TOPLINE:

The frequency of follow-up after fertility-sparing surgery for cervical cancer can be tailored based on high-risk human papillomavirus (HPV) tests and cytology.

METHODOLOGY:

• Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
• The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
• The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
• The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).

TAKEAWAY:

• Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
• Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
• By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
• Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.

IN PRACTICE:

“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”

“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.

SOURCE:

The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.

LIMITATIONS:

The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.

DISCLOSURES:

The authors declared no competing interests.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The frequency of follow-up after fertility-sparing surgery for cervical cancer can be tailored based on high-risk human papillomavirus (HPV) tests and cytology.

METHODOLOGY:

• Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
• The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
• The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
• The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).

TAKEAWAY:

• Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
• Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
• By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
• Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.

IN PRACTICE:

“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”

“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.

SOURCE:

The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.

LIMITATIONS:

The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.

DISCLOSURES:

The authors declared no competing interests.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The frequency of follow-up after fertility-sparing surgery for cervical cancer can be tailored based on high-risk human papillomavirus (HPV) tests and cytology.

METHODOLOGY:

• Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
• The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
• The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
• The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).

TAKEAWAY:

• Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
• Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
• By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
• Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.

IN PRACTICE:

“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”

“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.

SOURCE:

The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.

LIMITATIONS:

The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.

DISCLOSURES:

The authors declared no competing interests.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Overall survival among US patients with resected stage II or III gastric cancer differs by race and ethnicity, with Asian and Hispanic patients demonstrating better overall survival than White and Black patients.

METHODOLOGY:

• Studies have revealed disparities in gastric cancer outcomes among different racial and ethnic groups in the United States, but the reasons are unclear.
• To better understand the disparities, researchers analyzed survival outcomes by race and ethnicity, treatment type, and a range of other factors.
• The retrospective analysis included 6938 patients with clinical stages IIA-IIIC gastric adenocarcinoma who underwent partial or total gastrectomy between 2006 and 2019, excluding those with a history of cancer. Patient data came from the National Cancer Database, which covers about 70% of all new cancer diagnoses.
• The researchers compared factors, including race and ethnicity, surgical margins, and lymph nodes, as well as treatment modality (neoadjuvant or adjuvant chemotherapy only, neoadjuvant or adjuvant chemoradiation only, or perioperative chemotherapy with radiation or surgical care only).
• Just over half of the patients (53.6%) were White, 24.3% were Black, 17.8% were Hispanic, 15.8% were Asian, and 2.6% were other race or ethnicity (information was missing for 4.8%). White patients were more likely to be older and insured; Black and White patients had more comorbidities than Asian and Hispanic patients.

TAKEAWAY:

• Perioperative chemotherapy was associated with improved overall survival (hazard ratio [HR], 0.79), while surgical resection alone (HR, 1.79), more positive lymph nodes (HR, 2.95 for 10 or more), and positive surgical margins were associated with the biggest decreases in overall survival.
• Asian and Hispanic patients had significantly better overall survival (HR, 0.64 and 0.77, respectively) than White patients.
• In general, Black and White patients had similar overall survival (HR, 0.96), except among Black patients who received neoadjuvant therapy — these patients had better overall survival than White patients (HR, 0.78).
• Black and Asian patients were more likely to be downstaged or achieve a pathologic complete response after neoadjuvant therapy (34.4% and 35.3%, respectively) than White (28.4%) and Hispanic patients (30.8%).

IN PRACTICE:

The authors found that “Asian and Hispanic race and ethnicity were independently associated with improved [overall survival] compared with Black and White race,” even after adjusting for variables including multimodality treatment regimen and response to neoadjuvant therapy.

The authors explained that overall Asian and Black patients responded more favorably to neoadjuvant therapy, demonstrating significantly higher rates of downstaging or pathologic complete response, which may help explain why Black patients demonstrated better overall survival than White patients who received neoadjuvant therapy.

SOURCE:

The research, led by Steve Kwon, MD, MPH, of Roger Williams Medical Center and Boston University, Providence, Rhode Island, was published online on December 21 in JAMA Network Open.

LIMITATIONS:

The analysis is constrained by the database, which may limit the generalizability of the findings. The authors determined the response to neoadjuvant therapy by comparing clinical stage with postoperative pathologic stage.

DISCLOSURES:

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Overall survival among US patients with resected stage II or III gastric cancer differs by race and ethnicity, with Asian and Hispanic patients demonstrating better overall survival than White and Black patients.

METHODOLOGY:

• Studies have revealed disparities in gastric cancer outcomes among different racial and ethnic groups in the United States, but the reasons are unclear.
• To better understand the disparities, researchers analyzed survival outcomes by race and ethnicity, treatment type, and a range of other factors.
• The retrospective analysis included 6938 patients with clinical stages IIA-IIIC gastric adenocarcinoma who underwent partial or total gastrectomy between 2006 and 2019, excluding those with a history of cancer. Patient data came from the National Cancer Database, which covers about 70% of all new cancer diagnoses.
• The researchers compared factors, including race and ethnicity, surgical margins, and lymph nodes, as well as treatment modality (neoadjuvant or adjuvant chemotherapy only, neoadjuvant or adjuvant chemoradiation only, or perioperative chemotherapy with radiation or surgical care only).
• Just over half of the patients (53.6%) were White, 24.3% were Black, 17.8% were Hispanic, 15.8% were Asian, and 2.6% were other race or ethnicity (information was missing for 4.8%). White patients were more likely to be older and insured; Black and White patients had more comorbidities than Asian and Hispanic patients.

TAKEAWAY:

• Perioperative chemotherapy was associated with improved overall survival (hazard ratio [HR], 0.79), while surgical resection alone (HR, 1.79), more positive lymph nodes (HR, 2.95 for 10 or more), and positive surgical margins were associated with the biggest decreases in overall survival.
• Asian and Hispanic patients had significantly better overall survival (HR, 0.64 and 0.77, respectively) than White patients.
• In general, Black and White patients had similar overall survival (HR, 0.96), except among Black patients who received neoadjuvant therapy — these patients had better overall survival than White patients (HR, 0.78).
• Black and Asian patients were more likely to be downstaged or achieve a pathologic complete response after neoadjuvant therapy (34.4% and 35.3%, respectively) than White (28.4%) and Hispanic patients (30.8%).

