhelming, and many opportunities to improve patient outcomes are being missed.

“While the AHA/ACC/HFSA Guidelines are wonderful in that they collate all the latest scientific evidence, they don’t speak as much to the practicalities of delivering the care. This is what this Decision Pathway document comes in — it is designed to help frontline clinicians with the practical reality of managing these patients,” Dr. Maddox, who is director of the Healthcare Innovation Lab at BJC HealthCare and the Washington University School of Medicine in St Louis, Missouri, commented.

The document, “Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction,” was published online on March 8 in the Journal of the American College of Cardiology.

The authors provided guidance on introducing the numerous evidence-based therapies now available for HFrEF, improving adherence, overcoming treatment barriers, acknowledging contraindications and situations for which few data exist, affording expensive therapies, treating special cohorts, and making the transition to palliative care.

Rather than focusing on extensive text, the document provided practical tips, tables, and figures to make clear the steps, tools, and provisos needed to treat patients with heart failure successfully and expeditiously, they added.

Dr. Maddox reported that there are three main updated areas of advice on the treatment of heart failure in the new document.
 

Valsartan/Sacubitril First Line

One of the major changes involves an elevation for the status of the angiotensin receptor-neprilysin inhibitor (ARNI), Entresto (valsartan/sacubitril).

“It is now clear that this agent is superior to ACE-inhibitors or angiotensin receptor blockers in terms of reducing heart failure hospitalization and death, whereas previously it was seen as somewhat equivalent,” Dr. Maddox said. “So, barring a contraindication or another problem with getting the medication, this agent should be one of the first line medicines for all patients with heart failure and a reduced ejection fraction.”
 

Dual Sodium-Glucose Cotransporter 1/2 (SGLT1/2) Inhibitor

A second update involves the addition of sotagliflozin (a dual inhibitor of both SGLT1 and SGLT2) to the SGLT2 inhibitors as another first-line medication for patients with heart failure and reduced ejection fraction.

“We now have evidence that both SGLT2 and SGLT1 inhibitors are beneficial in reducing heart failure hospitalization and death. Previously we only had evidence on SGLT2 inhibitors — dapagliflozin and empagliflozin. Sotagliflozin is a newer agent, which inhibits both SGLT1 and SGLT2, and it turns out that inhibiting both are beneficial in heart failure. So, this gives us a third med in this category,” Dr. Maddox noted.
 

Rapid Initiation of the Four Pillars of Therapy

The document stated that more data have emerged recently to support early and rapid initiation and titration of the “four pillars” of medical therapy in heart failure to maximize the benefits of patient-reported outcomes and reduction in hospitalizations and mortality.

The four pillars of therapy are ARNI, a beta-blocker, a mineralocorticoid antagonist, and an SGLT inhibitor.

As an example, four-class medication initiation reduced the hazard of cardiovascular death or hospital admission for heart failure significantly (hazard ratio, 0.38) compared with therapy with just an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker plus a beta-blocker, the document reported.

“What we realize now is that the more quickly we can get patients on all four of these drug classes and escalate to target doses or maximally tolerated doses ideally within 3 months, the better the outcome,” Dr. Maddox said.

“Unfortunately, right now there is very incomplete realization and recognition of that in clinical practice. So, we are trying to highlight the importance of this to encourage clinicians to be more aggressive in making this happen.”

“In all patients with heart failure and reduced ejection fraction, getting them on all four of these medicines as quickly as possible will give the best outcome. We’ve seen evidence in support of this from several broad population trials,” he added. “There are times when they can’t take all four but we should do our best to get there.”
 

Practical Considerations

Dr. Maddox pointed out that the Consensus Document is also trying to account for practical realities and barriers to heart failure treatment.

“When we think about these recommendations — and evidence that getting patients on all these medicines is valuable, we also focus on the fact that there are three major barriers that can get in the way of this and how to think about overcoming those barriers,” he said.

The barriers are comorbidities/side effects of medications, costs of the medicines, and systems of care that are needed to ensure patients can be treated with multiple medications in a timely fashion.