IN PRACTICE:

The authors found that “Asian and Hispanic race and ethnicity were independently associated with improved [overall survival] compared with Black and White race,” even after adjusting for variables including multimodality treatment regimen and response to neoadjuvant therapy.

The authors explained that overall Asian and Black patients responded more favorably to neoadjuvant therapy, demonstrating significantly higher rates of downstaging or pathologic complete response, which may help explain why Black patients demonstrated better overall survival than White patients who received neoadjuvant therapy.

SOURCE:

The research, led by Steve Kwon, MD, MPH, of Roger Williams Medical Center and Boston University, Providence, Rhode Island, was published online on December 21 in JAMA Network Open.

LIMITATIONS:

The analysis is constrained by the database, which may limit the generalizability of the findings. The authors determined the response to neoadjuvant therapy by comparing clinical stage with postoperative pathologic stage.

DISCLOSURES:

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Overall survival among US patients with resected stage II or III gastric cancer differs by race and ethnicity, with Asian and Hispanic patients demonstrating better overall survival than White and Black patients.

METHODOLOGY:

• Studies have revealed disparities in gastric cancer outcomes among different racial and ethnic groups in the United States, but the reasons are unclear.
• To better understand the disparities, researchers analyzed survival outcomes by race and ethnicity, treatment type, and a range of other factors.
• The retrospective analysis included 6938 patients with clinical stages IIA-IIIC gastric adenocarcinoma who underwent partial or total gastrectomy between 2006 and 2019, excluding those with a history of cancer. Patient data came from the National Cancer Database, which covers about 70% of all new cancer diagnoses.
• The researchers compared factors, including race and ethnicity, surgical margins, and lymph nodes, as well as treatment modality (neoadjuvant or adjuvant chemotherapy only, neoadjuvant or adjuvant chemoradiation only, or perioperative chemotherapy with radiation or surgical care only).
• Just over half of the patients (53.6%) were White, 24.3% were Black, 17.8% were Hispanic, 15.8% were Asian, and 2.6% were other race or ethnicity (information was missing for 4.8%). White patients were more likely to be older and insured; Black and White patients had more comorbidities than Asian and Hispanic patients.

TAKEAWAY:

• Perioperative chemotherapy was associated with improved overall survival (hazard ratio [HR], 0.79), while surgical resection alone (HR, 1.79), more positive lymph nodes (HR, 2.95 for 10 or more), and positive surgical margins were associated with the biggest decreases in overall survival.
• Asian and Hispanic patients had significantly better overall survival (HR, 0.64 and 0.77, respectively) than White patients.
• In general, Black and White patients had similar overall survival (HR, 0.96), except among Black patients who received neoadjuvant therapy — these patients had better overall survival than White patients (HR, 0.78).
• Black and Asian patients were more likely to be downstaged or achieve a pathologic complete response after neoadjuvant therapy (34.4% and 35.3%, respectively) than White (28.4%) and Hispanic patients (30.8%).

IN PRACTICE:

The authors found that “Asian and Hispanic race and ethnicity were independently associated with improved [overall survival] compared with Black and White race,” even after adjusting for variables including multimodality treatment regimen and response to neoadjuvant therapy.

The authors explained that overall Asian and Black patients responded more favorably to neoadjuvant therapy, demonstrating significantly higher rates of downstaging or pathologic complete response, which may help explain why Black patients demonstrated better overall survival than White patients who received neoadjuvant therapy.

SOURCE:

The research, led by Steve Kwon, MD, MPH, of Roger Williams Medical Center and Boston University, Providence, Rhode Island, was published online on December 21 in JAMA Network Open.

LIMITATIONS:

The analysis is constrained by the database, which may limit the generalizability of the findings. The authors determined the response to neoadjuvant therapy by comparing clinical stage with postoperative pathologic stage.

DISCLOSURES:

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

Migraine is one of the most common neurologic diseases, affecting about 14% of the population. Migraines may also be associated with auras or visual or sensory symptoms that precede the headache. However, approximately 4% of people with migraine experience their usual migraines and sometimes also experience episodes of an aura that is not followed by a headache. Silent migraines, also known as acephalgic migraines or "migraine auras without headache," typically cause symptoms that accompany the phases of a migraine, but without the classic headache pain. It is most common among young adults in their 20s and 30s and older adults between 40 and 60 years of age, especially in those who had auras accompanied by migraine headaches when younger. 

According to the International Headache Society, a migraine aura develops gradually over 5 to 10 minutes and lasts for less than 1 hour. Although the symptoms of a silent migraine may vary from person to person, visual symptoms occur in more than 90% of migraine auras. Visual symptoms may also be accompanied by other neurologic symptoms such as dizziness, numbness or tingling, and aphasia. The most common visual symptoms are positive symptoms, such as flash scotoma, visual distortion, colored spots, and flash hallucinations. Visual symptoms may easily be confused with symptoms of a transient ischemic attack (TIA). However, migraine auras generally last 15 to 30 minutes. They are often described as dynamic, bright, multicolored forms in geometric patterns. In contrast, the visual symptoms of a TIA last on average 3 to 10 minutes and are described as a static, dark dimming of vision. 

The diagnosis of migraine aura without headache should be made after all other possible causes have been excluded, particularly TIAs and focal seizures because of the diagnostic, therapeutic, and prognostic implications. Testing may include a neurologic and eye examination, MRI, CT angiography, and laboratory testing for clotting disorders. 

Migraine aura without headache is a benign condition and generally does not require treatment. When symptoms of silent migraines are severe enough, low-dose aspirin and calcium-channel blockers may be considered as treatment options. However, triptans, which are often used in patients with migraine headaches, should not be used to treat silent migraines because they do not act fast enough to affect an aura. In addition, triptans should be used with caution in older patients, who may have vascular disease, hypertension, and other cardiovascular risk factors. 
 

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Migraine is one of the most common neurologic diseases, affecting about 14% of the population. Migraines may also be associated with auras or visual or sensory symptoms that precede the headache. However, approximately 4% of people with migraine experience their usual migraines and sometimes also experience episodes of an aura that is not followed by a headache. Silent migraines, also known as acephalgic migraines or "migraine auras without headache," typically cause symptoms that accompany the phases of a migraine, but without the classic headache pain. It is most common among young adults in their 20s and 30s and older adults between 40 and 60 years of age, especially in those who had auras accompanied by migraine headaches when younger. 

According to the International Headache Society, a migraine aura develops gradually over 5 to 10 minutes and lasts for less than 1 hour. Although the symptoms of a silent migraine may vary from person to person, visual symptoms occur in more than 90% of migraine auras. Visual symptoms may also be accompanied by other neurologic symptoms such as dizziness, numbness or tingling, and aphasia. The most common visual symptoms are positive symptoms, such as flash scotoma, visual distortion, colored spots, and flash hallucinations. Visual symptoms may easily be confused with symptoms of a transient ischemic attack (TIA). However, migraine auras generally last 15 to 30 minutes. They are often described as dynamic, bright, multicolored forms in geometric patterns. In contrast, the visual symptoms of a TIA last on average 3 to 10 minutes and are described as a static, dark dimming of vision. 

The diagnosis of migraine aura without headache should be made after all other possible causes have been excluded, particularly TIAs and focal seizures because of the diagnostic, therapeutic, and prognostic implications. Testing may include a neurologic and eye examination, MRI, CT angiography, and laboratory testing for clotting disorders. 

Migraine aura without headache is a benign condition and generally does not require treatment. When symptoms of silent migraines are severe enough, low-dose aspirin and calcium-channel blockers may be considered as treatment options. However, triptans, which are often used in patients with migraine headaches, should not be used to treat silent migraines because they do not act fast enough to affect an aura. In addition, triptans should be used with caution in older patients, who may have vascular disease, hypertension, and other cardiovascular risk factors. 
 

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Migraine is one of the most common neurologic diseases, affecting about 14% of the population. Migraines may also be associated with auras or visual or sensory symptoms that precede the headache. However, approximately 4% of people with migraine experience their usual migraines and sometimes also experience episodes of an aura that is not followed by a headache. Silent migraines, also known as acephalgic migraines or "migraine auras without headache," typically cause symptoms that accompany the phases of a migraine, but without the classic headache pain. It is most common among young adults in their 20s and 30s and older adults between 40 and 60 years of age, especially in those who had auras accompanied by migraine headaches when younger. 

According to the International Headache Society, a migraine aura develops gradually over 5 to 10 minutes and lasts for less than 1 hour. Although the symptoms of a silent migraine may vary from person to person, visual symptoms occur in more than 90% of migraine auras. Visual symptoms may also be accompanied by other neurologic symptoms such as dizziness, numbness or tingling, and aphasia. The most common visual symptoms are positive symptoms, such as flash scotoma, visual distortion, colored spots, and flash hallucinations. Visual symptoms may easily be confused with symptoms of a transient ischemic attack (TIA). However, migraine auras generally last 15 to 30 minutes. They are often described as dynamic, bright, multicolored forms in geometric patterns. In contrast, the visual symptoms of a TIA last on average 3 to 10 minutes and are described as a static, dark dimming of vision. 

The diagnosis of migraine aura without headache should be made after all other possible causes have been excluded, particularly TIAs and focal seizures because of the diagnostic, therapeutic, and prognostic implications. Testing may include a neurologic and eye examination, MRI, CT angiography, and laboratory testing for clotting disorders. 

Migraine aura without headache is a benign condition and generally does not require treatment. When symptoms of silent migraines are severe enough, low-dose aspirin and calcium-channel blockers may be considered as treatment options. However, triptans, which are often used in patients with migraine headaches, should not be used to treat silent migraines because they do not act fast enough to affect an aura. In addition, triptans should be used with caution in older patients, who may have vascular disease, hypertension, and other cardiovascular risk factors. 
 

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

SAN DIEGO — It’s one of the great mysteries of hematology: Why do children with acute lymphoblastic leukemia (ALL) fare well in the modern era of cancer treatment, while adolescents and younger adults continue to face stubbornly high mortality rates?

In a session at the annual meeting of the American Society of Hematology in December, clinicians defined the extent of the problem — which one described as a “survival cliff” — and they discussed potential strategies to turn things around.

Cleveland Clinic hematologist John Molina, MD, EdM, highlighted a 2022 study that revealed “the 5-year overall survival for younger pediatric patients is quite phenomenal at 93%. But as you start shifting even to 15-19 patients, that shifts to an overall survival of 74%.”

In the rest of the young adult population, from age 20 to 39, the overall survival rate dips down to 59%. What’s going on?

As Dr. Molina noted, a 2008 study revealed that outcomes in ALL for those aged 16-20 “historically depended on which door you walked into”: the pediatric setting or the adult setting. Patients fared better on pediatric regimens.

Currently, he explained, those who begin treatment in adult oncology clinics will start with either a pediatric-inspired treatment called CALGB 10403 or HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone plus methotrexate and cytarabine).

CALGB 10403 was developed based on a pediatric backbone of COG AALL0232, Dr. Molina said, and has higher doses of major myelosuppressive agents vs. HyperCVAD. A 2019 study determined that it was feasible to treat adolescents and young adults up to age 40 “with low treatment-related mortality and marked improvement in outcomes. OS [overall survival] at 3 years was 73%.”

However, Dr. Molina observed that only 39% of patients completed the treatment per protocol.

Which is better, CALGB 10403 or HyperCVAD? Dr. Molina said the risk of infertility and other long-term adverse effects is higher in HyperCVAD, but it has a lower risk of hepatic, pancreatic and thrombotic complications. And the CALGB 10403 regimen is more complicated to deliver, which is a potential obstacle in clinics without large numbers of patients.

As for outcomes, some research suggests they improve with pediatric-inspired regimens like CALGB 10403, he said, noting that “the debate continues.”

However, even with better regimens, Dr. Molina added, older ALL patients are still faring worse.

Also at the ASH presentation, Emory University/Children’s Healthcare of Atlanta pediatric cancer specialist Tamara Miller, MD, explored possible reasons that could explain the difference in outcomes based on age.

Cancer biology, response to chemotherapy, toxicities, psychosocial challenges, and low enrollment in clinical trials are all potential factors, she said. Specifically, aging into adulthood can lower tolerance of chemotherapy, and older patients are more prone to obesity, which is associated with worse outcomes, she said.