In terms of comorbidities/side effects, Dr. Maddox explained that patients with heart failure are generally older and are likely to have other comorbidities. “The more medicines we give, the more likely we are to run into side effects. So, we have produced some guidance on how to monitor for adverse effects and ways to mitigate these effects so the guideline recommended therapies can be continued without creating new harms.”

He gave the example of mineralocorticoid antagonists, which can sometimes elevate potassium levels, particularly if there is some underlying kidney disease, so clinicians are advised to recommend a low-potassium diet for these patients or the use of potassium binding agents that will also lower the amount of potassium in the blood stream; in this way, patients are able to continue the mineralocorticoid antagonist.

On costs, Dr. Maddox noted that the valsartan/sacubitril combination drug and SGLT inhibitors are new medicines and are expensive.

“They can be prohibitively expensive for patients who have suboptimal pharmacy benefits or who are uninsured.”

The Consensus Document therefore provided some guidance on ways to identify rebate programs, access insurance, and find different pathways to obtaining those drugs at a more reasonable price. It also advocated for policy changes to allow these medicines to be more accessible to more people.
 

More Use of Digital Tools

On the issue of systems of care, Dr. Maddox noted that the preexisting model of delivering care, which almost always involves the patient coming into the doctor’s office, invokes a high burden on both the system and most especially, the patient.

“Patients do not want to come back and forth to the doctor’s office multiple times in a few weeks. This is often a nonstarter, particularly for patients with busy lives,” he commented.

The Consensus Document advised more use of digital tools to provide remote care and contact with patients including sensors that can measure variables such as heart rate and blood pressure and video appointments.

“We are still working out what are the right models of care and how they can be performed safely and how they can be funded. But I think at the end of the day, this will give us more practical ways of getting people on multiple heart failure medicines and monitoring them safely without causing an undue burden for them logistically,” Dr. Maddox said.

He pointed out that there are a record number of medicines now available to treat heart failure, and while this is welcome, many of these patients are also on multiple other medications for other comorbidities as well.

“If you start giving patients seven, eight, or nine different medicines that they have to take every day, sometimes multiple times a day — that’s complicated medically, logistically, and financially. The potential for interaction and complications increases with every additional medication.”

Dr. Maddox also noted that patients have limits on how many medications they will accept. “It really helps if we have an engaged patient who has a good relationship with the care team to try to develop the right treatment plan that is going to meet their needs and give them the best possible health outcomes.”

It can take many visits to get the patient on all these medications and then up-titrate to target doses.

“We try and do a couple of things in each appointment. Often, we tend to start one or maybe two drugs at a time at a relatively low dose to avoid side effects, so we can be talking about 12-16 different encounters in total,” he said.

He recommended making a plan and the use of new technologies to manage each incremental step.
 

A Team Approach

Another issue that is discussed in the document is the use of a healthcare team to manage all the necessary appointments.

“It is no longer practical that one person can be the engineer for all this. It should be a team effort,” Dr. Maddox stated.

Responsibilities can be allocated across physicians, nurses, pharmacists, and even case managers, so that the team can take more of a population approach and develop a system to get patients on the multiple medications as quickly as possible.

“While this can still be quite a big burden for the patient, we need to figure out a system to make this as palatable as possible for them. Practices need to tailor this themselves according to what resources they have,” he added.

While most new patients will be routed to cardiologists to start their treatment plans, once on their initial medications and these have been up titrated to target levels, they should be able to be managed by primary care doctors, who will have the most holistic view of the patient and their other comorbidities, Dr. Maddox advised.

“Following this guidance should lead to more patients receiving evidence-based care which leads to better health outcomes, but delivered in a practical way that fits with their life reality and logistical needs,” he concluded.

A version of this article appeared on Medscape.com.

The American College of Cardiology has published a new update to its consensus decision pathway for the treatment of heart failure with reduced ejection fraction (HFrEF).

Chair of the consensus document Writing Committee Thomas M. Maddox, MD, explained to this news organization that this new Decision Pathway provides a practical, streamlined update to frontline clinicians treating patients with heart failure and incorporates evidence from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

The authors said that the treatment of heart failure can feel overwhelming, and many opportunities to improve patient outcomes are being missed.

“While the AHA/ACC/HFSA Guidelines are wonderful in that they collate all the latest scientific evidence, they don’t speak as much to the practicalities of delivering the care. This is what this Decision Pathway document comes in — it is designed to help frontline clinicians with the practical reality of managing these patients,” Dr. Maddox, who is director of the Healthcare Innovation Lab at BJC HealthCare and the Washington University School of Medicine in St Louis, Missouri, commented.

The document, “Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction,” was published online on March 8 in the Journal of the American College of Cardiology.

The authors provided guidance on introducing the numerous evidence-based therapies now available for HFrEF, improving adherence, overcoming treatment barriers, acknowledging contraindications and situations for which few data exist, affording expensive therapies, treating special cohorts, and making the transition to palliative care.

Rather than focusing on extensive text, the document provided practical tips, tables, and figures to make clear the steps, tools, and provisos needed to treat patients with heart failure successfully and expeditiously, they added.

Dr. Maddox reported that there are three main updated areas of advice on the treatment of heart failure in the new document.
 

Valsartan/Sacubitril First Line

One of the major changes involves an elevation for the status of the angiotensin receptor-neprilysin inhibitor (ARNI), Entresto (valsartan/sacubitril).

“It is now clear that this agent is superior to ACE-inhibitors or angiotensin receptor blockers in terms of reducing heart failure hospitalization and death, whereas previously it was seen as somewhat equivalent,” Dr. Maddox said. “So, barring a contraindication or another problem with getting the medication, this agent should be one of the first line medicines for all patients with heart failure and a reduced ejection fraction.”
 

Dual Sodium-Glucose Cotransporter 1/2 (SGLT1/2) Inhibitor

A second update involves the addition of sotagliflozin (a dual inhibitor of both SGLT1 and SGLT2) to the SGLT2 inhibitors as another first-line medication for patients with heart failure and reduced ejection fraction.

“We now have evidence that both SGLT2 and SGLT1 inhibitors are beneficial in reducing heart failure hospitalization and death. Previously we only had evidence on SGLT2 inhibitors — dapagliflozin and empagliflozin. Sotagliflozin is a newer agent, which inhibits both SGLT1 and SGLT2, and it turns out that inhibiting both are beneficial in heart failure. So, this gives us a third med in this category,” Dr. Maddox noted.
 

Rapid Initiation of the Four Pillars of Therapy

The document stated that more data have emerged recently to support early and rapid initiation and titration of the “four pillars” of medical therapy in heart failure to maximize the benefits of patient-reported outcomes and reduction in hospitalizations and mortality.

The four pillars of therapy are ARNI, a beta-blocker, a mineralocorticoid antagonist, and an SGLT inhibitor.

As an example, four-class medication initiation reduced the hazard of cardiovascular death or hospital admission for heart failure significantly (hazard ratio, 0.38) compared with therapy with just an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker plus a beta-blocker, the document reported.

“What we realize now is that the more quickly we can get patients on all four of these drug classes and escalate to target doses or maximally tolerated doses ideally within 3 months, the better the outcome,” Dr. Maddox said.

“Unfortunately, right now there is very incomplete realization and recognition of that in clinical practice. So, we are trying to highlight the importance of this to encourage clinicians to be more aggressive in making this happen.”

“In all patients with heart failure and reduced ejection fraction, getting them on all four of these medicines as quickly as possible will give the best outcome. We’ve seen evidence in support of this from several broad population trials,” he added. “There are times when they can’t take all four but we should do our best to get there.”
 

Practical Considerations

Dr. Maddox pointed out that the Consensus Document is also trying to account for practical realities and barriers to heart failure treatment.

“When we think about these recommendations — and evidence that getting patients on all these medicines is valuable, we also focus on the fact that there are three major barriers that can get in the way of this and how to think about overcoming those barriers,” he said.