As for psychosocial challenges, it can be hard for older patients to manage their own medications, and they may lack insurance coverage, she said. Some patients may have worries about fertility, she added, and some may rebel against the requirements of treatment. Adherence is crucial to reducing risk of relapse, she added.

University of Cincinnati leukemia specialist Emily Curran, MD, told the ASH audience that researchers are exploring various avenues to improve outcomes.

Philadelphia chromosome-like (Ph-like) ALL, a subset of B-ALL, is associated with worse outcomes, she said, but it has multiple targetable pathways. An ongoing trial is exploring ruxolitinib (Jakafi) and chemotherapy in patients aged 18-39 with Ph-like ALL, Dr. Curran said.

Researchers are also wondering if up-front immunotherapy can help overcome disease biology, she said. Another potential therapy, she added, is CAR-T therapy for T-ALL.

Beyond cancer biology, “psychosocial factors are an even more challenging area in which we have fewer ongoing and less solutions,” Dr. Curran said.

Dr. Molina disclosed honoraria and consulting relationships with Autolus. Dr. Curran reported ties with Kite, Amgen, Incyte, Pfizer, Jazz, and Servier. Dr. Miller has no disclosures.

SAN DIEGO — It’s one of the great mysteries of hematology: Why do children with acute lymphoblastic leukemia (ALL) fare well in the modern era of cancer treatment, while adolescents and younger adults continue to face stubbornly high mortality rates?

In a session at the annual meeting of the American Society of Hematology in December, clinicians defined the extent of the problem — which one described as a “survival cliff” — and they discussed potential strategies to turn things around.

Cleveland Clinic hematologist John Molina, MD, EdM, highlighted a 2022 study that revealed “the 5-year overall survival for younger pediatric patients is quite phenomenal at 93%. But as you start shifting even to 15-19 patients, that shifts to an overall survival of 74%.”

In the rest of the young adult population, from age 20 to 39, the overall survival rate dips down to 59%. What’s going on?

As Dr. Molina noted, a 2008 study revealed that outcomes in ALL for those aged 16-20 “historically depended on which door you walked into”: the pediatric setting or the adult setting. Patients fared better on pediatric regimens.

Currently, he explained, those who begin treatment in adult oncology clinics will start with either a pediatric-inspired treatment called CALGB 10403 or HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone plus methotrexate and cytarabine).

CALGB 10403 was developed based on a pediatric backbone of COG AALL0232, Dr. Molina said, and has higher doses of major myelosuppressive agents vs. HyperCVAD. A 2019 study determined that it was feasible to treat adolescents and young adults up to age 40 “with low treatment-related mortality and marked improvement in outcomes. OS [overall survival] at 3 years was 73%.”

However, Dr. Molina observed that only 39% of patients completed the treatment per protocol.

Which is better, CALGB 10403 or HyperCVAD? Dr. Molina said the risk of infertility and other long-term adverse effects is higher in HyperCVAD, but it has a lower risk of hepatic, pancreatic and thrombotic complications. And the CALGB 10403 regimen is more complicated to deliver, which is a potential obstacle in clinics without large numbers of patients.

As for outcomes, some research suggests they improve with pediatric-inspired regimens like CALGB 10403, he said, noting that “the debate continues.”

However, even with better regimens, Dr. Molina added, older ALL patients are still faring worse.

Also at the ASH presentation, Emory University/Children’s Healthcare of Atlanta pediatric cancer specialist Tamara Miller, MD, explored possible reasons that could explain the difference in outcomes based on age.

Cancer biology, response to chemotherapy, toxicities, psychosocial challenges, and low enrollment in clinical trials are all potential factors, she said. Specifically, aging into adulthood can lower tolerance of chemotherapy, and older patients are more prone to obesity, which is associated with worse outcomes, she said.

As for psychosocial challenges, it can be hard for older patients to manage their own medications, and they may lack insurance coverage, she said. Some patients may have worries about fertility, she added, and some may rebel against the requirements of treatment. Adherence is crucial to reducing risk of relapse, she added.

University of Cincinnati leukemia specialist Emily Curran, MD, told the ASH audience that researchers are exploring various avenues to improve outcomes.

Philadelphia chromosome-like (Ph-like) ALL, a subset of B-ALL, is associated with worse outcomes, she said, but it has multiple targetable pathways. An ongoing trial is exploring ruxolitinib (Jakafi) and chemotherapy in patients aged 18-39 with Ph-like ALL, Dr. Curran said.

Researchers are also wondering if up-front immunotherapy can help overcome disease biology, she said. Another potential therapy, she added, is CAR-T therapy for T-ALL.

Beyond cancer biology, “psychosocial factors are an even more challenging area in which we have fewer ongoing and less solutions,” Dr. Curran said.

Dr. Molina disclosed honoraria and consulting relationships with Autolus. Dr. Curran reported ties with Kite, Amgen, Incyte, Pfizer, Jazz, and Servier. Dr. Miller has no disclosures.

SAN DIEGO — It’s one of the great mysteries of hematology: Why do children with acute lymphoblastic leukemia (ALL) fare well in the modern era of cancer treatment, while adolescents and younger adults continue to face stubbornly high mortality rates?

In a session at the annual meeting of the American Society of Hematology in December, clinicians defined the extent of the problem — which one described as a “survival cliff” — and they discussed potential strategies to turn things around.

Cleveland Clinic hematologist John Molina, MD, EdM, highlighted a 2022 study that revealed “the 5-year overall survival for younger pediatric patients is quite phenomenal at 93%. But as you start shifting even to 15-19 patients, that shifts to an overall survival of 74%.”

In the rest of the young adult population, from age 20 to 39, the overall survival rate dips down to 59%. What’s going on?

As Dr. Molina noted, a 2008 study revealed that outcomes in ALL for those aged 16-20 “historically depended on which door you walked into”: the pediatric setting or the adult setting. Patients fared better on pediatric regimens.

Currently, he explained, those who begin treatment in adult oncology clinics will start with either a pediatric-inspired treatment called CALGB 10403 or HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone plus methotrexate and cytarabine).

CALGB 10403 was developed based on a pediatric backbone of COG AALL0232, Dr. Molina said, and has higher doses of major myelosuppressive agents vs. HyperCVAD. A 2019 study determined that it was feasible to treat adolescents and young adults up to age 40 “with low treatment-related mortality and marked improvement in outcomes. OS [overall survival] at 3 years was 73%.”

However, Dr. Molina observed that only 39% of patients completed the treatment per protocol.

Which is better, CALGB 10403 or HyperCVAD? Dr. Molina said the risk of infertility and other long-term adverse effects is higher in HyperCVAD, but it has a lower risk of hepatic, pancreatic and thrombotic complications. And the CALGB 10403 regimen is more complicated to deliver, which is a potential obstacle in clinics without large numbers of patients.

As for outcomes, some research suggests they improve with pediatric-inspired regimens like CALGB 10403, he said, noting that “the debate continues.”

However, even with better regimens, Dr. Molina added, older ALL patients are still faring worse.

Also at the ASH presentation, Emory University/Children’s Healthcare of Atlanta pediatric cancer specialist Tamara Miller, MD, explored possible reasons that could explain the difference in outcomes based on age.

Cancer biology, response to chemotherapy, toxicities, psychosocial challenges, and low enrollment in clinical trials are all potential factors, she said. Specifically, aging into adulthood can lower tolerance of chemotherapy, and older patients are more prone to obesity, which is associated with worse outcomes, she said.

As for psychosocial challenges, it can be hard for older patients to manage their own medications, and they may lack insurance coverage, she said. Some patients may have worries about fertility, she added, and some may rebel against the requirements of treatment. Adherence is crucial to reducing risk of relapse, she added.

University of Cincinnati leukemia specialist Emily Curran, MD, told the ASH audience that researchers are exploring various avenues to improve outcomes.

Philadelphia chromosome-like (Ph-like) ALL, a subset of B-ALL, is associated with worse outcomes, she said, but it has multiple targetable pathways. An ongoing trial is exploring ruxolitinib (Jakafi) and chemotherapy in patients aged 18-39 with Ph-like ALL, Dr. Curran said.

Researchers are also wondering if up-front immunotherapy can help overcome disease biology, she said. Another potential therapy, she added, is CAR-T therapy for T-ALL.

Beyond cancer biology, “psychosocial factors are an even more challenging area in which we have fewer ongoing and less solutions,” Dr. Curran said.

Dr. Molina disclosed honoraria and consulting relationships with Autolus. Dr. Curran reported ties with Kite, Amgen, Incyte, Pfizer, Jazz, and Servier. Dr. Miller has no disclosures.

ORLANDO — “There are similarities between Alzheimer’s disease and epilepsy,” said Delia Marias Talos, MD, at a session of the annual meeting of the American Epilepsy Society (AES).

A Closer Look at the Brain

“Phosphorylated tau correlates with cognitive function and executive function recorded presurgery, but it looks like the generative changes are more associated with temporal lobe and aging.”

Alzheimer’s disease is a degenerative condition marked by progressive memory deficits and cognitive decline noted by amyloid plaques and a formation of neurofibrillary tangles resulting from tau hyperphosphorylation.

Epilepsy, on the other hand, is a multifactorial condition with causes ranging from metabolic disorders, structural defects, infections, genetic mutations, and autoimmune disorders. In addition, nearly 50% of all epileptic seizures are idiopathic in nature.

Dr. Talos, professor of neurology at the University of Pennsylvania Perlman School of Medicine in Philadelphia, and her team did not see neurofibrillary tangles in the presurgical brains of epilepsy patients they studied; however, they saw tau plaques. In the future, they seek to investigate the features that distinguish epilepsy from Alzheimer’s disease.

Toxic fragments are probably there because amyloid precursor protein is highly upregulated, she told conference attendees. “We hypothesized that amyloid plaque is cleared but not impaired in epilepsy.”

The prognosis looks comparatively worse for patients who have Alzheimer’s disease and comorbid epilepsy than for patients who have only epilepsy. In addition, Dr. Talos stated that seizures appear to have an additive effort on Alzheimer’s disease.
 

Fyn-disruptive Therapy

Marson Putra, MD, PhD, a neuroscientist and postdoctoral researcher at Iowa State in Ames, Iowa, presented on the potential impact of a novel fyn-tau interaction as an unexplored target for epileptogensis and epilepsy.

Dr. Putra studied whether fyn-tau interactions exist in epilepsy. In both Alzheimer’s disease and epilepsy, Fyn belongs to the Src family of nonreceptor tyrosine kinases (SFKs), which are involved in cell proliferation and migration. Fyn contains an SH3 domain, which serves as a target for tau’s proline-rich (PxxP) motif. Fyn phosphorylates tau, specifically at tyrosine residue Y18, making fyn-disruptive therapy worth exploring.

Dr. Putra shared several currently proposed mechanisms of action regarding the pathogenesis of the tau plaque. In the first theory, the tau protein assumes a closed conformation in its normal state, thereby concealing the PxxP motif. However, in the second theory, pathogenesis causes the tau protein to assume an open conformation in the disease state, exposing pAT8 sites and making them available to fyn phosphorylation. In the second scenario, which involves Alzheimer’s disease, the fyn-tau interaction still occurs in open conformation state and is thought to occur in the postsynaptic terminal of the dendritic spine.

To investigate the proposed disease-causing mechanisms, Dr. Putra and her team studied status epilepticus in a rodent model of status epilepticus (SE). They used proximity ligation assay to measure interactions between Fyn and tau. They found AT8 and Y18 Fyn and N-methyl-D-aspartate (NMDA) receptor activation in a rat model and increased Fyn interaction. In addition, neuronal nitric oxide synthase levels were elevated 24 hours post-status. When investigating the fyn activity and interactions in the human brain, they found fyn phosphorylation – something that had never been reported before.

From there, Dr. Putra’s team sought to answer whether manipulating fyn-tau interactions could modify epilepsy. To do so, they conducted an experiment using the pharmacological Fyn inhibitor sarcatinib (SAR) and found it modified dysregulated postsynaptic proteins 24 hours post-SE in rat models. Longer exposure also bore a positive effect on epileptic rats.

After treating epileptic rats with SAR for 7 weeks, Dr. Putra found that SAR therapy reduces convulsive seizures during 7 weeks post-SE in rats. Recruiting pharmacological Fyn inhibition sufficiently decreased Fyn-tau interaction, NR-PSD95 complex, and convulsive seizures in chronic epilepsy.