The barriers are comorbidities/side effects of medications, costs of the medicines, and systems of care that are needed to ensure patients can be treated with multiple medications in a timely fashion.

In terms of comorbidities/side effects, Dr. Maddox explained that patients with heart failure are generally older and are likely to have other comorbidities. “The more medicines we give, the more likely we are to run into side effects. So, we have produced some guidance on how to monitor for adverse effects and ways to mitigate these effects so the guideline recommended therapies can be continued without creating new harms.”

He gave the example of mineralocorticoid antagonists, which can sometimes elevate potassium levels, particularly if there is some underlying kidney disease, so clinicians are advised to recommend a low-potassium diet for these patients or the use of potassium binding agents that will also lower the amount of potassium in the blood stream; in this way, patients are able to continue the mineralocorticoid antagonist.

On costs, Dr. Maddox noted that the valsartan/sacubitril combination drug and SGLT inhibitors are new medicines and are expensive.

“They can be prohibitively expensive for patients who have suboptimal pharmacy benefits or who are uninsured.”

The Consensus Document therefore provided some guidance on ways to identify rebate programs, access insurance, and find different pathways to obtaining those drugs at a more reasonable price. It also advocated for policy changes to allow these medicines to be more accessible to more people.
 

More Use of Digital Tools

On the issue of systems of care, Dr. Maddox noted that the preexisting model of delivering care, which almost always involves the patient coming into the doctor’s office, invokes a high burden on both the system and most especially, the patient.

“Patients do not want to come back and forth to the doctor’s office multiple times in a few weeks. This is often a nonstarter, particularly for patients with busy lives,” he commented.

The Consensus Document advised more use of digital tools to provide remote care and contact with patients including sensors that can measure variables such as heart rate and blood pressure and video appointments.

“We are still working out what are the right models of care and how they can be performed safely and how they can be funded. But I think at the end of the day, this will give us more practical ways of getting people on multiple heart failure medicines and monitoring them safely without causing an undue burden for them logistically,” Dr. Maddox said.

He pointed out that there are a record number of medicines now available to treat heart failure, and while this is welcome, many of these patients are also on multiple other medications for other comorbidities as well.

“If you start giving patients seven, eight, or nine different medicines that they have to take every day, sometimes multiple times a day — that’s complicated medically, logistically, and financially. The potential for interaction and complications increases with every additional medication.”

Dr. Maddox also noted that patients have limits on how many medications they will accept. “It really helps if we have an engaged patient who has a good relationship with the care team to try to develop the right treatment plan that is going to meet their needs and give them the best possible health outcomes.”

It can take many visits to get the patient on all these medications and then up-titrate to target doses.

“We try and do a couple of things in each appointment. Often, we tend to start one or maybe two drugs at a time at a relatively low dose to avoid side effects, so we can be talking about 12-16 different encounters in total,” he said.

He recommended making a plan and the use of new technologies to manage each incremental step.
 

A Team Approach

Another issue that is discussed in the document is the use of a healthcare team to manage all the necessary appointments.

“It is no longer practical that one person can be the engineer for all this. It should be a team effort,” Dr. Maddox stated.

Responsibilities can be allocated across physicians, nurses, pharmacists, and even case managers, so that the team can take more of a population approach and develop a system to get patients on the multiple medications as quickly as possible.

“While this can still be quite a big burden for the patient, we need to figure out a system to make this as palatable as possible for them. Practices need to tailor this themselves according to what resources they have,” he added.

While most new patients will be routed to cardiologists to start their treatment plans, once on their initial medications and these have been up titrated to target levels, they should be able to be managed by primary care doctors, who will have the most holistic view of the patient and their other comorbidities, Dr. Maddox advised.

“Following this guidance should lead to more patients receiving evidence-based care which leads to better health outcomes, but delivered in a practical way that fits with their life reality and logistical needs,” he concluded.

A version of this article appeared on Medscape.com.

The American College of Cardiology has published a new update to its consensus decision pathway for the treatment of heart failure with reduced ejection fraction (HFrEF).