Ultimately, her findings showed that SE exacerbates fyn-tau interactions, with chronic epilepsy modeling showing sustained elevation. In addition, fyn-tau interactions mediate and sustain neuronal hyperexcitability in the epileptic population.

“The impact on clinical care will be bidirectional relevant therapeutic targets in epilepsy and Alzheimer’s disease,” Dr. Putra told the audience.
 

Trends in epilepsy comorbidity and mortality

The final presenter, University of Washington researcher Aaron del Pozo, PhD, explained the impact of early-onset Alzheimer’s disease on overall outcomes and epilepsy.

“Early-onset Alzheimer’s disease carries a high seizure risk that affects quality of life as well as mortality,” Dr. del Pozo said.

According to data published in the British Medical Journal in 2020, the number of patients with epilepsy who had degenerative disease of the central nervous system or vascular dementia and delirium increased by approximately 210% from 1999 to 2017. Cerebral palsy trailed in second place with malignant neoplasms increasing by 50%. Cerebrovascular disease­–related death in the epileptic population showed nearly negligible change, and ischemic heart disease and epilepsy decreased by approximately 25% and 15%, respectively. In addition, patients who have both epilepsy and Alzheimer’s disease are less likely to survive than patients who develop epilepsy after Alzheimer’s disease.

“We found that having epilepsy alone has decreased mortality, but having it in addition to other generative diseases of the central nervous system has a 200% increase in mortality,” Dr. del Pozo said.

ORLANDO — “There are similarities between Alzheimer’s disease and epilepsy,” said Delia Marias Talos, MD, at a session of the annual meeting of the American Epilepsy Society (AES).

A Closer Look at the Brain

“Phosphorylated tau correlates with cognitive function and executive function recorded presurgery, but it looks like the generative changes are more associated with temporal lobe and aging.”

Alzheimer’s disease is a degenerative condition marked by progressive memory deficits and cognitive decline noted by amyloid plaques and a formation of neurofibrillary tangles resulting from tau hyperphosphorylation.

Epilepsy, on the other hand, is a multifactorial condition with causes ranging from metabolic disorders, structural defects, infections, genetic mutations, and autoimmune disorders. In addition, nearly 50% of all epileptic seizures are idiopathic in nature.

Dr. Talos, professor of neurology at the University of Pennsylvania Perlman School of Medicine in Philadelphia, and her team did not see neurofibrillary tangles in the presurgical brains of epilepsy patients they studied; however, they saw tau plaques. In the future, they seek to investigate the features that distinguish epilepsy from Alzheimer’s disease.

Toxic fragments are probably there because amyloid precursor protein is highly upregulated, she told conference attendees. “We hypothesized that amyloid plaque is cleared but not impaired in epilepsy.”

The prognosis looks comparatively worse for patients who have Alzheimer’s disease and comorbid epilepsy than for patients who have only epilepsy. In addition, Dr. Talos stated that seizures appear to have an additive effort on Alzheimer’s disease.
 

Fyn-disruptive Therapy

Marson Putra, MD, PhD, a neuroscientist and postdoctoral researcher at Iowa State in Ames, Iowa, presented on the potential impact of a novel fyn-tau interaction as an unexplored target for epileptogensis and epilepsy.

Dr. Putra studied whether fyn-tau interactions exist in epilepsy. In both Alzheimer’s disease and epilepsy, Fyn belongs to the Src family of nonreceptor tyrosine kinases (SFKs), which are involved in cell proliferation and migration. Fyn contains an SH3 domain, which serves as a target for tau’s proline-rich (PxxP) motif. Fyn phosphorylates tau, specifically at tyrosine residue Y18, making fyn-disruptive therapy worth exploring.

Dr. Putra shared several currently proposed mechanisms of action regarding the pathogenesis of the tau plaque. In the first theory, the tau protein assumes a closed conformation in its normal state, thereby concealing the PxxP motif. However, in the second theory, pathogenesis causes the tau protein to assume an open conformation in the disease state, exposing pAT8 sites and making them available to fyn phosphorylation. In the second scenario, which involves Alzheimer’s disease, the fyn-tau interaction still occurs in open conformation state and is thought to occur in the postsynaptic terminal of the dendritic spine.

To investigate the proposed disease-causing mechanisms, Dr. Putra and her team studied status epilepticus in a rodent model of status epilepticus (SE). They used proximity ligation assay to measure interactions between Fyn and tau. They found AT8 and Y18 Fyn and N-methyl-D-aspartate (NMDA) receptor activation in a rat model and increased Fyn interaction. In addition, neuronal nitric oxide synthase levels were elevated 24 hours post-status. When investigating the fyn activity and interactions in the human brain, they found fyn phosphorylation – something that had never been reported before.

From there, Dr. Putra’s team sought to answer whether manipulating fyn-tau interactions could modify epilepsy. To do so, they conducted an experiment using the pharmacological Fyn inhibitor sarcatinib (SAR) and found it modified dysregulated postsynaptic proteins 24 hours post-SE in rat models. Longer exposure also bore a positive effect on epileptic rats.

After treating epileptic rats with SAR for 7 weeks, Dr. Putra found that SAR therapy reduces convulsive seizures during 7 weeks post-SE in rats. Recruiting pharmacological Fyn inhibition sufficiently decreased Fyn-tau interaction, NR-PSD95 complex, and convulsive seizures in chronic epilepsy.

Ultimately, her findings showed that SE exacerbates fyn-tau interactions, with chronic epilepsy modeling showing sustained elevation. In addition, fyn-tau interactions mediate and sustain neuronal hyperexcitability in the epileptic population.

“The impact on clinical care will be bidirectional relevant therapeutic targets in epilepsy and Alzheimer’s disease,” Dr. Putra told the audience.
 

Trends in epilepsy comorbidity and mortality

The final presenter, University of Washington researcher Aaron del Pozo, PhD, explained the impact of early-onset Alzheimer’s disease on overall outcomes and epilepsy.

“Early-onset Alzheimer’s disease carries a high seizure risk that affects quality of life as well as mortality,” Dr. del Pozo said.

According to data published in the British Medical Journal in 2020, the number of patients with epilepsy who had degenerative disease of the central nervous system or vascular dementia and delirium increased by approximately 210% from 1999 to 2017. Cerebral palsy trailed in second place with malignant neoplasms increasing by 50%. Cerebrovascular disease­–related death in the epileptic population showed nearly negligible change, and ischemic heart disease and epilepsy decreased by approximately 25% and 15%, respectively. In addition, patients who have both epilepsy and Alzheimer’s disease are less likely to survive than patients who develop epilepsy after Alzheimer’s disease.

“We found that having epilepsy alone has decreased mortality, but having it in addition to other generative diseases of the central nervous system has a 200% increase in mortality,” Dr. del Pozo said.

ORLANDO — “There are similarities between Alzheimer’s disease and epilepsy,” said Delia Marias Talos, MD, at a session of the annual meeting of the American Epilepsy Society (AES).

A Closer Look at the Brain

“Phosphorylated tau correlates with cognitive function and executive function recorded presurgery, but it looks like the generative changes are more associated with temporal lobe and aging.”

Alzheimer’s disease is a degenerative condition marked by progressive memory deficits and cognitive decline noted by amyloid plaques and a formation of neurofibrillary tangles resulting from tau hyperphosphorylation.

Epilepsy, on the other hand, is a multifactorial condition with causes ranging from metabolic disorders, structural defects, infections, genetic mutations, and autoimmune disorders. In addition, nearly 50% of all epileptic seizures are idiopathic in nature.

Dr. Talos, professor of neurology at the University of Pennsylvania Perlman School of Medicine in Philadelphia, and her team did not see neurofibrillary tangles in the presurgical brains of epilepsy patients they studied; however, they saw tau plaques. In the future, they seek to investigate the features that distinguish epilepsy from Alzheimer’s disease.

Toxic fragments are probably there because amyloid precursor protein is highly upregulated, she told conference attendees. “We hypothesized that amyloid plaque is cleared but not impaired in epilepsy.”

The prognosis looks comparatively worse for patients who have Alzheimer’s disease and comorbid epilepsy than for patients who have only epilepsy. In addition, Dr. Talos stated that seizures appear to have an additive effort on Alzheimer’s disease.
 

Fyn-disruptive Therapy

Marson Putra, MD, PhD, a neuroscientist and postdoctoral researcher at Iowa State in Ames, Iowa, presented on the potential impact of a novel fyn-tau interaction as an unexplored target for epileptogensis and epilepsy.

Dr. Putra studied whether fyn-tau interactions exist in epilepsy. In both Alzheimer’s disease and epilepsy, Fyn belongs to the Src family of nonreceptor tyrosine kinases (SFKs), which are involved in cell proliferation and migration. Fyn contains an SH3 domain, which serves as a target for tau’s proline-rich (PxxP) motif. Fyn phosphorylates tau, specifically at tyrosine residue Y18, making fyn-disruptive therapy worth exploring.

Dr. Putra shared several currently proposed mechanisms of action regarding the pathogenesis of the tau plaque. In the first theory, the tau protein assumes a closed conformation in its normal state, thereby concealing the PxxP motif. However, in the second theory, pathogenesis causes the tau protein to assume an open conformation in the disease state, exposing pAT8 sites and making them available to fyn phosphorylation. In the second scenario, which involves Alzheimer’s disease, the fyn-tau interaction still occurs in open conformation state and is thought to occur in the postsynaptic terminal of the dendritic spine.

To investigate the proposed disease-causing mechanisms, Dr. Putra and her team studied status epilepticus in a rodent model of status epilepticus (SE). They used proximity ligation assay to measure interactions between Fyn and tau. They found AT8 and Y18 Fyn and N-methyl-D-aspartate (NMDA) receptor activation in a rat model and increased Fyn interaction. In addition, neuronal nitric oxide synthase levels were elevated 24 hours post-status. When investigating the fyn activity and interactions in the human brain, they found fyn phosphorylation – something that had never been reported before.

From there, Dr. Putra’s team sought to answer whether manipulating fyn-tau interactions could modify epilepsy. To do so, they conducted an experiment using the pharmacological Fyn inhibitor sarcatinib (SAR) and found it modified dysregulated postsynaptic proteins 24 hours post-SE in rat models. Longer exposure also bore a positive effect on epileptic rats.

After treating epileptic rats with SAR for 7 weeks, Dr. Putra found that SAR therapy reduces convulsive seizures during 7 weeks post-SE in rats. Recruiting pharmacological Fyn inhibition sufficiently decreased Fyn-tau interaction, NR-PSD95 complex, and convulsive seizures in chronic epilepsy.

Ultimately, her findings showed that SE exacerbates fyn-tau interactions, with chronic epilepsy modeling showing sustained elevation. In addition, fyn-tau interactions mediate and sustain neuronal hyperexcitability in the epileptic population.

“The impact on clinical care will be bidirectional relevant therapeutic targets in epilepsy and Alzheimer’s disease,” Dr. Putra told the audience.
 

Trends in epilepsy comorbidity and mortality

The final presenter, University of Washington researcher Aaron del Pozo, PhD, explained the impact of early-onset Alzheimer’s disease on overall outcomes and epilepsy.

“Early-onset Alzheimer’s disease carries a high seizure risk that affects quality of life as well as mortality,” Dr. del Pozo said.

According to data published in the British Medical Journal in 2020, the number of patients with epilepsy who had degenerative disease of the central nervous system or vascular dementia and delirium increased by approximately 210% from 1999 to 2017. Cerebral palsy trailed in second place with malignant neoplasms increasing by 50%. Cerebrovascular disease­–related death in the epileptic population showed nearly negligible change, and ischemic heart disease and epilepsy decreased by approximately 25% and 15%, respectively. In addition, patients who have both epilepsy and Alzheimer’s disease are less likely to survive than patients who develop epilepsy after Alzheimer’s disease.

“We found that having epilepsy alone has decreased mortality, but having it in addition to other generative diseases of the central nervous system has a 200% increase in mortality,” Dr. del Pozo said.

On January 5, the Food and Drug Administration (FDA) approved berdazimer gel 10.3% for the treatment of molluscum contagiosum (MC) in adults and children aged 1 year or older.