Chair of the consensus document Writing Committee Thomas M. Maddox, MD, explained to this news organization that this new Decision Pathway provides a practical, streamlined update to frontline clinicians treating patients with heart failure and incorporates evidence from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

The authors said that the treatment of heart failure can feel overwhelming, and many opportunities to improve patient outcomes are being missed.

“While the AHA/ACC/HFSA Guidelines are wonderful in that they collate all the latest scientific evidence, they don’t speak as much to the practicalities of delivering the care. This is what this Decision Pathway document comes in — it is designed to help frontline clinicians with the practical reality of managing these patients,” Dr. Maddox, who is director of the Healthcare Innovation Lab at BJC HealthCare and the Washington University School of Medicine in St Louis, Missouri, commented.

The document, “Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction,” was published online on March 8 in the Journal of the American College of Cardiology.

The authors provided guidance on introducing the numerous evidence-based therapies now available for HFrEF, improving adherence, overcoming treatment barriers, acknowledging contraindications and situations for which few data exist, affording expensive therapies, treating special cohorts, and making the transition to palliative care.

Rather than focusing on extensive text, the document provided practical tips, tables, and figures to make clear the steps, tools, and provisos needed to treat patients with heart failure successfully and expeditiously, they added.

Dr. Maddox reported that there are three main updated areas of advice on the treatment of heart failure in the new document.
 

Valsartan/Sacubitril First Line

One of the major changes involves an elevation for the status of the angiotensin receptor-neprilysin inhibitor (ARNI), Entresto (valsartan/sacubitril).

“It is now clear that this agent is superior to ACE-inhibitors or angiotensin receptor blockers in terms of reducing heart failure hospitalization and death, whereas previously it was seen as somewhat equivalent,” Dr. Maddox said. “So, barring a contraindication or another problem with getting the medication, this agent should be one of the first line medicines for all patients with heart failure and a reduced ejection fraction.”
 

Dual Sodium-Glucose Cotransporter 1/2 (SGLT1/2) Inhibitor

A second update involves the addition of sotagliflozin (a dual inhibitor of both SGLT1 and SGLT2) to the SGLT2 inhibitors as another first-line medication for patients with heart failure and reduced ejection fraction.

“We now have evidence that both SGLT2 and SGLT1 inhibitors are beneficial in reducing heart failure hospitalization and death. Previously we only had evidence on SGLT2 inhibitors — dapagliflozin and empagliflozin. Sotagliflozin is a newer agent, which inhibits both SGLT1 and SGLT2, and it turns out that inhibiting both are beneficial in heart failure. So, this gives us a third med in this category,” Dr. Maddox noted.
 

Rapid Initiation of the Four Pillars of Therapy

The document stated that more data have emerged recently to support early and rapid initiation and titration of the “four pillars” of medical therapy in heart failure to maximize the benefits of patient-reported outcomes and reduction in hospitalizations and mortality.

The four pillars of therapy are ARNI, a beta-blocker, a mineralocorticoid antagonist, and an SGLT inhibitor.

As an example, four-class medication initiation reduced the hazard of cardiovascular death or hospital admission for heart failure significantly (hazard ratio, 0.38) compared with therapy with just an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker plus a beta-blocker, the document reported.

“What we realize now is that the more quickly we can get patients on all four of these drug classes and escalate to target doses or maximally tolerated doses ideally within 3 months, the better the outcome,” Dr. Maddox said.

“Unfortunately, right now there is very incomplete realization and recognition of that in clinical practice. So, we are trying to highlight the importance of this to encourage clinicians to be more aggressive in making this happen.”

“In all patients with heart failure and reduced ejection fraction, getting them on all four of these medicines as quickly as possible will give the best outcome. We’ve seen evidence in support of this from several broad population trials,” he added. “There are times when they can’t take all four but we should do our best to get there.”
 

Practical Considerations

Dr. Maddox pointed out that the Consensus Document is also trying to account for practical realities and barriers to heart failure treatment.