Approval of berdazimer, a topical nitric oxide–releasing agent, was based largely on a 12-week pivotal phase 3 trial known as B-SIMPLE4, in which 891 patients with a mean age of 6.6 years (range, 0.9-47.5 years) were randomly assigned to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily. At 12 weeks, 32.4% of patients in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% of those in the vehicle group (P < .001).

Only 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events in both groups were application-site pain and erythema, and most of these were mild or moderate.

According to a press release announcing the approval from Ligand Pharmaceuticals, which acquired berdazimer topical gel from Novan in September 2023, the development makes berdazimer topical gel 10.3% the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home; outside of a physician›s office; or outside of other medical settings to treat MC. Nitric oxide has been shown to have antiviral effects, although the mechanism of action of berdazimer for treating molluscum “is unknown,” the company said in the release. 

The drug will be marketed under the name Zelsuvmi and is expected to be available in the second half of 2024.

On July 21, 2023, topical cantharidin became the first approved treatment of MC for adults and pediatric patients aged 2 years or older, with the FDA approval of a drug-device combination (Ycanth) that contains a formulation of cantharidin solution 0.7% and is administered by healthcare professionals. 

A version of this article appeared on Medscape.com.

On January 5, the Food and Drug Administration (FDA) approved berdazimer gel 10.3% for the treatment of molluscum contagiosum (MC) in adults and children aged 1 year or older.

Approval of berdazimer, a topical nitric oxide–releasing agent, was based largely on a 12-week pivotal phase 3 trial known as B-SIMPLE4, in which 891 patients with a mean age of 6.6 years (range, 0.9-47.5 years) were randomly assigned to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily. At 12 weeks, 32.4% of patients in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% of those in the vehicle group (P < .001).

Only 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events in both groups were application-site pain and erythema, and most of these were mild or moderate.

According to a press release announcing the approval from Ligand Pharmaceuticals, which acquired berdazimer topical gel from Novan in September 2023, the development makes berdazimer topical gel 10.3% the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home; outside of a physician›s office; or outside of other medical settings to treat MC. Nitric oxide has been shown to have antiviral effects, although the mechanism of action of berdazimer for treating molluscum “is unknown,” the company said in the release. 

The drug will be marketed under the name Zelsuvmi and is expected to be available in the second half of 2024.

On July 21, 2023, topical cantharidin became the first approved treatment of MC for adults and pediatric patients aged 2 years or older, with the FDA approval of a drug-device combination (Ycanth) that contains a formulation of cantharidin solution 0.7% and is administered by healthcare professionals. 

A version of this article appeared on Medscape.com.

On January 5, the Food and Drug Administration (FDA) approved berdazimer gel 10.3% for the treatment of molluscum contagiosum (MC) in adults and children aged 1 year or older.

Approval of berdazimer, a topical nitric oxide–releasing agent, was based largely on a 12-week pivotal phase 3 trial known as B-SIMPLE4, in which 891 patients with a mean age of 6.6 years (range, 0.9-47.5 years) were randomly assigned to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily. At 12 weeks, 32.4% of patients in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% of those in the vehicle group (P < .001).

Only 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events in both groups were application-site pain and erythema, and most of these were mild or moderate.

According to a press release announcing the approval from Ligand Pharmaceuticals, which acquired berdazimer topical gel from Novan in September 2023, the development makes berdazimer topical gel 10.3% the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home; outside of a physician›s office; or outside of other medical settings to treat MC. Nitric oxide has been shown to have antiviral effects, although the mechanism of action of berdazimer for treating molluscum “is unknown,” the company said in the release. 

The drug will be marketed under the name Zelsuvmi and is expected to be available in the second half of 2024.

On July 21, 2023, topical cantharidin became the first approved treatment of MC for adults and pediatric patients aged 2 years or older, with the FDA approval of a drug-device combination (Ycanth) that contains a formulation of cantharidin solution 0.7% and is administered by healthcare professionals. 

A version of this article appeared on Medscape.com.

Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.

The move is seen as a major shift in the way these popular medications can reach patients. 

For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.

But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.

But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:

Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.

New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.

The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.

LillyDirect

Eli Lilly launched its direct-to-patient portal on Thursday, providing its obesity medicine (as well as diabetes and migraine drugs) direct to the consumer. Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases. 

Eli Lilly officials did not respond to requests for comment. 

Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.

“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.” 

“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.” 

There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”

He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest. 

The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”

The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”

Heart Attack, Stroke Reduction Benefits

Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.

In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period. 

The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.

As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.

Insurance Coverage

In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.

“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”

Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.

In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”

He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.” 

Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”

“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said. 

Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.

However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.

Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said. 

Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.

Long-Term Picture

Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.

Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.

Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.

A version of this article appeared on WebMD.com.

Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.

The move is seen as a major shift in the way these popular medications can reach patients. 

For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.

But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.

But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:

Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.

New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.

The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.

LillyDirect

Eli Lilly launched its direct-to-patient portal on Thursday, providing its obesity medicine (as well as diabetes and migraine drugs) direct to the consumer. Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases. 

Eli Lilly officials did not respond to requests for comment. 

Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.

“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.” 

“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.” 

There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”

He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest. 

The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”

The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”

Heart Attack, Stroke Reduction Benefits

Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.

In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period. 

The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.

As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.

Insurance Coverage

In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.

“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”

Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.

In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”

He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.” 

Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”

“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said. 

Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.

However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.

Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said. 

Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.

Long-Term Picture

Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.

Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.

Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.

A version of this article appeared on WebMD.com.

Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.

The move is seen as a major shift in the way these popular medications can reach patients. 

For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.

But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.

But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:

Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.

New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.

The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.

LillyDirect

Eli Lilly launched its direct-to-patient portal on Thursday, providing its obesity medicine (as well as diabetes and migraine drugs) direct to the consumer. Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases. 

Eli Lilly officials did not respond to requests for comment. 

Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.

“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.” 

“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.” 

There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”

He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest. 

The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”

The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”

Heart Attack, Stroke Reduction Benefits

Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.

In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period. 

The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.

As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.

Insurance Coverage

In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.

“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”

Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.

In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”

He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.” 

Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”

“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said. 

Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.

However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.

Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said. 

Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.

Long-Term Picture

Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.

Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.

Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.

A version of this article appeared on WebMD.com.