“When we think about these recommendations — and evidence that getting patients on all these medicines is valuable, we also focus on the fact that there are three major barriers that can get in the way of this and how to think about overcoming those barriers,” he said.

The barriers are comorbidities/side effects of medications, costs of the medicines, and systems of care that are needed to ensure patients can be treated with multiple medications in a timely fashion.

In terms of comorbidities/side effects, Dr. Maddox explained that patients with heart failure are generally older and are likely to have other comorbidities. “The more medicines we give, the more likely we are to run into side effects. So, we have produced some guidance on how to monitor for adverse effects and ways to mitigate these effects so the guideline recommended therapies can be continued without creating new harms.”

He gave the example of mineralocorticoid antagonists, which can sometimes elevate potassium levels, particularly if there is some underlying kidney disease, so clinicians are advised to recommend a low-potassium diet for these patients or the use of potassium binding agents that will also lower the amount of potassium in the blood stream; in this way, patients are able to continue the mineralocorticoid antagonist.

On costs, Dr. Maddox noted that the valsartan/sacubitril combination drug and SGLT inhibitors are new medicines and are expensive.

“They can be prohibitively expensive for patients who have suboptimal pharmacy benefits or who are uninsured.”

The Consensus Document therefore provided some guidance on ways to identify rebate programs, access insurance, and find different pathways to obtaining those drugs at a more reasonable price. It also advocated for policy changes to allow these medicines to be more accessible to more people.
 

More Use of Digital Tools

On the issue of systems of care, Dr. Maddox noted that the preexisting model of delivering care, which almost always involves the patient coming into the doctor’s office, invokes a high burden on both the system and most especially, the patient.

“Patients do not want to come back and forth to the doctor’s office multiple times in a few weeks. This is often a nonstarter, particularly for patients with busy lives,” he commented.

The Consensus Document advised more use of digital tools to provide remote care and contact with patients including sensors that can measure variables such as heart rate and blood pressure and video appointments.

“We are still working out what are the right models of care and how they can be performed safely and how they can be funded. But I think at the end of the day, this will give us more practical ways of getting people on multiple heart failure medicines and monitoring them safely without causing an undue burden for them logistically,” Dr. Maddox said.

He pointed out that there are a record number of medicines now available to treat heart failure, and while this is welcome, many of these patients are also on multiple other medications for other comorbidities as well.

“If you start giving patients seven, eight, or nine different medicines that they have to take every day, sometimes multiple times a day — that’s complicated medically, logistically, and financially. The potential for interaction and complications increases with every additional medication.”

Dr. Maddox also noted that patients have limits on how many medications they will accept. “It really helps if we have an engaged patient who has a good relationship with the care team to try to develop the right treatment plan that is going to meet their needs and give them the best possible health outcomes.”

It can take many visits to get the patient on all these medications and then up-titrate to target doses.

“We try and do a couple of things in each appointment. Often, we tend to start one or maybe two drugs at a time at a relatively low dose to avoid side effects, so we can be talking about 12-16 different encounters in total,” he said.

He recommended making a plan and the use of new technologies to manage each incremental step.
 

A Team Approach

Another issue that is discussed in the document is the use of a healthcare team to manage all the necessary appointments.

“It is no longer practical that one person can be the engineer for all this. It should be a team effort,” Dr. Maddox stated.

Responsibilities can be allocated across physicians, nurses, pharmacists, and even case managers, so that the team can take more of a population approach and develop a system to get patients on the multiple medications as quickly as possible.

“While this can still be quite a big burden for the patient, we need to figure out a system to make this as palatable as possible for them. Practices need to tailor this themselves according to what resources they have,” he added.

While most new patients will be routed to cardiologists to start their treatment plans, once on their initial medications and these have been up titrated to target levels, they should be able to be managed by primary care doctors, who will have the most holistic view of the patient and their other comorbidities, Dr. Maddox advised.

“Following this guidance should lead to more patients receiving evidence-based care which leads to better health outcomes, but delivered in a practical way that fits with their life reality and logistical needs,” he concluded.

A version of this article appeared on Medscape.com.